On this page, you can search all tDCS peer reviewed research publications. To narrow down the results, enter a keyword for the subject that you are interested in. Additionaly, some articles have links to online full text copies of the paper.


693 research article(s) found
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Transcranial Direct Current Stimulation (tDCS) of the visual cortex: a proof-of-concept study based on interictal electrophysiological abnormalities in migraine.

2013 Dec

Preventive pharmacotherapy for migraine is not satisfactory because of the low efficacy/tolerability ratio of many available drugs. Novel and more efficient preventive strategies are therefore warranted. Abnormal excitability of cortical areas appears to play a pivotal role in migraine pathophysiology. Transcranial direct current stimulation (tDCS) is a non-invasive and safe technique that is able to durably modulate the activity of the underlying cerebral cortex, and is being tested in various medical indications. The results of small open studies using tDCS in migraine prophylaxis are conflicting, possibly because the optimal stimulation settings and the brain targets were not well chosen. We have previously shown that the cerebral cortex, especially the visual cortex, is hyperresponsive in migraine patients between attacks and provided evidence from evoked potential studies that this is due to a decreased cortical preactivation level. If one accepts this concept, anodal tDCS over the visual cortex may have therapeutic potentials in migraine prevention, as it is able to increase neuronal firing.To study the effects of anodal tDCS on visual cortex activity in healthy volunteers (HV) and episodic migraine without aura patients (MoA), and its potentials for migraine prevention.We recorded pattern-reversal visual evoked potentials (VEP) before and after a 15-min session of anodal tDCS over the visual cortex in 11 HV and 13 MoA interictally. Then 10 MoA patients reporting at least 4 attacks/month subsequently participated in a therapeutic study, and received 2 similar sessions of tDCS per week for 8 weeks as migraine preventive therapy.In HV as well as in MoA, anodal tDCS transiently increased habituation of the VEP N1P1 component. VEP amplitudes were not modified by tDCS. Preventive treatment with anodal tDCS turned out to be beneficial in MoA: migraine attack frequency, migraine days, attack duration and acute medication intake significantly decreased during the treatment period compared to pre-treatment baseline (all p < 0.05), and this benefit persisted on average 4.8 weeks after the end of tDCS.Anodal tDCS over the visual cortex is thus able to increase habituation to repetitive visual stimuli in healthy volunteers and in episodic migraineurs, who on average lack habituation interictally. Moreover, 2 weekly sessions of anodal tDCS had a significant preventive anti- migraine effect, proofing the concept that the low preactivation level of the visual cortex in migraine patients can be corrected by an activating neurostimulation. The therapeutic results indicate that a larger sham-controlled trial using the same tDCS protocol is worthwhile.

The journal of headache and pain

Viganò, A; D'Elia, TS; Sava, SL; Auvé, M; De Pasqua, V; Colosimo, A; Di Piero, V; Schoenen, J; Magis, D


Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: a basis for high-definition tDCS.

2013 Jul

Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4 × 1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4 × 1 montage (4 × cathode, surrounding a single central anode; montage radius ~3 cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4 × 1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject. We provide direct evidence in humans that TES with a 4 × 1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4 × 1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4 × 1-Ring montage for cortically targeted neuromodulation.

NeuroImage

Edwards, D; Cortes, M; Datta, A; Minhas, P; Wassermann, EM; Bikson, M


Transcranial direct current stimulation (tDCS) of Broca's area in chronic aphasia: A controlled outcome study.

2013 Jun

In the last decade transcranial direct current stimulation (tDCS) has been introduced in aphasia post-stroke recovery as a tool for modulating neuroplasticity. However, it is still unclear whether tDCS should be applied at rest (off-line) or combined with behavioral treatment strategies (on-line), therefore, this study investigates the effect of repeated sessions of off-line tDCS on language recovery in post-stroke chronic aphasic patients.Eight post-stroke patients with different type and degree of chronic aphasia underwent two weeks of off-line anodal tDCS (2mA intensity for 20min a day) on Broca's area and two weeks of sham stimulation as a control condition. Language recovery was measured assessing object and action naming abilities with a computerized picture naming task.No significant difference between anodal tDCS and sham stimulation, both for object and action naming tasks, was found. Descriptive analysis of single cases showed that after tDCS only one patient improved substantially on action naming task.With the exception of one patient, the overall results suggest that in chronic aphasic patients the off-line tDCS protocol applied in this study is not effective in improving noun and verb naming abilities.

Behavioural brain research

Volpato, C; Cavinato, M; Piccione, F; Garzon, M; Meneghello, F; Birbaumer, N


Safety of repeated transcranial direct current stimulation in impaired skin: a case report.

2013 Jun

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique based on the application of a weak, direct electric current via 2 or more electrodes (anode and cathode) over the scalp. One concern when applying tDCS is skin burn. It has been suggested that skin lesions are related to changes in the local dermal homeostasis, and therefore, caution is warranted in patients with skin diseases (Loo et al [Int J Neuropsychopharmacol. 2011;14:425-426]). In this context, we believe that it would be useful for this emerging field of tDCS to report the preliminary safety of repeated application of tDCS in a patient with vitiligo, an autoimmune disorder characterized by depigmentation sites of the skin or mucous membranes. We report the case of a 31-year-old male patient with schizophrenia who underwent 10-daily tDCS sessions. He has had generalized vitiligo since childhood, and despite previous treatment, no current dermatologic follow-up was being carried out. Depigmentation sites were evident in different areas, particularly under the anodal area. We found that repeated anodal tDCS in 1 patient did not lead to skin lesions when applied over a vitiligo skin area. Some of the procedures that we used to buffer changes in skin temperature may have contributed to prevent tDCS-induced skin damage. Nevertheless, the exact conditions that lead to skin lesion are still unknown. Given the growing use and testing of tDCS, continuous assessment and reporting of local adverse effects are still warranted especially in conditions with increased risk of skin lesions such as in dermatologic conditions, skin burns, and previous skin damage.

The journal of ECT

Shiozawa, P; da Silva, ME; Raza, R; Uchida, RR; Cordeiro, Q; Fregni, F; Brunoni, AR


Bifrontal tDCS prevents implicit learning acquisition in antidepressant-free patients with major depressive disorder.

2013 Jun

The findings for implicit (procedural) learning impairment in major depression are mixed. We investigated this issue using transcranial direct current stimulation (tDCS), a method that non-invasively increases/decreases cortical activity. Twenty-eight age- and gender-matched, antidepressant-free depressed subjects received a single-session of active/sham tDCS. We used a bifrontal setup - anode and cathode over the left and the right dorsolateral prefrontal cortex (DLPFC), respectively. The probabilistic classification-learning (PCL) task was administered before and during tDCS. The percentage of correct responses improved during sham; although not during active tDCS. Procedural or implicit learning acquisition between tasks also occurred only for sham. We discuss whether DLPFC activation decreased activity in subcortical structures due to the depressive state. The deactivation of the right DLPFC by cathodal tDCS can also account for our results. To conclude, active bifrontal tDCS prevented implicit learning in depressive patients. Further studies with different tDCS montages and in other samples are necessary.

Progress in neuro-psychopharmacology & biological psychiatry

Brunoni, AR; Zanao, TA; Ferrucci, R; Priori, A; Valiengo, L; de Oliveira, JF; Boggio, PS; Lotufo, PA; Benseñor, IM; Fregni, F


Non-invasive brain stimulation: A new frontier in the treatment of neurogenic speech-language disorders.

2013 Jun

Abstract There is a growing body of evidence to support the use of non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) for the treatment of acquired speech and language disorders. The aim of the present paper is to review evidence to support the use of these procedures in the treatment of aphasia and dysarthria. Both TMS and tDCS are described in terms of their underlying principles and biophysics and their relative advantages and disadvantages for rehabilitation of acquired neurogenic communication disorders. Several studies have documented positive effects of inhibitory repetitive TMS (rTMS) to right Broca's area homologue on language recovery in non-fluent aphasia post-stroke. Improved language outcomes subsequent to high frequency rTMS applied to the lesioned hemisphere have also been documented. Similarly, therapeutic benefits have also been reported following tDCS, although the findings are less consistent than is the case with rTMS. Improved articulatory function and speech intelligibility has been noted in response to stimulation with excitatory rTMS in Parkinson's disease. It is suggested that the use of brain stimulation techniques in combination with more traditional therapies may represent the most innovative future approach to the treatment of acquired communication disorders.

International journal of speech-language pathology

Murdoch, BE; Barwood, CH


Polarity Independent Effects of Cerebellar tDCS on Short Term Ankle Visuomotor Learning.

2013 May

BACKGROUND: Transcranial direct current stimulation (tDCS), an emerging technique of noninvasive brain stimulation, has shown to produce beneficial neural effects in consequence with improvements in motor behavior. There are not many studies examining the use of tDCS for lower limb motor control and learning. Most studies using tDCS for facilitating lower limb motor coordination have applied tDCS to the lower limb motor cortex (M1). As the cerebellum is also critically involved in movement control, it is important to dissociate the effect of tDCS on the cerebellum and M1 with respect to lower limb motor control before we begin the application of tDCS as a neuromodulatory tool. OBJECTIVE/HYPOTHESIS: The purpose of this study was to determine the effects of cerebellar vs. motor cortical tDCS on short term ankle visuomotor learning in healthy individuals. METHODS: Eight healthy individuals practiced a skilled ankle motor tracking task while receiving either facilitatory anodal tDCS to cerebellum, inhibitory cathodal tDCS to cerebellum, facilitatory anodal tDCS to M1, inhibitory cathodal tDCS to M1 or sham stimulation. Pre- and post-measures of changes in cortical excitability of the tibialis anterior muscle and measures of tracking accuracy were assessed. RESULTS: Anodal cerebellar, cathodal cerebellar, and anodal M1 stimulation improved target-tracking accuracy of the ankle. This was not dependent on the observed changes in motor cortical excitability of the tibialis anterior muscle. CONCLUSION(S): Polarity independent effects of tDCS on cerebellum were observed. The present study shows that modulation effects of tDCS can occur because of changes in the cerebellum, a structure implicated in several forms of motor learning, providing an additional way in which tDCS can be used to improve motor coordination.

Brain stimulation

Shah, B; Nguyen, TT; Madhavan, S


Enhancement of Affective Processing Induced by Bifrontal Transcranial Direct Current Stimulation in Patients With Major Depression.

2013 May

OBJECTIVE: Our aim was to evaluate whether one single section of transcranial direct current stimulation (tDCS), a neuromodulatory technique that noninvasively modifies cortical excitability, could induce acute changes in the negative attentional bias in patients with major depression. SUBJECTS AND METHODS: Randomized, double-blind, sham-controlled, parallel design enrolling 24 age-, gender-matched, drug-free, depressed subjects. Anode and cathode were placed over the left and right dorsolateral prefrontal cortex. We performed a word Emotional Stroop Task collecting the response times (RTs) for positive-, negative-, and neutral-related words. The emotional Stroop effect for negative vs. neutral and vs. positive words was used as the measure of attentional bias. RESULTS: At baseline, RTs were significantly slower for negative vs. positive words. We found that active but not sham tDCS significantly modified the negative attentional bias, abolishing slower RT for negative words. CONCLUSION: Active but not sham tDCS significantly modified the negative attentional bias. These findings add evidence that a single tDCS session transiently induces potent changes in affective processing, which might be one of the mechanisms of tDCS underlying mood changes.

Neuromodulation : journal of the International Neuromodulation Society

Brunoni, AR; Zanao, TA; Vanderhasselt, MA; Valiengo, L; de Oliveira, JF; Boggio, PS; Lotufo, PA; Benseñor, IM; Fregni, F


Effects of non-pharmacological pain treatments on brain states.

2013 May

OBJECTIVE: To (1) evaluate the effects of a single session of four non-pharmacological pain interventions, relative to a sham tDCS procedure, on pain and electroencephalogram- (EEG-) assessed brain oscillations, and (2) determine the extent to which procedure-related changes in pain intensity are associated with changes in brain oscillations. METHODS: 30 individuals with spinal cord injury and chronic pain were given an EEG and administered measures of pain before and after five procedures (hypnosis, meditation, transcranial direct current stimulation [tDCS], neurofeedback, and a control sham tDCS procedure). RESULTS: Each procedure was associated with a different pattern of changes in brain activity, and all active procedures were significantly different from the control procedure in at least three bandwidths. Very weak and mostly non-significant associations were found between changes in EEG-assessed brain activity and pain. CONCLUSIONS: Different non-pharmacological pain treatments have distinctive effects on brain oscillation patterns. However, changes in EEG-assessed brain oscillations are not significantly associated with changes in pain, and therefore such changes do not appear useful for explaining the benefits of these treatments. SIGNIFICANCE: The results provide new findings regarding the unique effects of four non-pharmacological treatments on pain and brain activity.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Jensen, MP; Sherlin, LH; Askew, RL; Fregni, F; Witkop, G; Gianas, A; Howe, JD; Hakimian, S


Differential effects of dual and unihemispheric motor cortex stimulation in older adults.

2013 May

Bihemispheric transcranial direct current stimulation (tDCS) is thought to upregulate excitability of the primary motor cortex (M1) using anodal stimulation while concurrently downregulating contralateral M1 using cathodal stimulation. This "dual" tDCS method enhances motor learning in healthy subjects and facilitates motor recovery after stroke. However, its impact on motor system activity and connectivity remains unknown. Therefore, we assessed neural correlates of dual and unihemispheric anodal tDCS effects in 20 healthy older subjects in a randomized, sham-controlled study using a cross-over design. Participants underwent tDCS and simultaneous functional magnetic resonance imaging during a choice reaction time task and at rest. Diffusion tensor imaging (DTI) allowed us to relate potential functional changes to structural parameters. The resting-state analysis demonstrated that, compared with sham, both dual and anodal tDCS decreased connectivity of right hippocampus and M1 (contralateral to the anode position) while increasing connectivity in the left prefrontal cortex. Notably, dual but not anodal tDCS enhanced connectivity of the left dorsal posterior cingulate cortex. Furthermore, dual tDCS yielded stronger activations in bilateral M1 compared with anodal tDCS when participants used either their left or right hand during the motor task. The corresponding tDCS-induced changes in laterality of activations were related to the microstructural status of transcallosal motor fibers. In conclusion, our results suggest that the impact of bihemispheric tDCS cannot be explained by mere add-on effects of anodal and concurrent cathodal stimulation, but rather by complex network modulations involving interhemispheric interactions and areas associated with motor control in the dorsal posterior cingulate cortex.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Lindenberg, R; Nachtigall, L; Meinzer, M; Sieg, MM; Flöel, A


Non-invasive brain stimulation and the autonomic nervous system.

2013 May

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive methods of brain stimulation (NIBS) that can induce significant effects on cortical and subcortical neural networks. Both methods are relatively safe if appropriate guidelines are followed, and both can exert neuromodulatory effects that may be applied to the investigation of the autonomic nervous system (ANS). In addition, ANS measures can shed important light onto the neurobiologic mechanisms of NIBS. Here we present a systematic review on studies testing NIBS and ANS simultaneously. We structure our findings into four broad (not mutually exclusive) categories: (i) studies in which ANS function was modified by NIBS versus those in which it was not; (ii) studies in which NIBS was used to understand ANS function, (iii) studies in which ANS was used to understand NIBS mechanisms and (iv) NIBS/ANS studies conducted in healthy subjects versus those in patients with neuropsychiatric diseases. Forty-four articles were identified and no conclusive evidence of the effects of NIBS on ANS was observed, mainly because of the heterogeneity of included studies. Based on a comprehensive summary of this literature we propose how NIBS might be further developed to enhance our understanding of the cortical mechanisms of autonomic regulation and perhaps to modulate autonomic activity for therapeutic purposes.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Schestatsky, P; Simis, M; Freeman, R; Pascual-Leone, A; Fregni, F


Effect of Serotonin on Paired Associative Stimulation-Induced Plasticity in the Human Motor Cortex.

2013 May

Serotonin modulates diverse brain functions. Beyond its clinical antidepressant effects, it improves motor performance, learning and memory formation. These effects might at least be partially caused by the impact of serotonin on neuroplasticity, which is thought to be an important foundation of the respective functions. In principal accordance, selective serotonin reuptake inhibitors (SSRI) enhance long-term potentiation (LTP)-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. Since other neuromodulators have discernable effects on different kinds of plasticity in humans, here we were interested to explore the impact of serotonin on paired associative stimulation (PAS)-induced plasticity, which induces a more focal kind of plasticity, as compared to tDCS, shares some features with spike timing-dependent plasticity, and is thought to be relative closely related to learning processes. In this single-blinded, placebo-controlled, randomized crossover study, we administered a single dose of 20 mg citalopram or placebo medication and applied facilitatory and excitability-diminishing PAS to the left motor cortex of 14 healthy subjects. Cortico-spinal excitability was explored via single pulse transcranial magnetic stimulation (TMS)-elicited MEP amplitudes up to the next evening after plasticity induction. After citalopram administration, inhibitory PAS-induced after-effects were abolished and excitatory PAS-induced after-effects were enhanced trendwise, as compared to the respective placebo conditions. These results show that serotonin modulates PAS-induced neuroplasticity by shifting it into the direction of facilitation, which might help to explain mechanism of positive therapeutic effects of serotonin in learning and medical conditions characterized by enhanced inhibitory or reduced facilitatory plasticity, including depression and stroke.Neuropsychopharmacology accepted article preview online, 17 May 2013; doi:10.1038/npp.2013.127.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Batsikadze, G; Paulus, W; Kuo, MF; Nitsche, MA


Modulation of Chest Wall Intermuscular Coherence: Effects of Lung Volume Excursion and Transcranial Direct Current Stimulation.

2013 May

Chest wall muscle recruitment varies as a function of the breathing task performed. However, the cortical control of the chest wall muscles during different breathing tasks is not known. We studied chest wall intermuscular coherence during various task-related lung volume excursions in 10 healthy adults (34±15 years; 2 males, 8 females), and determined if transcranial direct current stimulation (tDCS) could modulate chest wall intermuscular coherence during these tasks. Simultaneous assessment of regional intercostal and oblique electromyographic (EMG) activity was measured while participants performed standardized tidal breathing, speech, maximum phonation, and vital capacity tasks. Lung volume and chest wall kinematics were determined using variable inductance plethysmography. We found that chest wall area of intermuscular coherence was greater during tidal and speech breathing compared to phonation and vital capacity (all P<0.05), and between tidal breathing compared to speech breathing (P<0.05). Anodal-tDCS increased chest wall area of intermuscular coherence from 0.04±0.09 pre-stimulation to 0.18±0.19 post-stimulation for vital capacity (P<0.05). Sham-tDCS and cathodal-tDCS had no effect on coherence during lung volume excursions. Chest wall kinematics were not affected by tDCS. Our findings indicate that lung volume excursions about the midrange of vital capacity elicit a greater area of chest wall intermuscular coherence compared to lung volume excursions spanning the entire range of vital capacity in healthy adults. Our findings also demonstrate that brief tDCS may modulate the cortical control of the chest wall muscles in a stimulation and lung volume excursion task dependent manner, but does not affect chest wall kinematics in healthy adults.

Journal of neurophysiology

Tomczak, CR; Greidanus, KR; Boliek, CA


Right but not left angular gyrus modulates the metric component of the mental body representation: a tDCS study.

2013 May

The parietal lobes contribute to body-space representation. The present work aims at characterizing the functional role of the inferior parietal lobe in body-space representation and at studying the different roles of the angular gyrus in the right and left hemisphere. We conducted three separate transcranial direct current stimulation (tDCS) experiments using "tactile distance task" as an implicit measure of body representation. Whereas anodal tDCS on the right angular gyrus influences vocal reaction times (vRT) for stimuli delivered on the ipsilateral body parts without changes of accuracy, right tDCS improved both vRT and accuracy for tactile stimuli on the contralateral limbs. Sham or left parietal anodal tDCS had no effect. These evidences support the view that right parietal areas have a crucial role in the metric component of the body representation.

Experimental brain research. Experimentelle Hirnforschung. Experimentation cerebrale

Spitoni, GF; Pireddu, G; Cimmino, RL; Galati, G; Priori, A; Lavidor, M; Jacobson, L; Pizzamiglio, L


Transcranial cerebellar direct current stimulation (tcDCS): Motor control, cognition, learning and emotions.

2013 May

The neurological manifestations of cerebellar diseases range from motor to sensory symptoms, and cognitive or behavioral abnormalities. Experimental data in healthy subjects extend the cerebellar role to learning, emotional and mood control. The need for a non-invasive tool to influence cerebellar function in normal and pathological conditions led researchers to develop transcranial cerebellar direct current stimulation (tcDCS). tcDCS, like tDCS, depends on the principle that weak direct currents delivered at around 2mA for minutes over the cerebellum through surface electrodes induce prolonged changes in cerebellar function. tcDCS modulates several cerebellar skills in humans including motor control, learning and emotional processing. tcDCS also influences the cerebello-brain interactions induced by transcranial magnetic stimulation (TMS), walking adaptation, working memory and emotional recognition. Hence tcDCS is a simple physiological tool that can improve our physiological understanding of the human cerebellum, and should prove useful also in patients with cerebellar dysfunction or psychiatric disorders and those undergoing neurorehabilitation to enhance neuroplasticity.

NeuroImage

Ferrucci, R; Priori, A


Serum levels of brain-derived neurotrophic factor are unchanged after transcranial direct current stimulation in treatment-resistant depression.

2013 May

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays an important role in differentiation and repair of neurons in the adult brain. BDNF serum levels have been found to be lower in depressed patients than in healthy subjects. In a couple of studies, effective antidepressant treatment including electroconvulsive therapy led to an increase in BDNF serum levels. As transcranial direct current stimulation (tDCS) is currently discussed as novel therapeutic intervention in major depression, we investigated BDNF serum levels during tDCS in therapy-resistant depression. METHODS: Twenty-two patients with a major depressive episode participated in a double-blind placebo-controlled trial and received randomized cross over treatment with 2 weeks active and 2 weeks sham tDCS (1 or 2mA for 20min, anode over the left dorsolateral prefrontal cortex, cathode right supraorbital cortex). RESULTS: Clinical assessment only showed a modest and non-significant improvement in HAMD, BDI and CGI in both groups. BDNF serum levels were measured at baseline, after 2 and after 4 weeks. There was neither a significant change of BDNF levels following active tDCS, nor were severity of depressive symptoms and BDNF levels correlated. LIMITATIONS: The small sample size, its heterogeneity, the short observation period and a cross-over design without an interval between both conditions. CONCLUSIONS: tDCS did not change BDNF serum levels unlike other established antidepressant interventions in this treatment resistant sample. However, larger studies are needed.

Journal of affective disorders

Palm, U; Fintescu, Z; Obermeier, M; Schiller, C; Reisinger, E; Keeser, D; Pogarell, O; Bondy, B; Zill, P; Padberg, F


Cellular effects of acute direct current stimulation: somatic and synaptic terminal effects.

2013 May

Abstract  Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique to modulate cortical excitability. Although increased/decreased excitability under the anode/cathode electrode is nominally associated with membrane depolarization/hyperpolarization, which cellular compartments (somas, dendrites, axons and their terminals) mediate changes in cortical excitability remains unaddressed. Here we consider the acute effects of DCS on excitatory synaptic efficacy. Using multi-scale computational models and rat cortical brain slices, we show the following. (1) Typical tDCS montages produce predominantly tangential (relative to the cortical surface) direction currents (4-12 times radial direction currents), even directly under electrodes. (2) Radial current flow (parallel to the somatodendritic axis) modulates synaptic efficacy consistent with somatic polarization, with depolarization facilitating synaptic efficacy. (3) Tangential current flow (perpendicular to the somatodendritic axis) modulates synaptic efficacy acutely (during stimulation) in an afferent pathway-specific manner that is consistent with terminal polarization, with hyperpolarization facilitating synaptic efficacy. (4) Maximal polarization during uniform DCS is expected at distal (the branch length is more than three times the membrane length constant) synaptic terminals, independent of and two-three times more susceptible than pyramidal neuron somas. We conclude that during acute DCS the cellular targets responsible for modulation of synaptic efficacy are concurrently somata and axon terminals, with the direction of cortical current flow determining the relative influence.

The Journal of physiology

Rahman, A; Reato, D; Arlotti, M; Gasca, F; Datta, A; Parra, LC; Bikson, M


Performance of motor imagery brain-computer interface based on anodal transcranial direct current stimulation modulation.

2013 May

Voluntarily modulating neural activity plays a key role in brain-computer interface (BCI). In general, the self-regulated neural activation patterns are used in the current BCI systems involving the repetitive trainings with feedback for an attempt to achieve a high-quality control performance. With the limitation posed by the training procedure in most BCI studies, the present work aims to investigate whether directly modulating the neural activity by using an external method could facilitate the BCI control. We designed an experimental paradigm that combines anodal transcranial direct current stimulation (tDCS) with a motor imagery (MI)-based feedback EEG BCI system. Thirty-two young and healthy human subjects were randomly assigned to the real and sham stimulation groups to evaluate the effect of tDCS-induced EEG pattern changes on BCI classification accuracy. Results showed that the anodal tDCS obviously induces sensorimotor rhythm (SMR)-related event-related desynchronization (ERD) pattern changes in the upper-mu (10-14 Hz) and beta (14-26 Hz) rhythm components. Both the online and offline BCI classification results demonstrate that the enhancing ERD patterns could conditionally improve BCI performance. This pilot study suggests that the tDCS is a promising method to help the users to develop reliable BCI control strategy in a relatively short time.

IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society

Wei, P; He, W; Zhou, Y; Wang, L


Transcranial direct current stimulation (tDCS) for catatonic schizophrenia: a case study.

2013 May

Schizophrenia research

Shiozawa, P; da Silva, ME; Cordeiro, Q; Fregni, F; Brunoni, AR


Transcranial direct current stimulation improves swallowing function in stroke patients.

2013 May

Poststroke dysphagia can persist, leading to many complications.We investigated whether noninvasive brain stimulation to the pharyngeal motor cortex combined with intensive swallowing therapy can improve dysphagia.A total of 20 patients who had dysphagia for at least 1 month after stroke were randomly assigned to receive 10 sessions lasting 20 minutes each of either 1-mA anodal transcranial direct current stimulation (tDCS) or a sham procedure to the ipsilesional pharyngeal motor cortex, along with simultaneous conventional swallowing therapies. We evaluated swallowing function with the dysphagia outcome and severity scale (DOSS) before, immediately after, and 1 month after the last session.Anodal tDCS resulted in an improvement of 1.4 points in DOSS (P = .006) immediately after the last session and 2.8 points (P = .004) 1 month after the last session. The sham tDCS group improved 0.5 points (P = .059) after the last session and 1.2 points (P = .026) 1 month after the final session. The improvements in the anodal tDCS group were significantly greater than those in the sham tDCS group (P = .029 after the last session, and P = .007 1 month after the last session).Anodal tDCS to the ipsilesional hemisphere and simultaneous peripheral sensorimotor activities significantly improved swallowing function as assessed by the DOSS.

Neurorehabilitation and neural repair

Shigematsu, T; Fujishima, I; Ohno, K


Neuromodulation of early multisensory interactions in the visual cortex.

2013 May

Merging information derived from different sensory channels allows the brain to amplify minimal signals to reduce their ambiguity, thereby improving the ability of orienting to, detecting, and identifying environmental events. Although multisensory interactions have been mostly ascribed to the activity of higher-order heteromodal areas, multisensory convergence may arise even in primary sensory-specific areas located very early along the cortical processing stream. In three experiments, we investigated early multisensory interactions in lower-level visual areas, by using a novel approach, based on the coupling of behavioral stimulation with two noninvasive brain stimulation techniques, namely, TMS and transcranial direct current stimulation (tDCS). First, we showed that redundant multisensory stimuli can increase visual cortical excitability, as measured by means of phosphene induction by occipital TMS; such physiological enhancement is followed by a behavioral facilitation through the amplification of signal intensity in sensory-specific visual areas. The more sensory inputs are combined (i.e., trimodal vs. bimodal stimuli), the greater are the benefits on phosphene perception. Second, neuroelectrical activity changes induced by tDCS in the temporal and in the parietal cortices, but not in the occipital cortex, can further boost the multisensory enhancement of visual cortical excitability, by increasing the auditory and tactile inputs from temporal and parietal regions, respectively, to lower-level visual areas.

Journal of cognitive neuroscience

Convento, S; Vallar, G; Galantini, C; Bolognini, N


Brain stimulation methods to treat tobacco addiction.

2013 May

Tobacco smoking is the leading cause of preventable deaths worldwide, but many smokers are simply unable to quit. Psychosocial and pharmaceutical treatments have shown modest results on smoking cessation rates, but there is an urgent need to develop treatments with greater efficacy. Brain stimulation methods are gaining increasing interest as possible addiction therapeutics.The purpose of this paper is to review the studies that have evaluated brain stimulation techniques on tobacco addiction, and discuss future directions for research in this novel area of addiction interventions.Electronic and manual literature searches identified fifteen studies that administered repetitive transcranial magnetic stimulation (rTMS), cranial electrostimulation (CES), transcranial direct current stimulation (tDCS) or deep brain stimulation (DBS).rTMS was found to be the most well studied method with respect to tobacco addiction. Results indicate that rTMS and tDCS targeted to the dorsolateral prefrontal cortex (DLPFC) were the most efficacious in reducing tobacco cravings, an effect that may be mediated through the brain reward system involved in tobacco addiction. While rTMS was shown to reduce consumption of cigarettes, as yet no brain stimulation technique has been shown to significantly increase abstinence rates. It is possible that the therapeutic effects of rTMS and tDCS may be improved by optimization of stimulation parameters and increasing the duration of treatment.Although further studies are needed to confirm the ability of brain stimulation methods to treat tobacco addiction, this review indicates that rTMS and tDCS both represent potentially novel treatment modalities.

Brain stimulation

Wing, VC; Barr, MS; Wass, CE; Lipsman, N; Lozano, AM; Daskalakis, ZJ; George, TP


Motor and parietal cortex stimulation for phantom limb pain and sensations.

2013 Apr

Limb amputation may lead to chronic painful sensations referred to as the absent limb, ie phantom limb pain (PLP), which is likely subtended by maladaptive plasticity. The present study investigated whether transcranial direct current stimulation (tDCS), a noninvasive technique of brain stimulation that can modulate neuroplasticity, can reduce PLP. In 2 double-blind, sham-controlled experiments in subjects with unilateral lower or upper limb amputation, we measured the effects of a single session of tDCS (2mA, 15min) of the primary motor cortex (M1) and of the posterior parietal cortex (PPC) on PLP, stump pain, nonpainful phantom limb sensations and telescoping. Anodal tDCS of M1 induced a selective short-lasting decrease of PLP, whereas cathodal tDCS of PPC induced a selective short-lasting decrease of nonpainful phantom sensations; stump pain and telescoping were not affected by parietal or by motor tDCS. These findings demonstrate that painful and nonpainful phantom limb sensations are dissociable phenomena. PLP is associated primarily with cortical excitability shifts in the sensorimotor network; increasing excitability in this system by anodal tDCS has an antalgic effect on PLP. Conversely, nonpainful phantom sensations are associated to a hyperexcitation of PPC that can be normalized by cathodal tDCS. This evidence highlights the relationship between the level of excitability of different cortical areas, which underpins maladaptive plasticity following limb amputation and the phenomenology of phantom limb, and it opens up new opportunities for the use of tDCS in the treatment of PLP.

Pain

Bolognini, N; Olgiati, E; Maravita, A; Ferraro, F; Fregni, F


[Electroconvulsive therapy in schizophrenia].

2013 Apr

Electroconvulsive therapy (ECT) was initially developed as a treatment for schizophrenia. Currently, the application of ECT for schizophrenia is controversial because of several international guidelines; however, catatonia is acceptable for the indications by all guidelines. Schizophrenic patients with affective, catatonic, and positive symptoms of recent onset may respond favorably to ECT. Additionally, ECT may improve responsivity to pharmacotherapy for some indications. Therefore, a combination of ECT with pharmacotherapy including clozapine may be effective for the pharmacotherapy -resistant schizophrenia. Another argument is that the relapse rate after ECT response is very high compared to that of mood disorders; development of maintenance therapy(pharmacotherapy or ECT) is anticipated for the prevention of relapse. Because maintenance ECT seems to be a burden on remitted patients, to study both maintenance pharmacotherapy and the novel application of non-invasive treatment, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), for maintenance therapy instead of ECT could be fruitful.

Nihon rinsho. Japanese journal of clinical medicine

Takebayashi, M


a-tDCS Differential Modulation of Corticospinal Excitability: The Effects of Electrode Size.

2013 Apr

BACKGROUND: Novel noninvasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have been developed in recent years. tDCS-induced corticospinal excitability changes depend on two important factors: current density and electrodes size. Despite clinical success with existing tDCS parameters; optimal protocols are still not entirely set. OBJECTIVE: The current study aimed to investigate the effects of anodal tDCS (a-tDCS) with three electrode sizes on corticospinal excitability. METHODS: a-tDCS was applied with three active electrode sizes of 12, 24 and 35 cm(2) with a constant current density of 0.029 mA/cm(2) on twelve right handed healthy individuals (mean age: 34.5 ± 10.32 years) in different sessions at least 48 h apart. a-tDCS was applied continuously for 10 min, with a constant reference electrode size of 35 cm(2). The corticospinal excitability of extensor carpi radialis muscle (ECR) was measured before and immediately after the intervention and at 10, 20 and 30 min thereafter. RESULTS: We found that smaller electrode may produce more focal current density and could lead to more effective and localized neural modulation than the larger ones. Post hoc comparisons showed that active electrode of 12 cm(2) size induces the biggest increase in the corticospinal excitability compared to bigger electrode sizes, 24 cm(2) (P = 0.002) and 35 cm(2) (P = 0.000). There was no significant difference between two larger electrode sizes (24 cm(2) and 35 cm(2)) (P = 0.177). a-tDCS resulted in significant excitability enhancement lasting for 30 min after the end of stimulation in the 12 and 24 cm(2) electrode size conditions (P < 0.005). However, in 35 cm(2) electrode size condition, the MEP amplitudes of the ECR did not differ significantly from baseline value in 20 and 30 min post stimulation (P > 0.005). CONCLUSION: Reducing stimulation electrode size to one third of the conventional one results in spatially more focused stimulation and increases the efficacy of a-tDCS for induction of larger corticospinal excitability. This may be due to the fact that larger electrodes stimulate nearby cortical functional areas which can have inhibitory effects on primary motor cortex.

Brain stimulation

Bastani, A; Jaberzadeh, S


Temporal accuracy and variability in the left and right posterior parietal cortex.

2013 Apr

Several brain-imaging and lesion studies have suggested a role for the posterior parietal cortex (PPC) in computing interval-timing tasks. PPC also seems to have a key role in modulating visuospatial mechanisms, which are known to affect temporal performance. By applying transcranial direct current stimulation (tDCS) over the left and right PPC, we aimed to modulate timing ability performance in healthy humans performing a cognitively controlled timing task. In two separate experiments we compared time-processing abilities of two groups of healthy adults submitted to anodal, cathodal or sham tDCS over right or left PPC, by employing a supra-second time reproduction task. Cathodal stimulation over the right PPC affected temporal accuracy by leading participants to overestimate time intervals. Moreover, when applied to the left PPC, it reduced variability in reproducing temporal intervals. No effect was reported for anodal stimulation. These results expand current knowledge on the role of the parietal cortex on temporal processing. We provide evidence that the parietal cortex of both hemispheres is involved in temporal processing by acting on distinct components of timing performance such as accuracy and variability.

Neuroscience

Vicario, CM; Martino, D; Koch, G


Lateralization of activity in the parietal cortex predicts the effectiveness of bilateral transcranial direct current stimulation on performance of a mental calculation task.

2013 Apr

Transcranial direct current stimulation (tDCS) is a non-invasive technique that moderates cognitive and motor function. The effects of tDCS on cognitive and motor tasks vary among individuals. However, the source of the inter-individual variability remains unknown. The purpose of the present study was to examine whether the effect of bilateral tDCS on the performance of mental calculations differs among individuals according to the functional lateralization of parietal activity observed during a mental calculation task. Sixteen healthy subjects (11 males and five females, aged 20-23 years) participated. Laterality of parietal activity during a mental calculation task was evaluated using functional magnetic resonance imaging. Subjects also performed the mental calculation task pre-, during-, 30min post-, and 60min post-tDCS. Bilateral tDCS with the anode over the left parietal cortex and the cathode over the right parietal cortex shortened response times of the mental calculation task in subjects with left-hemispheric parietal lateralization, but not in subjects with bilateral parietal activation. This indicates that inter-individual variability in laterality of brain activity might be an important factor underlying the effect of bilateral tDCS. In conclusion, bilateral tDCS over the parietal cortex enhanced the performance of mental calculations in subjects with left-hemispheric parietal lateralization.

Neuroscience letters

Kasahara, K; Tanaka, S; Hanakawa, T; Senoo, A; Honda, M


THE SERTRALINE VERSUS ELECTRICAL CURRENT THERAPY FOR TREATING DEPRESSION CLINICAL STUDY (SELECT-TDCS): RESULTS OF THE CROSSOVER AND FOLLOW-UP PHASES.

2013 Apr

BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising nonpharmacological therapy for major depression. In the Sertraline versus Electrical Current Therapy for Treating Depression Clinical Trial (SELECT-TDCS) trial, phase-I (Brunoni et al., JAMA Psychiatry, 2013) we found that tDCS is effective for the acute episode. Here, we describe tDCS effects during phases II (crossover) and III (follow-up) of this trial (NCTs: 01149889 and 01149213). METHODS: Phase II (n = 25) was the open-label, crossover phase in which phase-I nonresponders who had received sham-tDCS received a 10-day course of active-tDCS. In phase-III (n = 42), all active-tDCS responders (>50% Montgomery-Asberg Depression Rating Scale (MADRS) improvement or MADRS ≤ 12) were enrolled to a 24-week, follow-up phase in which a maximum of nine tDCS sessions were performed-every other week for 3 months and, thereafter, once a month for the subsequent 3 months-sessions would be interrupted earlier whether the subject relapsed. TDCS was applied at 2 mA/30 min, with the anode over the left and the cathode over the right dorsolateral prefrontal cortex. Relapse was the outcome measure. RESULTS: In phase-II, 52% of completers responded to tDCS. In phase-III, the mean response duration was 11.7 weeks. The survival rate per Kaplan-Meier analysis was 47%. Patients with treatment-resistant depression presented a much lower 24-week survival rate as compared to nonrefractory patients (10% vs. 77%, OR = 5.52; P < .01). Antidepressant use (sertraline 50 mg/day, eight patients) was not a predictor of relapse. TDCS was well tolerated and with few side effects. CONCLUSION: Continuation tDCS protocols should be optimized as to prevent relapse among tDCS responders, particularly for patients with baseline treatment-resistant depression.

Depression and anxiety

Valiengo, L; Benseñor, IM; Goulart, AC; de Oliveira, JF; Zanao, TA; Boggio, PS; Lotufo, PA; Fregni, F; Brunoni, AR


Impact of 5-HTTLPR and BDNF polymorphisms on response to sertraline versus transcranial direct current stimulation: Implications for the serotonergic system.

2013 Apr

Transcranial direct current stimulation (tDCS) has been intensively investigated as a non-pharmacological treatment for major depressive disorder (MDD). While many studies have examined the genetic predictors of antidepressant medications, this issue remains to be investigated for tDCS. In the current study, we evaluated whether the BDNF Val66Met and the 5-HTT (5-HTTLPR) polymorphisms were associated with tDCS antidepressant response. We used data from a factorial trial that evaluated the efficacy of tDCS and sertraline and enrolled 120 moderate-to-severe, antidepressant-free participants. In the present study, we used analyses of variance to evaluate whether the BDNF (Val/Val vs. Met-carries) and 5-HTTLPR alleles (long/long vs short-carriers) were predictors of tDCS (active/sham) and sertraline (sertraline/placebo) response. Analyses were conducted on the polymorphisms separately and also on their interaction. Genotype frequencies were in Hardy-Weinberg equilibrium. BDNF polymorphism was not associated with treatment response. We found that 5-HTTLPR predicted tDCS effects as long/long homozygotes displayed a larger improvement comparing active vs. sham tDCS, while short-allele carriers did not. A dose-response relationship between active-sham differences with the long allele was also suggested. These results strengthen the role of the serotonergic system in the tDCS antidepressant effects and expand previous findings that reported that tDCS mechanisms of action partially involve serotonergic receptors. Therefore, we hypothesize that tDCS is a neuromodulation technique that acts over depression through the modulation of serotonergic system and that tDCS "top-down" antidepressant effects might not be optimal in brain networks with a hyperactive amygdala inducing bottom-up effects, such as occurs in short-carriers.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Brunoni, AR; Kemp, AH; Shiozawa, P; Cordeiro, Q; Valiengo, LC; Goulart, AC; Coprerski, B; Lotufo, PA; Brunoni, D; Perez, AB; Fregni, F; Benseñor, IM


Effect of Anodal Versus Cathodal Transcranial Direct Current Stimulation on Stroke Rehabilitation: A Pilot Randomized Controlled Trial.

2013 Apr

OBJECTIVE: . We compared the long-term effect of anodal versus cathodal transcranial direct current stimulation (tDCS) on motor recovery in patients after subacute stroke. METHODS: . Forty patients with ischemic stroke undergoing rehabilitation were randomly assigned to 1 of 3 groups: Anodal, Cathodal (over-affected and unaffected hemisphere, respectively), and Sham. Each group received tDCS at an intensity of 2 mA for 25 minutes daily for 6 consecutive days over of the motor cortex hand area. Patients were assessed with the National Institutes of Health Stroke Scale (NIHSS), Orgogozo's MCA scale (OMCASS), the Barthel index (BI), and the Medical Research Council (MRC) muscle strength scale at baseline, after the sixth tDCS session and then 1, 2, and 3 months later. Motor cortical excitability was measured with transcranial magnetic stimulation (TMS) at baseline and after the sixth session. RESULTS: . By the 3-month follow-up, all groups had improved on all scales with P values ranging from .01 to .0001. Improvement was equal in the Anodal and Cathodal groups. When these treated groups were combined and compared with Sham, significant interactions were seen for the OMCASS and BI scales of functional ability (P = .002 for each). There was increased cortical excitability of the affected hemisphere in all groups with the changes being greater in the real versus sham groups. There were borderline significant improvements in muscle strength. CONCLUSION: . A brief course of 2 types of tDCS stimulation is superior to sham stimulation in enhancing the effect of rehabilitation training to improve motor recovery after stroke.

Neurorehabilitation and neural repair

Khedr, EM; Shawky, OA; El-Hammady, DH; Rothwell, JC; Darwish, ES; Mostafa, OM; Tohamy, AM


Modulating arithmetic fact retrieval: A single-blind, sham-controlled tDCS study with repeated fMRI measurements.

2013 Apr

Transcranial direct current stimulation (tDCS) is a non-invasive technique which has been used to modulate various cognitive functions in healthy participants as well as stroke patients. Despite the increasing number of tDCS studies, it still remains questionable whether tDCS is suitable for modulating performance in arithmetic tasks and whether a single tDCS session may cause brain activity changes that can be detected with functional magnetic resonance imaging (fMRI). We asked healthy participants to repeatedly solve simple multiplication tasks in three conditions: STIMULATION (anodal tDCS over the right angular gyrus, AG), SHAM (identical electrode set-up without stimulation), and CONTROL (no electrodes attached). Before and after tDCS, we used fMRI to examine changes in brain activity. Behavioural results indicate that a single session of tDCS did not modulate task performance significantly. However, fMRI measurements revealed that the neural correlates of multiplication were modified following a single session of anodal tDCS. In the bilateral AG, activity was significantly higher for multiplication problems rehearsed during active tDCS, as compared to multiplication problems rehearsed without tDCS or during sham tDCS. In sum, we present first neuro-functional evidence that tDCS modulates arithmetic processing. Implications of these findings for future tDCS studies and for the rehabilitation of acalculic patients with deficits in arithmetic fact retrieval are discussed.

Neuropsychologia

Clemens, B; Jung, S; Zvyagintsev, M; Domahs, F; Willmes, K


Transcranial Direct Current Stimulation (tDCS) for the Treatment of Persistent Visual and Auditory Hallucinations in Schizophrenia: A Case Study.

2013 Apr

Brain stimulation

Shiozawa, P; da Silva, ME; Cordeiro, Q; Fregni, F; Brunoni, AR


Electrode montage dependent effects of transcranial direct current stimulation on semantic fluency.

2013 Apr

Transcranial direct current stimulation (tDCS) has proved to be valuable in improving many language processes. However, its influence on verbal fluency still needs to be fully proved. In the present study, we explored the effects of different electrode montages on a semantic fluency task, aimed at comparing their effectiveness in affecting language production. Ninety healthy, right-handed volunteers were randomly assigned to receive one of the following stimulation protocols: (1) anode over the left frontal cortex/cathode over the right supraorbital (rSO) area, (2) anode over the left fronto-temporal (lFT) cortex/cathode over the rSO area, (3) anode over the lFT cortex/cathode over the right FT cortex, (4) anode over the lFT cortex/big-size cathode over the rSO area, (5) sham. In the active stimulation conditions, 2mA current was delivered for 20min. Participants performed the semantic fluency task before the stimulation, immediately after it, and 15min after the first post-stimulation task. Although none of the different protocols improved language production immediately after the stimulation, anodal stimulation over the left frontal cortex (standard-size cathode over the rSO area) improved fluency at the second post-stimulation task. This proved that small differences in either active electrode positioning, or reference positioning/size can impact tDCS behavioral effects also in the cognitive domain. These findings, which can be sometimes missed when tested immediately after the stimulation only, add new information on tDCS spatial and temporal features, thus providing new indications to increase the effectiveness of stimulation protocols.

Behavioural brain research

Penolazzi, B; Pastore, M; Mondini, S


Semantic processing in subliminal face stimuli: An EEG and tDCS study.

2013 Apr

Whether visual subliminal processing involves semantic processing is still being debated. To examine this, we combined a passive electroencephalogram (EEG) study with an application of transcranial direct current stimulation (tDCS). In the masked-face priming paradigm, we presented a subliminal prime preceding the target stimulus. Participants were asked to determine whether the target face was a famous face, indicated by a button press. The prime and target pair were either the same person's face (congruent) or different person's faces (incongruent), and were always both famous or both non-famous faces. Experiments were performed over 2 days: 1 day for a real tDCS session and another for a sham session as a control condition. In the sham session, a priming effect, reflected in the difference in amplitude of the late positive component (250-500ms to target onset), was observed only in the famous prime condition. According to a previous study, this effect might indicate a subliminal semantic process [10]. Alternatively, a priming effect toward famous primes disappeared after tDCS stimulation. Our results suggested that a subliminal process might not be limited to processes in the occipital and temporal areas, but may proceed to the semantic level processed in prefrontal cortex.

Neuroscience letters

Kongthong, N; Minami, T; Nakauchi, S


Differential contribution of cortical and subcortical visual pathways to the implicit processing of emotional faces: a tDCS study.

2013 Apr

The visual processing of emotional faces is subserved by both a cortical and a subcortical route. To investigate the specific contribution of these two functional pathways, two groups of neurologically healthy humans were tested using transcranial direct current stimulation (tDCS). In Experiment 1, participants received sham and active cathodal-inhibitory tDCS over the left occipital cortex, while, in control Experiment 2, participants received sham and active cathodal-inhibitory tDCS over the vertex, to exclude any unspecific effect of tDCS. After tDCS, participants performed a go/no-go task responding to happy or fearful target faces presented in the left visual field, while backwardly masked faces (emotionally congruent, incongruent, or neutral) were concurrently displayed in the right visual field. After both suppressing activity in the vertex (Experiment 2) and sham stimulation (Experiment 1 and 2) a reduction of reaction times was found for pairs of emotionally congruent stimuli. However, after suppressing the activity in the left occipital cortex, the congruency-dependent response facilitation disappeared, while a specific facilitative affect was evident when masked fearful faces were coupled with happy target faces. These results parallel the performances of hemianopic patients and suggest that when the occipital cortex is damaged or inhibited, and the visual processing for emotional faces is mainly dependent on the activation of the "low road" subcortical route, fearful faces represent the only visually processed stimuli capable of facilitating a behavioral response. This effect might reflect an adaptive mechanism implemented by the brain to quickly react to potential threats before their conscious identification.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Cecere, R; Bertini, C; Làdavas, E


Anodal tDCS to V1 blocks visual perceptual learning consolidation.

2013 Apr

This study examined the effects of visual cortex transcranial direct current stimulation (tDCS) on visual processing and learning. Participants performed a contrast detection task on two consecutive days. Each session consisted of a baseline measurement followed by measurements made during active or sham stimulation. On the first day, one group received anodal stimulation to primary visual cortex (V1), while another received cathodal stimulation. Stimulation polarity was reversed for these groups on the second day. The third (control) group of subjects received sham stimulation on both days. No improvements or decrements in contrast sensitivity relative to the same-day baseline were observed during real tDCS, nor was any within-session learning trend observed. However, task performance improved significantly from Day 1 to Day 2 for the participants who received cathodal tDCS on Day 1 and for the sham group. No such improvement was found for the participants who received anodal stimulation on Day 1, indicating that anodal tDCS blocked overnight consolidation of visual learning, perhaps through engagement of inhibitory homeostatic plasticity mechanisms or alteration of the signal-to-noise ratio within stimulated cortex. These results show that applying tDCS to the visual cortex can modify consolidation of visual learning.

Neuropsychologia

Peters, MA; Thompson, B; Merabet, LB; Wu, AD; Shams, L


Evidence for longlasting subcortical facilitation by transcranial direct current stimulation (tDCS) in the cat.

2013 Apr

The main aim of the study was to examine effects of transcranial polarization on neurons in two descending motor systems, rubro- and reticulo-spinal. Anodal DC current was applied through an electrode in contact with the skull over the contralateral sensori-motor cortex, against an electrode placed between the skull and the ipsilateral temporal muscles in deeply anaesthetized cats. Its effects were estimated from changes in descending volleys evoked by electrical stimuli applied in the Red Nucleus (RN), Medial Longitudinal Fascicle (MLF; to reticulospinal fibres) and the Pyramidal Tract (PT; to corticospinal or corticoreticular fibres). The descending volleys were recorded from the surface of the spinal cord at a cervical level. Rubrospinal neurones were activated either directly or indirectly, via interpositorubral fibres. Reticulospinal neurons were likewise activated directly and indirectly, via other reticulospinal or corticospinal fibres. Transcranial polarization facilitated transsynaptic activation of both rubrospinal and reticulospinal neurons, shortening the latency of the indirect descending volleys and/or increasing them, Direct activation of descending axons was much less affected. The facilitation of all subcortical neurons examined was potentiated by repeated applications of tDCS and outlasted the polarization by at least 1-2 hours, replicating tDCS effects on indirect activation of cortical neurons. The results indicate that beneficial effects of tDCS on motor performance in humans may be due to more efficient activation not only of cortical but also subcortical neuronal systems. Combined actions of tDCS on cortical and subcortical neurones might thus further improve recovery of motor functions during rehabilitation after central injuries.

The Journal of physiology

Bolzoni, F; Pettersson, LG; Jankowska, E


Focal modulation of the primary motor cortex in fibromyalgia using 4×1-ring high-definition transcranial direct current stimulation (HD-tDCS): immediate and delayed analgesic effects of cathodal and anodal stimulation.

2013 Apr

Fibromyalgia is a prevalent chronic pain syndrome characterized by altered pain and sensory processing in the central nervous system, which is often refractory to multiple therapeutic approaches. Given previous evidence supporting analgesic properties of noninvasive brain stimulation techniques in this condition, this study examined the effects of a novel, more focal method of transcranial direct current stimulation (tDCS), using the 4×1-ring configuration of high-definition (HD)-tDCS, on overall perceived pain in fibromyalgia patients. In this patient- and assessor-blind, sham-controlled, crossover trial, 18 patients were randomized to undergo single 20-minute sessions of anodal, cathodal, and sham HD-tDCS at 2.0 mA in a counterbalanced fashion. The center electrode was positioned over the left primary motor cortex. Pain scales and sensory testing were assessed before and after each intervention. A finite element method brain model was generated to predict electric field distribution. We found that both active stimulation conditions led to significant reduction in overall perceived pain as compared to sham. This effect occurred immediately after cathodal HD-tDCS and was evident for both anodal and cathodal HD-tDCS 30 minutes after stimulation. Furthermore, active anodal stimulation induced a significant bilateral increase in mechanical detection thresholds. These interventions proved well tolerated in our patient population.4×1-ring HD-tDCS, a novel noninvasive brain stimulation technique capable of more focal and targeted stimulation, provides significant reduction in overall perceived pain in fibromyalgia patients as compared to sham stimulation, irrespective of current polarity. This technique may have other applications in research and clinical settings, which should be further explored.

The journal of pain : official journal of the American Pain Society

Villamar, MF; Wivatvongvana, P; Patumanond, J; Bikson, M; Truong, DQ; Datta, A; Fregni, F


The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial.

2013 Apr

Transcranial direct current stimulation (tDCS) trials for major depressive disorder (MDD) have shown positive but mixed results.To assess the combined safety and efficacy of tDCS vs a common pharmacological treatment (sertraline hydrochloride, 50 mg/d).Double-blind, controlled trial. Participants were randomized using a 2 × 2 factorial design to sertraline/placebo and active/sham tDCS.Outpatient, single-center academic setting in São Paulo, Brazil.One hundred twenty antidepressant-free patients with moderate to severe, nonpsychotic, unipolar MDD.Six-week treatment of 2-mA anodal left/cathodal right prefrontal tDCS (twelve 30-minute sessions: 10 consecutive sessions once daily from Monday to Friday plus 2 extra sessions every other week) and sertraline hydrochloride (50 mg/d). MAIN OUTCOME MEASURES In this intention-to-treat analysis, the primary outcome measure was the change in Montgomery-Asberg depression rating scale score at 6 weeks (end point). We considered a difference of at least 3 points to be clinically relevant. The analysis plan was previously published. Safety was measured with an adverse effects questionnaire, the young mania rating scale, and cognitive assessment. Secondary measures were rates of clinical response and remission and scores on other scales.At the main end point, there was a significant difference in Montgomery-Asberg depression rating scale scores when comparing the combined treatment group (sertraline/active tDCS) vs sertraline only (mean difference, 8.5 points; 95% CI, 2.96 to 14.03; P = .002), tDCS only (mean difference, 5.9 points; 95% CI, 0.36 to 11.43; P = .03), and placebo/sham tDCS (mean difference, 11.5 points; 95% CI, 6.03 to 17.10; P < .001). Analysis of tDCS only vs sertraline only presented comparable efficacies (mean difference, 2.6 points; 95% CI, -2.90 to 8.13; P = .35). Use of tDCS only (but not sertraline only) was superior to placebo/sham tDCS. Common adverse effects did not differ between interventions, except for skin redness on the scalp in active tDCS (P = .03). There were 7 episodes of treatment-emergent mania or hypomania, 5 occurring in the combined treatment group.In MDD, the combination of tDCS and sertraline increases the efficacy of each treatment. The efficacy and safety of tDCS and sertraline did not differ. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01033084.

JAMA psychiatry (Chicago, Ill.)

Brunoni, AR; Valiengo, L; Baccaro, A; Zanão, TA; de Oliveira, JF; Goulart, A; Boggio, PS; Lotufo, PA; Benseñor, IM; Fregni, F


Modulating lexical and semantic processing by transcranial direct current stimulation.

2013 Apr

Here we aim to evaluate the ability of transcranial direct current stimulation (tDCS), which is applied over Wernicke's area and its right homologue, to influence lexical decisions and semantic priming and establish an involvement for temporo-parietal areas in lexical and semantic processing. Thirty-two subjects (17 women) completed a lexical decision task and a semantic priming task while receiving 20 min of bilateral tDCS stimulation (right anodal/left cathodal or left anodal/right cathodal stimulation) or sham stimulation. We hypothesized that right anodal/left cathodal stimulation over temporo-parietal areas would selectively interrupt the typical lexical processing dominance of the left hemisphere and facilitate mediated priming, while left anodal/right cathodal stimulation would selectively facilitate lexical processing and direct priming. Results showed impaired lexical processing under right anodal/left cathodal stimulation in comparison with sham and left anodal/right cathodal stimulation. Results are discussed in light of previous findings and hemispheric lateralization models.

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Weltman, K; Lavidor, M


Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans.

2013 Apr

Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI and ICF towards inhibition. No significant changes were observed in the other protocols. Sham tDCS did not induce significant MEP alterations. These results suggest that an enhancement of tDCS intensity does not necessarily increase efficacy of stimulation, but might also shift the direction of excitability alterations. This should be taken into account for applications of the stimulation technique using different intensities and durations in order to achieve stronger or longer lasting after-effects.

The Journal of physiology

Batsikadze, G; Moliadze, V; Paulus, W; Kuo, MF; Nitsche, MA


Comparing immediate transient tinnitus suppression using tACS and tDCS: a placebo-controlled study.

2013 Apr

Tinnitus is an auditory phantom percept with a tone, hissing, or buzzing sound in the absence of any objective physical sound source. Two forms of low-intensity cranial electrical stimulation exist for clinical and research purposes: transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS). In a recent study, it was demonstrated that a single session of tDCS over the dorsolateral prefrontal cortex (DLPFC) (anode over right DLPFC) yields a transient improvement in subjects with chronic tinnitus and that repeated sessions can possibly be used as a treatment. In the present study, the effect of a single-session individual alpha-modulated tACS and tDCS applied at the DLPFC bilaterally is compared with tinnitus loudness and tinnitus annoyance. A total of fifty tinnitus patients were selected and randomly assigned to the tACS or tDCS treatment. Our main result was that bifrontal tDCS modulates tinnitus annoyance and tinnitus loudness, whereas individual alpha-modulated tACS does not yield a similar result. This study provides additional insights into the role of DLPFC in tinnitus modulation as well as the intersection between tinnitus and affective/attentional processing.

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Vanneste, S; Walsh, V; Van De Heyning, P; De Ridder, D


Amelioration of cognitive control in depression by transcranial direct current stimulation.

2013 Apr

Deficient cognitive control over emotional distraction is a central characteristic of major depressive disorder (MDD). Hypoactivation of the dorsolateral prefrontal cortex (dlPFC) has been linked with this deficit. In this study, we aimed to enhance the activity of the dlPFC in MDD patients by anodal transcranial direct current stimulation (tDCS) and thus ameliorate cognitive control.In a double-blinded, balanced, randomized, sham-controlled crossover trial, we determined the effect of a single-session tDCS to the left dlPFC on the cognitive control in 22 MDD patients and 22 healthy control subjects. To assess the cognitive control, we used a delayed response working memory task with pictures of varying content (emotional vs. neutral) presented during the delay period.Emotional pictures presented during the delay period impaired accuracy and response time of patients with MDD, indicating an attentional bias for emotional stimuli. Anodal tDCS to the dlPFC was associated with an enhanced working memory performance both in patients and control subjects. Specifically in subjects with MDD, the attentional bias was completely abolished by anodal tDCS.The present study demonstrates that anodal tDCS applied to the left dlPFC improves deficient cognitive control in MDD. Based on these data, tDCS might be suitable to support the effects of behavioral training to enhance cognitive control in MDD.

Biological psychiatry

Wolkenstein, L; Plewnia, C


Impaired Motor Cortex Responses in Non-Psychotic First-Degree Relatives of Schizophrenia Patients: A Cathodal tDCS Pilot Study.

2013 Mar

BACKGROUND: Schizophrenia has recently been described as a disorder of impaired plasticity and dysconnectivity. Several lines of evidence suggest that alterations in glutamatergic neurotransmission underlie different symptom domains of schizophrenia. Little is known about the impact of genetic liability on cortical plasticity and connectivity in schizophrenia. OBJECTIVE: To compare N-methyl-d-aspartate receptor (NMDAR)-dependent cortical plasticity and connectivity in schizophrenia patients and unaffected first-degree relatives to that in healthy subjects. METHODS: Cortical plasticity can be induced in the motor cortex with cathodal transcranial direct current stimulation (tDCS). Animal and human research indicates that this long-term depression-like plasticity (LTD-like) is NMDAR dependent, and that these plasticity shifts can last for several hours. tDCS-induced plasticity was assessed by measuring motor-evoked potentials (MEPs) generated by applying transcranial magnetic stimulation (TMS) to both hemispheres in healthy controls, chronically ill schizophrenia patients and unaffected first-degree relatives. RESULTS: Compared to healthy controls, both first-degree relatives and schizophrenia patients showed abolished motor-cortical LTD-like plasticity of the stimulated hemisphere. On the non-stimulated hemisphere, plasticity was again abolished in schizophrenia patients, whereas first-degree relatives had a reversed plasticity. CONCLUSIONS: Non-psychotic and clinically unaffected first-degree relatives showed an alteration and a reversal of LTD-like cortical plasticity, indicating functional alterations of glutamatergic transmission as a result of a genetic liability for developing schizophrenia. These results provide new evidence for the association between plasticity dysregulation and functional cortical connectivity, and the importance of these networks in the pathophysiology of schizophrenia.

Brain stimulation

Hasan, A; Misewitsch, K; Nitsche, MA; Gruber, O; Padberg, F; Falkai, P; Wobrock, T


Does Prefrontal Cortex Transcranial Direct Current Stimulation Influence the Oxygen Uptake at Rest and Post-exercise?

2013 Mar

The study evaluated the effect of transcranial direct current stimulation (tDCS) applied over prefrontal cortex on the oxygen uptake (V˙ O2) at rest and during post-exercise recovery. The V˙ O2 was assessed in eleven healthy subjects before, during tDCS (sham or anodal tDCS, 2 mA, 20 min), and 30-min following isocaloric aerobic exercise (~200 kcal). During tDCS, no changes were observed on V˙ O2 compared to baseline (P=0.95) and sham condition (P=0.85). The association between isocaloric exercise and anodal tDCS increased the V˙ O2 throughout 30-min recovery compared to sham condition (P<0.001). Therefore, the energy expenditure within the excess post-exercise oxygen consumption (EPOC) period, after anodal tDCS was approximately 19% higher compared to the sham condition (P<0.05). In conclusion, anodal tDCS applied on the prefrontal cortex combined with submaximal aerobic exercise increased the EPOC, enhancing the V˙ O2 and energy expenditure at least for 30-min of recovery.

International journal of sports medicine

Montenegro, R; Okano, AH; Cunha, FA; Fontes, EB; Farinatti, P


Transcranial direct current stimulation (tDCS) for depression: Analysis of response using a three-factor structure of the Montgomery-Åsberg depression rating scale.

2013 Mar

BACKGROUND: There is growing evidence that transcranial direct current stimulation (tDCS) may be an effective treatment for depression. However, no study to date has profiled the antidepressant effects of tDCS using items or factors on depression symptom severity rating scales. This could potentially provide information about the mechanisms by which tDCS achieves its antidepressant effects and also identify clinical predictors of response. METHODS: The present study analysed scores on the Montgomery-Åsberg depression rating scale (MADRS) from a randomised, sham-controlled trial of tDCS (Loo et al., 2012. British Journal of Psychiatry. 200, 52-59) using a three-factor model of MADRS items (Suzuki et al., 2005. Depression and Anxiety. 21, 95-97) encompassing dysphoria, retardation and vegetative symptoms. RESULTS: Participants in the active tDCS treatment group showed significant improvement in dysphoria while participants in the sham treatment group did not. While both groups showed improvement in retardation symptoms, improvement was significantly greater in the active tDCS group. Both groups also showed improvement in vegetative symptoms but there were no between-group differences. LIMITATIONS: Further studies with larger sample sizes are warranted to investigate the generalisability of results and whether the MADRS factor structure may change as a result of the specific treatment used. CONCLUSIONS: tDCS appears to be particularly effective in treating dysphoria and retardation, but not vegetative symptoms of depression. This may have implications for selection of types of depression most likely to respond to this treatment.

Journal of affective disorders

Alonzo, A; Chan, G; Martin, D; Mitchell, PB; Loo, C


Single Session of Dual-tDCS Transiently Improves Precision Grip and Dexterity of the Paretic Hand After Stroke.

2013 Mar

BACKGROUND: . After stroke, deregulated interhemispheric interactions influence residual paretic hand function. Anodal or cathodal transcranial direct current stimulation (tDCS) can rebalance these abnormal interhemispheric interactions and improve motor function. OBJECTIVE: . We explored whether dual-hemisphere tDCS (dual-tDCS) in participants with chronic stroke can improve fine hand motor function in 2 important aspects: precision grip and dexterity. METHODS: . In all, 19 chronic hemiparetic individuals with mild to moderate impairment participated in a double-blind, randomized trial. During 2 separate cross-over sessions (real/sham), they performed 10 precision grip movements with a manipulandum and the Purdue Pegboard Test (PPT) before, during, immediately after, and 20 minutes after dual-tDCS applied simultaneously over the ipsilesional (anodal) and contralateral (cathodal) primary motor cortices. RESULTS: . The precision grip performed with the paretic hand improved significantly 20 minutes after dual-tDCS, with reduction of the grip force/load force ratio by 7% and in the preloading phase duration by 18% when compared with sham. The dexterity of the paretic hand started improving during dual-tDCS and culminated 20 minutes after the end of dual-tDCS (PPT score +38% vs +5% after sham). The maximal improvements in precision grip and dexterity were observed 20 minutes after dual-tDCS. These improvements correlated negatively with residual hand function quantified with ABILHAND. CONCLUSIONS: . One bout of dual-tDCS improved the motor control of precision grip and digital dexterity beyond the time of stimulation. These results suggest that dual-tDCS should be tested in longer protocols for neurorehabilitation and with moderate to severely impaired patients. The precise timing of stimulation after stroke onset and associated training should be defined.

Neurorehabilitation and neural repair

Lefebvre, S; Thonnard, JL; Laloux, P; Peeters, A; Jamart, J; Vandermeeren, Y


Targeted transcranial direct current stimulation for rehabilitation after stroke.

2013 Mar

Transcranial direct current stimulation (tDCS) is being investigated as an adjunctive technique to behavioral rehabilitation treatment after stroke. The conventional "dosage", consisting of a large (25cm(2)) anode over the target with the cathode over the contralateral hemisphere, has been previously shown to yield broadly distributed electric fields whose intensities at the target region are less than maximal. Here, we report the results of a systematic targeting procedure with small "high-definition" electrodes that was used in preparation for a pilot study on 8 stroke patients with chronic aphasia. We employ functional and anatomical magnetic resonance imagery (fMRI/MRI) to define a target and optimize (with respect to the electric field magnitude at the target) the electrode configuration, respectively, and demonstrate that electric field strengths in targeted cortex can be substantially increased (63%) over the conventional approach. The optimal montage exhibits significant variation across subjects as well as when perturbing the target location within a subject. However, for each displacement of the target co-ordinates, the algorithm is able to determine a montage which delivers a consistent amount of current to that location. These results demonstrate that MRI-based models of current flow yield maximal stimulation of target structures, and as such, may aid in reliably assessing the efficacy of tDCS in neuro-rehabilitation.

NeuroImage

Dmochowski, JP; Datta, A; Huang, Y; Richardson, JD; Bikson, M; Fridriksson, J; Parra, LC


Anodal transcranial direct current stimulation increases brain intracellular pH and modulates bioenergetics.

2013 Mar

Transcranial direct current stimulation is an emerging treatment for brain disorders but its mode of action is not well understood. We applied 10 min 1 mA anodal transcranial direct current stimulation (tDCS) inside the bore of a 3 T MRI scanner to the left dorsolateral prefrontal cortex of 13 healthy volunteers (aged 19-28 yr) in a blinded, sham-controlled, cross-over design. Brain bioenergetics were measured from the left temporo-frontal region using 31P magnetic resonance spectroscopy before, during and for 20 min following tDCS. Brain pH rose during tDCS and remained elevated afterwards. Phosphomonoesters were significantly decreased while inorganic phosphate (Pi) also fell. Partial-least squares discriminant analysis of the data revealed two significantly different subject groups: one where phosphocreatine (PCr), ATP and Pi fell along with a larger increase in pH and one where PCr and ATP increased along with a smaller increase in pH and a slower and more sustained decrease in Pi. Group membership was predicted by baseline pH and ATP. We interpreted the effects of tDCS as driving two biochemical processes: cellular consumption of ATP causing hydrolysis of PCr via the creatine kinase reaction driving the increase in pH; synthesis of ATP and PCr by mitochondria with concomitant drop in Pi and phosphomonoester levels.

The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)

Rae, CD; Lee, VH; Ordidge, RJ; Alonzo, A; Loo, C


Anodal tDCS Applied during Strength Training Enhances Motor Cortical Plasticity.

2013 Mar

Purpose: To assess the effect of anodal transcranial direct current stimulation (a-tDCS) on voluntary dynamic strength and cortical plasticity when applied during a three week strength training program for the wrist extensors. Methods: 30 right handed participants were randomly allocated to the tDCS, sham, or control group. The tDCS and sham group underwent three weeks of heavy load strength training of the right wrist extensors, with 20 min of a-tDCS (2 mA) or sham tDCS applied during training (double blinded). Outcome measures included voluntary dynamic wrist extension strength, muscle thickness, corticospinal excitability, short-interval intracortical inhibition (SICI), and silent period duration. Results: Maximal voluntary strength increased in both the tDCS and sham groups (14.89% and 11.17% respectively, both p < 0.001). There was no difference in strength gain between the two groups (p = 0.229), and no change in muscle thickness (p = 0.15). The tDCS group demonstrated an increase in motor evoked potential (MEP) amplitude at 15, 20 and 25% above active motor threshold, which was accompanied by a decrease in SICI during 50% maximal voluntary isometric contraction (MVIC) and 20% MVIC (all p < 0.05). Silent period decreased for both the tDCS and sham groups (p < 0.001). Conclusion: The application of a-tDCS in combination with strength training of the wrist extensors in a healthy population did not provide additional benefit for voluntary dynamic strength gains when compared with standard strength training. However, strength training with a-tDCS appears to differentially modulate cortical plasticity via increases in corticospinal excitability and decreases in SICI, which did not occur following strength training alone.

Medicine and science in sports and exercise

Hendy, AM; Kidgell, DJ


Acute working memory improvement after tDCS in antidepressant-free patients with major depressive disorder.

2013 Mar

Based on previous studies showing that transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique that employs weak, direct currents to induce cortical-excitability changes, might be useful for working memory (WM) enhancement in healthy subjects and also in treating depressive symptoms, our aim was to evaluate whether tDCS could acutely enhance WM in depressed patients. Twenty-eight age- and gender-matched, antidepressant-free depressed subjects received a single-session of active/sham tDCS in a randomized, double-blind, parallel design. The anode was positioned over the left and the cathode over the right dorsolateral prefrontal cortex. The n-back task was used for assessing WM and it was performed immediately before and 15min after tDCS onset. We found that active vs. sham tDCS led to an increase in the rate of correct responses. We also used signal detection theory analyses to show that active tDCS increased both discriminability, i.e., the ability to discriminate signal (correct responses) from noise (false alarms), and response criterion, indicating a lower threshold to yield responses. All effect sizes were large. In other words, one session of tDCS acutely enhanced WM in depressed subjects, suggesting that tDCS can improve "cold" (non affective-loaded) working memory processes in MDD. Based on these findings, we discuss the effects of tDCS on WM enhancement in depression. We also suggest that the n-back task could be used as a biomarker in future tDCS studies investigating prefrontal activity in healthy and depressed samples.

Neuroscience letters

Oliveira, JF; Zanão, TA; Valiengo, L; Lotufo, PA; Benseñor, IM; Fregni, F; Brunoni, AR


Opposite effects of weak transcranial direct current stimulation on different phases of short interval intracortical inhibition (SICI).

2013 Mar

Short interval intracortical inhibition (SICI) is a common paired-pulse TMS technique that is used to measure GABAa-ergic inhibition in the cerebral motor cortex. However, inhibition evaluated with an interstimulus interval (ISI) between the TMS pulses of 2.5 ms has quite different properties from that seen at 1 ms. It is thought that the latter may represent either (or both) a different type of synaptic inhibition or refractoriness of neural membranes. The present experiments provide further evidence about the early and late components of SICI using transcranial direct current stimulation (tDCS), a technique thought to change neural excitability by polarising the nerve membranes. We assessed SICI using a threshold tracking method at a range of ISIs during concurrent application of tDCS in 11 healthy volunteers (8 males, 27-43 years old). Each subject underwent both anodal and cathodal tDCS with two different intensities of stimulation (1 and 2 mA). Because there was no significant difference between the results at the two intensities, the data were combined. Principal component analysis was used to separate the contributions of early and late SICI to the time course of inhibition from 1 to 5 ms tDCS had opposite effects on early and late SICI. Anodal tDCS reduced late SICI but enhanced early SICI, whereas cathodal tDCS had the opposite effect. This is further evidence that the two phases of SICI are produced by different mechanisms, perhaps involving different sets of neurones or different locations on the same neurone that respond oppositely to tDCS.

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Cengiz, B; Murase, N; Rothwell, JC


Site-specific effects of mental practice combined with transcranial direct current stimulation on motor learning.

2013 Mar

Mental practice can induce significant neural plasticity and result in motor performance improvement if associated with motor imagery tasks. Given the effects of transcranial direct current stimulation (tDCS) on neuroplasticity, the current study tested whether tDCS, using different electrode montages, can increase the neuroplastic effects of mental imagery on motor learning. Eighteen healthy right-handed adults underwent a randomised sham-controlled crossover experiment to receive mental training combined with either sham or active anodal tDCS of the right primary motor cortex (M1), right supplementary motor area, right premotor area, right cerebellum or left dorsolateral prefrontal cortex (DLPFC). Motor performance was assessed by a blinded rater using: non-dominant handwriting time and legibility, and mentally trained task at baseline (pre) and immediately after (post) mental practice combined with tDCS. Active tDCS significantly enhances the motor-imagery-induced improvement in motor function as compared with sham tDCS. There was a specific effect for the site of stimulation such that effects were only observed after M1 and DLPFC stimulation during mental practice. These findings provide new insights into motor imagery training and point out that two cortical targets (M1 and DLPFC) are significantly associated with the neuroplastic effects of mental imagery on motor learning. Further studies should explore a similar paradigm in patients with brain lesions.

The European journal of neuroscience

Foerster, A; Rocha, S; Wiesiolek, C; Chagas, AP; Machado, G; Silva, E; Fregni, F; Monte-Silva, K


Letter to the editor: transcranial direct current stimulation (tDCS) has a history reaching back to the 19th century.

2013 Mar

Psychological medicine

Steinberg, H


Could dual-hemisphere transcranial direct current stimulation (tDCS) reduce spasticity after stroke?

2013 Mar

Acta neurologica Belgica

Vandermeeren, Y; Lefebvre, S; Desfontaines, P; Laloux, P


Methods for extra-low voltage transcranial direct current stimulation: current and time dependent impedance decreases.

2013 Mar

Though tDCS is well tolerated, it is desirable to further limit the voltage applied for additional safety factors and optimized device design. We investigated the minimum voltage required for tDCS using 1.5 and 2.5mA.Impedance data has been collected prior to, during and after 18 tDCS sessions, using 1.5mA and 2.5mA tDCS currents and three different test current magnitudes. Data was pooled and tested for differences using t-tests, corrected for multiple comparisons. Average impedance data was fitted into a RLC circuit model with additional double integrator.We report that the impedance drop during tDCS initiation significantly reduces the voltage compliance required to achieve the target current (14.5V for 1.5mA, 18.5V for 2.5mA). Data was well approximated by a 4th order linear impedance model.In addition to indicating the feasibility of reduced voltage tDCS, we propose an extra-low voltage "Limited Total Energy" approach where stimulation is continued at voltage compliance allowing time for impedance to decrease and target current to be reached.Reduced-voltage and Limited Total Energy tDCS are viable approaches towards more protective and robust tDCS protocols.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Hahn, C; Rice, J; Macuff, S; Minhas, P; Rahman, A; Bikson, M


Cathodal transcranial direct current stimulation affects seizures and cognition in fully amygdala-kindled rats.

2013 Feb

This study evaluated the effects of weak transcranial direct current stimulation (tDCS), a new non-invasivebrain stimulation technique, on amygdala-kindled rats. The seizure severity, i.e. seizure stage, afterdischarge duration (ADD), and AD threshold (ADT) in the animals were measured one day after thelast cathodal tDCS session, comparing with those of pre-treatment controls. Furthermore, the effects ofcathodal tDCS on cognitive function were also studied by a water maze test (WMT) two days after the lasttDCS session. Cathodal tDCS treatment significantly improved the seizure stage and decreased ADDtogether with elevated ADT one day after the last tDCS session. The treatment also showed significantimprovement in the performance of WMT. The findings suggest that cathodal tDCS has anticonvulsive aftereffectslast at least for one day on the amygdale-kindled rats and positively affects cognitive performance.

Neurological research

Kamida, T; Kong, S; Eshima, N; Fujiki, M


Brain stimulation modulates the autonomic nervous system, rating of perceived exertion and performance during maximal exercise.

2013 Feb

BACKGROUND: The temporal and insular cortex (TC, IC) have been associated with autonomic nervous system (ANS) control and the awareness of emotional feelings from the body. Evidence shows that the ANS and rating of perceived exertion (RPE) regulate exercise performance. Non-invasive brain stimulation can modulate the cortical area directly beneath the electrode related to ANS and RPE, but it could also affect subcortical areas by connection within the cortico-cortical neural networks. This study evaluated the effects of transcranial direct current stimulation (tDCS) over the TC on the ANS, RPE and performance during a maximal dynamic exercise. METHODS: Ten trained cyclists participated in this study (33±9 years; 171.5±5.8 cm; 72.8±9.5 kg; 10-11 training years). After 20-min of receiving either anodal tDCS applied over the left TC (T3) or sham stimulation, subjects completed a maximal incremental cycling exercise test. RPE, heart rate (HR) and R-R intervals (as a measure of ANS function) were recorded continuously throughout the tests. Peak power output (PPO) was recorded at the end of the tests. RESULTS: With anodal tDCS, PPO improved by ∼4% (anodal tDCS: 313.2±29.9 vs 301.0±19.8 watts: sham tDCS; p=0.043), parasympathetic vagal withdrawal was delayed (anodal tDCS: 147.5±53.3 vs 125.0±35.4 watts: sham tDCS; p=0.041) and HR was reduced at submaximal workloads. RPE also increased more slowly during exercise following anodal tDCS application, but maximal RPE and HR values were not affected by cortical stimulation. CONCLUSIONS: The findings suggest that non-invasive brain stimulation over the TC modulates the ANS activity and the sensory perception of effort and exercise performance, indicating that the brain plays a crucial role in the exercise performance regulation.

British journal of sports medicine

Okano, AH; Fontes, EB; Montenegro, RA; Farinatti, PD; Cyrino, ES; Li, LM; Bikson, M; Noakes, TD


Transcranial direct current stimulation increases resting state interhemispheric connectivity.

2013 Feb

Transcranial direct current stimulation (tDCS) has been increasingly used to investigate human brain functions. Especially, tDCS on the dorsolateral prefrontal cortex (DLPFC) enhances cognitive functions in both healthy subjects and patients with neuropsychiatric disorders. In spite of its effects on behavioral improvement, neural correlates of tDCS on the DLPFC have not been fully described. In this study, we acquired resting state functional magnetic resonance imaging data before and after real or sham stimulation on the left DLPFC. Resting state functional connectivity of the stimulated brain region was compared between the two groups. Compared to the sham stimulation group, the tDCS group showed increased DLPFC connectivity to the right hemisphere and decreased DLPFC connectivity to the brain regions around the stimulation site in the left hemisphere. Application of tDCS on the DLPFC may induce increased interhemispheric connectivity even at rest, possibly associated with the behavioral effects of tDCS.

Neuroscience letters

Park, CH; Chang, WH; Park, JY; Shin, YI; Kim, ST; Kim, YH


Evaluation of sham transcranial direct current stimulation for randomized, placebo-controlled clinical trials.

2013 Feb

BACKGROUND: Transcranial direct current stimulation (tDCS) has been investigated as therapeutic intervention in various psychiatric and neurologic disorders. As placebo responses to technical interventions may be pronounced in many clinical conditions, it is important to thoroughly develop placebo conditions which meet the requirements for application in randomized double-blind controlled trials. OBJECTIVE: The two-part experiment reported here aims at evaluating a new sham tDCS condition in healthy subjects and device operators. Sham or active tDCS is delivered after entering a number code to the device and allows blinding of the operator before and during tDCS. The sham mode has no short stimulation period. METHODS: The experimental sequence was as follows: 1) Evaluation of successful blinding by comparing placebo to active stimulation at prefrontal sites based on the rating of subjects undergoing tDCS, 2) Evaluation of successful blinding by comparing placebo to active stimulation at prefrontal sites based on the operator/observer ratings. RESULTS: Subjects were not able to distinguish between active and sham tDCS for prefrontal stimulation. Overall there was no relevant discomfort and tDCS was well tolerated. Operators/observers were able to identify sham stimulation based on skin reddening after active, but not after sham tDCS. CONCLUSIONS: The tDCS sham condition investigated here may be suitable for placebo-controlled trials keeping subjects blind to treatment conditions. However, operators can easily be aware of the condition applied and they should not get involved in rating outcome measures during the course of high standard placebo-controlled trials.

Brain stimulation

Palm, U; Reisinger, E; Keeser, D; Kuo, MF; Pogarell, O; Leicht, G; Mulert, C; Nitsche, MA; Padberg, F


Transcranial direct current stimulation for treatment of refractory childhood focal epilepsy.

2013 Feb

BACKGROUND: Cathodal transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation method for suppressing regional cortical excitability. We examine the safety and antiepileptic efficacy of cathodal tDCS in children with refractory focal epilepsy. Although a prior cathodal tDCS trial in adults with epilepsy revealed EEG improvement, neither the antiepileptic potential nor the safety and tolerability of tDCS has been tested in children. METHOD: The study consisted of three phases: 1) a 4-week pre-treatment monitoring period with vital sign measures, EEG, seizure diary, and baseline quality of life (QOL) questionnaire; 2) a single treatment with 1 mA cathodal tDCS for 20 min with cathode positioned over the seizure focus and anode on the contralateral shoulder; 3) follow-ups immediately after stimulation, and at 24, 48 h, and 4 weeks after tDCS with continued seizure diary and epileptic discharge counts on EEG; the QOL questionnaire was also repeated 4 weeks after stimulation. Patients were randomized to receive either single session active or sham tDCS 1 mA, 20 min. RESULTS: Thirty six children (6-15 years) with focal epilepsy were enrolled, 27 in active and 9 in sham group. All patients tolerated tDCS well. No serious adverse events occurred. Active tDCS treatment was associated with significant reductions in epileptic discharge frequency immediately and 24 and 48 h after tDCS. Four weeks after treatment, a small (clinically negligible but statistically significant) decrease in seizure frequency was also detected. CONCLUSION: A single session of cathodal tDCS improves epileptic EEG abnormalities for 48 h and is well-tolerated in children.

Brain stimulation

Auvichayapat, N; Rotenberg, A; Gersner, R; Ngodklang, S; Tiamkao, S; Tassaneeyakul, W; Auvichayapat, P


Effects of anodal and cathodal transcranial direct current stimulation combined with robotic therapy on severely affected arms in chronic stroke patients.

2013 Feb

The purpose of this study was to examine the effects of combined therapy using transcranial direct current stimulation (tDCS) with robot-assisted arm training (AT) for impairment of the upper limb in chronic stroke patients, and to clarify whether differences exist in the effect of anodal tDCS on the affected hemisphere (tDCS(a) + AT) and cathodal tDCS on the unaffected hemisphere (tDCS(c) + AT).Subjects in this randomized, double-blinded, crossover study comprised 18 chronic stroke patients with moderate-to-severe arm paresis. Each patient underwent 2 different treatments: tDCS(a) + AT; and tDCS(c) + AT. Each intervention was administered for 5 days, and comprised AT with 1 mA of tDCS during the first 10 min. Outcomes were identified as changes in Fugl-Meyer Assessment (FMUL), modified Ashworth scale (MAS) and Motor Activity Log (MAL) for the upper limb.Both interventions showed significant improvements in FMUL and MAS, but not in MAL. Distal spasticity was significantly improved with tDCS(c) + AT compared with tDCS(a) + AT for right hemispheric lesions (median -1 vs 0), but not for left hemispheric lesions.Although this study demonstrated that combined therapy could achieve limited effects in the hemiplegic arm of chronic stroke patients, a different effect of polarity of tDCS was seen for patients with right hemispheric lesions.

Journal of rehabilitation medicine : official journal of the UEMS European Board of Physical and Rehabilitation Medicine

Ochi, M; Saeki, S; Oda, T; Matsushima, Y; Hachisuka, K


Transcranial direct current stimulation (tDCS) priming of 1Hz repetitive transcranial magnetic stimulation (rTMS) modulates experimental pain thresholds.

2013 Feb

Transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) modulate cortical excitability. Both techniques have been demonstrated to modulate chronic pain and experimental pain thresholds, but with inconsistent effects. Preconditioning M1 with weak tDCS (1mA) standardizes the effects of subsequent stimulation via rTMS on levels of cortical excitability. Here we examine whether 1Hz rTMS, primed with tDCS, could effectively standardize the modulation of pain thresholds. Thermal pain thresholds were determined using quantitative sensory testing (QST) of the palmar thenar of both hands in 12 healthy males pre and post tDCS - 1Hz rTMS over the hand area of the left M1. Cathodal tDCS preconditioning of 1Hz rTMS successfully reversed the normal suppressive effect of low frequency rTMS and effectively modulated cold and heat pain thresholds. Conversely, anodal tDCS - 1Hz rTMS led to a decrease in cold pain thresholds. Therefore, this study supports that preconditioning M1 using cathodal tDCS before subsequent stimulation via 1Hz rTMS facilitates the production of analgesia.

Neuroscience letters

Moloney, TM; Witney, AG


New modalities of brain stimulation for stroke rehabilitation.

2013 Feb

Stroke is a leading cause of disability, and the number of stroke survivors continues to rise. Traditional neurorehabilitation strategies aimed at restoring function to weakened limbs provide only modest benefit. New brain stimulation techniques designed to augment traditional neurorehabilitation hold promise for reducing the burden of stroke-related disability. Investigators discovered that repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and epidural cortical stimulation (ECS) can enhance neural plasticity in the motor cortex post-stroke. Improved outcomes may be obtained with activity-dependent stimulation, in which brain stimulation is contingent on neural or muscular activity during normal behavior. We review the evidence for improved motor function in stroke patients treated with rTMS, tDCS, and ECS and discuss the mediating physiological mechanisms. We compare these techniques to activity-dependent stimulation, discuss the advantages of this newer strategy for stroke rehabilitation, and suggest future applications for activity-dependent brain stimulation.

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Edwardson, MA; Lucas, TH; Carey, JR; Fetz, EE


Electroencephalographic changes following direct current deep brain stimulation of auditory cortex: a new model for investigating neuromodulation.

2013 Feb

Although deep brain (DBS) and transcranial direct current stimulation (tDCS) are used as investigative tools and therapies for a variety of neurological and psychiatric conditions, their mechanisms of action remain poorly understood. Therefore, there is a need for new animal models of neuromodulation.To introduce and validate a direct current DBS (DC-DBS) model that will use the anatomic precision of intracranial electrodes, as used in DBS, to apply direct current, as used in tDCS, over primary auditory cortex (A1) and induce electroencephalographic (EEG) changes.Twenty-four mice were assigned to 1 of 2 stimulation groups or a sham group and were implanted with electrodes in A1. Stimulation groups underwent DC-DBS stimulation for 20 minutes at 20 μA. Auditory EEG was recorded before stimulation and at 1 hour, 1 week, and 2 weeks poststimulation. EEG was analyzed for changes in N1 (N100 in humans, N40 in mice) amplitude and latency as well as delta and theta power.DC-DBS led to significant EEG changes (all P values < .05). Among the stimulated animals, there were durable reductions in delta and theta power. There were no differences within the sham group, and neither N40 latencies nor amplitudes changed across time.Our results show DC-DBS-induced reductions in slow-wave activity consistent with recent tDCS studies. We propose that this model will provide a means to explore basic mechanisms of neuromodulation and could facilitate future application of DC-DBS in humans.

Neurosurgery

De Rojas, JO; Saunders, JA; Luminais, C; Hamilton, RH; Siegel, SJ


Transcranial direct current stimulation intensity and duration effects on tinnitus suppression.

2013 Feb

Perception of sound in the absence of an external auditory source is called tinnitus, which may negatively affect quality of life. Anodal transcranial direct current stimulation (tDCS) of the left temporoparietal area (LTA) was explored for tinnitus relief.This pilot study examined tDCS dose (current intensity and duration) and response effects for tinnitus suppression.Twenty-five participants with chronic tinnitus and a mean age of 54 years took part. Anodal tDCS of LTA was carried out. Current intensity (1 mA and 2 mA) and duration (10 minutes, 15 minutes, and 20 minutes) were varied and their impact on tinnitus measured.tDCS was well tolerated. Fifty-six percent of participants (14) experienced transient suppression of tinnitus, and 44% of participants (11) experienced long-term improvement of symptoms (overnight-less annoyance, more relaxed, and better sleep). There was an interaction between duration and intensity of the stimulus on the change in rated loudness of tinnitus, F(2, 48) = 4.355, P = .018, and clinical global improvement score, F(2, 48) = 3.193, P = .050, after stimulation.Current intensity of 2 mA for 20 minutes was the more effective stimulus parameter for anodal tDCS of LTA. tDCS can be a potential clinical tool for reduction of tinnitus, although longer term trials are needed.

Neurorehabilitation and neural repair

Shekhawat, GS; Stinear, CM; Searchfield, GD


[Transcranial direct current stimulation: a new tool for neurostimulation].

2013 Feb

Transcranial direct current stimulation (tDCS) is a safe method to modulate cortical excitability. Anodal stimulation can improve the stimulated area's functions whereas cathodal stimulation reduces them. Currently, a lot of clinical trials have been conducted to study the effect of tDCS on post-stroke motor and language deficits, in depression, chronic pain, memory impairment and tinnitus in order to decrease symptoms. Results showed that, if an effect is observed with tDCS, it does not persist over time. Current studies suggest that direct current stimulation is a promising technique that helps to improve rehabilitation after stroke, to enhance cognitive deficiencies, to reduce depression and to relieve chronic pain. Moreover, it is a safe, simple and cheap device that could be easily integrated in a rehabilitation program.

Revue neurologique

Thibaut, A; Chatelle, C; Gosseries, O; Laureys, S; Bruno, MA


Once- to Twice-Daily, 3-Year Domiciliary Maintenance Transcranial Direct Current Stimulation for Severe, Disabling, Clozapine-Refractory Continuous Auditory Hallucinations in Schizophrenia.

2013 Jan

BACKGROUND: Some patients with schizophrenia suffer from continuous auditory hallucinations that are refractory to antipsychotic medications. METHODS: Transcranial direct current stimulation (tDCS) was used to treat a 24-year-old female schizophrenia patient who had severe, clozapine-refractory, continuous, psychosocially and cognitively disabling auditory hallucinations. The tDCS cathode was placed midway between T3 and P3, and the anode over F3, in the 10-20 electroencephalogram electrode positioning system. RESULTS: Once daily, 20-minute tDCS sessions at 1-mA intensity produced noticeable improvement within a week: cognitive and psychosocial functioning improved, followed by attenuation in the experience of hallucinations. There was greater than 90% self-reported improvement within 2 months. Benefits accelerated when the current was raised to 3 mA; treatment duration was increased to 30-minute sessions, and session frequency was increased to twice daily. The patient improved from a psychosocially vegetative state to near-normal functioning. Once- to twice-daily domiciliary tDCS was continued across nearly 3 years and is still ongoing. Benefits attenuated or were even lost when alternate day session spacing was attempted, or when electrode positioning was changed; benefits were regained when the original stimulation protocol was reintroduced. There was confirmation of benefit in 2 separate on-off-on situations, which occurred inadvertently and under blinded conditions. There were no adverse events attributable to tDCS. CONCLUSIONS: This is the first report in literature of the safe and effective use of daily to twice-daily, domiciliary, 30-min, 1- to 3-mA tDCS sessions across nearly 3 years for the treatment of continuous, disabling, clozapine-refractory auditory hallucinations in schizophrenia. Key learning points emerging from this case are presented and discussed.

The journal of ECT

Andrade, C


Transcranial Direct Current Stimulation (tDCS) Reduces Postsurgical Opioid Consumption in Total Knee Arthroplasty (TKA).

2013 Jan

BACKGROUND:: Although pain is often a symptom that precedes total knee arthroplasty (TKA), the procedure itself is associated with considerable postoperative pain lasting days to weeks. Postoperative pain control is an important factor in determining recovery time, hospital length of stay, and rehabilitation success. Several brain stimulation technologies including transcranial direct current stimulation (tDCS) have demonstrated promise as treatments for a variety of pain conditions. The present study examined the effects of 4 sessions of tDCS on post-TKA pain and opioid consumption. MATERIALS AND METHODS:: Forty patients undergoing unilateral TKA were randomly assigned to receive a total of 80 minutes of real (n=20) or sham tDCS (n=20) with the anode over the knee representation of the motor strip (C1h or C2h corresponding to the target knee) and cathode over the right dorsolateral prefrontal cortex (F3; located by the EEG 10-20 System). Patient-controlled analgesia ( hydromorphone) use was tracked during the ∼48 hours postsurgery. RESULTS:: Patients in the real tDCS group used an average of 6.6 mg (SD=5.3) of patient-controlled analgesia hydromorphone, whereas those in the sham group used 12.3 mg (SD=6.6; t37=2.93, P=0.006). Despite using less opioid medication, participants in the real tDCS group reported no pain exacerbation or worse mood with respect to those in the sham tDCS group. CONCLUSIONS:: Results from this pilot feasibility study suggest that tDCS may be able to reduce post-TKA opioid requirements. Although these results are preliminary, the data support further research in the area of adjunctive cortical stimulation in the management of postsurgical pain.

The Clinical journal of pain

Borckardt, JJ; Reeves, ST; Robinson, SM; May, JT; Epperson, TI; Gunselman, RJ; Schutte, HD; Demos, HA; Madan, A; Fredrich, S; George, MS


The role of timing in the induction of neuromodulation in perceptual learning by transcranial electric stimulation.

2013 Jan

BACKGROUND: Transcranial electric stimulation (tES) protocols are able to induce neuromodulation, offering important insights to focus and constrain theories of the relationship between brain and behavior. Previous studies have shown that different types of tES (i.e., direct current stimulation - tDCS, and random noise stimulation - tRNS) induce different facilitatory behavioral effects. However to date is not clear which is the optimal timing to apply tES in relation to the induction of robust facilitatory effects. OBJECTIVE/HYPOTHESIS: The goal of this work was to investigate how different types of tES (tDCS and tRNS) can modulate behavioral performance in the healthy adult brain in relation to their timing of application. We applied tES protocols before (offline) or during (online) the execution of a visual perceptual learning (PL) task. PL is a form of implicit memory that is characterized by an improvement in sensory discrimination after repeated exposure to a particular type of stimulus and is considered a manifestation of neural plasticity. Our aim was to understand if the timing of tES is critical for the induction of differential neuromodulatory effects in the primary visual cortex (V1). METHODS: We applied high-frequency tRNS, anodal tDCS and sham tDCS on V1 before or during the execution of an orientation discrimination task. The experimental design was between subjects and performance was measured in terms of d' values. RESULTS: The ideal timing of application varied depending on the stimulation type. tRNS facilitated task performance only when it was applied during task execution, whereas anodal tDCS induced a larger facilitation if it was applied before task execution. CONCLUSION: The main result of this study is the finding that the timing of identical tES protocols yields opposite effects on performance. These results provide important guidelines for designing neuromodulation induction protocols and highlight the different optimal timing of the two excitatory techniques.

Brain stimulation

Pirulli, C; Fertonani, A; Miniussi, C


Modulating Human Procedural Learning by Cerebellar Transcranial Direct Current Stimulation.

2013 Jan

Neuroimaging studies suggest that the cerebellum contributes to human cognitive processing, particularly procedural learning. This type of learning is often described as implicit learning and involves automatic, associative, and unintentional learning processes. Our aim was to investigate whether cerebellar transcranial direct current stimulation (tDCS) influences procedural learning as measured by the serial reaction time task (SRTT), in which subjects make speeded key press responses to visual cues. A preliminary modeling study demonstrated that our electrode montage (active electrode over the cerebellum with an extra-cephalic reference) generated the maximum electric field amplitude in the cerebellum. We enrolled 21 healthy subjects (aged 20-49 years). Participants did the SRTT, a visual analogue scale and a visual attention task, before and 35 min after receiving 20-min anodal and sham cerebellar tDCS in a randomized order. To avoid carry-over effects, experimental sessions were held at least 1 week apart. For our primary outcome measure (difference in RTs for random and repeated blocks) anodal versus sham tDCS, RTs were significantly slower for sham tDCS than for anodal cerebellar tDCS (p = 0.04), demonstrating that anodal tDCS influenced implicit learning processes. When we assessed RTs for procedural learning across the one to eight blocks, we found that RTs changed significantly after anodal stimulation (interaction "time" × "blocks 1/8": anodal, p = 0.006), but after sham tDCS, they remained unchanged (p = 0.094). No significant changes were found in the other variables assessed. Our finding that anodal cerebellar tDCS improves an implicit learning type essential to the development of several motor skills or cognitive activity suggests that the cerebellum has a critical role in procedural learning. tDCS could be a new tool for improving procedural learning in daily life in healthy subjects and for correcting abnormal learning in neuropsychiatric disorders.

Cerebellum (London, England)

Ferrucci, R; Brunoni, AR; Parazzini, M; Vergari, M; Rossi, E; Fumagalli, M; Mameli, F; Rosa, M; Giannicola, G; Zago, S; Priori, A


Transcranial Direct Current Stimulation (tDCS) Relieved Itching in a Patient With Chronic Neuropathic Pain.

2013 Jan

ABSTRACT:: Itching is often called the second modality of nociception besides pain, and affects many chronic pain patients. OBJECTIVES:: This case report presents a first note on beneficial effects of transcranial direct current stimulation (tDCS) on itching associated with chronic neuropathic pain in a patient diagnosed with syringomyelia. METHODS:: tDCS is a novel noninvasive neuromodulatory method with promising therapeutic potential in pain and symptom management. The primary mechanism of tDCS is subthreshold modulation of the neuronal resting membrane potential that induces a polarity-dependent modification of N-Methyl-D-aspartate receptor function that plays a role in neuroplasticity. The patient, a 46-year-old white male diagnosed with syringomyelia 2 decades ago, continuously reported weakness in the arms and dyesthesias including pain and itch that fluctuated in severity. Pharmacological treatment with baclofen, duloxetine, and bupropion was partially helpful; however, did not prevent flares of pain and other dysesthesias, including itch. The patient underwent 3 tDCS treatment courses consisting of 20 minutes of tDCS on 5 consecutive days at each course over 13 months. RESULTS:: Although there was no change in pain intensity or quality during or after tDCS, the treatment resulted in a reduction in itch to a mild, tolerable intensity that persisted for 3 to 4 months after each course, before returning to the pretreatment level. The patient has agreed to a plan of care that will incorporate neurostimulation every 4 to 6 months, as long as its effectiveness continues. DISCUSSION:: This case provides a rationale for future studies of neuromodulatory treatments for itch, and indicates a potential clinical use of neuromodulation in patients with unrelieved itching.

The Clinical journal of pain

Knotkova, H; Portenoy, RK; Cruciani, RA


Neuroenhancement of the aging brain: restoring skill acquisition in old subjects.

2013 Jan

Decline in cognitive functions, including impaired acquisition of novel skills, is a feature of older age that impacts activities of daily living, independence, and integration in modern societies.We tested whether the acquisition of a complex motor skill can be enhanced in old subjects by the application of transcranial direct current stimulation (tDCS) to the motor cortex.The main finding was that old participants experienced substantial improvements when training was applied concurrent with tDCS, with effects lasting for at least 24 hours.These results suggest noninvasive brain stimulation as a promising and safe tool to potentially assist functional independence of aged individuals in daily life.

Annals of neurology

Zimerman, M; Nitsch, M; Giraux, P; Gerloff, C; Cohen, LG; Hummel, FC


Transcranial direct current stimulation of the motor cortex in the treatment of chronic nonspecific low back pain: a randomized, double-blind exploratory study.

2013 Jan

To test the proof of principle that active anodal transcranial direct current stimulation (tDCS) applied to the motor cortex reduces pain significantly more than sham stimulation in a group of participants with chronic nonspecific low back pain.The study utilized a within-participants sham-controlled, interrupted time series design. A sample of 8 participants was recruited. After 3 days of baseline measures, patients entered a 15-day experimental period (Mondays to Fridays) for 3 consecutive weeks. During this period each patient received sham stimulation daily until a randomly allocated day when active stimulation was commenced. Active stimulation was then given daily for the remaining days of the experimental period. Both the participants and the assessors were blinded. The primary outcomes were average pain intensity and unpleasantness in the last 24 hours measured using a visual analogue scale. Secondary outcomes included self-reported disability, depression and anxiety, a battery of cognitive tests to monitor for unwanted effects of stimulation, and patients' perceptions of whether they had received active or sham stimulation. Data were analyzed using generalized estimating equations.No significant effect was seen in the primary outcomes between active and sham stimulation (average pain intensity P = 0.821, unpleasantness P = 0.937) or across any other clinical variables. There was evidence that patients may have been able to distinguish between the active and sham conditions (P = 0.035).These results do not provide evidence that tDCS is effective in the treatment of chronic back pain. The use of a small convenience sample limits the generalizability of these findings and precludes definitive conclusions on the efficacy of tDCS in chronic nonspecific low back pain.

The Clinical journal of pain

O'Connell, NE; Cossar, J; Marston, L; Wand, BM; Bunce, D; De Souza, LH; Maskill, DW; Sharp, A; Moseley, GL


Noninvasive transcranial direct current stimulation in a genetic absence model.

2013 Jan

The proposed area of onset for absence epilepsy characteristic of spontaneously occurring spike and slow-wave discharges (SWDs) in the genetic absence rat model is the subgranular layer of the somatosensory cortex. Modulation of the hyperexcitable cortical foci by bilateral transcranial direct current stimulation (tDCS) might change the expression of SWDs. The effects of cathodal and anodal tDCS as well as cumulative effects of different intensities of repeated cathodal stimulation on EEG and behavior were examined. Cathodal tDCS reduced the number of SWDs during stimulation and affected the mean duration after stimulation both in an intensity-dependent manner. Behavior was changed after the highest stimulation intensity. Spectral analyses of the EEG during stimulation revealed an increase in sub-delta and delta frequency ranges, suggesting that cortical cells were hyperpolarized. Cathodal tDCS might be an effective non-invasive tool to decrease cortical excitability, presumably in focal zone in this genetic model.

Epilepsy & behavior : E&B

Zobeiri, M; van Luijtelaar, G


Anodal transcranial direct current stimulation modulates GABAB-related intracortical inhibition in the M1 of healthy individuals.

2013 Jan

It is known that transcranial direct current stimulation (tDCS) can induce polarity-specific shifts in brain excitability of the primary motor cortex (M1) with anodal tDCS enhancing and cathodal tDCS reducing cortical excitability. However, less is known about its impact on specific intracortical inhibitory mechanisms, such as γ-aminobutyric acid B (GABAB)-mediated inhibition. Consequently, the aim of the present study was to assess the impact of anodal and cathodal tDCS on M1 intracortical inhibition in healthy individuals. Long-interval intracortical inhibition (LICI) and cortical silent period (CSP) duration, both presumably mediated by GABAB receptors, were assessed using transcranial magnetic stimulation immediately before and after a 20 min session of tDCS over the left M1. Anodal tDCS significantly enhanced motor evoked potential size and reduced CSP duration, whereas it had no effect on LICI. Cathodal stimulation did not significantly modulate motor evoked potential size, CSP duration or LICI. This study provides evidence that anodal tDCS, presumably by synaptic plasticity mechanisms, has a direct effect on GABAB-meditated inhibition assessed by the CSP, but not by LICI. Our results further suggest that CSP and LICI probe distinct intracortical inhibitory mechanisms as they are differentially modulated by anodal tDCS. Finally, these data may have clinical value in patients in whom a pathological increase in CSP duration is present, such as schizophrenia.

Neuroreport

Tremblay, S; Beaulé, V; Lepage, JF; Théoret, H


Transcranial alternating current stimulation reduces symptoms in intractable idiopathic cervical dystonia: a case study.

2013 Jan

Idiopathic cervical dystonia (ICD) is a movement disorder often resulting in profound disability and pain. Treatment options include oral medications or other invasive procedures, whereas intractable ICD has been shown to respond to invasive (deep) brain stimulation. In the present blinded, placebo-controlled case study, transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) has been applied to a 54-year old patient with intractable ICD. Results showed that 15 Hz tACS had both immediate and cumulative effects in dystonic symptom reduction, with a 54% reduction in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score, and a 75% in the TWSTRS Pain Scale. These effects were persistent at 30-days follow-up. This is the first report to demonstrate a significant and lasting therapeutic effect of non-invasive electrical brain stimulation in dystonia.

Neuroscience letters

Angelakis, E; Liouta, E; Andreadis, N; Leonardos, A; Ktonas, P; Stavrinou, LC; Miranda, PC; Mekonnen, A; Sakas, DE


Continuation transcranial direct current stimulation for the prevention of relapse in major depression.

2013 Jan

Transcranial direct current stimulation (tDCS) is gaining attention as an effective new treatment for major depression. Little is known, however, of the duration of antidepressant effects following acute treatment. In this study, we describe the use of continuation tDCS treatment for up to 6 months following clinical response to an acute treatment course.Twenty-six participants pooled from two different studies involving different tDCS protocols received continuation tDCS treatment on a weekly basis for 3 months and then once per fortnight for the final 3 months. Mood ratings were completed at 3 and 6 months. Analyses examined clinical predictors of relapse during continuation tDCS treatment.The cumulative probability of surviving without relapse was 83.7% at 3 months and 51.1% at 6 months. Medication resistance was found to be a predictor of relapse during continuation tDCS.This was an open label prospective study with no control group. Two different forms of tDCS were used.Similar to other antidepressant treatments, continuation tDCS appears to be a useful strategy to prevent relapse following clinical response. These preliminary data suggest that the majority of patients maintained antidepressant benefit with a continuation schedule of at least weekly treatment. Future controlled studies are required to confirm these findings.

Journal of affective disorders

Martin, DM; Alonzo, A; Ho, KA; Player, M; Mitchell, PB; Sachdev, P; Loo, CK


A novel ring electrode setup for the recording of somatosensory evoked potentials during transcranial direct current stimulation (tDCS).

2013 Jan

Transcranial direct current stimulation (tDCS) modulates cortical excitability thereby influencing behavior and learning. While previous studies focused on tDCS after-effects, limited information about "online" tDCS effects is available. This in turn is an important prerequisite to better characterize and/or optimize tDCS effects. Here, we aimed to explore the feasibility of recording low-artifact somatosensory evoked potentials (SEPs) during tDCS using a novel ring electrode setup. We recorded SEP before, during and after 10 min of anodal or sham tDCS using a full-band direct current (DC) EEG system in a total number of 3 subjects. SEPs were recorded in the bore of the tDCS ring electrode. Using this approach, no tDCS-induced artifacts could be observed after the application of a standard EEG filter. This new setup might help to better characterize how tDCS alters evoked brain responses thus providing novel insight into underlying physiological effects during stimulation.

Journal of neuroscience methods

Sehm, B; Hoff, M; Gundlach, C; Taubert, M; Conde, V; Villringer, A; Ragert, P


Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials.

2013 Jan

tDCS is a promising novel therapeutic intervention for major depression (MD). However, clinical trials to date have reported conflicting results concerning its efficacy, which likely resulted from low statistical power. Thus, we carried out a systematic review and meta-analysis on randomized, double-blind and controlled trials of tDCS in MD with a focus on clinically relevant outcomes, namely response and remission rates.We searched the literature for English language randomized, double-blind and sham-controlled trials (RCTs) on tDCS for treating MD from 1998 through July 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials and SCOPUS. We also consulted the Web of Science's Citations Index Expanded for the selected RCTs up to July 2012. The main outcome measures were response and remission rates. We used a random-effects model and Odds Ratios (OR).Data were obtained from 6 RCTs that included a total of 200 subjects with MD. After an average of 10.8 ± 3.76 tDCS sessions, no significant difference was found between active and sham tDCS in terms of both response (23.3% [24/103] vs. 12.4% [12/97], respectively; OR = 1.97; 95% CI = 0.85-4.57; p = 0.11) and remission (12.2% [12/98] vs. 5.4% [5/92], respectively; OR = 2.13; 95% CI = 0.64-7.06; p = 0.22). Also, no differences between mean baseline depression scores and dropout rates in the active and sham tDCS groups were found. Furthermore, sensitivity analyses excluding RCTs that involved less than 10 treatment sessions or stimulus intensity of less than 2 mA did not alter the findings. However, tDCS used as monotherapy was associated with higher response rates when compared to sham tDCS (p = 0.043). Finally, the risk of publication bias in this meta-analysis was found to be low.The clinical utility of tDCS as a treatment for MD remains unclear when clinically relevant outcomes such as response and remission rates are considered. Future studies should include larger and more representative samples, investigate how tDCS compares to other therapeutic neuromodulation techniques, as well as identify optimal stimulation parameters.

Journal of psychiatric research

Berlim, MT; Van den Eynde, F; Daskalakis, ZJ


Cranial electrotherapy stimulation and transcranial pulsed current stimulation: a computer based high-resolution modeling study.

2013 Jan

The field of non-invasive brain stimulation has developed significantly over the last two decades. Though two techniques of noninvasive brain stimulation--transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS)--are becoming established tools for research in neuroscience and for some clinical applications, related techniques that also show some promising clinical results have not been developed at the same pace. One of these related techniques is cranial electrotherapy stimulation (CES), a class of transcranial pulsed current stimulation (tPCS). In order to understand further the mechanisms of CES, we aimed to model CES using a magnetic resonance imaging (MRI)-derived finite element head model including cortical and also subcortical structures. Cortical electric field (current density) peak intensities and distributions were analyzed. We evaluated different electrode configurations of CES including in-ear and over-ear montages. Our results confirm that significant amounts of current pass the skull and reach cortical and subcortical structures. In addition, depending on the montage, induced currents at subcortical areas, such as midbrain, pons, thalamus and hypothalamus are of similar magnitude than that of cortical areas. Incremental variations of electrode position on the head surface also influence which cortical regions are modulated. The high-resolution modeling predictions suggest that details of electrode montage influence current flow through superficial and deep structures. Finally we present laptop based methods for tPCS dose design using dominant frequency and spherical models. These modeling predictions and tools are the first step to advance rational and optimized use of tPCS and CES.

NeuroImage

Datta, A; Dmochowski, JP; Guleyupoglu, B; Bikson, M; Fregni, F


Numerical investigation of white matter anisotropic conductivity in defining current distribution under tDCS.

2013 Jan

The study investigates the impact of white matter directional conductivity on brain current density under the influence of Transcranial direct current stimulation (tDCS). The study employed different conductivity estimation algorithms to represent conductivity distribution in the white matter (WM) of the brain. Two procedures, one mathematically driven and the second one based on the Diffusion tensor imaging (DTI) are considered. The finite element method has been applied to estimate the current density distribution across the head models. Strengths and weaknesses of these algorithms have been compared by analyzing the variation in current density magnitude and distribution patterns with respect to the isotropic case. Results indicate that anisotropy has a profound influence on the strength of current density (up to ≈50% in WM) as it causes current flow to deviate from its isotropically defined path along with diffused distribution patterns across the gray and WM. The extent of this variation is highly correlated with the degree of the anisotropy of the regions. Regions of high anisotropy and models of fixed anisotropic ratio displayed higher and wider degree of variations across the structures (topographic variations up to 48%), respectively. In contrast, models, which are correlated with the magnitude of local diffusion tensor behaved in a less exacerbated manner (≈10% topographic changes in WM). Anisotropy increased the current density strength across the cortical gyri under and between the stimulating electrodes, whereas a significant drop has been recorded in deeper regions of the GM (max % difference ≈±10). In addition, it has been observed that Equivalent isotropic trace algorithm is more suitable to incorporate directional conductivity under tDCS paradigm, than other considered approaches, as this algorithm is computationally less expensive and insensitive to the limiting factor imposed by the volume constraint.

Computer methods and programs in biomedicine

Shahid, S; Wen, P; Ahfock, T


Effects on decreasing upper-limb poststroke muscle tone using transcranial direct current stimulation: a randomized sham-controlled study.

2013 Jan

To assess the efficacy of transcranial direct current stimulation (tDCS) on decreasing upper-limb (UL) muscle tone after stroke.A prospective, sham-controlled, randomized controlled trial with 4-weeks follow-up. Randomization into the tDCS group or the control group.Rehabilitation education and research hospital.Inpatients (N=90, 45 per group; age range, 15-70y; 69 men, 21 women; duration of stroke, 2-12mo) with poststroke UL spasticity. No participant withdrew because of adverse effects.The tDCS group received tDCS to the primary sensorimotor cortex of the affected side with cathodal stimulation, 20 minutes per day, 5 days per week, for 4 weeks and conventional physical therapy. The control group received sham stimulation (same area as the tDCS group) and conventional physical therapy.Modified Ashworth scale (MAS), Fugl-Meyer Assessment of motor recovery, and Barthel Index. All outcomes were measured at admission, after treatment, and after follow-up. A clinically important difference (CID) was defined as a reduction of ≥1 in the MAS score.Compared with the sham tDCS group, the active tDCS group had significantly more patients with a clinically important difference after treatment (80% and 78% vs 6% and 9%) and at 4-week follow-up (84% and 82% vs 7% and 4%), and UL motor function and activities of daily living (ADL) assessment improved more significantly in the active tDCS group (Fugl-Meyer Assessment of motor recovery from 12 [range, 4-26] to 22 [range, 7-50] to 32 [range, 28-41], Barthel Index from 55 [range, 0-85] to 85 [range, 5-100] to 90 [range, 10-100 vs Fugl-Meyer Assessment of motor recovery from 8 [range, 3-34] to 10 [range, 8-25] to 15 [range, 6-40], Barthel Index from 55 [range, 25-95] to 65 [range, 30-100] to 75 [range, 40-100], respectively, P<.01).UL muscle tone after stroke can be decreased using cathodal tDCS. Combined with conventional physical therapy, tDCS appears to improve motor function and ADL. Cathodal tDCS over ipsilesional primary sensorimotor cortex may inhibit primary sensorimotor cortex hyperactivation, resulting in significant reductions in muscle tone.

Archives of physical medicine and rehabilitation

Wu, D; Qian, L; Zorowitz, RD; Zhang, L; Qu, Y; Yuan, Y


tDCS over the Left Prefrontal Cortex Enhances Cognitive Control for Positive Affective Stimuli.

2013

Transcranial Direct Current Stimulation (tDCS) is a neuromodulation technique with promising results for enhancing cognitive information processes. So far, however, research has mainly focused on the effects of tDCS on cognitive control operations for non-emotional material. Therefore, our aim was to investigate the effects on cognitive control considering negative versus positive material. For this sham-controlled, within-subjects study, we selected a homogeneous sample of twenty-five healthy participants. By using behavioral measures and event related potentials (ERP) as indexes, we aimed to investigate whether a single session of anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) would have specific effects in enhancing cognitive control for positive and negative valenced stimuli. After tDCS over the left DLPFC (and not sham control stimulation), we observed more negative N450 amplitudes along with faster reaction times when inhibiting a habitual response to happy compared to sad facial expressions. Gender did not influence the effects of tDCS on cognitive control for emotional information. In line with the Valence Theory of side-lateralized activity, this stimulation protocol might have led to a left dominant (relative to right) prefrontal cortical activity, resulting in augmented cognitive control specifically for positive relative to negative stimuli. To verify that tDCS induces effects that are in line with all aspects of the well known Valence Theory, future research should investigate the effects of tDCS over the left vs. right DLPFC on cognitive control for emotional information.

PloS one

Vanderhasselt, MA; De Raedt, R; Brunoni, AR; Campanhã, C; Baeken, C; Remue, J; Boggio, PS


A Comparison between Uni- and Bilateral tDCS Effects on Functional Connectivity of the Human Motor Cortex.

2013

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been shown to induce changes in motor performance and learning. Recent studies indicate that tDCS is capable of modulating widespread neural network properties within the brain. However the temporal evolution of online- and after-effects of tDCS on functional connectivity (FC) within and across the stimulated motor cortices (M1) still remain elusive. In the present study, two different tDCS setups were investigated: (i) unilateral M1 tDCS (anode over right M1, cathode over the contralateral supraorbital region) and (ii) bilateral M1 tDCS (anode over right M1, cathode over left M1). In a randomized single-blinded cross-over design, 12 healthy subjects underwent functional magnetic resonance imaging at rest before, during and after 20 min of either bi-, unilateral, or sham M1 tDCS. Seed-based FC analysis was used to investigate tDCS-induced changes across and within M1. We found that bilateral M1 tDCS induced (a) a decrease in interhemispheric FC during stimulation and (b) an increase in intracortical FC within right M1 after termination of the intervention. While unilateral M1 tDCS also resulted in similar effects during stimulation, no such changes could be observed after termination of tDCS. Our results provide evidence that depending on the electrode montage, tDCS acts upon a modulation of either intracortical and/or interhemispheric processing of M1.

Frontiers in human neuroscience

Sehm, B; Kipping, J; Schäfer, A; Villringer, A; Ragert, P


Transcranial direct-current stimulation increases extracellular dopamine levels in the rat striatum.

2013

Background: Transcranial direct-current stimulation (tDCS) is a non-invasive procedure that achieves polarity-dependent modulation of neuronal membrane potentials. It has recently been used as a functional intervention technique for the treatment of psychiatric and neurological diseases; however, its neuronal mechanisms have not been fully investigated in vivo. Objective/Hypothesis: To investigate whether the application of cathodal or anodal tDCS affects extracellular dopamine and serotonin levels in the rat striatum. Methods: Stimulation and in vivo microdialysis were carried out under urethane anesthesia, and microdialysis probes were slowly inserted into the striatum. After the collection of baseline fractions in the rat striatum, cathodal or anodal tDCS was applied continuously for 10 min with a current intensity of 800 μA from an electrode placed on the skin of the scalp. Dialysis samples were collected every 10 min until at least 400 min after the onset of stimulation. Results: Following the application of cathodal, but not anodal, tDCS for 10 min, extracellular dopamine levels increased for more than 400 min in the striatum. There were no significant changes in extracellular serotonin levels. Conclusion: These findings suggest that tDCS has a direct and/or indirect effect on the dopaminergic system in the rat basal ganglia.

Frontiers in systems neuroscience

Tanaka, T; Takano, Y; Tanaka, S; Hironaka, N; Kobayashi, K; Hanakawa, T; Watanabe, K; Honda, M


Different current intensities of anodal transcranial direct current stimulation do not differentially modulate motor cortex plasticity.

2013

Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates the excitability of neurons within the motor cortex (M1). Although the aftereffects of anodal tDCS on modulating cortical excitability have been described, there is limited data describing the outcomes of different tDCS intensities on intracortical circuits. To further elucidate the mechanisms underlying the aftereffects of M1 excitability following anodal tDCS, we used transcranial magnetic stimulation (TMS) to examine the effect of different intensities on cortical excitability and short-interval intracortical inhibition (SICI). Using a randomized, counterbalanced, crossover design, with a one-week wash-out period, 14 participants (6 females and 8 males, 22-45 years) were exposed to 10 minutes of anodal tDCS at 0.8, 1.0, and 1.2 mA. TMS was used to measure M1 excitability and SICI of the contralateral wrist extensor muscle at baseline, immediately after and 15 and 30 minutes following cessation of anodal tDCS. Cortical excitability increased, whilst SICI was reduced at all time points following anodal tDCS. Interestingly, there were no differences between the three intensities of anodal tDCS on modulating cortical excitability or SICI. These results suggest that the aftereffect of anodal tDCS on facilitating cortical excitability is due to the modulation of synaptic mechanisms associated with long-term potentiation and is not influenced by different tDCS intensities.

Neural plasticity

Kidgell, DJ; Daly, RM; Young, K; Lum, J; Tooley, G; Jaberzadeh, S; Zoghi, M; Pearce, AJ


Transcranial direct current stimulation in stroke rehabilitation: a review of recent advancements.

2013

Transcranial direct current stimulation (tDCS) is a promising technique to treat a wide range of neurological conditions including stroke. The pathological processes following stroke may provide an exemplary system to investigate how tDCS promotes neuronal plasticity and functional recovery. Changes in synaptic function after stroke, such as reduced excitability, formation of aberrant connections, and deregulated plastic modifications, have been postulated to impede recovery from stroke. However, if tDCS could counteract these negative changes by influencing the system's neurophysiology, it would contribute to the formation of functionally meaningful connections and the maintenance of existing pathways. This paper is aimed at providing a review of underlying mechanisms of tDCS and its application to stroke. In addition, to maximize the effectiveness of tDCS in stroke rehabilitation, future research needs to determine the optimal stimulation protocols and parameters. We discuss how stimulation parameters could be optimized based on electrophysiological activity. In particular, we propose that cortical synchrony may represent a biomarker of tDCS efficacy to indicate communication between affected areas. Understanding the mechanisms by which tDCS affects the neural substrate after stroke and finding ways to optimize tDCS for each patient are key to effective rehabilitation approaches.

Stroke research and treatment

Gomez Palacio Schjetnan, A; Faraji, J; Metz, GA; Tatsuno, M; Luczak, A


High-frequency TRNS reduces BOLD activity during visuomotor learning.

2013

Transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS) consist in the application of electrical current of small intensity through the scalp, able to modulate perceptual and motor learning, probably by changing brain excitability. We investigated the effects of these transcranial electrical stimulation techniques in the early and later stages of visuomotor learning, as well as associated brain activity changes using functional magnetic resonance imaging (fMRI). We applied anodal and cathodal tDCS, low-frequency and high-frequency tRNS (lf-tRNS, 0.1-100 Hz; hf-tRNS 101-640 Hz, respectively) and sham stimulation over the primary motor cortex (M1) during the first 10 minutes of a visuomotor learning paradigm and measured performance changes for 20 minutes after stimulation ceased. Functional imaging scans were acquired throughout the whole experiment. Cathodal tDCS and hf-tRNS showed a tendency to improve and lf-tRNS to hinder early learning during stimulation, an effect that remained for 20 minutes after cessation of stimulation in the late learning phase. Motor learning-related activity decreased in several regions as reported previously, however, there was no significant modulation of brain activity by tDCS. In opposition to this, hf-tRNS was associated with reduced motor task-related-activity bilaterally in the frontal cortex and precuneous, probably due to interaction with ongoing neuronal oscillations. This result highlights the potential of lf-tRNS and hf-tRNS to differentially modulate visuomotor learning and advances our knowledge on neuroplasticity induction approaches combined with functional imaging methods.

PloS one

Saiote, C; Polanía, R; Rosenberger, K; Paulus, W; Antal, A


Clinical effectiveness of primary and secondary headache treatment by transcranial direct current stimulation.

2013

The clinical effectiveness of primary and secondary headache treatment by transcranial direct current stimulation (tDCS) with various locations of stimulating electrodes on the scalp was analyzed retrospectively. The results of the treatment were analyzed in 90 patients aged from 19 to 54 years (48 patients had migraine without aura, 32 - frequent episodic tension-type HAs, 10 - chronic tension-type HAs) and in 44 adolescents aged 11-16 years with chronic post-traumatic HAs after a mild head injury. Clinical effectiveness of tDCS with 70-150 μA current for 30-45 min via 6.25 cm(2) stimulating electrodes is comparable to that of modern pharmacological drugs, with no negative side effects. The obtained result has been maintained on average from 5 to 9 months. It has been demonstrated that effectiveness depends on localization of stimulating electrodes used for different types of HAs.

Frontiers in neurology

Pinchuk, D; Pinchuk, O; Sirbiladze, K; Shugar, O


A review of computational models of transcranial electrical stimulation.

2013

Transcranial electrical stimulation (tES), which includes transcranial direct current stimulation (tDCS) and electroconvulsive therapy (ECT), has played an important role in the treatment of various psychiatric disorders. Decades of empirical research and clinical experience have led to new and improved brain stimulation techniques, but the mechanisms underlying treatment efficacy and side effects are poorly understood. As part of the ongoing research effort in tES, the value of computational models of transcranial electric current flow has been increasingly recognized, and a proliferation of modeling studies have been published. The complexity of these tES models ranges from simple sphere-based models of the head to high-resolution anatomical reconstructions based on head-image scans. This review provides an up-to-date description and comparison of existing computational models of tES (primarily tDCS and ECT), focusing on the modeling approaches adopted in previous studies and their significant finding.

Critical reviews in biomedical engineering

Bai, S; Loo, C; Dokos, S


Early optimization in finger dexterity of skilled pianists: implication of transcranial stimulation.

2013

It has been shown that non-invasive transcranial direct current stimulation (tDCS) facilitates motor functions in healthy adults and stroke patients. However, little is known about neuroplastic changes induced by tDCS in highly-trained individuals. Here we addressed this issue by assessing the effect of tDCS on dexterity of finger movements in healthy adult pianists. Twelve pianists practiced bimanual keystrokes in an in-phase manner while bilateral tDCS (left anodal/right cathodal or vice versa) of the primary motor cortex was performed. Before and after stimulation, each participant was asked to perform the trained successive keystrokes, and to repetitively strike a key with each of the fingers as fast and accurate as possible while keeping the remaining fingers immobilized voluntarily.In contrast to previous findings in untrained individuals, tDCS yielded overall no apparent improvement of fine control of finger movements in the professional pianists. However, for some movement features, pianists who commenced training at later age demonstrated larger improvements of fine motor control following tDCS.These findings, in combination with lack of any correlation between the age at which pianists commenced the training and motor improvements for sham stimulation conditions, supports the idea that selectively late-started players benefit from tDCS, which we interpret as early optimization of neuroplasticity of the motor system.

BMC neuroscience

Furuya, S; Nitsche, MA; Paulus, W; Altenmüller, E


Evolution of premotor cortical excitability after cathodal inhibition of the primary motor cortex: a sham-controlled serial navigated TMS study.

2013

Premotor cortical regions (PMC) play an important role in the orchestration of motor function, yet their role in compensatory mechanisms in a disturbed motor system is largely unclear. Previous studies are consistent in describing pronounced anatomical and functional connectivity between the PMC and the primary motor cortex (M1). Lesion studies consistently show compensatory adaptive changes in PMC neural activity following an M1 lesion. Non-invasive brain modification of PMC neural activity has shown compensatory neurophysiological aftereffects in M1. These studies have contributed to our understanding of how M1 responds to changes in PMC neural activity. Yet, the way in which the PMC responds to artificial inhibition of M1 neural activity is unclear. Here we investigate the neurophysiological consequences in the PMC and the behavioral consequences for motor performance of stimulation mediated M1 inhibition by cathodal transcranial direct current stimulation (tDCS).The primary goal was to determine how electrophysiological measures of PMC excitability change in order to compensate for inhibited M1 neural excitability and attenuated motor performance.Cathodal inhibition of M1 excitability leads to a compensatory increase of ipsilateral PMC excitability.We enrolled 16 healthy participants in this randomized, double-blind, sham-controlled, crossover design study. All participants underwent navigated transcranial magnetic stimulation (nTMS) to identify PMC and M1 corticospinal projections as well as to evaluate electrophysiological measures of cortical, intracortical and interhemispheric excitability. Cortical M1 excitability was inhibited using cathodal tDCS. Finger-tapping speeds were used to examine motor function.Cathodal tDCS successfully reduced M1 excitability and motor performance speed. PMC excitability was increased for longer and was the only significant predictor of motor performance.The PMC compensates for attenuated M1 excitability and contributes to motor performance maintenance.

PloS one

Schmidt, S; Fleischmann, R; Bathe-Peters, R; Irlbacher, K; Brandt, SA


The effect of transcranial direct current stimulation on the motor suppression in stop-signal task.

2013

This study examined whether transcranial direct current stimulation (tDCS) of the primary motor cortex alters the response time in motor suppression using the stop-signal task (SST).Forty healthy subjects were enrolled in this study. The subjects were assigned randomly to either the tDCS condition or sham control condition. All subjects performed a stop-signal task in three consecutive phases: without, during or after the delivery of anodal tDCS on the primary motor cortex (the pre-tDCS motor phase, on-tDCS motor phase, and after-tDCS motor phase).The response times of the stopping process were significantly lower in each SST motor phase during or after tDCS (p < 0.05) and shorter immediately during delivery of the tDCS, whereas there was no change after the delivery of tDCS compared to sham condition. In contrast, the response times of the going process were similar under the two conditions (p > 0.05). No subjects complained of any adverse symptoms or signs.Anodal tDCS enhances voluntary going and stopping of movement in executive control. tDCS appears to be an effective modality to modulate motor suppression and its related dynamic behavioral changes in motor sequential learning.

NeuroRehabilitation

Kwon, JW; Nam, SH; Lee, NK; Son, SM; Choi, YW; Kim, CS


The ABC of tDCS: Effects of Anodal, Bilateral and Cathodal Montages of Transcranial Direct Current Stimulation in Patients with Stroke-A Pilot Study.

2013

Transcranial direct current stimulation (tDCS) is a noninvasive technique that is emerging as a prospective therapy for different neurologic disorders. Previous studies have demonstrated that anodal and cathodal stimulation can improve motor performance in terms of dexterity and manual force. The objective of this study was to determine whether different electrodes' setups (anodal, cathodal, and simultaneous bilateral tDCS) provide different motor performance and which montage was more effective. As secondary outcome, we have asked to the patients about their satisfaction, and to determine if the bilateral tDCS was more uncomfortable than unilateral tDCS. Nine patients with stroke in subacute phase were enrolled in this study and randomly divided in three groups. Our results showed that tDCS was an effective treatment if compared to Sham stimulation (P = 0.022). In particular, anodal stimulation provided the higher improvement in terms of manual dexterity. Cathodal stimulation seemed to have a little effect in terms of force improvement, not observed with other setups. Bipolar stimulation seemed to be the less effective. No significant differences have been noted for the different set-ups for patients' judgment. These results highlight the potential efficacy of tDCS for patients with stroke in subacute phase.

Stroke research and treatment

Fusco, A; De Angelis, D; Morone, G; Maglione, L; Paolucci, T; Bragoni, M; Venturiero, V


Differential involvement of the left frontal and temporal regions in verb naming: a tDCS treatment study.

2013

In aphasic patients, some studies have already emphasized the efficacy of transcranial direct current stimulation (tDCS) during the treatment of noun retrieval deficits. To date, in the same population, there are have been no studies addressing tDCS effects in the recovery of verb retrieval deficits. In this study, we wanted to test the potential of tDCS to improve verb production in a group of aphasic patients.Seven chronic subjects participated in an intensive language training for their difficulties in action naming. Each subject was treated with tDCS (20 min., 1 mA) over the left hemisphere in three different conditions: anodic tDCS over Wernicke's area, anodic tDCS and sham stimulation over Broca's area. Each experimental condition was performed in five consecutive daily sessions over three weeks with 6 days of intersession interval.In all patients, results showed a significantly better response accuracy during the anodic tDCS over Broca's area with respect to the other two conditions which still persisted at one month after the end of the treatment suggesting a long-term effect on the recovery of their verb retrieval deficits.These findings further confirm that tDCS represents a useful new therapeutic interventions for the rehabilitation of lexical deficits in aphasic patients.

Restorative neurology and neuroscience

Marangolo, P; Fiori, V; Di Paola, M; Cipollari, S; Razzano, C; Oliveri, M; Caltagirone, C


Differential frontal involvement in shifts of internal and perceptual attention.

2012 Dec

BACKGROUND: Perceptual attention enhances the processing of items in the environment, whereas internal attention enhances processing of items encoded in visual working memory. In perceptual and internal attention cueing paradigms, cues indicate the to-be-probed item before (pre-cueing) or after (retro-cueing) the memory display, respectively. Pre- and retro-cues confer similar behavioral accuracy benefits (pre-: 14-19%, retro-: 11-17%) and neuroimaging data show that they activate overlapping frontoparietal networks. Yet reports of behavioral and neuroimaging differences suggest that pre- and retro-cueing differentially recruit frontal and parietal cortices (Lepsien and Nobre, 2006). OBJECTIVE/HYPOTHESIS: This study examined whether perceptual and internal attention are equally disrupted by neurostimulation to frontal and parietal cortices. We hypothesized that neurostimulation applied to frontal cortex would disrupt internal attention to a greater extent than perceptual attention. METHODS: Cathodal transcranial direct current stimulation (tDCS) was applied to frontal or parietal cortices. After stimulation, participants completed a change detection task coupled with either pre- or retro-cues. RESULTS: Cathodal tDCS across site (frontal, parietal) hindered performance. However, frontal tDCS had a greater negative impact on the retro-cued trials demonstrating greater frontal involvement during shifts of internal attention. CONCLUSIONS: These results complement the neuroimaging data and provide further evidence suggesting that perceptual and internal attention are not identical processes. We conclude that although internal and perceptual attention are mediated by similar frontoparietal networks, the weight of contribution of these structures differs, with internal attention relying more heavily on the frontal cortex.

Brain stimulation

Tanoue, RT; Jones, KT; Peterson, DJ; Berryhill, ME


Modulation of Cold Pain Perception by Transcranial Direct Current Stimulation in Healthy Individuals.

2012 Dec

OBJECTIVES: The aim of the current study was to evaluate the effect of transcranial direct current stimulation (tDCS) on cold pain perception in healthy individuals. METHODS: Anodal, cathodal (2 mA), or sham tDCSs were applied on the primary motor cortex of 22 healthy subjects in a random order. A cold pressor test was performed ten minutes after initiation of stimulation. Pain threshold and tolerance were defined as time latencies to the onset of pain perception and to the withdrawal from cold stimulus, respectively. Furthermore, pain intensity (on a scale from 0 to 10) was rated at tolerance. RESULTS: Time latencies to pain threshold and tolerance were altered by the type of stimulation (p < 0.05). Pairwise post hoc analysis revealed that anodal tDCS led to increment in pain threshold and tolerance compared with sham stimulation (13.3 ± 7.4 vs. 10.9 ± 6.0 sec for the comparison of pain threshold and 54.6 ± 26.0 vs. 45.3 ± 17.9 for the comparison of pain tolerance following anodal and sham stimulations, respectively, p < 0.05 for both comparisons). However, cathodal stimulation did not alter pain perception in comparison to anodal and sham stimulations (p > 0.05). Furthermore, pain intensity score at tolerance was not significantly affected by the type of stimulation (p > 0.05). CONCLUSION: Anodal stimulation of the primary motor area can be utilized to alleviate cold pain perception in healthy individuals.

Neuromodulation : journal of the International Neuromodulation Society

Zandieh, A; Parhizgar, SE; Fakhri, M; Taghvaei, M; Miri, S; Shahbabaie, A; Esteghamati, S; Ekhtiari, H


Enhancing vigilance in operators with prefrontal cortex transcranial direct current stimulation (tDCS).

2012 Dec

Sustained attention, often referred to as vigilance in humans, is the ability to maintain goal-directed behavior for extended periods of time and respond to intermittent targets in the environment. With greater time-on-task the ability to detect targets decreases and reaction time increases-a phenomenon termed the vigilance decrement. The purpose of this study was to examine the role of dorsolateral prefrontal cortex in the vigilance decrement. Subjects (n=19) received prefrontal transcranial direct current stimulation (tDCS) at one of two different time points during a vigilance task (early or late). The impact of tDCS was examined using measures of behavior, hemispheric blood flow velocity, and regional blood oxygenation relative to sham stimulation. In the sham condition greater time-on-task was accompanied by fewer target detections and slower reaction times, indicating a vigilance decrement, and decreased blood flow velocity. tDCS significantly altered baseline task-induced physiologic and behavioral changes, dependent on the time of stimulation administration and electrode configuration (determining polarity of stimulation). Compared to the sham condition, with more time-on-task blood flow velocity decreased less and cerebral oxygenation increased more in the tDCS condition. Behavioral measures showed a significant improvement in target detection performance with tDCS compared to the sham stimulation. Signal detection analysis revealed a significant change in operator discriminability and response bias with increased time-on-task, as well as interactions between time of stimulation administration and electrode configuration. Current density modeling of tDCS showed high densities in the medial prefrontal cortex and anterior cingulate cortex. These findings confirm that cerebral hemodynamic measures provide an index of resource utilization and point to the central role of the frontal cortex in vigilance. Further, they suggest that modulation of the frontal cortices-and connected structures-influences the availability of vigilance resources. These findings indicate that tDCS may be well-suited to mitigate performance degradation in work settings requiring sustained attention or as a possible treatment for neurological or psychiatric disorders involving sustained attention.

NeuroImage

Nelson, JT; McKinley, RA; Golob, EJ; Warm, JS; Parasuraman, R


Enhancing social ability by stimulating right temporoparietal junction.

2012 Dec

The temporoparietal junction (TPJ) is a key node within the "social brain". Several studies suggest that the TPJ controls representations of the self or another individual across a variety of low-level (agency discrimination, visual perspective taking, control of imitation) and high-level (mentalizing, empathy) sociocognitive processes. We explored whether sociocognitive abilities relying on on-line control of self and other representations could be modulated with transcranial direct current stimulation (tDCS) of TPJ. Participants received excitatory (anodal), inhibitory (cathodal), or sham stimulation before completing three sociocognitive tasks. Anodal stimulation improved the on-line control of self-other representations elicited by the imitation and perspective-taking tasks while not affecting attribution of mental states during a self-referential task devoid of such a requirement. Our findings demonstrate the efficacy of tDCS to improve social cognition and highlight the potential for tDCS to be used as a tool to aid self-other processing in clinical populations.

Current biology : CB

Santiesteban, I; Banissy, MJ; Catmur, C; Bird, G


Disruption of motor network connectivity post-stroke and its noninvasive neuromodulation.

2012 Dec

We review the latest evidence for the neural underpinnings of hand motor function recovery after stroke with particular emphasis on how the latter can be enhanced by noninvasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS).New data from longitudinal studies in which rTMS of the lesioned or contralesional motor cortex was combined with motor training showed ambiguous effects: some patients improved whereas others did not show any rTMS effect (compared with control stimulation). In contrast, novel studies using tDCS point to a more consistent effect on distal upper limb function, especially for inhibitory (cathodal) tDCS applied over contralesional M1. Neuroimaging data reveal that the effects of rTMS/tDCS on the functional architecture of the motor system depend upon lesion location, degree of impairment and number of treatment sessions. Furthermore, analyses of regional brain activity and motor network connectivity allow prediction of the behavioural effects of brain stimulation.rTMS and tDCS can be used to modulate stroke-induced changes of motor network activity and connectivity thereby improving hand motor function. The interindividual variability in response to brain stimulation calls for the identification of treatment-associated surrogate markers, which may be provided by neuroimaging.

Current opinion in neurology

Grefkes, C; Fink, GR


Non-invasive cerebral stimulation for the upper limb rehabilitation after stroke: a review.

2012 Dec

Numerous studies have recently been published on improving upper-limb motor function after stroke. There has been a particular interest in brain stimulation techniques, which could promote brain plasticity. In this review, transcranial Direct Current Stimulation (tDCS) and repetitive Transcranial Magnetic Stimulation (rTMS) are presented as techniques that could be relevant in Physical Medicine and Rehabilitation (PM&R) centers in the future. We are presenting a comprehensive literature review on the studies using tDCS or rTMS for upper-limb rehabilitation after a stroke. Both techniques have shown their ability to modify cortical excitability and to transitorily improve upper-limb function after one single stimulation session. The first placebo-controlled, blinded therapeutic trials, which included repeated daily sessions, seem quite promising, and deserve to be validated by further trials.

Annals of physical and rehabilitation medicine

Kandel, M; Beis, JM; Le Chapelain, L; Guesdon, H; Paysant, J


Reversal of chronic stress-induced pain by transcranial direct current stimulation (tDCS) in an animal model.

2012 Dec

Transcranial direct current stimulation (tDCS) has been suggested as a therapeutic tool for pain syndromes. Although initial results in human subjects are encouraging, it still remains unclear whether the effects of tDCS can reverse maladaptive plasticity associated with chronic pain. To investigate this question, we tested whether tDCS can reverse the specific behavioral effects of chronic stress in the pain system, and also those indexed by corticosterone and interleukin-1β levels in serum and TNFα levels in the hippocampus, in a well-controlled rat model of chronic restraint stress (CRS). Forty-one adult male Wistar rats were divided into two groups control and stress. The stress group was exposed to CRS for 11 weeks for the establishment of hyperalgesia and mechanical allodynia as shown by the hot plate and von Frey tests, respectively. Rats were then divided into four groups control, stress, stress+sham tDCS and stress+tDCS. Anodal or sham tDCS was applied for 20min/day over 8 days and the tests were repeated. Then, the animals were killed, blood collected and hippocampus removed for ELISA testing. This model of CRS proved effective to induce chronic pain, as the animals exhibited hyperalgesia and mechanical allodynia. The hot plate test showed an analgesic effect, and the von Frey test, an anti-allodynic effect after the last tDCS session, and there was a significant decrease in hippocampal TNFα levels. These results support the notion that tDCS reverses the detrimental effects of chronic stress on the pain system and decreases TNFα levels in the hippocampus.

Brain research

Spezia Adachi, LN; Caumo, W; Laste, G; Fernandes Medeiros, L; Ripoll Rozisky, J; de Souza, A; Fregni, F; Torres, IL


tDCS modulation of visually induced analgesia.

2012 Dec

Multisensory interactions can produce analgesic effects. In particular, viewing one's own body reduces pain levels, perhaps because of changes in connectivity between visual areas specialized for body representation, and sensory areas underlying pain perception. We tested the causal role of the extrastriate visual cortex in triggering visually induced analgesia by modulating the excitability of this region with transcranial direct current stimulation (tDCS). Anodal, cathodal, or sham tDCS (2 mA, 10 min) was administered to 24 healthy participants over the right occipital or over the centro-parietal areas thought to be involved in the sensory processing of pain. Participants were required to rate the intensity of painful electrical stimuli while viewing either their left hand or an object occluding the left hand, both before and immediately after tDCS. We found that the analgesic effect of viewing the body was enhanced selectively by anodal stimulation of the occipital cortex. The effect was specific for the polarity and the site of stimulation. The present results indicate that visually induced analgesia may depend on neural signals from the extrastriate visual cortex.

Journal of cognitive neuroscience

Mancini, F; Bolognini, N; Haggard, P; Vallar, G


Effects of transcranial direct current stimulation on hemichannel pannexin-1 and neural plasticity in rat model of cerebral infarction.

2012 Dec

The aim of this study was to investigate the effects of transcranial direct current stimulation (TDCS) on hemichannel pannexin-1 (PX1) in cortical neurons and neural plasticity, and explore the optimal time window of TDCS therapy after stroke. Adult male Sprague-Dawley rats (n=90) were randomly assigned to sham operation, middle cerebral artery occlusion (MCAO), and TDCS groups, and underwent sham operation, unilateral middle cerebral artery (MCA) electrocoagulation, and unilateral MCA electrocoagulation plus TDCS (daily anodal and cathodal 10 Hz, 0.1 mA TDCS for 30 min beginning day 1 after stroke), respectively. Motor function was assessed using the beam walking test (BWT), and density of dendritic spines (DS) and PX1 mRNA expression were compared among groups on days 3, 7, and 14 after stroke. Effects of PX1 blockage on DS in hippocampal neurons after hypoxia-ischemia were observed. TDCS significantly improved motor function on days 7 and 14 after stroke as indicated by reduced BWT scores compared with the MCAO group. The density of DS was decreased after stroke; the TDCS group had increased DS density compared with the MCAO group on days 3, 7, and 14 (all P<0.0001). Cerebral infarction induced increased PX1 mRNA expression on days 3, 7, and 14 (P<0.0001), and the peak PX1 mRNA expression was observed on day 7. TDCS did not decrease the up-regulated PX1 mRNA expression after stroke on day 3, but did reduce the increased post-stroke PX1 mRNA expression on days 7 and 14 (P<0.0001). TDCS increased the DS density after stroke, indicating that it may promote neural plasticity after stroke. TDCS intervention from day 7 to day 14 after stroke demonstrated motor function improvement and can down-regulate the elevated PX1 mRNA expression after stroke.

Neuroscience

Jiang, T; Xu, RX; Zhang, AW; Di, W; Xiao, ZJ; Miao, JY; Luo, N; Fang, YN


Dynamic modulation of intrinsic functional connectivity by transcranial direct current stimulation.

2012 Dec

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique capable of modulating cortical excitability and thereby influencing behavior and learning. Recent evidence suggests that bilateral tDCS over both primary sensorimotor cortices (SM1) yields more prominent effects on motor performance in both healthy subjects and chronic stroke patients than unilateral tDCS over SM1. To better characterize the underlying neural mechanisms of this effect, we aimed to explore changes in resting-state functional connectivity during both stimulation types. In a randomized single-blind crossover design, 12 healthy subjects underwent functional magnetic resonance imaging at rest before, during, and after 20 min of unilateral, bilateral, and sham tDCS stimulation over SM1. Eigenvector centrality mapping (ECM) was used to investigate tDCS-induced changes in functional connectivity patterns across the whole brain. Uni- and bilateral tDCS over SM1 resulted in functional connectivity changes in widespread brain areas compared with sham stimulation both during and after stimulation. Whereas bilateral tDCS predominantly modulated changes in primary and secondary motor as well as prefrontal regions, unilateral tDCS affected prefrontal, parietal, and cerebellar areas. No direct effect was seen under the stimulating electrode in the unilateral condition. The time course of changes in functional connectivity in the respective brain areas was nonlinear and temporally dispersed. These findings provide evidence toward a network-based understanding regarding the underpinnings of specific tDCS interventions.

Journal of neurophysiology

Sehm, B; Schäfer, A; Kipping, J; Margulies, D; Conde, V; Taubert, M; Villringer, A; Ragert, P


Effects of transcranial direct current stimulation (tDCS) on executive functions: Influence of COMT Val/Met polymorphism.

2012 Nov

INTRODUCTION: Transcranial direct current stimulation (tDCS) is a frequently used technique to investigate healthy and impaired neuronal functions. Its modulatory effect on executive functions is of particular interest for understanding the mechanisms underlying integration of cognition and behavior. The key role of prefrontal dopamine function for executive functions suggest that differences of the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene would interact with tDCS interventions in this domain. In this study, we hypothesized that the COMT Met allele homozygosity, associated with higher levels of prefrontal dopamine, would influence the effect of tDCS on higher-level executive functions. METHOD: Forty-six healthy subjects participated in a double-blind sham-controlled crossover study and underwent COMT genotyping. Anodal tDCS (20 min, 1 mA) to the left dorsolateral prefrontal cortex (dlPFC) or sham stimulation was applied during the performance of a parametric Go/No-Go (PGNG) test measuring sustained attention, response inhibition and cognitive flexibility as measured by set-shifting. RESULTS: In COMT Met/Met allele carrier anodal tDCS of the dlPFC was associated with a deterioration of set-shifting ability, which is assessed by the most challenging level of the PGNG. Without regard to the carrier status of the COMT Val158Met polymorphism no effects of anodal tDCS on executive functions could be determined. CONCLUSIONS: In line with the model of non-linear effects of l-dopa on cortical plasticity high dopaminergic prefrontal activity mediated by COMT Val158Met polymorphism predicts a detrimental effect of anodal tDCS on cognitive flexibility. Therefore, we suggest that the individual genetic profile may modulate behavioral effect of tDCS. More precise application of brain stimulation techniques according to the individual genetic patterns may support the development of personalized treatment approaches.

Cortex; a journal devoted to the study of the nervous system and behavior

Plewnia, C; Zwissler, B; Längst, I; Maurer, B; Giel, K; Krüger, R


Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the Major Depressive Episode: Findings from a naturalistic study.

2012 Nov

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive, neuromodulatory technique with an emerging role for treating major depression. OBJECTIVE: To investigate the interactions between tDCS and drug therapy in unipolar and bipolar depressed patients who were refractory for at least one pharmacological treatment. METHODS: This was a naturalistic study using data from 54 female and 28 male patients (mean age of 54 years) that consecutively visited our psychiatric unit. They received active tDCS (five consecutive days, 2mA, anodal stimulation over the left and cathodal over the right dorsolateral prefrontal cortex, twice a day, 20minutes). The outcome variable (mood) was evaluated using the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS). Predictor variables were age, gender, disorder and pharmacological treatment (seven dummy variables). We performed univariate and multivariate analyses as to identify predictors associated to the outcome. RESULTS: After 5 days of treatment, BDI and HDRS scores decreased significantly (29%±36%, 18%±9%, respectively, P<0.01 for both). Benzodiazepine use was independently associated with a worse outcome in both univariate (β=4.92, P<0.01) and multivariate (β=5.8, P<0.01) analyses; whereas use of dual-reuptake inhibitors positively changed tDCS effects in the multivariate model (β=-4.7, P=0.02). A similar trend was observed for tricyclics (β=-4, P=0.06) but not for antipsychotics, non-benzodiazepine anticonvulsants and other drugs. CONCLUSION: tDCS over the DLPFC acutely improved depressive symptoms. Besides the inherent limitations of our naturalistic design, our results suggest that tDCS effects might vary according to prior pharmacological treatment, notably benzodiazepines and some antidepressant classes. This issue should be further explored in controlled studies.

European psychiatry : the journal of the Association of European Psychiatrists

Brunoni, AR; Ferrucci, R; Bortolomasi, M; Scelzo, E; Boggio, PS; Fregni, F; Dell'osso, B; Giacopuzzi, M; Altamura, AC; Priori, A


Modulation of top-down control of visual attention by cathodal tDCS over right IPS.

2012 Nov

The right intraparietal sulcus (rIPS) is a key region for the endogenous control of selective visual attention in the human brain. Previous studies suggest that the rIPS is especially involved in top-down control and spatial distribution of attention across both visual hemifields. We further explored these attentional functions using transcranial direct current stimulation (tDCS) of the rIPS to modulate behavioral performance in a partial report task. Performance was analyzed according to the theory of visual attention (TVA) (Bundesen, 1990), which provides a computational framework to investigate different parameters of visuo-attentional processing such as top-down control, attentional weighting, capacity of visual short term memory, and processing speed. We investigated the effects of different tDCS current strengths (1 mA and 2 mA) in two experiments: 1 mA tDCS (anodal, cathodal, sham) did not affect any of the TVA parameters, but cathodal 2 mA stimulation significantly enhanced top-down control as evidenced by a reduction of the α parameter of TVA, regardless of hemifield. This differential impact on the top-down control component of attentional processing suggests that the horizontal rIPS is mainly involved in attentional selection as none of the spatial or resource variables of TVA were altered. Furthermore, the data add evidence to previous work highlighting (1) the importance of using appropriate current strength in stimulation protocols, and (2) that the often reported inhibitory effect of cathodal stimulation in e.g., motor tasks might not extend to cognitive paradigms.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Moos, K; Vossel, S; Weidner, R; Sparing, R; Fink, GR


The effects of cross-hemispheric dorsolateral prefrontal cortex transcranial direct current stimulation (tDCS) on task switching.

2012 Nov

BACKGROUND: Task switching, defined as the ability to flexibly switch between tasks in the face of goal shifting, is a central mechanism in cognitive control. Task switching is thought to involve both prefrontal cortex (PFC) and parietal regions. Our previous work has shown that it is possible to modulate set shifting tasks using 1 mA tDCS on both the left dorsolateral prefrontal cortex and the left primary motor area. However, it remains unclear whether the effects of PFC tDCS on task switching are hemisphere-dependent. OBJECTIVES: We aimed to test the effects of three types of cross-hemispheric tDCS over the PFC (left anode-right cathode [LA-RC], left cathode-right anode [LC-RA] and sham stimulation) on participants' performance (reaction time) and accuracy (correct responses) in two task-switching paradigms (i.e., letter/digit naming and vowel-consonant/parity tasks). METHODS: Sixteen participants received cross-hemispheric tDCS over the PFC in two task-switching paradigms. RESULTS: The results show that cross-hemispheric tDCS over the PFC modulates task-switching ability in both paradigms. Our results were task and hemisphere-specific, such that in the letter/digit naming task, LA-RC tDCS increased switching performance, whereas LC-RA tDCS improved accuracy. On the other hand, in the vowel-consonant/parity task, LA-RC improved accuracy, and decreased switching performance. CONCLUSIONS: Our findings confirm the notion that involvement of the PFC on task switching depends critically on laterality, implying the existence of different roles for the left hemisphere and the right hemisphere in task switching.

Brain stimulation

Leite, J; Carvalho, S; Fregni, F; Boggio, PS; Gonçalves, OF


Transcranial direct current stimulation (tDCS) and language.

2012 Nov

Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique inducing prolonged brain excitability changes and promoting cerebral plasticity, is a promising option for neurorehabilitation. Here, we review progress in research on tDCS and language functions and on the potential role of tDCS in the treatment of post-stroke aphasia. Currently available data suggest that tDCS over language-related brain areas can modulate linguistic abilities in healthy individuals and can improve language performance in patients with aphasia. Whether the results obtained in experimental conditions are functionally important for the quality of life of patients and their caregivers remains unclear. Despite the fact that important variables are yet to be determined, tDCS combined with rehabilitation techniques seems a promising therapeutic option for aphasia.

Journal of neurology, neurosurgery, and psychiatry

Monti, A; Ferrucci, R; Fumagalli, M; Mameli, F; Cogiamanian, F; Ardolino, G; Priori, A


Feasibility of focal transcranial DC polarization with simultaneous EEG recording: preliminary assessment in healthy subjects and human epilepsy.

2012 Nov

We aimed to investigate the feasibility of an experimental system for simultaneous transcranial DC stimulation (tDCS) and EEG recording in human epilepsy. We report tolerability of this system in a cross-over controlled trial with 15 healthy subjects and preliminary effects of its use, testing repeated tDCS sessions, in two patients with drug-refractory Continuous Spike-Wave Discharges During Slow Sleep (CSWS). Our system combining continuous recording of the EEG with tDCS allows detailed evaluation of the interictal activity during the entire process. Stimulation with 1 mA was well-tolerated in both healthy volunteers and patients with refractory epilepsy. The large reduction in interictal epileptiform EEG discharges in the two subjects with epilepsy supports further investigation of tDCS using this combined method of stimulation and monitoring in epilepsy. Continuous monitoring of epileptic activity throughout tDCS improves safety and allows detailed evaluation of epileptic activity changes induced by tDCS in patients.

Epilepsy & behavior : E&B

Faria, P; Fregni, F; Sebastião, F; Dias, AI; Leal, A


Influence of anisotropic conductivity in the skull and white matter on transcranial direct current stimulation via an anatomically realistic finite element head model.

2012 Nov

To establish safe and efficient transcranial direct current stimulation (tDCS), it is of particular importance to understand the electrical effects of tDCS in the brain. Since the current density (CD) and electric field (EF) in the brain generated by tDCS depend on various factors including complex head geometries and electrical tissue properties, in this work, we investigated the influence of anisotropic conductivity in the skull and white matter (WM) on tDCS via a 3D anatomically realistic finite element head model. We systematically incorporated various anisotropic conductivity ratios into the skull and WM. The effects of anisotropic tissue conductivity on the CD and EF were subsequently assessed through comparisons to the conventional isotropic solutions. Our results show that the anisotropic skull conductivity significantly affects the CD and EF distribution: there is a significant reduction in the ratio of the target versus non-target total CD and EF on the order of 12-14%. In contrast, the WM anisotropy does not significantly influence the CD and EF on the targeted cortical surface, only on the order of 1-3%. However, the WM anisotropy highly alters the spatial distribution of both the CD and EF inside the brain. This study shows that it is critical to incorporate anisotropic conductivities in planning of tDCS for improved efficacy and safety.

Physics in medicine and biology

Suh, HS; Lee, WH; Kim, TS


Good vibrations: oscillatory phase shapes perception.

2012 Nov

In the current study, we provide compelling evidence to answer the long-standing question whether perception is continuous or periodic. Spontaneous brain oscillations are assumed to be the underlying mechanism of periodic perception. Depending on the phase angle of the oscillations, an identical stimulus results in different perceptual outcomes. Past results, however, can only account for a correlation of perception with the phase of the ongoing brain oscillations. Therefore, it is desirable to demonstrate a causal relation between phase and perception. One way to address this question is to entrain spontaneous brain oscillations by applying an external oscillation and then demonstrate behavioral consequences of this oscillation. We conducted an auditory detection experiment with humans, recorded the electroencephalogram (EEG) concurrently and simultaneously applied oscillating transcranial direct current stimulation at 10Hz (α-tDCS). Our approach revealed that detection thresholds were dependent on the phase of the oscillation that was entrained by α-tDCS. This behavioral effect was accompanied by an electrophysiological effect: α-power was enhanced after α-tDCS as compared to a pre-stimulation period. By showing a causal relation between phase and perception, our results extend findings of previous studies that were only able to demonstrate a correlation. We found that manipulation of the phase resulted in different detection thresholds, which supports the notion that perception can be periodically modulated by oscillatory processes. This demonstrates that tDCS can serve as a tool in neuroscience to extend the knowledge of the functional significance of brain oscillations.

NeuroImage

Neuling, T; Rach, S; Wagner, S; Wolters, CH; Herrmann, CS


Improvement of the working memory and naming by transcranial direct current stimulation.

2012 Oct

To investigate the effects of transcranial direct current stimulation (tDCS) applied over the prefrontal cortex on the improvement of verbal, visuospatial working memory and naming in healthy adults.Thirty two healthy adults (15 males and 17 females, mean age 37.3±13.0 years) were enrolled in this study. The subjects were divided into four groups randomly. They underwent sham or anodal tDCS over the left or right prefrontal cortex, for 20 minutes at a direct current of 1 mA. Before and immediately after tDCS, the subjects performed the Korean version of the mini-mental state exam (K-MMSE) and stroop test (color/word/interference) for the screening of cognitive function. For working memory and language evaluation, the digit span test (forward/backward), the visuospatial attention test in computer assisted cognitive program (CogPack®) and the Korean-Boston Naming Test (K-BNT) were assessed before tDCS, immediately after tDCS, and 2 weeks after tDCS.The stroop test (word/interference), backward digit span test and K-BNT were improved in the left prefrontal tDCS group compared with that of the sham group (p<0.05). The stroop test (interference) and visuospatial attention test were in the right prefrontal tDCS group compared with that of the sham group (p<0.05). Their improvement lasted for 2 weeks after stimulation.tDCS can induce verbal working memory improvement and naming facilitation by stimulating the left prefrontal cortex. It can also improve the visuospatial working memory by stimulating the right prefrontal cortex. Further studies which are lesion and symptom specific tDCS treatment for rehabilitation of stroke can be carried out.

Annals of rehabilitation medicine

Jeon, SY; Han, SJ


Comparing cortical plasticity induced by conventional and high-definition 4 × 1 ring tDCS: A neurophysiological study.

2012 Oct

BACKGROUND: Transcranial direct current stimulation (tDCS) induces long-lasting NMDA receptor-dependent cortical plasticity via persistent subthreshold polarization of neuronal membranes. Conventional bipolar tDCS is applied with two large (35 cm(2)) rectangular electrodes, resulting in directional modulation of neuronal excitability. Recently a newly designed 4 × 1 high-definition (HD) tDCS protocol was proposed for more focal stimulation according to the results of computational modeling. HD tDCS utilizes small disc electrodes deployed in 4 × 1 ring configuration whereby the physiological effects of the induced electric field are thought to be grossly constrained to the cortical area circumscribed by the ring. OBJECTIVE: We aim to compare the physiological effects of both tDCS electrode arrangements on motor cortex excitability. METHODS: tDCS was applied with 2 mA for 10 min. Fourteen healthy subjects participated, and motor cortex excitability was monitored by transcranial magnetic stimulation (TMS) before and after tDCS. RESULTS: Excitability enhancement following anodal and a respective reduction after cathodal stimulation occurred in both, conventional and HD tDCS. However, the plastic changes showed a more delayed peak at 30 min and longer lasting after-effects for more than 2 h after HD tDCS for both polarities, as compared to conventional tDCS. CONCLUSION: The results show that this new electrode arrangement is efficient for the induction of neuroplasticity in the primary motor cortex. The pattern of aftereffects might be compatible with the concept of GABA-mediated surround inhibition, which should be explored in future studies directly.

Brain stimulation

Kuo, HI; Bikson, M; Datta, A; Minhas, P; Paulus, W; Kuo, MF; Nitsche, MA


Transcranial direct current stimulation (tDCS) enhances reconsolidation of long-term memory.

2012 Oct

A new and weak memory trace undergoes consolidation to gain resistance against interfering stimuli. When an encoded memory is recalled, it becomes labile and another round of consolidation, or reconsolidation, is required to restore its stability. Transcranial direct current stimulation (tDCS) is a non-invasive method of altering cortical excitability. The aim of this study was to examine the effects of tDCS on the reconsolidation of long-term verbal memory. Participants (n = 15) memorized words in the encoding session, then reactivated the memory of the words 3 h later using an old-new recognition task under anodal, cathodal and sham stimulation to the left dorsolateral prefrontal cortex (DLPFC). Finally, after another 5 h, they performed another round of the old-new recognition task and rated their confidence. Anodal tDCS during the second session resulted in significantly more words recognized in the third session as compared to cathodal and sham stimulation. Cathodal tDCS did not affect the recognition performance compared to sham stimulation. These results cannot be attributed to differences in response times and confidence ratings, as they were comparable in all conditions. In order to study whether the activation of a memory was crucial for the enhancing effects of anodal tDCS, a group of controls (n = 15) did not perform the recognition task in the second session but still underwent stimulation. Contrary to the main group, anodal stimulation did not enhance the memory performance for the control group. This result suggests that anodal tDCS over the left DLPFC can enhance the reconsolidation of long-term memory only when the memory has been reactivated.

Brain stimulation

Javadi, AH; Cheng, P


Transcranial direct current stimulation ameliorates tactile sensory deficit in multiple sclerosis.

2012 Oct

BACKGROUND: Deficit of tactile sensation in patients with MS is frequent and can be associated with interference with daily life activities. Transcranial direct current stimulation (tDCS) showed to increase tactile discrimination in healthy subjects. OBJECTIVE: In the present study, we investigated whether tDCS may be effective in ameliorating tactile sensory deficit in MS patients. METHODS: Patients received sham or real anodal tDCS of the somatosensory cortex for 5 consecutive days in a randomized, double blind, sham-controlled study. Discrimination thresholds of spatial tactile sensation were measured using the grating orientation task (GOT). As secondary outcomes we also measured subjective perception of tactile sensory deficit through a visual analog scale (VAS), quality of life and overall disability to evaluate the impact of the treatment on patients daily life. Evaluations were performed at baseline and during a 4-week follow-up period. RESULTS: Following anodal but not sham tDCS over the somatosensory cortex, there was a significant improvement of discriminatory thresholds at the GOT and increased VAS for sensation scores. Quality of life, and disability changes were not observed. CONCLUSION: Our results indicate that a five day course of anodal tDCS is able to ameliorate tactile sensory loss with long-lasting beneficial effects and could thus represent a therapeutic tool for the treatment of tactile sensory deficit in MS patients.

Brain stimulation

Mori, F; Nicoletti, CG; Kusayanagi, H; Foti, C; Restivo, DA; Marciani, MG; Centonze, D


Cerebellar transcranial direct current stimulation modulates verbal working memory.

2012 Oct

BACKGROUND: Neuroimaging studies show cerebellar activations in a wide range of cognitive tasks and patients with cerebellar lesions often present cognitive deficits suggesting a cerebellar role in higher-order cognition. OBJECTIVE: We used cathodal transcranial direct current stimulation (tDCS), known to inhibit neuronal excitability, over the cerebellum to investigate if cathodal tDCS impairs verbal working memory, an important higher-order cognitive faculty. METHOD: We tested verbal working memory as measured by forward and backward digit spans in 40 healthy young participants before and after applying cathodal tDCS (2 mA, stimulation duration 25 min) to the right cerebellum using a randomized, sham-controlled, double-blind, cross-over design. In addition, we tested the effect of cerebellar tDCS on word reading, finger tapping and a visually cued sensorimotor task. RESULTS: In line with lower digit spans in patients with cerebellar lesions, cerebellar tDCS reduced forward digit spans and blocked the practice dependent increase in backward digit spans. No effects of tDCS on word reading, finger tapping or the visually cued sensorimotor task were found. CONCLUSION: Our results support the view that the cerebellum contributes to verbal working memory as measured by forward and backward digit spans. Moreover, the induction of reversible "virtual cerebellar lesions" in healthy individuals by means of tDCS may improve our understanding of the mechanistic basis of verbal working memory deficits in patients with cerebellar lesions.

Brain stimulation

Boehringer, A; Macher, K; Dukart, J; Villringer, A; Pleger, B


Imaging artifacts induced by electrical stimulation during conventional fMRI of the brain.

2012 Oct

Functional magnetic resonance imaging (fMRI) of brain activation during transcranial electrical stimulation is used to provide insight into the mechanisms of neuromodulation and targeting of particular brain structures. However, the passage of current through the body may interfere with the concurrent detection of blood oxygen level-dependent (BOLD) signal, which is sensitive to local magnetic fields. To test whether these currents can affect concurrent fMRI recordings we performed conventional gradient echo-planar imaging (EPI) during transcranial direct current (tDCS) and alternating current stimulation (tACS) on two post-mortem subjects. tDCS induced signals in both superficial and deep structures. The signal was specific to the electrode montage, with the strongest signal near cerebrospinal fluid (CSF) and scalp. The direction of change relative to non-stimulation reversed with tDCS stimulation polarity. For tACS there was no net effect of the MRI signal. High-resolution individualized modeling of current flow and induced static magnetic fields suggested a strong coincidence of the change EPI signal with regions of large current density and magnetic fields. These initial results indicate that (1) fMRI studies of tDCS must consider this potentially confounding interference from current flow and (2) conventional MRI imaging protocols can be potentially used to measure current flow during transcranial electrical stimulation. The optimization of current measurement and artifact correction techniques, including consideration of the underlying physics, remains to be addressed.

NeuroImage

Antal, A; Bikson, M; Datta, A; Lafon, B; Dechent, P; Parra, LC; Paulus, W


Interaction between simultaneously applied neuromodulatory interventions in humans.

2012 Oct

BACKGROUND: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique with the potential to enhance the efficacy of traditional therapies such as neuromuscular electrical stimulation (NMES). Yet, concurrent application of tDCS/NMES may also activate homeostatic mechanisms that block or reverse effects on corticomotor excitability. It is unknown how tDCS and NMES interact in the human primary motor cortex (M1) and whether effects are summative (increase corticomotor excitability beyond that of tDCS or NMES applied alone) or competitive (block or reduce corticomotor excitability effects of tDCS or NMES applied alone). OBJECTIVE: To investigate corticomotor excitability in response to NMES after concurrent application of tDCS protocols that enhance (anodal tDCS) or suppress (cathodal tDCS) excitability of M1. METHODS: We used transcranial magnetic stimulation (TMS) to examine corticomotor excitability before and after the concurrent application of: i) NMES with anodal tDCS; and ii) NMES with cathodal tDCS. Effects were contrasted to four control conditions: i) NMES alone, ii) anodal tDCS alone, iii) cathodal tDCS alone, and iv) sham stimulation. RESULTS: Concurrent application of two protocols that enhance excitability when applied alone (NMES and anodal tDCS) failed to induce summative effects on corticomotor excitability, as predicted by homeostatic plasticity mechanisms. Combined cathodal tDCS and NMES suppressed the enhanced excitation induced by NMES, an effect that might be explained by calcium dependent anti-gating models. CONCLUSIONS: These novel findings highlight the complex mechanisms involved when two neuromodulatory techniques are combined and suggest that careful testing of combined interventions is necessary before application in clinical contexts.

Brain stimulation

Schabrun, SM; Chipchase, LS; Zipf, N; Thickbroom, GW; Hodges, PW


Transcranial direct current stimulation effects on the excitability of corticospinal axons of the human cerebral cortex.

2012 Oct

BACKGROUND: Transcranial direct current stimulation (tDCS) of the human cerebral cortex modulates cortical excitability non-invasively in a polarity-specific manner: anodal tDCS leads to lasting facilitation of motor cortex excitability. OBJECTIVE: To further elucidate the underlying physiological mechanisms of tDCS. METHODS: We recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation of the primary motor cortex before and after a 20 min period of anodal tDCS in a conscious patient who had electrode implanted in the cervical epidural space for the control of pain. We performed magnetic stimulation of the motor cortex using a direction of the induced current in the brain capable of activating both corticospinal axons, evoking D-wave activity, and cortico-cortical axons projecting upon corticospinal cells, evoking I-wave activity. RESULTS: Anodal tDCS increased the excitability of cortical circuits generating both D and I-wave activity, with a more prolonged effect on D-wave activity. The changes in motor evoked potential recorded from hand muscles produced by tDCS were in agreement with the effects produced on intracortical circuitry. CONCLUSIONS: Epidural recordings of corticospinal activity in our patient indicate that anodal tDCS develops its facilitatory effects by an increase in the excitability of corticospinal axons and by an increase of activity in cortico-cortical projections onto pyramidal tract neurones, modulating motor cortex excitability with both synaptic (I waves) and non-synaptic (D waves) mechanisms.

Brain stimulation

Di Lazzaro, V; Ranieri, F; Profice, P; Pilato, F; Mazzone, P; Capone, F; Insola, A; Oliviero, A


Bilateral temporal cortex transcranial direct current stimulation worsens male performance in a multisensory integration task.

2012 Oct

Somatosensory integration is a critical cognitive function for human social interaction. Though somatosensory integration has been highly explored in cognitive studies; only a few studies have explored focal modulation of cortical excitability using a speech perception paradigm. In the current study, we aimed to investigate the effects of tDCS applied over the temporal cortex of healthy subjects during a go-no-go task in which stimuli were shapes and non-words. Twenty-eight subjects were randomized to receive cathodal, anodal or sham tDCS bilaterally over the superior temporal cortex (the reference electrode was on deltoid) in a counterbalanced order. The effects on judgment of congruency between shapes and non-words in healthy volunteers were measured by a go-no-go task. Our findings show a significant modification of performance according to the polarity of stimulation, task and subject gender. We found that men performed worse on the no-go condition for congruent stimuli during cathodal tDCS. For reaction time, on the other hand, there was a similar effect for anodal and cathodal stimulation. There were significantly faster responses on incongruent trials during both anodal and cathodal tDCS. Along with previous literature showing gender differences in tasks associated with speech perception, the findings of this study provide additional evidence suggesting that men may have a more focal and restricted neural processing in this multisensory integration task.

Neuroscience letters

Lapenta, OM; Fregni, F; Oberman, LM; Boggio, PS


Neural correlates of the semantic interference effect: new evidence from transcranial direct current stimulation.

2012 Oct

In two experiments, we combined a semantic blocked naming paradigm with anodal transcranial direct current stimulation (tDCS) to shed light on the neural correlates of the semantic interference (SI) effect. In particular, prior to the naming task, anodal tDCS was applied over the left superior temporal gyrus (STG, Experiment 1) or the left inferior frontal gyrus (IFG, Experiment 2) to enhance cortical excitability in these regions. In both experiments, participants were tested in two sessions in which either real or sham tDCS was delivered. We found that anodal tDCS over the left STG significantly increased the SI effect, whereas anodal tDCS over the left IFG led to a reduction of the SI effect. Overall, our data confirm the existence of a distributed cortical network involved in lexical retrieval and show that both the left IFG and the left STG play a causal role in this process. In particular, the left IFG is likely to be critical in resolving the conflict between competitor lexical representations, while the left STG seems to be the neural locus of the lexical representational system, where competition among different lexical representations occurs.

Neuroscience

Pisoni, A; Papagno, C; Cattaneo, Z


The current perspective of neuromodulation techniques in the treatment of alcohol addiction: a systematic review.

2012 Sep

Alcohol dependency can be considered as a chronic mental disorder characterized by frequent relapses even when treated with appropriate medical or psychotherapeutic interventions. Here, the efficacy of different neuromodulation techniques in alcohol addiction, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), vagal nerve stimulation (VNS) and electroconvulsive therapy (ECT) is critically evaluated.A broad literature search on electronic databases such as NCBI PubMed, the Web of Knowledge, the Cochrane Library was conducted. Additionally, we searched recent handbooks on neuromodulation and/or addiction.Studies investigating these neuromodulation techniques in alcohol addiction remain to date rather limited and especially tDCS and rTMS applications have been investigated. Overall, the clinical effects seem modest. The use of VNS and ECT has yet to be investigated in alcohol dependent patients.Neuromodulation techniques have only recently been subject to investigation in alcohol addiction and methodological differences between the few studies restrict clear-cut conclusions. Nevertheless, the scarce results encourage further investigation in alcohol addiction.

Psychiatria Danubina

Herremans, SC; Baeken, C


Can tDCS enhance treatment of aphasia after stroke?

2012 Sep

BACKGROUND: Recent advances in the application of transcranial direct current stimulation (tDCS) in healthy populations have led to the exploration of the technique as an adjuvant method to traditional speech therapies in patients with post-stroke aphasia. AIMS: THE PURPOSE OF THE REVIEW IS: (i) to review the features of tDCS that make it an attractive tool for research and potential future use in clinical contexts; (ii) to describe recent studies exploring the facilitation of language performance using tDCS in post-stroke aphasia; (iii) to explore methodological considerations of tDCS that may be key to understanding tDCS in treatment of aphasia post stroke; and (iv) to highlight several caveats and outstanding questions that need to be addressed in future work. MAIN CONTRIBUTION: This review aims to highlight our current understanding of the methodological and theoretical issues surrounding the use of tDCS as an adjuvant tool in the treatment of language difficulties after stroke. CONCLUSIONS: Preliminary evidence shows that tDCS may be a useful tool to complement treatment of aphasia, particularly for speech production in chronic stroke patients. To build on this exciting work, further systematic research is needed to understand the mechanisms of tDCS-induced effects, its application to current models of aphasia recovery, and the complex interactions between different stimulation parameters and language rehabilitation techniques. The potential of tDCS is to optimise language rehabilitation techniques and promote long-term recovery of language. A stimulating future for aphasia rehabilitation!

Aphasiology

Holland, R; Crinion, J


Transcranial Current Brain Stimulation (tCS):Models and Technologies.

2012 Sep

In this paper we provide a broad overview of models and technologies pertaining to transcranial current brain stimulation (tCS), a family of related non-invasive techniques including direct current (tDCS), alternating current (tACS) and random noise current stimulation (tRNS). These techniques are based on the delivery of weak currents through the scalp (with electrode current intensity to area ratios of about 0.3-5 A/m2) at low frequencies (typically < 1 kHz) resulting in weak electric fields in the brain (with amplitudes of about 0.2-2 V/m). Here we review the biophysics and simulation of non-invasive, current-controlled generation of electric fields in the human brain and the models for the interaction of these electric fields with neurons, including a survey of in-vitro and in-vivo related studies. Finally, we outline directions for future fundamental and technological research.

IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society

Ruffini, G; Wendling, F; Merlet, I; Molaee-Ardekani, B; Mekkonen, A; Salvador, R; Soria-Frisch, A; Grau, C; Dunne, S; Miranda, P


Testing the activation-orientation account of spatial attentional asymmetries using transcranial direct current stimulation.

2012 Sep

The general population shows an attentional bias to the left, known as pseudoneglect. This bias is thought to be driven by higher levels of activation in right parietal areas. Using transcranial direct current stimulation (tDCS) to manipulate activation, this study examined whether tDCS over the left and right posterior parietal cortices (PPC) affects pseudoneglect. Normal participants received tDCS over the left or right PPCs (15 in each group). Pseudoneglect was measured using the greyscales task, which requires a forced-choice discrimination of luminance between two opposing luminance gradients. The greyscales task was administered both before and after; (a) anodal (b) cathodal and (c) sham tDCS. Participants who received tDCS over the left PPC demonstrated pseudoneglect for the greyscales task, which was significantly reduced by anodal tDCS, but was unaffected by sham or cathodal tDCS. In contrast, for those participants who received right PPC tDCS, pseudoneglect for the greyscales task was unaffected by tDCS. Anodal tDCS, which is known to elevate neural excitation, may have overcome lower levels of activation in the left PPC, resulting in decreased pseudoneglect. These findings provide convincing evidence in support of an activation-orientation model of pseudoneglect and have implications for models of left neglect.

Neuropsychologia

Loftus, AM; Nicholls, ME


Transcranial direct current stimulation modulates motor responses evoked by repetitive transcranial magnetic stimulation.

2012 Aug

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques able to induce changes in corticospinal excitability. In this study, we combined rTMS and tDCS to understand possible interactions between the two techniques, and investigate whether they are polarity dependent.Eleven healthy subjects participated in the study. Each patient underwent both anodal and cathodal conditioning tDCS in two separate sessions; brief 5Hz-rTMS trains were delivered over the primary motor cortex at an intensity of 120% the resting motor threshold (RMT) before tDCS (T0), immediately after (T1) and 10min after current offset (T2). We then analysed changes induced by cathodal and anodal tDCS on TMS variables.Our results showed that in both anodal and cathodal sessions, the motor evoked potential (MEP) amplitude increased significantly in size before stimulation (T0). Conversely, after anodal tDCS, the MEP facilitation measured at T1 and T2 was absent, whereas after cathodal tDCS it was preserved.Our findings provide new direct neurophysiological evidence that tDCS influences primary motor cortex excitability.

Neuroscience letters

Cambieri, C; Scelzo, E; Li Voti, P; Priori, A; Accornero, N; Inghilleri, M


Cerebellum and processing of negative facial emotions: Cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness.

2012 Aug

Some evidence suggests that the cerebellum participates in the complex network processing emotional facial expression. To evaluate the role of the cerebellum in recognising facial expressions we delivered transcranial direct current stimulation (tDCS) over the cerebellum and prefrontal cortex. A facial emotion recognition task was administered to 21 healthy subjects before and after cerebellar tDCS; we also tested subjects with a visual attention task and a visual analogue scale (VAS) for mood. Anodal and cathodal cerebellar tDCS both significantly enhanced sensory processing in response to negative facial expressions (anodal tDCS, p=.0021; cathodal tDCS, p=.018), but left positive emotion and neutral facial expressions unchanged (p>.05). tDCS over the right prefrontal cortex left facial expressions of both negative and positive emotion unchanged. These findings suggest that the cerebellum is specifically involved in processing facial expressions of negative emotion.

Cognition & emotion

Ferrucci, R; Giannicola, G; Rosa, M; Fumagalli, M; Boggio, PS; Hallett, M; Zago, S; Priori, A


Migraine prophylaxis by anodal transcranial direct current stimulation, a randomized, placebo-controlled trial.

2012 Aug

Migraine is a common headache syndrome in adult populations. Prophylaxis is necessary to improve the quality of life but some patients with migraine have contraindication or suffer from side effects of medication, and therefore, establishing non-medical, neuromodulatory approaches is necessary. Past evidence had shown that consecutive motor cortex (M1) stimulation with anodal transcranial direct current stimulation (tDCS) was effective to relieve central pain.To determine whether 20 consecutive days of the left M1 can be an effective prophylactic treatment for migraine.Forty-two episodic migraine patients who had never received any prophylactic treatment, failed prophylactic treatment, or discontinued treatment due to adverse events were recruited in the present study. Patients were randomized to receive either active tDCS or sham tDCS 1mA, 20 m for 20 consecutive days and followed up for 12 weeks. Differences between and within groups were determined using repeated measures ANOVA. The level of significance was set at p < 0.05.Thirty-seven patients participated in the final analyses (active: n = 20, sham: n = 17). Between-groups comparison of attack frequency, pain intensity, and abortive medications used were performed at 4, 8, and 12 weeks after treatment. The results showed statistically significant reduction in attack frequency and abortive medications at week 4 and 8 after treatment. The pain intensity was statistically significant reduced at week 4, 8, and 12. All patients tolerated the tDCS well without any serious adverse events.The present study suggests that anodal M1 tDCS may be a safe and useful clinical tool in migraine prophylaxis. The mechanism of action of anodal tDCS on neuromodulation in migraine patients needs further investigation.

Journal of the Medical Association of Thailand = Chotmaihet thangphaet

Auvichayapat, P; Janyacharoen, T; Rotenberg, A; Tiamkao, S; Krisanaprakornkit, T; Sinawat, S; Punjaruk, W; Thinkhamrop, B; Auvichayapat, N


Stroke rehabilitation using noninvasive cortical stimulation: hemispatial neglect.

2012 Aug

The rehabilitation of neuropsychological sequels of cerebral stroke such as hemispatial neglect by noninvasive cortical stimulation (NICS) attracts increasing attention from the scientific community. The NICS techniques include primarily repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). They are based on the concept of either reactivating a hypoactive cortical region affected by the stroke (the right hemisphere in case of neglect) or reducing cortical hyperactivity of the corresponding cortical region in the contralateral hemisphere (the left hemisphere). In the studies published to date on the topic of neglect rehabilitation, rTMS was used to inhibit the left parietal cortex and tDCS to either activate the right or inhibit the left parietal cortex. Sham-controlled NICS studies assessed short-term effects, whereas long-term effects were only assessed in noncontrolled rTMS studies. Further controlled studies of large series of patients are necessary to determine the best parameters of stimulation (including the optimal cortical target location) according to each subtype of neglect presentation and to the time course of stroke recovery. To date, even if there are serious therapeutic perspectives based on imaging data and experimental studies, the evidence is not compelling enough to recommend any particular NICS protocol to treat this disabling condition in clinical practice.

Expert review of neurotherapeutics

Mylius, V; Ayache, SS; Zouari, HG; Aoun-Sebaïti, M; Farhat, WH; Lefaucheur, JP


Stroke rehabilitation using noninvasive cortical stimulation: motor deficit.

2012 Aug

Noninvasive cortical stimulation (NICS) has been used during the acute, postacute and chronic poststroke phases to improve motor recovery in stroke patients having upper- and/or lower-limb paresis. This paper reviews the rationale for using the different NICS modalities to promote motor stroke rehabilitation. The changes in cortical excitability after stroke and the possible mechanisms of action of cortical stimulation in this context are outlined. A number of open and placebo-controlled trials have investigated the clinical effect of repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) of the primary motor cortex in patients with motor stroke. These studies attempted to improve motor performance by increasing cortical excitability in the stroke-affected hemisphere (via high-frequency rTMS or anodal tDCS) or by decreasing cortical excitability in the contralateral hemisphere (via low-frequency rTMS or cathodal tDCS). The goal of these studies was to reduce the inhibition exerted by the unaffected hemisphere on the affected hemisphere and to then restore a normal balance of interhemispheric inhibition. All these NICS techniques administered alone or in combination with various methods of neurorehabilitation were found to be safe and equally effective at the short term on various aspects of poststroke motor abilities. However, the long-term effect of NICS on motor stroke needs to be further evaluated before considering the use of such a technique in the daily routine management of stroke.

Expert review of neurotherapeutics

Ayache, SS; Farhat, WH; Zouari, HG; Hosseini, H; Mylius, V; Lefaucheur, JP


Unleashing potential: transcranial direct current stimulation over the right posterior parietal cortex improves change detection in low-performing individuals.

2012 Aug

The limits of human visual short-term memory (VSTM) have been well documented, and recent neuroscientific studies suggest that VSTM performance is associated with activity in the posterior parietal cortex. Here we show that artificially elevating parietal activity via positively charged electric current through the skull can rapidly and effortlessly improve people's VSTM performance. This artificial improvement, however, comes with an interesting twist: it interacts with people's natural VSTM capability such that low performers who tend to remember less information benefitted from the stimulation, whereas high performers did not. This behavioral dichotomy is explained by event-related potentials around the parietal regions: low performers showed increased waveforms in N2pc and contralateral delay activity (CDA), which implies improvement in attention deployment and memory access in the current paradigm, respectively. Interestingly, these components are found during the presentation of the test array instead of the retention interval, from the parietal sites ipsilateral to the target location, thus suggesting that transcranial direct current stimulation (tDCS) was mainly improving one's ability to suppress no-change distractors located on the irrelevant side of the display during the comparison stage. The high performers, however, did not benefit from tDCS as they showed equally large waveforms in N2pc and CDA, or SPCN (sustained parietal contralateral negativity), before and after the stimulation such that electrical stimulation could not help any further, which also accurately accounts for our behavioral observations. Together, these results suggest that there is indeed a fixed upper limit in VSTM, but the low performers can benefit from neurostimulation to reach that maximum via enhanced comparison processes, and such behavioral improvement can be directly quantified and visualized by the magnitude of its associated electrophysiological waveforms.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Tseng, P; Hsu, TY; Chang, CF; Tzeng, OJ; Hung, DL; Muggleton, NG; Walsh, V; Liang, WK; Cheng, SK; Juan, CH


[Transcranial brain stimulation after stroke].

2012 Aug

Stroke is the leading cause of disability in adults. In Germany an estimated 1.5 million stroke survivors have to cope with persisting sensorimotor or cognitive deficits and effective therapies are scarce. The idea of using non-invasive brain stimulation to treat neuropsychiatric diseases was already born more than 2,000 years ago (Scribonius largus, 43-48 AD). However, only the development of modern non-invasive brain stimulation methods, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) has made it possible to evaluate these ideas. The therapeutic value of these non-invasive brain stimulation methods is currently under study for several neuropsychiatric diseases, mostly in a proof-of-principle fashion. In this article the focus will be on non-invasive brain stimulation to enhance functional regeneration after stroke.

Der Nervenarzt

Hummel, FC; Gerloff, C


[Transcranial and invasive brain stimulation for depression].

2012 Aug

Considering the substantial proportion of depressed patients which does not sufficiently benefit from antidepressant pharmacotherapy or psychotherapy, there is increasing interest in non-pharmacological antidepressant strategies. Thus, a whole array of stimulation approaches has been developed as potential new antidepressant interventions. These methods include transcranial convulsive and non-convulsive approaches, e.g. electroconvulsive therapy (ECT), magnetic seizure therapy (MST), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) as well as invasive techniques, e.g. deep brain stimulation (DBS), vagus nerve stimulation (VNS) and epidural cortical stimulation (ECS). Each method represents a specific therapeutic approach with distinct targets within neural networks involved in the pathophysiology of depression. The ECT procedure is an established treatment with the highest efficacy of all antidepressant interventions and TMS reaches the highest level of evidence among the novel neurostimulation approaches and may be clinically used. However, the field yields a promising rapid development which may substantially enrich the armamentarium of antidepressant interventions in the near future.

Der Nervenarzt

Plewnia, C; Padberg, F


Modulation of event-related desynchronization during motor imagery with transcranial direct current stimulation (tDCS) in patients with chronic hemiparetic stroke.

2012 Jul

Electroencephalogram-based brain-computer interface (BCI) has been developed as a new neurorehabilitative tool for patients with severe hemiparesis. However, its application has been limited because of difficulty detecting stable brain signals from the affected hemisphere. It has been reported that transcranial direct current stimulation (tDCS) can modulate event-related desynchronization (ERD) in healthy persons. The objective of this study was to test the hypothesis that anodal tDCS could modulate ERD in patients with severe hemiparetic stroke. The participants were six patients with chronic hemiparetic stroke (mean age, 56.8 ± 9.5 years; mean time from the onset, 70.0 ± 19.6 months; Fugl-Meyer Assessment upper extremity motor score, 30.8 ± 16.5). We applied anodal tDCS (10 min, 1 mA) and sham stimulation over the affected primary motor cortex in a random order. ERD of the mu rhythm (mu ERD) with motor imagery of extension of the affected finger was assessed before and after anodal tDCS and sham stimulation. Mu ERD of the affected hemisphere increased significantly after anodal tDCS, whereas it did not change after sham stimulation. Our results show that anodal tDCS can increase mu ERD in patients with hemiparetic stroke, indicating that anodal tDCS could be used as a conditioning tool for BCI in stroke patients.

Experimental brain research. Experimentelle Hirnforschung. Experimentation cerebrale

Kasashima, Y; Fujiwara, T; Matsushika, Y; Tsuji, T; Hase, K; Ushiyama, J; Ushiba, J; Liu, M


High-Resolution Modeling Assisted Design of Customized and Individualized Transcranial Direct Current Stimulation Protocols.

2012 Jul

Objectives:  Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity currents facilitating or inhibiting spontaneous neuronal activity. tDCS is attractive since dose is readily adjustable by simply changing electrode number, position, size, shape, and current. In the recent past, computational models have been developed with increased precision with the goal to help customize tDCS dose. The aim of this review is to discuss the incorporation of high-resolution patient-specific computer modeling to guide and optimize tDCS. Methods:  In this review, we discuss the following topics: 1) The clinical motivation and rationale for models of transcranial stimulation is considered pivotal in order to leverage the flexibility of neuromodulation; 2) the protocols and the workflow for developing high-resolution models; 3) the technical challenges and limitations of interpreting modeling predictions; and 4) real cases merging modeling and clinical data illustrating the impact of computational models on the rational design of rehabilitative electrotherapy. Conclusions:  Though modeling for noninvasive brain stimulation is still in its development phase, it is predicted that with increased validation, dissemination, simplification, and democratization of modeling tools, computational forward models of neuromodulation will become useful tools to guide the optimization of clinical electrotherapy.

Neuromodulation : journal of the International Neuromodulation Society

Bikson, M; Rahman, A; Datta, A; Fregni, F; Merabet, L


Suppression of premotor cortex disrupts motor coding of peripersonal space.

2012 Jul

Peripersonal space (PPS) representation depends on the activity of a fronto-parietal network including the premotor cortex (PMc) and the posterior parietal cortex (PPc). PPS representation has a direct effect on the motor system: a stimulus activating the PPS around the hand modulates the excitability of hand representation in the primary motor cortex. However, to date, direct information about the involvement of the PMc-PPc network in the motor mapping of sensory events occurring within PPS is lacking. To address this issue, we used a 'perturb-and-measure' paradigm based on the combination of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) techniques. Cathodal tDCS was applied to transiently suppress neural activity in PMc, PPc and primary visual cortex (V1; serving as an active control site); single-pulse TMS was used to induce motor-evoked potentials (MEPs) from hand muscles and so to measure the excitability of the hand motor representation. MEPs were compared when a sound was presented either near the hand or at a distance. In experimental sessions performed after sham-tDCS and after tDCS over the control area V1, we found a spatially dependent modulation of the hand motor representation: sounds presented near the hand induced an inhibitory motor response as compared to sounds presented far apart. Critically, this effect was selectively abolished after tDCS suppression of neural activity in PMc, but not when perturbing the activity of PPc. These findings suggest that PMc has a critical role in mapping sensory representations of space onto the motor system.

NeuroImage

Annela, L; Avenanti, A; Serino, A


Primary motor and premotor cortex in implicit sequence learning - evidence for competition between implicit and explicit human motor memory systems.

2012 Jul

Implicit and explicit memory systems for motor skills compete with each other during and after motor practice. Primary motor cortex (M1) is known to be engaged during implicit motor learning, while dorsal premotor cortex (PMd) is critical for explicit learning. To elucidate the neural substrates underlying the interaction between implicit and explicit memory systems, adults underwent a randomized crossover experiment of anodal transcranial direct current stimulation (AtDCS) applied over M1, PMd or sham stimulation during implicit motor sequence (serial reaction time task, SRTT) practice. We hypothesized that M1-AtDCS during practice will enhance online performance and offline learning of the implicit motor sequence. In contrast, we also hypothesized that PMd-AtDCS will attenuate performance and retention of the implicit motor sequence. Implicit sequence performance was assessed at baseline, at the end of acquisition (EoA), and 24 h after practice (retention test, RET). M1-AtDCS during practice significantly improved practice performance and supported offline stabilization compared with Sham tDCS. Performance change from EoA to RET revealed that PMd-AtDCS during practice attenuated offline stabilization compared with M1-AtDCS and sham stimulation. The results support the role of M1 in implementing online performance gains and offline stabilization for implicit motor sequence learning. In contrast, enhancing the activity within explicit motor memory network nodes such as the PMd during practice may be detrimental to offline stabilization of the learned implicit motor sequence. These results support the notion of competition between implicit and explicit motor memory systems and identify underlying neural substrates that are engaged in this competition.

The European journal of neuroscience

Kantak, SS; Mummidisetty, CK; Stinear, JW


After-effects of consecutive sessions of transcranial direct current stimulation (tDCS) in a rat model of chronic inflammation.

2012 Jul

Transcranial direct current stimulation (tDCS) induces cortical excitability changes in animals and humans that can last beyond the duration of stimulation. Preliminary evidence suggests that tDCS may have an analgesic effect; however, the timing of these effects, especially when associated with consecutive sessions of stimulation in a controlled animal experiment setting, has yet to be fully explored. To evaluate the effects of tDCS in inflammatory chronic pain origin immediately and 24 h after the last treatment session, complete Freund's adjuvant (CFA) was injected (100 μl) in the right footpad to induce inflammation. On the 15th day after CFA injection, rats were divided into two groups: tDCS (n = 9) and sham (n = 9). The tDCS was applied for 8 days. The hot plate and Von Frey tests were applied immediately and 24 h after the last tDCS session. Eight 20-min sessions of 500 μA anodal tDCS resulted in antinociceptive effects as assessed by the hot plate test immediately (P = 0.04) and 24 h after the last tDCS session (P = 0.006), for the active tDCS group only. There was increased withdrawal latency in the Von Frey test at 24 h after the last session (P = 0.01). Our findings confirm the hypothesis that tDCS induces significant, long-lasting, neuroplastic effects and expands these findings to a chronic pain model of peripheral inflammation, thus supporting the exploration of this technique in conditions associated with chronic pain and peripheral inflammation, such as osteoarthritis.

Experimental brain research. Experimentelle Hirnforschung. Experimentation cerebrale

Laste, G; Caumo, W; Adachi, LN; Rozisky, JR; de Macedo, IC; Filho, PR; Partata, WA; Fregni, F; Torres, IL


Comparison of the after-effects of transcranial direct current stimulation over the motor cortex in patients with stroke and healthy volunteers.

2012 Jul

Abstract It is known that weak transcranial direct current stimulation (tDCS) induces persistent excitability changes in the cerebral cortex. There are, however, few studies that compare the after-effects of anodal versus cathodal tDCS in patients with stroke. This study assessed the after-effects of transcranial direct current stimulation (tDCS) over the motor cortex in patients with hemiparetic stroke and healthy volunteers. Seven stroke patients and nine healthy volunteers were recruited. Ten minutes of anodal and cathodal tDCS (1mA) and sham stimulation were applied to the affected primary motor cortex (M1) on different days. In healthy subjects, tDCS was applied to the right M1. Before and after tDCS, motor evoked potentials (MEPs) in the first dorsal interosseous (FDI) muscle and silent period were measured. Anodal tDCS increased the MEPs of the affected FDI in patients with stroke as well as in healthy subjects. Cathodal tDCS increased the MEPs of the affected FDI in patients with stroke. In healthy subjects, however, cathodal tDCS decreased the MEPs. We found no significant change in the duration of the silent period after anodal or cathodal tDCS. We found that both anodal and cathodal tDCS increased the affected M1 excitability in patients with stroke. It is thought that the after-effects of tDCS are different in patients with stroke compared with healthy subjects.

The International journal of neuroscience

Suzuki, K; Fujiwara, T; Tanaka, N; Tsuji, T; Masakado, Y; Hase, K; Kimura, A; Liu, M


tDCS selectively improves working memory in older adults with more education.

2012 Jul

Cognitive performance, including performance on working memory (WM) tasks declines with age. Changes in brain activations are one presumed contributor to WM decline in the healthy aging population. In particular, neuroimaging studies show that when older adults perform WM tasks there tends to be greater bilateral frontal activity than in younger adults. We hypothesized that stimulating the prefrontal cortex in healthy older adults would improve WM performance. To test this hypothesis we employed transcranial direct current stimulation (tDCS), a neurostimulation technique in which small amounts of electrical current are applied to the scalp with the intent of modulating the activity in underlying neurons. Across three testing sessions we applied sham stimulation or anodal tDCS to the left (F3) or right (F4) prefrontal cortex to healthy older adults as they performed trials of verbal and visual 2-back WM tasks. Surprisingly, tDCS was uniformly beneficial across site and WM task, but only in older adults with more education. In the less educated group, tDCS provided no benefit to verbal or visual WM performance. We interpret these findings as evidence for differential frontal recruitment as a function of strategy when older adults perform WM tasks.

Neuroscience letters

Berryhill, ME; Jones, KT


Noninvasive cortical modulation of experimental pain.

2012 Jul

Noninvasive cortical stimulation (NICS) can produce analgesic effects by means of repetitive transcranial magnetic stimulation or transcranial direct current stimulation (tDCS). Such effects have been demonstrated on chronic ongoing pain, as in acute provoked pain. The investigation of induced changes in the perception of experimental pain by NICS could help clinicians and researchers to better understand the mechanisms of action involved with these techniques and the role played by the cortex in the integration of nociceptive information. This review presents current literature data on the modulation of experimental pain perception by cortical stimulation. The observations found that NICS analgesic effects depend on the method used to provoke pain (referring to the type of nerve fibers and neural circuits that are recruited to mediate pain) and the parameters of cortical stimulation (especially the nature of the cortical target). The motor cortex (precentral cortical area) is the most widely used target for pain modulation. However, other targets, such as the dorsolateral prefrontal cortex, could be of particular interest to modulate various components of pain. Further developments in NICS techniques, such as image-guided navigated brain stimulation, might lead to improvement in the beneficial effects of NICS on pain. Finally, we discuss whether the results obtained in experimental pain can be transposed to the problem of chronic pain and whether they can be used to optimize cortical stimulation therapy for pain disorders.

Pain

Mylius, V; Borckardt, JJ; Lefaucheur, JP


Effects of transcranial electrical stimulation on cognition.

2012 Jul

Alterations of cortical excitability, oscillatory as well as non-oscillatory, are physiological derivates of cognitive processes, such as perception, working memory, learning, and long-term memory formation. Since noninvasive electrical brain stimulation is capable of inducing alterations in the human brain, these stimulation approaches might be attractive tools to modulate cognition. Transcranial direct current stimulation (tDCS) alters spontaneous cortical activity, while transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS) are presumed to induce or interfere with oscillations of cortical networks. Via these mechanisms, the respective stimulation techniques have indeed been shown to modulate cognitive processes in a multitude of studies conducted during the last years. In this review, we will gather knowledge about the potential of noninvasive electrical brain stimulation to study and modify cognitive processes in healthy humans and discuss directions of future research.

Clinical EEG and neuroscience : official journal of the EEG and Clinical Neuroscience Society (ENCS)

Kuo, MF; Nitsche, MA


Computational models of transcranial direct current stimulation.

2012 Jul

During transcranial direct current stimulation (tDCS), controllable dose parameters are electrode number (typically 1 anode and 1 cathode), position, size, shape, and applied electric current. Because different electrode montages result in distinct brain current flow patterns across the brain, tDCS dose parameters can be adjusted, in an application-specific manner, to target or avoid specific brain regions. Though the tDCS electrode montage often follows basic rules of thumb (increased/decreased excitability "under" the anode/cathode electrode), computational forward models of brain current flow provide more accurate insight into detailed current flow patterns and, in some cases, can even challenge simplified electrode-placement assumptions. With the increased recognized value of computational forward models in informing tDCS montage design and interpretation of results, there have been recent advances in modeling tools and a greater proliferation of publications.  In addition, the importance of customizing tDCS for potentially vulnerable populations (eg, skull defects, brain damage/stroke, and extremes of age) can be considered. Finally, computational models can be used to design new electrode montages, for example, to improve spatial targeting such as high-definition tDCS. Pending further validation and dissemination of modeling tools, computational forward models of neuromodulation will become standard tools to guide the optimization of clinical trials and electrotherapy.

Clinical EEG and neuroscience : official journal of the EEG and Clinical Neuroscience Society (ENCS)

Bikson, M; Rahman, A; Datta, A


Investigating neuroplastic changes in the human brain induced by transcranial direct (tDCS) and alternating current (tACS) stimulation methods.

2012 Jul

Clinical EEG and neuroscience : official journal of the EEG and Clinical Neuroscience Society (ENCS)

Antal, A; Paulus, W


Noninvasive brain stimulation to modulate neuroplasticity in traumatic brain injury.

2012 Jul

To review the use of noninvasive brain stimulation (NBS) as a therapeutic tool to enhance neuroplasticity following traumatic brain injury (TBI).Based on a literature search, we describe the pathophysiological events following TBI and the rationale for the use of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in this setting.The pathophysiological mechanisms occurring after TBI vary across time and therefore require differential interventions. Theoretically, given the neurophysiological effects of both TMS and tDCS, these tools may: 1) decrease cortical hyperexcitability acutely after TBI; 2) modulate long-term synaptic plasticity as to avoid maladaptive consequences; and 3) combined with physical and behavioral therapy, facilitate cortical reorganization and consolidation of learning in specific neural networks. All of these interventions may help decrease the burden of disabling sequelae after brain injury.Evidence from animal and human studies reveals the potential benefit of NBS in decreasing the extent of injury and enhancing plastic changes to facilitate learning and recovery of function in lesioned neural tissue. However, this evidence is mainly theoretical at this point. Given safety constraints, studies in TBI patients are necessary to address the role of NBS in this condition as well as to further elucidate its therapeutic effects and define optimal stimulation parameters.

Neuromodulation : journal of the International Neuromodulation Society

Villamar, MF; Santos Portilla, A; Fregni, F; Zafonte, R


Non-invasive stimulation therapies for the treatment of refractory pain.

2012 Jul

Drug-refractory pain is an indication for neurostimulation therapy, which can be either non-invasive [mainly transcutaneous electrical nerve stimulation (TENS), repetitive Transcranial Magnetic Stimulation (rTMS), and transcranial direct current stimulation (tDCS)] or invasive which requires the intervention of a surgeon to implant electrodes and a pulse generator [peripheral nerve stimulation (PNS), nerve root stimulation (NRS), spinal cord stimulation (SCS), deep brain stimulation (DBS), and motor cortex stimulation (MCS)]. In this review, the respective mechanisms of action and efficacy of TENS, rTMS, and tDCS are discussed. The advantages of TENS include non-invasiveness and ease to use, so that the technique can be operated by the patient. TENS can be indicated as a first-line treatment in patients suffering from peripheral neuropathic pain if the painful area is limited and the sensory deficit moderate. The current best indications are chronic radiculopathies, mononeuropathies, and postherpetic pain. Test sessions allow to select suitable patients and to determine the site, frequency, and optimal intensity of stimulation. Three to four 30- to 60-minute sessions per day are usually recommended. With regard to rTMS, published randomized controlled studies in chronic neuropathic and non-neuropathic pain (fibromyalgia) reached a sufficient level of evidence to recommend this technique for the indication of implanted motor cortex stimulation for the treatment of refractory neuropathic pain or as a long-term treatment for pain syndromes, in which surgery is not indicated, such as fibromyalgia. Other indications, concerning either chronic or acute pain syndromes, such as postoperative pain, should be developed in parallel with the optimization of stimulation parameters. This also includes the availability of new coils and magnetic field waveforms and progress in neuronavigation techniques, especially by the integration of functional imaging and high-resolution EEG data.

Discovery medicine

Nizard, J; Lefaucheur, JP; Helbert, M; de Chauvigny, E; Nguyen, JP


Transcranial direct current stimulation accelerates allocentric target detection.

2012 Jun

BACKGROUND: Previous research on hemispatial neglect has provided evidence for dissociable mechanisms for egocentric and allocentric processing. Although a few studies have examined whether tDCS to posterior parietal cortex can be beneficial for attentional processing in neurologically intact individuals, none have examined the potential effect of tDCS on allocentric and/or egocentric processing. OBJECTIVE/HYPOTHESIS: Our objective was to examine whether transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique that can increase (anodal) or decrease (cathodal) cortical activity, can affect visuospatial processing in an allocentric and/or egocentric frame of reference. METHODS: We tested healthy individuals on a target detection task in which the target - a circle with a gap - was either to the right or left of the viewer (egocentric), or contained a gap on the right or left side of the circle (allocentric). Individuals performed the task before, during, and after tDCS to the posterior parietal cortex in one of three stimulation conditions - right anodal/left cathodal, right cathodal/left anodal, and sham. RESULTS: We found an allocentric hemispatial effect both during and after tDCS, such that right anodal/left cathodal tDCS resulted in faster reaction times for detecting stimuli with left-sided gaps compared to right-sided gaps. CONCLUSIONS: Our study suggests that right anodal/left cathodal tDCS has a facilitatory effect on allocentric visuospatial processing, and might be useful as a therapeutic technique for individuals suffering from allocentric neglect.

Brain stimulation

Medina, J; Beauvais, J; Datta, A; Bikson, M; Coslett, HB; Hamilton, RH


Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders?

2012 Jun

Cognitive impairment is a core symptom of many neuropsychiatric diseases and a key contributor to the patient's quality of life. However, an effective therapeutic strategy has yet to be developed. Noninvasive brain stimulation techniques, namely transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), are promising techniques that are under investigation for a variety of otherwise treatment-resistant neuropsychiatric diseases. Notably, these tools can induce alterations in neural networks subserving cognitive operations and thus may provide a means for cognitive restoration. The purpose of this article is to review the available evidence concerning cognitive enhancing properties of noninvasive brain stimulation in neuropsychiatry. We specifically focus on major depression, Alzheimer's disease, schizophrenia, autism and attention deficit hyperactivity disorder (ADHD), where cognitive dysfunction is a major symptom and some studies have been completed with promising results. We provide a critical assessment of the available research and suggestions to guide future efforts. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Neuropharmacology

Demirtas-Tatlidede, A; Vahabzadeh-Hagh, A; Pascual-Leone, A


Unilateral prefrontal direct current stimulation effects are modulated by working memory load and gender.

2012 Jun

BACKGROUND: Recent studies revealed that anodal transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) may improve verbal working memory (WM) performance in humans. In the present study, we evaluated executive attention, which is the core of WM capacity, considered to be significantly involved in tasks that require active maintenance of memory representations in interference-rich conditions, and is highly dependent on DLPFC function. OBJECTIVES: We investigated verbal WM accuracy using a WM task that is highly sensitive to executive attention function. We were interested in how verbal WM accuracy may be affected by WM load, unilateral DLPFC stimulation, and gender, as previous studies showed gender-dependent brain activation during verbal WM tasks. METHODS: We utilized a modified verbal n-Back task hypothesized to increase demands on executive attention. We examined "online" WM performance while participants received transcranial direct current stimulation (tDCS), and implicit learning performance in a post-stimulation WM task. RESULTS: Significant lateralized "online" stimulation effects were found only in the highest WM load condition revealing that males benefit from left DLPFC stimulation, while females benefit from right DLPFC stimulation. High WM load performance in the left DLPFC stimulation was significantly related to post-stimulation recall performance. CONCLUSIONS: Our findings support the idea that lateralized stimulation effects in high verbal WM load may be gender-dependent. Further, our post-stimulation results support the idea that increased left hemisphere activity may be important for encoding verbal information into episodic memory as well as for facilitating retrieval of context-specific targets from semantic memory.

Brain stimulation

Meiron, O; Lavidor, M


The effects of prolonged cathodal direct current stimulation on the excitatory and inhibitory circuits of the ipsilateral and contralateral motor cortex.

2012 Jun

Weak cathodal transcranial direct current stimulation (tDCS) of the human hand area modulates corticospinal excitability with a suppression of motor-evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS). The changes in excitability persist beyond the time of stimulation if tDCS is given for several minutes and can remain stable for an hour or more. The aim of present study was to evaluate whether a long-lasting suppression of cortical excitability could be induced by prolonged cathodal tDCS (20 min of stimulation). We also explored the impact of brain-derived neurotrophic factor (BDNF) gene polymorphisms, on tDCS after-effects. Cortical excitability to single and paired-pulse TMS was evaluated both for the stimulated and contralateral hemisphere, before and up to 24 h after 20 min of cathodal tDCS. We evaluated threshold and amplitude of MEPs, short interval intracortical inhibition (SICI), and intracortical facilitation (ICF). tDCS produced a pronounced suppression of MEP amplitude that was still significant at 3 h after the end of stimulation. The BDNF genotype had not influence on tDCS after-effects. Thresholds for MEPs, SICI and ICF were not affected. No significant effect was observed in the contralateral hemisphere. Twenty minutes of cathodal tDCS is capable of inducing a long-lasting suppression of the excitability of the human motor cortex.

Journal of neural transmission (Vienna, Austria : 1996)

Di Lazzaro, V; Manganelli, F; Dileone, M; Notturno, F; Esposito, M; Capasso, M; Dubbioso, R; Pace, M; Ranieri, F; Minicuci, G; Santoro, L; Uncini, A


Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation.

2012 Jun

BACKGROUND: Non-invasive brain stimulation enables the induction of neuroplasticity in humans, however, with so far restricted duration of the respective cortical excitability modifications. Conventional anodal transcranial direct current stimulation (tDCS) protocols including one stimulation session induce NMDA receptor-dependent excitability enhancements lasting for about 1 h. OBJECTIVE: We aimed to extend the duration of tDCS effects by periodic stimulation, consisting of two stimulation sessions, since periodic stimulation protocols are able to induce neuroplastic excitability alterations stable for days or weeks, termed late phase long term potentiation (l-LTP), in animal slice preparations. Since both, l-LTP and long term memory formation, require gene expression and protein synthesis, and glutamatergic receptor activity modifications, l-LTP might be a candidate mechanism for the formation of long term memory. METHODS: The impact of two consecutive tDCS sessions on cortical excitability was probed in the motor cortex of healthy humans, and compared to that of a single tDCS session. The second stimulation was applied without an interval (temporally contiguous tDCS), during the after-effects of the first stimulation (during after-effects; 3, or 20 min interval), or after the after-effects of the first stimulation had vanished (post after-effects; 3 or 24 h interval). RESULTS: The during after-effects condition resulted in an initially reduced, but then relevantly prolonged excitability enhancement, which was blocked by an NMDA receptor antagonist. The other conditions resulted in an abolishment, or a calcium channel-dependent reversal of neuroplasticity. CONCLUSION: Repeated tDCS within a specific time window is able to induce l-LTP-like plasticity in the human motor cortex.

Brain stimulation

Monte-Silva, K; Kuo, MF; Hessenthaler, S; Fresnoza, S; Liebetanz, D; Paulus, W; Nitsche, MA


Prefrontal control during a semantic decision task that involves idiom comprehension: A transcranial direct current stimulation study.

2012 Jun

Language processing and comprehension can be understood in terms of both linguistic and non-linguistic processes. To make a decision regarding the meaning of complex linguistic inputs such as idiomatic expressions, one has to perform multiple complex cognitive operations such as prediction, selection and inhibition. In the current study, we used transcranial direct current stimulation (tDCS) to test the hypotheses that (I) a prefrontal cognitive control network is involved in directing decisions required for the comprehension of idioms, and (II) that this prefrontal control may be biased by motivational mechanisms. Participants were randomly allocated to one of two stimulation groups (LH anodal/RH cathodal or RH anodal/LH Cathodal). Over a one-week interval, participants were tested twice, completing a semantic decision task after either receiving active or sham stimulation. The semantic decision task required participants to judge the relatedness of an idiom and a target word, with the idiom being predictable or not. The target word was either figuratively related, literally related, or unrelated to the idiom. Each participant also completed a trait motivation questionnaire and a control task. After DC stimulation, a general deceleration in reaction times to targets was found. In addition, the results indicate that the neural enhancement of a left lateralized prefrontal network improved performance when participants had to make decisions to figurative targets of highly predictable idioms, whereas the neural enhancement of the opposite network improved participants' performance to literal targets of unpredictable idioms. These effects were more pronounced in individuals rated as being most sensitive to reward likelihood. The results are discussed in terms of cognitive control over semantic processing.

Neuropsychologia

Sela, T; Ivry, RB; Lavidor, M


Non-invasive brain stimulation in neurological diseases.

2012 Jun

Non-invasive brain stimulation has shown its potential to modulate brain plasticity in humans. Endeavour has been made to utilize brain stimulation in neurological diseases to enhance adaptive processes and prevent potential maladaptive ones. In stroke for instance both sensorimotor and higher cognitive impairment, such as aphasia and neglect, has been addressed to facilitate functional recovery. In Parkinson's disease, brain stimulation has been evaluated to improve motor and non-motor symptoms. In the present review we provide an update of the field of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) as non-invasive brain stimulation techniques to improve motor and higher cognitive functions in patients suffering from stroke and Parkinson's disease. Rather than attempting to be comprehensive in regard of the reviewed scientific field, this article may be considered as a present day's framework of the application of non-invasive brain stimulation on selected examples of common neurological diseases. At the end we will briefly discuss open controversies and future directions of the field which has to be addressed in upcoming studies. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Neuropharmacology

Schulz, R; Gerloff, C; Hummel, FC


tDCS of the primary motor cortex improves the detection of semantic dissonance.

2012 Jun

Increasing evidences show that the linguistic representation of motor activities induces simulative processes that involve motor neural systems normally engaged in actual execution of movements. However, other researches suggest that the motor cortex is not an integral part of the network for action-word representation but is recruited only to execute tasks that critically require the retrieval of sensorimotor attributes associated with words. In order to enlighten this controversial literature, three groups of healthy participants were submitted to transcranial direct current stimulation (tDCS) (cathodal, anodal and sham stimulations) of the left primary motor cortex during the execution of a picture recognition task. Results show that cathodal stimulation improves the participants' ability to detect either mismatching motor vs. no motor sentence-drawing associations, while no significant difference has not been reported for compatible associations. The current result is in line with the suggestion that motor regions play a critical role in detecting dissonant outcomes.

Neuroscience letters

Vicario, CM; Rumiati, RI


Neurostimulation therapies for primary headache disorders: present and future.

2012 Jun

Most pharmacological treatments of primary headache disorders are partially effective and have cumbersome side effects. Therapies with better efficacy and tolerance are needed. Neurostimulation techniques may have this potential. This is an attempt to summarize the latest clinical trial results published in the field.Hypothalamic deep brain stimulation is effective in drug-resistant chronic cluster headache (drCCH) but not riskless. Recent anatomical MRI studies indicate that the effective stimulation sites are rather widespread. Occipital nerve stimulation (ONS) seems to be effective in up to 76% of drCCH patients and its benefit long-lasting. A minority of patients are able to abandon preventive drugs. Its mechanism of action appears nonspecific. In chronic migraine, randomized controlled trials of ONS showed recently encouraging results, but long-term studies are missing. An ongoing sham-controlled trial suggests sphenopalatine ganglion neurostimulation (SPGS) efficacy in drCCH acute treatment, but possibly also in preventive therapy. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) modulate cortical excitability and connectivity. TMS could prevent headache when applied over the occipital cortex during the migraine aura. Repetitive TMS and tDCS have provided mixed results in a few small studies and warrant further trials.Neurostimulation therapies inaugurate a new era in headache management and offer a promising alternative to medications. Future studies are necessary to provide evidence-based efficacy data, knowledge on their mode of action and information about their pharmaco-economic advantages.

Current opinion in neurology

Magis, D; Jensen, R; Schoenen, J


Modulating behavioral inhibition by tDCS combined with cognitive training.

2012 Jun

Cognitive training is an effective tool to improve a variety of cognitive functions, and a small number of studies have now shown that brain stimulation accompanying these training protocols can enhance their effects. In the domain of behavioral inhibition, little is known about how training can affect this skill. As for transcranial direct current stimulation (tDCS), it was previously found that stimulation over the right inferior frontal gyrus (rIFG) facilitates behavioral inhibition performance and modulates its electrophysiological correlates. This study aimed to investigate this behavioral facilitation in the context of a learning paradigm by giving tDCS over rIFG repetitively over four consecutive days of training on a behavioral inhibition task (stop signal task (SST)). Twenty-two participants took part; ten participants were assigned to receive anodal tDCS (1.5 mA, 15 min), 12 were assigned to receive training but not active stimulation. There was a significant effect of training on learning and performance in the SST, and the integration of the training and rIFG-tDCS produced a more linear learning slope. Better performance was also found in the active stimulation group. Our findings show that tDCS-combined cognitive training is an effective tool for improving the ability to inhibit responses. The current study could constitute a step toward the use of tDCS and cognitive training as a therapeutic tool for cognitive control impairments in conditions such as attention-deficit hyperactivity disorder (ADHD) or schizophrenia.

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Ditye, T; Jacobson, L; Walsh, V; Lavidor, M


Transcranial direct current stimulation (tDCS) of the inferior frontal gyrus disrupts interpersonal motor resonance.

2012 Jun

Interpersonal motor resonance (IMR) is presumed to result from activity within the human mirror neuron system, which itself is thought to comprise the inferior parietal lobule (IPL) and inferior frontal gyrus (IFG). Twenty healthy adults underwent anodal, cathodal, and sham transcranial direct current stimulation (tDCS) to either IPL or IFG immediately before the assessment of IMR (using transcranial magnetic stimulation). IMR (i.e., motor-evoked potential amplitude during transitive action observation relative to static observation) was significantly reduced following both anodal and cathodal stimulation of IFG (relative to sham), but there was no effect of stimulation for IPL. These data support the role of IFG, a presumed mirror neuron region, in IMR.

Neuropsychologia

Enticott, PG; Arnold, SL; Fitzgibbon, BM; Hoy, KE; Susilo, DA; Fitzgerald, PB


Impact of tDCS on performance and learning of target detection: interaction with stimulus characteristics and experimental design.

2012 Jun

We have previously found that transcranial direct current stimulation (tDCS) over right inferior frontal cortex (RIFC) enhances performance during learning of a difficult visual target detection task (Clark et al., 2012). In order to examine the cognitive mechanisms of tDCS that lead to enhanced performance, here we analyzed its differential effects on responses to stimuli that varied by repetition and target presence, differences related to expectancy by comparing performance in single- and double-blind task designs, and individual differences in skin stimulation and mood. Participants were trained for 1h to detect target objects hidden in a complex virtual environment, while anodal tDCS was applied over RIFC at 0.1 mA or 2.0 mA for the first 30 min. Participants were tested immediately before and after training and again 1h later. Higher tDCS current was associated with increased performance for all test stimuli, but was greatest for repeated test stimuli with the presence of hidden-targets. This finding was replicated in a second set of subjects using a double-blind task design. Accuracy for target detection discrimination sensitivity (d'; Z(hits)-Z(false alarms)) was greater for 2.0 mA current (1.77) compared with 0.1 mA (0.95), with no differences in response bias (β). Taken together, these findings indicate that the enhancement of performance with tDCS is sensitive to stimulus repetition and target presence, but not to changes in expectancy, mood, or type of blinded task design. The implications of these findings for understanding the cognitive mechanisms of tDCS are discussed.

Neuropsychologia

Coffman, BA; Trumbo, MC; Flores, RA; Garcia, CM; van der Merwe, AJ; Wassermann, EM; Weisend, MP; Clark, VP


Modulating locomotor adaptation with cerebellar stimulation.

2012 Jun

Human locomotor adaptation is necessary to maintain flexibility of walking. Several lines of research suggest that the cerebellum plays a critical role in motor adaptation. In this study we investigated the effects of noninvasive stimulation of the cerebellum to enhance locomotor adaptation. We found that anodal cerebellar transcranial direct current stimulation (tDCS) applied during adaptation expedited the adaptive process while cathodal cerebellar tDCS slowed it down, without affecting the rate of de-adaptation of the new locomotor pattern. Interestingly, cerebellar tDCS affected the adaptation rate of spatial but not temporal elements of walking. It may be that spatial and temporal control mechanisms are accessible through different neural circuits. Our results suggest that tDCS could be used as a tool to modulate locomotor training in neurological patients with gait impairments.

Journal of neurophysiology

Jayaram, G; Tang, B; Pallegadda, R; Vasudevan, EV; Celnik, P; Bastian, A


Direct current stimulation (tDCS) reveals parietal asymmetry in local/global and salience-based selection.

2012 May

Data from neuropsychology and neuroimaging studies indicate hemispheric asymmetries in processing object's global form versus local parts. However the attentional mechanisms subtending visual selection of different levels of information are poorly understood. The classical left hemisphere/local-right hemisphere/global dichotomy has been recently challenged by studies linking the asymmetry of activation in the posterior parietal cortex (PPC) with the relative salience of the stimulus rather than with the local/global level. The present study aimed to assess hemispheric asymmetry in local-global and salience-based selection in hierarchical stimuli by using transcranial direct current stimulation (tDCS). To this end, tDCS has been applied to the PPC of both the hemispheres. Our data revealed that tDCS did affect the selection of the target on the basis of its relative salience in a manner that depended on the tDCS polarity applied to the two hemispheres. This result is in line with previous findings that the left PPC is critically involved in attention for low-salience stimuli in the presence of high-salience distractor information, while right PPC is involved in attending to more salient stimuli. Hemispheric asymmetries were also found in local/global selection. Overall the results suggest that neural activation in the PPC is related to both the salience and the level of stimulus representations mediating responses to hierarchical stimuli. The comparison of the results from Experiments 1 and 2 in local/global-based selection suggests that the effect of stimulation could be completely opposite depending on subtle differences in demands of attentional control (sustained attention vs task switching).

Cortex; a journal devoted to the study of the nervous system and behavior

Bardi, L; Kanai, R; Mapelli, D; Walsh, V


[Treatment of chronic pain: transcranial stimulation of the motor cortex?].

2012 May

Chronic pain refractory to medical therapy poses a therapeutic challenge. The repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) modulate brain activity offering a new approach. Current evidence suggests a potential therapeutic efficacy of motor cortex stimulation for the treatment of pain, but does not (yet) support their recommendation for clinical practice. These methods allow to deepen our knowledge in the pathophysiology of chronic pain while providing new therapeutic approaches.

Revue médicale suisse

Benninger, D; Kuntzer, T


Anodal transcranial direct current stimulation (tDCS) over supplementary motor area (SMA) but not pre-SMA promotes short-term visuomotor learning.

2012 May

BACKGROUND: Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) has been shown to modulate cortical excitability and thereby influencing motor behaviour and learning. HYPOTHESIS: While there is increasing knowledge about the importance of the primary motor cortex (M1) in short- and long-term motor skill learning, little is known about the role of secondary motor areas such as the supplementary and pre-supplementary motor area (SMA/pre-SMA) especially in short-term motor performance. Since SMA but not pre-SMA is directly connected to M1, we hypothesize that anodal tDCS over SMA but not pre-SMA will facilitate visuomotor learning. METHODS: We applied anodal tDCS (tDCS(anodal)) over left SMA, pre-SMA or M1 (n=12 in each group) while subjects performed a visuomotor pinch force task (VPFT) with their right hand and compared VPFT performance relative to sham (tDCS(sham)). RESULTS: For the first time, we could show that apart from tDCS(anodal) over left M1 also SMA but not pre-SMA stimulation promotes short-term improvements in visuomotor learning relative to tDCS(sham). CONCLUSIONS: Our findings provide novel evidence about the role of SMA in short-term visuomotor performance. This knowledge might be beneficial in developing hypothesis-driven clinical studies in neurorehabilitation.

Brain stimulation

Vollmann, H; Conde, V; Sewerin, S; Taubert, M; Sehm, B; Witte, OW; Villringer, A; Ragert, P


Transcranial direct current stimulation for the treatment of major depressive disorder: A summary of preclinical, clinical and translational findings.

2012 May

Major depressive disorder (MDD) is a common psychiatric illness, with 6-12% lifetime prevalence. It is also among the five most disabling diseases worldwide. Current pharmacological treatments, although relatively effective, present important side effects that lead to treatment discontinuation. Therefore, novel treatment options for MDD are needed. Here, we discuss the recent advancements of one new neuromodulatory technique - transcranial direct current stimulation (tDCS) - that has undergone intensive research over the past decade with promising results. tDCS is based on the application of weak, direct electric current over the scalp, leading to cortical hypo- or hyper-polarization according to the specified parameters. Recent studies have shown that tDCS is able to induce potent changes in cortical excitability as well as to elicit long-lasting changes in brain activity. Moreover, tDCS is a technique with a low rate of reported side effects, relatively easy to apply and less expensive than other neuromodulatory techniques - appealing characteristics for clinical use. In the past years, 4 of 6 phase II clinical trials and one recent meta-analysis have shown positive results in ameliorating depression symptoms. tDCS has some interesting, unique aspects such as noninvasiveness and low rate of adverse effects, being a putative substitutive/augmentative agent for antidepressant drugs, and low-cost and portability, making it suitable for use in clinical practice. Still, further phase II and phase III trials are needed as to better clarify tDCS role in the therapeutic arsenal of MDD.

Progress in neuro-psychopharmacology & biological psychiatry

Brunoni, AR; Ferrucci, R; Fregni, F; Boggio, PS; Priori, A


Efficacy of Transcranial Direct Current Stimulation and Repetitive Transcranial Magnetic Stimulation for Treating Fibromyalgia Syndrome: A Systematic Review.

2012 May

Objective:  To systematically review the literature to date applying repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) for patients with fibromyalgia syndrome (FMS). Method:  Electronic bibliography databases screened included PubMed, Ovid MEDLINE, PsychINFO, CINAHL, and Cochrane Library. The keyword "fibromyalgia" was combined with ("transcranial" and "stimulation") or "TMS" or "tDCS" or "transcranial magnetic stimulation" or "transcranial direct current stimulation". Results:  Nine of 23 studies were included; brain stimulation sites comprised either the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC). Five studies used rTMS (high-frequency-M1: 2, low-frequency-DLPFC: 2, high-frequency-DLPFC: 1), while 4 applied tDCS (anodal-M1: 1, anodal-M1/DLPFC: 3). Eight were double-blinded, randomized controlled trials. Most (80%) rTMS studies that measured pain reported significant decreases, while all (100%) tDCS studies with pain measures reported significant decreases. Greater longevity of significant pain reductions was observed for excitatory M1 rTMS/tDCS. Conclusion:  Studies involving excitatory rTMS/tDCS at M1 showed analogous pain reductions as well as considerably fewer side effects compared to FDA approved FMS pharmaceuticals. The most commonly reported side effects were mild, including transient headaches and scalp discomforts at the stimulation site. Yearly use of rTMS/tDCS regimens appears costly ($11,740 to 14,507/year); however, analyses to appropriately weigh these costs against clinical and quality of life benefits for patients with FMS are lacking. Consequently, rTMS/tDCS should be considered when treating patients with FMS, particularly those who are unable to find adequate symptom relief with other therapies. Further work into optimal stimulation parameters and standardized outcome measures is needed to clarify associated efficacy and effectiveness.

Pain practice : the official journal of World Institute of Pain

Marlow, NM; Bonilha, HS; Short, EB


Polarity- and valence-dependent effects of prefrontal transcranial direct current stimulation on heart rate variability and salivary cortisol.

2012 May

Recent evidence has supported the notion that the hypothalamic-pituitary-adrenal (HPA) and the sympatho-adreno-medullary (SAM) systems are modulated by cortical structures such as the prefrontal cortex. This top-down modulation may play a major role in the neuroendocrine changes associated with stressful events. We aimed to investigate further this hypothesis by modulating directly prefrontal cortex excitability using transcranial direct current stimulation (tDCS) - a non-invasive, neuromodulatory tool that induces polarity-dependent changes in cortical excitability - and measuring effects on salivary cortisol and heart rate variability as proxies of the HPA and SAM systems. Twenty healthy participants with no clinical and neuropsychiatric conditions were randomized to receive bifrontal tDCS (left anodal/right cathodal or left cathodal/right anodal) or sham stimulation, in a within-subject design. During each stimulation session, after a resting period, subjects were shown images with neutral or negative valence. Our findings showed that excitability enhancing left anodal tDCS induced a decrease in cortisol levels. This effect is more pronounced during emotional negative stimuli. Moreover, vagal activity was higher during left anodal tDCS and emotional negative stimuli, as compared to sham stimulation and neutral images. We also observed an association between higher mood scores, higher vagal activation and lower cortisol levels for anodal stimulation. Subjective mood and anxiety evaluation revealed no specific changes after stimulation. Our findings suggest that tDCS induced transient, polarity specific modulatory top-down effects with anodal tDCS leading to a down-regulation of HPA and SAM systems. Further research using tDCS and neuroendocrine markers should explore the mechanisms of stress regulation in healthy and clinical samples.

Psychoneuroendocrinology

Brunoni, AR; Vanderhasselt, MA; Boggio, PS; Fregni, F; Dantas, EM; Mill, JG; Lotufo, PA; Benseñor, IM


When Less Is More: Evidence for a Facilitative Cathodal tDCS Effect in Attentional Abilities.

2012 May

Many previous studies reported that the hyperpolarization of cortical neurons following cathodal stimulation (in transcranial direct current stimulation) has resulted in cognitive performance degradation. Here, we challenge this assumption by showing that cathodal stimulation will not always degrade cognitive performance. We used an attentional load paradigm in which irrelevant stimuli are processed only under low but not under high attentional load. Thirty healthy participants were randomly allocated into three interventional groups with different brain stimulation parameters (active anodal posterior parietal cortex [PPC], active cathodal PPC, and sham). Cathodal but not anodal stimulation enabled flanker processing even in high-loaded scenes. A second experiment was carried out to assert whether the improved flanker processing under cathodal stimulation is because of altered attention allocation between center and surround or, alternatively, enhanced attentional resources. In this experiment, the flanker was presented centrally. The results of Experiment 2 replicated Experiment 1's finding of improved flanker processing. We interpret the results from these two experiments as evidence for the ability of cathodal stimulation to enhance attentional resources rather than simply change attention allocation between center and periphery. Cathodal stimulation in high-loaded scenes can act like a noise filter and may in fact enhance cognitive performance. This study contributes to understanding the way the PPC is engaged with attentional functions and explains the cathodal effects, which thus might lead to more efficient brain stimulation protocols.

Journal of cognitive neuroscience

Weiss, M; Lavidor, M


Modulation of Soleus H-reflex by spinal DC stimulation in humans.

2012 May

Transcranial direct current stimulation (tDCS) of the human motor cortex induces changes in excitability within cortical and spinal circuits which occur during and after the stimulation. Recently, transcutaneous spinal direct current stimulation (tsDCS) has been shown to modulate spinal conduction properties, as assessed by somatosensory-evoked potentials, and trans-synaptic properties of the spinal neurons, as tested by post-activation depression of the H reflex or by the RIII nociceptive component of the flexion reflex in the lower limb. To further explore tsDCS-induced plastic changes in spinal excitability, we examined, in a double-blind crossover randomized study, the stimulus-response curves of the Soleus H reflex before, during, at current offset and 15min after anodal, cathodal and sham tsDCS delivered at Th11 level (2.5mA, 15min, 0.071mA/cm(2), 0.064C/cm(2)) in 17 healthy subjects. Anodal tsDCS induced a progressive leftward shift of the recruitment curve of the soleus H reflex during the stimulation; the effects persisted for at least 15min after current offset. In contrast, both cathodal and sham tsDCS had no significant effects. This exploratory study provides further evidence for the use of tsDCS as an expedient, non-invasive tool to induce long-lasting plastic changes in spinal circuitry. Increased spinal excitability after anodal tsDCS may have potential for spinal neuromodulation in patients with central nervous system lesions.

Journal of neurophysiology

Lamy, JC; Ho, C; Badel, A; Arrigo, RT; Boakye, M


Modulation of Training by Single-Session Transcranial Direct Current Stimulation to the Intact Motor Cortex Enhances Motor Skill Acquisition of the Paretic Hand.

2012 May

BACKGROUND AND PURPOSE: Mechanisms of skill learning are paramount components for stroke recovery. Recent noninvasive brain stimulation studies demonstrated that decreasing activity in the contralesional motor cortex might be beneficial, providing transient functional improvements after stroke. The more crucial question, however, is whether this intervention can also enhance the acquisition of complex motor tasks, yielding longer-lasting functional improvements. In the present study, we tested the capacity of cathodal transcranial direct current stimulation (tDCS) applied over the contralesional motor cortex during training to enhance the acquisition and retention of complex sequential finger movements of the paretic hand.Method-Twelve well-recovered chronic patients with subcortical stroke attended 2 training sessions during which either cathodal tDCS or a sham intervention were applied to the contralesional motor cortex in a double-blind, crossover design. Two different motor sequences, matched for their degree of complexity, were tested in a counterbalanced order during as well as 90 minutes and 24 hours after the intervention. Potential underlying mechanisms were evaluated with transcranial magnetic stimulation. RESULTS: tDCS facilitated the acquisition of a new motor skill compared with sham stimulation (P=0.04) yielding better task retention results. A significant correlation was observed between the tDCS-induced improvement during training and the tDCS-induced changes of intracortical inhibition (R(2)=0.63). CONCLUSIONS: These results indicate that tDCS is a promising tool to improve not only motor behavior, but also procedural learning. They further underline the potential of noninvasive brain stimulation as an adjuvant treatment for long-term recovery, at least in patients with mild functional impairment after stroke.

Stroke; a journal of cerebral circulation

Zimerman, M; Heise, KF; Hoppe, J; Cohen, LG; Gerloff, C; Hummel, FC


The effects of transcranial direct current stimulation with visual illusion in neuropathic pain due to spinal cord injury: An evoked potentials and quantitative thermal testing study.

2012 May

BACKGROUND: Neuropathic pain (NP) is common in spinal cord injury (SCI) patients. One of its manifestations is a lowering of pain perception threshold in quantitative thermal testing (QTT) in dermatomes rostral to the injury level. Transcranial direct current stimulation (tDCS) combined with visual illusion (VI) improves pain in SCI patients. We studied whether pain relief with tDCS + VI intervention is accompanied by a change in contact heat- evoked potentials (CHEPs) or in QTT. METHODS: We examined 18 patients with SCI and NP before and after 2 weeks of daily tDCS + VI intervention. Twenty SCI patients without NP and 14 healthy subjects served as controls. We assessed NP intensity using a numerical rating scale (NRS) and determined heat and pain thresholds with thermal probes. CHEPs were recorded to stimuli applied at C4 level, and subjects rated their perception of evoked pain using NRS during CHEPs. RESULTS: Thirteen patients reported a mean decrease of 50% in the NRS for NP after tDCS + VI. Evoked pain perception was significantly higher than in the other two groups, and reduced significantly together with CHEPs amplitude after tDCS + VI with respect to baseline. Pain perception threshold was significantly lower than in the other two groups before tDCS + VI intervention, and increased significantly afterwards. CONCLUSION: Two weeks of tDCS + VI induced significant changes in CHEPs, evoked pain and heat pain threshold in SCI patients with NP. These neurophysiological tests might be objective biomarkers of treatment effects for NP in patients with SCI.

European journal of pain (London, England)

Kumru, H; Soler, D; Vidal, J; Navarro, X; Tormos, JM; Pascual-Leone, A; Valls-Sole, J


Examining Transcranial Direct-Current Stimulation (tDCS) as a Treatment for Hallucinations in Schizophrenia.

2012 May

OBJECTIVE: Some 25%-30% of patients with schizophrenia have auditory verbal hallucinations that are refractory to antipsychotic drugs. Outcomes in studies of repetitive transcranial magnetic stimulation suggest the possibility that application of transcranial direct-current stimulation (tDCS) with inhibitory stimulation over the left temporo-parietal cortex and excitatory stimulation over the left dorsolateral prefrontal cortex could affect hallucinations and negative symptoms, respectively. The authors investigated the efficacy of tDCS in reducing the severity of auditory verbal hallucinations as well as negative symptoms. METHOD: Thirty patients with schizophrenia and medication-refractory auditory verbal hallucinations were randomly allocated to receive 20 minutes of active 2-mA tDCS or sham stimulation twice a day on 5 consecutive weekdays. The anode was placed over the left dorsolateral prefrontal cortex and the cathode over the left temporo-parietal cortex. RESULTS: Auditory verbal hallucinations were robustly reduced by tDCS relative to sham stimulation, with a mean diminution of 31% (SD=14; d=1.58, 95% CI=0.76-2.40). The beneficial effect on hallucinations lasted for up to 3 months. The authors also observed an amelioration with tDCS of other symptoms as measured by the Positive and Negative Syndrome Scale (d=0.98, 95% CI=0.22-1.73), especially for the negative and positive dimensions. No effect was observed on the dimensions of disorganization or grandiosity/excitement. CONCLUSIONS: Although this study is limited by the small sample size, the results show promise for treating refractory auditory verbal hallucinations and other selected manifestations of schizophrenia.

The American journal of psychiatry

Brunelin, J; Mondino, M; Gassab, L; Haesebaert, F; Gaha, L; Suaud-Chagny, MF; Saoud, M; Mechri, A; Poulet, E


Wolf Motor Function Test for Characterizing Moderate to Severe Hemiparesis in Stroke Patients.

2012 May

Hodics TM, Nakatsuka K, Upreti B, Alex A, Smith PS, Pezzullo JC. Wolf Motor Function Test for characterizing moderate to severe hemiparesis in stroke patients. OBJECTIVE: To extend the applicability of the Wolf Motor Function Test (WMFT) to describe the residual functional abilities of moderate to severely affected stroke patients. DESIGN: Data were collected as part of 2 double-blind, sham-controlled, randomized interventional studies: the Transcranial Direct Current Stimulation (tDCS) in Chronic Stroke Recovery and the tDCS Enhanced Stroke Recovery and Cortical Reorganization. Stroke patients were evaluated with the upper extremity Fugl-Meyer (UFM) and the WMFT in the same setting before treatment. SETTING: University inpatient rehabilitation and outpatient clinic. PARTICIPANTS: Stroke patients (N=32) with moderate to severe hemiparesis enrolled in the tDCS in Chronic Stroke Recovery and the tDCS Enhanced Stroke Recovery and Cortical Reorganization studies. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: WMFT scores were calculated using (1) median performance times and (2) a new calculation using the mean rate of performance. We compared the distribution of values from the 2 methods and examined the WMFT-UFM correlation for the traditional and the new calculation. RESULTS: WMFT rate values were more evenly distributed across their range than median WMFT time scores. The association between the WMFT rate and UFM was as good as the association between the median WMFT time scores and UFM (Spearman ρ, .84 vs -.79). CONCLUSIONS: The new WMFT mean rate of performance is valid and a more sensitive measure in describing the functional activities of the moderate to severely affected upper extremity of stroke subjects and avoids the pitfalls of the median WMFT time calculations.

Archives of physical medicine and rehabilitation

Hodics, TM; Nakatsuka, K; Upreti, B; Alex, A; Smith, PS; Pezzullo, JC


Modulation of affective symptoms and resting state activity by brain stimulation in a treatment-resistant case of obsessive-compulsive disorder.

2012 May

The effect of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) on psychopathological symptoms and resting state brain activity was assessed in a patient with obsessive-compulsive disorder (OCD). tDCS and rTMS had no effect on OC symptoms. tDCS, however, improved depression and anxiety. Functional magnetic resonance imaging at baseline showed an interhemispheric asymmetry with hyperactivation of the left and hypoactivation of the right anterior neural circuits. A reduction of interhemispheric imbalance was detected after tDCS but not after rTMS. tDCS seems to be more effective than rTMS in restoring interhemispheric imbalance and improving anxiety and depression in OCD.

Neurocase

Volpato, C; Piccione, F; Cavinato, M; Duzzi, D; Schiff, S; Foscolo, L; Venneri, A


Anodal tDCS of dorsolateral prefontal cortex during an Implicit Association Test.

2012 May

Anodal stimulation of dorsolateral prefrontal cortex by transcranial Direct Current Stimulation (tDCS) has been shown to enhance performance on working memory tasks. However, it is not yet known precisely which aspects of working memory - a broad theoretical concept including short-term memory and various executive functions - are involved in such effects. In the current study, we aimed to determine whether tDCS would reduce bias effects on an Implicit Association Test, in which subjects must respond either congruently or incongruently to pre-existing evaluative associations. Such biases reflect a conflict between automatic associations and executive function, and tDCS was hypothesized to cause a shift in this balance in favor of executive function. The results clearly contradicted this hypothesis: tDCS did improve reaction times, but in the congruent rather than incongruent mapping condition. We conclude that DLPFC tDCS does not directly improve the ability to overcome bias; previous findings concerning working memory enhancement appear to reflect effects on a different component of executive function.

Neuroscience letters

Gladwin, TE; den Uyl, TE; Wiers, RW


The tDCS effect on alpha brain oscillation for correct vs. incorrect object use. The contribution of the left DLPFC.

2012 May

Representation of the instrumentally incorrect use of an object was explored in the present research taking into account the role of the dorsolateral prefrontal cortex (DLPFC). Specifically the "inhibitory" effect performed by tDCS (transcranial Direct Current Stimulation) on DLPFC was analyzed by measuring alpha frequency band modulation when subjects processed congruous/incongruous object-related action. Thirty-four subjects performed the congruence detection task within a dynamic context (a sequence of four action frames), where the final one could be congruous or incongruous. The stimulation effect (cathode applied on the DLPFC and anode on the control site) was analyzed comparing the RTs (response times) and alpha modifications before and after the stimulation. A significant alpha increasing was found for incongruous actions in case of cathodic stimulation of DLPFC compared with the pre-stimulation condition. Moreover, RTs showed a significant reduction in response to incongruous condition after tDCS stimulation. It was suggested that the inhibition of DLPFC may limit the "incongruence effect" induced by the semantic anomaly. Secondly, the contribution of the frontal area for the semantic processing of action was demonstrated. Finally, tDCS influence on cortical oscillations was largely supported, showing alpha modulation induced by DLPFC inhibition.

Neuroscience letters

Balconi, M; Vitaloni, S


Effects of motor cortex modulation and descending inhibitory systems on pain thresholds in healthy subjects.

2012 May

Pain modulation can be achieved using neuromodulatory tools that influence various levels of the nervous system. Transcranial direct current stimulation (tDCS), for instance, has been shown to reduce chronic pain when applied to the primary motor cortex. In contrast to this central neuromodulatory technique, diffuse noxious inhibitory controls (DNIC) refers to endogenous analgesic mechanisms that decrease pain following the introduction of heterotopic noxious stimuli. We examined whether combining top-down motor cortex modulation using anodal tDCS with a bottom-up DNIC induction paradigm synergistically increases the threshold at which pain is perceived. The pain thresholds of 15 healthy subjects were assessed before and after administration of active tDCS, sham tDCS, cold-water-induced DNIC, and combined tDCS and DNIC. We found that both tDCS and the DNIC paradigm significantly increased pain thresholds and that these approaches appeared to have additive effects. Increase in pain threshold following active tDCS was positively correlated with baseline N-acetylaspartate in the cingulate cortex and negatively correlated with baseline glutamine levels in the thalamus as measured by magnetic resonance spectroscopy. These results suggest that motor cortex modulation may have a greater analgesic effect when combined with bottom-up neuromodulatory mechanisms, presenting new avenues for modulation of pain using noninvasive neuromodulatory approaches. PERSPECTIVE: This article demonstrates that both noninvasive motor cortex modulation and a descending noxious inhibitory controls paradigm significantly increase pain thresholds in healthy subjects and appear to have an additive effect when combined. These results suggest that existing pain therapies involving DNIC may be enhanced through combination with noninvasive brain stimulation.

The journal of pain : official journal of the American Pain Society

Reidler, JS; Mendonca, ME; Santana, MB; Wang, X; Lenkinski, R; Motta, AF; Marchand, S; Latif, L; Fregni, F


Brain stimulation in the treatment of chronic neuropathic and non-cancerous pain.

2012 May

Chronic neuropathic pain is one of the most prevalent and debilitating disorders. Conventional medical management, however, remains frustrating for both patients and clinicians owing to poor specificity of pharmacotherapy, delayed onset of analgesia and extensive side effects. Neuromodulation presents as a promising alternative, or at least an adjunct, as it is more specific in inducing analgesia without associated risks of pharmacotherapy. Here, we discuss common clinical and investigational methods of neuromodulation. Compared to clinical spinal cord stimulation (SCS), investigational techniques of cerebral neuromodulation, both invasive (deep brain stimulation [DBS] and motor cortical stimulation [MCS]) and noninvasive (repetitive transcranial magnetic stimulation [rTMS] and transcranial direct current stimulation [tDCS]), may be more advantageous. By adaptively targeting the multidimensional experience of pain, subtended by integrative pain circuitry in the brain, including somatosensory and thalamocortical, limbic and cognitive, cerebral methods may modulate the sensory-discriminative, affective-emotional and evaluative-cognitive spheres of the pain neuromatrix. Despite promise, the current state of results alludes to the possibility that cerebral neuromodulation has thus far not been effective in producing analgesia as intended in patients with chronic pain disorders. These techniques, thus, remain investigational and off-label. We discuss issues implicated in inadequate efficacy, variability of responsiveness, and poor retention of benefit, while recommending design and conceptual refinements for future trials of cerebral neuromodulation in management of chronic neuropathic pain. PERSPECTIVE: This critical review focuses on factors contributing to poor therapeutic utility of invasive and noninvasive brain stimulation in the treatment of chronic neuropathic and pain of noncancerous origin. Through key clinical trial design and conceptual refinements, retention and consistency of response may be improved, potentially facilitating the widespread clinical applicability of such approaches.

The journal of pain : official journal of the American Pain Society

Plow, EB; Pascual-Leone, A; Machado, A


Cerebellar modulation of human associative plasticity.

2012 May

Paired associative stimulation (PAS) is a method commonly used in human studies of motor cortex synaptic plasticity. It involves repeated pairs of electrical stimuli to the median nerve and transcranial magnetic stimulation (TMS) of the motor cortex. If the interval between peripheral and TMS stimulation is around 21–25 ms, corticospinal excitability is increased for the following 30–60 min via a long term potentiation (LTP)-like effect within the primary motor cortex. Previous work has shown that PAS depends on the present and previous levels of activity in cortex, and that it can be modified by motor learning or attention. Here we show that simultaneous transcranial direct current stimulation (TDCS; 2 mA) over the cerebellum can abolish the PAS effect entirely. Surprisingly, the effect is seen when the PAS interval is 25 ms but not when it is 21.5 ms. There are two implications from this work. First, the cerebellum influences PAS effects in motor cortex; second, LTP-like effects of PAS have at least two different mechanisms. The results are relevant for interpretation of pathological changes that have been reported in response to PAS in people with movement disorders and to changes in healthy individuals following exercise or other interventions.

The Journal of physiology

Hamada, M; Strigaro, G; Murase, N; Sadnicka, A; Galea, JM; Edwards, MJ; Rothwell, JC


Functional improvement and neuroplastic effects of anodal transcranial direct current stimulation (tDCS) delivered 1 day vs. 1 week after cerebral ischemia in rats.

2012 May

Transcranial direct current stimulation (tDCS) is an emerging tool for improving recovery from stroke. However, there has been no trial to determine whether it has a therapeutic benefit in the early stage of cerebral ischemia, and there is no consensus on the optimal time window of stimulation. Here, we described the effects of anodal tDCS in early cerebral ischemia, assessing functional improvements and changes in neuronal plasticity, and identifying the optimal time window for delivering tDCS to maximize functional gains. Thirty rats were randomly assigned to three groups: sham (n=10); early tDCS (ET), receiving tDCS 1day after ischemia for 5 days (n=10), and late tDCS (LT), receiving tDCS 1 week after ischemia for 5 days (n=10). Both ET and LT groups showed improved Barnes maze performance and motor behavioral index scores. However, only the LT group exhibited improvement in beam balance test. Immunohistochemical stainings showed that the ET group reinforced notable MAP-2 expression and the LT group enhanced mainly the level of GAP-43 in both peri-lesional and contralesional cortex. These immunohistochemical results had significant correlation with behavioral and cognitive functions. However, brain MRI and (1)H MRS showed no significant differences among the three groups in ischemic volume and metabolic alteration. These results suggest that anodal tDCS has the potential to modulate neural plasticity around the ischemic penumbra and even in the contralesional area without aggravating infarction volume and metabolic alteration. The degree of functional improvement was slightly greater when tDCS was applied 1 week rather than 1 day after ischemic injury.

Brain research

Yoon, KJ; Oh, BM; Kim, DY


Brain stimulation enables the solution of an inherently difficult problem.

2012 May

Certain problems are inherently difficult for the normal human mind. Yet paradoxically they can be effortless for those with an unusual mind. We discovered that an atypical protocol for non-invasive brain stimulation enabled the solution of a problem that was previously unsolvable. The majority of studies over the last century find that no participants can solve the nine-dot problem - a fact we confirmed. But with 10 min of right lateralising transcranial direct current stimulation (tDCS), more than 40% of participants did so. Specifically, whereas no participant solved this extremely difficult problem before stimulation or with sham stimulation, 14 out of 33 participants did so with cathodal stimulation of the left anterior temporal lobe together with anodal stimulation of the right anterior temporal lobe. This finding suggests that our stimulation paradigm might be helpful for mitigating cognitive biases or dealing with a broader class of tasks that, although deceptively simple, are nonetheless extremely difficult due to our cognitive makeup.

Neuroscience letters

Chi, RP; Snyder, AW


Developing Patient-Centered Treatment Protocols in Brain Stimulation: A Rationale for Combining Quantitative and Qualitative Approaches in Persons With HIV.

2012 May

This article reports and discusses how quantitative (physiological and behavioral) and qualitative methods are being combined in an open-label pilot feasibility study. The study evaluates safety, tolerability, and acceptability of a protocol to treat depression in HIV-infected individuals, using a 2-week block of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex. Major depressive disorder (MDD) is the second most prevalent psychiatric disorder after substance abuse among HIV-positive adults, and novel antidepressant treatments are needed for this vulnerable population. The authors describe the challenges and contributions derived from different research perspectives and methodological approaches and provide a philosophical framework for combining quantitative and qualitative measurements for a fuller examination of the disorder. Four methodological points are presented: (1) the value of combining quantitative and qualitative approaches; (2) the need for context-specific measures when studying patients with medical and psychiatric comorbidities; (3) the importance of research designs that integrate physiological, behavioral, and qualitative approaches when evaluating novel treatments; and (4) the need to explore the relationships between biomarkers, clinical symptom assessments, patient self-evaluations, and patient experiences when developing new, patient-centered protocols. The authors conclude that the complexity of studying novel treatments in complex and new patient populations requires complex research designs to capture the richness of data that inform translational research.

Journal of the American Psychiatric Nurses Association

Rosedale, M; Malaspina, D; Malamud, D; Strauss, SM; Horne, JD; Abouzied, S; Cruciani, RA; Knotkova, H


Clinical Applications of Noninvasive Electrical Stimulation: Problems and Potential.

2012 Apr

Both transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) can produce lasting aftereffects on cortical function that are thought to be due to the initial stages of synaptic potentiation/depression. They can also interact with processes of normal learning to increase or decrease the rate of learning and retention. These features have spurred a number of investigators to test whether there is any clinical therapeutic potential for the methods to improve recovery of function after damage to the brain by injury or disease. The only condition where there is sufficient evidence is in certain forms of depression where excitatory rTMS is a recommended treatment protocol; there is insufficient evidence for any other condition. The problem facing investigators is the variety of possible paradigms that can be applied. Particularly for TDCS, only a small range of possible parameters has been tested, even in healthy volunteers; in addition, it is unclear whether stimulation should be applied at the same time as a behavioral therapy or whether stimulation should be applied at rest. Present trials give some evidence that can be used to address these questions, but until they are answered more securely it will be difficult to reach a consensus about "standard" protocols that can then be tested widely in multicenter trials.

Clinical EEG and neuroscience : official journal of the EEG and Clinical Neuroscience Society (ENCS)

Rothwell, JC


Translational application of neuromodulation of decision-making.

2012 Apr

Recent cognitive neuroscience studies indicate that noninvasive brain stimulation can modulate a wide spectrum of behaviors in healthy individuals. Such modulation of behaviors provides novel insights into the fundamentals and neurobiology of cognitive functions in the healthy brain, but also suggests promising prospects for translational applications into clinical populations. One type of behavior that can be modulated with noninvasive brain stimulation is decision-making. For instance, brain stimulation can induce more cautious or riskier behaviors. The capacity of influencing processes involved in decision-making is of particular interest because such processes are at the core of human social and emotional functioning (or dysfunctioning). We review cognitive neuroscience studies that have successfully modulated processes involved in decision-making with transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS), including risk taking, reward seeking, impulsivity, and fairness consideration. We also discuss potential clinical relevance of these findings for patients who have still unmet therapeutic need and whose alterations in decision-making represent hallmarks of their clinical symptomatology, such as individuals with addictive disorders.

Brain stimulation

Levasseur-Moreau, J; Fecteau, S


tDCS-Induced Analgesia and Electrical Fields in Pain-Related Neural Networks in Chronic Migraine.

2012 Apr

Objective.- We investigated in a sham-controlled trial the analgesic effects of a 4-week treatment of transcranial direct current stimulation (tDCS) over the primary motor cortex in chronic migraine. In addition, using a high-resolution tDCS computational model, we analyzed the current flow (electric field) through brain regions associated with pain perception and modulation. Methods.- Thirteen patients with chronic migraine were randomized to receive 10 sessions of active or sham tDCS for 20 minutes with 2 mA over 4 weeks. Data were collected during baseline, treatment and follow-up. For the tDCS computational analysis, we adapted a high-resolution individualized model incorporating accurate segmentation of cortical and subcortical structures of interest. Results.- There was a significant interaction term (time vs group) for the main outcome (pain intensity) and for the length of migraine episodes (ANOVA, P < .05 for both analyses). Post-hoc analysis showed a significant improvement in the follow-up period for the active tDCS group only. Our computational modeling studies predicted electric current flow in multiple cortical and subcortical regions associated with migraine pathophysiology. Significant electric fields were generated, not only in targeted cortical regions but also in the insula, cingulate cortex, thalamus, and brainstem regions. Conclusions.- Our findings give preliminary evidence that patients with chronic migraine have a positive, but delayed, response to anodal tDCS of the primary motor cortex. These effects may be related to electrical currents induced in pain-related cortical and subcortical regions.

Headache

Dasilva, AF; Mendonca, ME; Zaghi, S; Lopes, M; Dossantos, MF; Spierings, EL; Bajwa, Z; Datta, A; Bikson, M; Fregni, F


Task-specific facilitation of cognition by cathodal transcranial direct current stimulation of the cerebellum.

2012 Apr

A role for the cerebellum in cognition is controversial, but it is a view that is becoming increasingly popular. The aim of the current study was to investigate this issue using transcranial Direct Current Stimulation (tDCS) during two cognitive tasks that require comparable motor skills, but different levels of working memory and attention. Three groups of twenty-two participants each performed the Paced Auditory Serial Addition Task (PASAT) and a novel variant of this task called the Paced Auditory Serial Subtraction Task (PASST), together with a verb generation task and its two controls, before and after the modulation of cortico-cerebellar connectivity using anodal or cathodal tDCS over the cerebellum. Participants' performance in the difficult PASST task significantly improved after cathodal stimulation compared to sham or anodal stimulation. Improvement in the easier PASAT was equal across all three stimulation conditions. Improvement in verbal response latencies were also greatest during the PASST task after cathodal stimulation, compared to sham and anodal stimulation, and became less variable. Results for the verb generation task complimented those for the PASST, such that the rate and consistency of participants' verbal responses were facilitated by cathodal stimulation, compared to sham and anodal stimulation. These findings suggest that DC stimulation over the right cerebellum affects working memory and attention differently depending on task difficulty. They support a role for the cerebellum in cognitive aspects of behaviour, whereby activity in the prefrontal cortex is likely dis-inhibited by cathodal tDCS stimulation over the right cerebellar cortex, which normally exerts an overall inhibitory tone on the cerebral cortex. We speculate that the cerebellum is capable of releasing cognitive resources by dis-inhibition of prefrontal regions of cerebral cortex, enhancing performance when tasks become demanding.

Brain stimulation

Pope, PA; Miall, RC

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Brain stimulation and inhibitory control.

2012 Apr

Inhibitory control mechanisms are important in a range of behaviours to prevent execution of motor acts which, having been planned, are no longer necessary or appropriate. Examples of this can be seen in a range of sports, such as cricket and baseball, where the choice between execution and inhibition of a bat swing must be made in a very brief time window. Deficits in inhibitory control have been associated with problems in behavioural regulation in impulsive violence as well as a range of clinical disorders. The roles of various areas, including the frontal eye fields (FEF), the pre-supplementary motor area (pre-SMA) and the inferior frontal gyrus, in inhibitory control have been investigated using an inhibitory control task and both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Typically effects on response inhibition but no effects on response generation have been seen. The contributions of these areas to performance seem to differ with, for example, pre-SMA being involved when the task is relatively novel whereas this is not the case for FEF. The findings from brain stimulation studies offer both insight into which areas are necessary for effective inhibitory control and recent extension of findings for the role of the inferior frontal gyrus illustrate how the specific functions by which these areas contribute may be further clarified. Future work, including making use of the temporal specificity of TMS and combination of TMS/tDCS with other neuroimaging techniques, may further clarify the nature and functions played by the network of areas involved in inhibitory control.

Brain stimulation

Juan, CH; Muggleton, NG


Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits.

2012 Apr

Transcranial direct-current stimulation (tDCS) is a noninvasive brain stimulation technique that has been successfully applied for modulation of cortical excitability. tDCS is capable of inducing changes in neuronal membrane potentials in a polarity-dependent manner. When tDCS is of sufficient length, synaptically driven after-effects are induced. The mechanisms underlying these after-effects are largely unknown, and there is a compelling need for animal models to test the immediate effects and after-effects induced by tDCS in different cortical areas and evaluate the implications in complex cerebral processes. Here we show in behaving rabbits that tDCS applied over the somatosensory cortex modulates cortical processes consequent to localized stimulation of the whisker pad or of the corresponding area of the ventroposterior medial (VPM) thalamic nucleus. With longer stimulation periods, poststimulation effects were observed in the somatosensory cortex only after cathodal tDCS. Consistent with the polarity-specific effects, the acquisition of classical eyeblink conditioning was potentiated or depressed by the simultaneous application of anodal or cathodal tDCS, respectively, when stimulation of the whisker pad was used as conditioned stimulus, suggesting that tDCS modulates the sensory perception process necessary for associative learning. We also studied the putative mechanisms underlying immediate effects and after-effects of tDCS observed in the somatosensory cortex. Results when pairs of pulses applied to the thalamic VPM nucleus (mediating sensory input) during anodal and cathodal tDCS suggest that tDCS modifies thalamocortical synapses at presynaptic sites. Finally, we show that blocking the activation of adenosine A1 receptors prevents the long-term depression (LTD) evoked in the somatosensory cortex after cathodal tDCS.

Proceedings of the National Academy of Sciences of the United States of America

Márquez-Ruiz, J; Leal-Campanario, R; Sánchez-Campusano, R; Molaee-Ardekani, B; Wendling, F; Miranda, PC; Ruffini, G; Gruart, A; Delgado-García, JM

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Enhancing cognitive control components of insight problems solving by anodal tDCS of the left dorsolateral prefrontal cortex.

2012 Apr

Executive functions play a vital role in semantic processing. Recently, transcranial direct current stimulation (tDCS) over frontal regions associated with cognitive control has been found to enhance verbal insight problem solving. The aim of the current study was to extend our understanding of the cognitive control processes modulating verbal insight problem solving.Anodal stimulation over the left Dorsolateral Prefrontal Cortex (DLPFC) was predicted to improve performance in solving insight problems. Particularly, it was expected that this effect would be focused on solution recognition, which is hypothesized to be directly related to control processes, and would be more pronounced for difficult problems, hypothesized to require more cognitive demand. Moreover, we predicted that this effect would be modulated by approach motivation tendencies, due to cognition and motivation interactions in the DLPFC.21 participants performed a verbal insight problem task twice, once under active anodal tDCS over the left DLPFC and once under sham stimulation, with a one week interval between sessions. Participants had 7 s to generate a solution for each problem, and then were requested to indicate whether a target word was the correct solution or not.Stimulation significantly enhanced solution recognition for difficult problems. This effect was modulated by trait motivation, i.e. was larger for participants with lower approach motivation. No effects were found for easy problems, or solution generation.Left DLPFC executive control modulates semantic processing of verbal insight problems. The observed synergy between language, cognition and motivation carries theoretical implication as well as practical consideration for future stimulation research.

Brain stimulation

Metuki, N; Sela, T; Lavidor, M


tDCS possibly stimulates glial cells.

2012 Apr

OBJECTIVE: Explore the possibility that transcranial direct current stimulation (tDCS) of the brain affects glial cells. METHODS: Cable theory is used to estimate roughly transmembrane potential in neurons and glial cells. tDCS is additionally compared to neuronal stimulation techniques for which the mechanisms are well known. RESULTS: Theoretical calculations indicated that tDCS can affect the glial transmembrane potential. The change is similar to what is physiologically observed in astrocytes during neuronal activation. In neurons, transmembrane potential changes are much weaker than the threshold for eliciting action potentials. CONCLUSIONS: Based on simplified cable theory, tDCS may affect glial cells' transmembrane potential and thereby the balance of neurotransmitters. No physiological evidence or proof is available, however. SIGNIFICANCE: It is an exciting possibility that tDCS could manipulate glial cells because they are active participants in brain function, and have multiple essential roles in the human brain. This approach may change greatly the therapeutic potential of tDCS, and also affects the safety considerations.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Ruohonen, J; Karhu, J


Evaluation of local electric fields generated by transcranial direct current stimulation with an extracephalic reference electrode based on realistic 3D body modeling.

2012 Apr

In this study, local electric field distributions generated by transcranial direct current stimulation (tDCS) with an extracephalic reference electrode were evaluated to address extracephalic tDCS safety issues. To this aim, we generated a numerical model of an adult male human upper body and applied the 3D finite element method to electric current conduction analysis. In our simulations, the active electrode was placed over the left primary motor cortex (M1) and the reference electrode was placed at six different locations: over the right temporal lobe, on the right supraorbital region, on the right deltoid, on the left deltoid, under the chin, and on the right buccinator muscle. The maximum current density and electric field intensity values in the brainstem generated by the extracephalic reference electrodes were comparable to, or even less than, those generated by the cephalic reference electrodes. These results suggest that extracephalic reference electrodes do not lead to unwanted modulation of the brainstem cardio-respiratory and autonomic centers, as indicated by recent experimental studies. The volume energy density was concentrated at the neck area by the use of deltoid reference electrodes, but was still smaller than that around the active electrode locations. In addition, the distributions of elicited cortical electric fields demonstrated that the use of extracephalic reference electrodes might allow for the robust prediction of cortical modulations with little dependence on the reference electrode locations.

Physics in medicine and biology

Im, CH; Park, JH; Shim, M; Chang, WH; Kim, YH


Recovery of motor function after stroke.

2012 Apr

The human brain possesses a remarkable ability to adapt in response to changing anatomical (e.g., aging) or environmental modifications. This form of neuroplasticity is important at all stages of life but is critical in neurological disorders such as amblyopia and stroke. This review focuses upon our new understanding of possible mechanisms underlying functional deficits evidenced after adult-onset stroke. We review the functional interactions between different brain regions that may contribute to motor disability after stroke and, based on this information, possible interventional approaches to motor stroke disability. New information now points to the involvement of non-primary motor areas and their interaction with the primary motor cortex as areas of interest. The emergence of this new information is likely to impact new efforts to develop more effective neurorehabilitative interventions using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) that may be relevant to other neurological disorders such as amblyopia.

Developmental psychobiology

Sharma, N; Cohen, LG


Does anodal transcranial direct current stimulation enhance excitability of the motor cortex and motor function in healthy individuals and subjects with stroke: A systematic review and meta-analysis.

2012 Apr

The primary aim of this review is to evaluate the effects of anodal transcranial direct current stimulation (a-tDCS) on corticomotor excitability and motor function in healthy individuals and subjects with stroke. The secondary aim is to find a-tDCS optimal parameters for its maximal effects. Electronic databases were searched for studies into the effect of a-tDCS when compared to no stimulation. Studies which met the inclusion criteria were assessed and methodological quality was examined using PEDro and Downs and Black (D&B) assessment tools. Data from seven studies revealed increase in corticomotor excitability with a small but significant effect size (0.31 [0.14, 0.48], p=0.0003) in healthy subjects and data from two studies in subjects with stroke indicated significant results with moderate effect size (0.59 [0.24, 0.93], p=0.001) in favor of a-tDCS. Likewise, studies examining motor function demonstrated a small and non-significant effect (0.39 [-0.17, 0.94], p=0.17) in subjects with stroke and a large but non-significant effect (0.92 [-1.02, 2.87], p=0.35) in healthy subjects in favor of improvement in motor function. The results also indicate that efficacy of a-tDCS is dependent on current density and duration of application. A-tDCS increases corticomotor excitability in both healthy individuals and subjects with stroke. The results also show a trend in favor of motor function improvement following a-tDCS. A-tDCS is a non-invasive, cheap and easy-to-apply modality which could be used as a stand-alone technique or as an adds-on technique to enhance corticomotor excitability and the efficacy of motor training approaches. However, the small sample size of the included studies reduces the strength of the presented evidences and any conclusion in this regard should be considered cautiously.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Bastani, A; Jaberzadeh, S


Enhancing lexical ambiguity resolution by brain polarization of the right posterior superior temporal sulcus.

2012 Mar

Previous studies have reported a hemispheric asymmetry in processing dominant (e.g., paper) and subordinate (e.g., farmer) associations of ambiguous words (pen). Here we applied sham and anodal Transcranial Direct Current Stimulation (tDCS) over Wernicke's area and its right homologue to test whether we can modulate the selective hemispheric expertise in processing lexical ambiguity. Ambiguous prime words were presented followed by target words that could be associated to the dominant or subordinate meaning of the prime in a semantic relatedness task. Anodal stimulation of the right Wernicke's area significantly decreased response time (RTs) to subordinate but not dominant associations compared to sham stimulation. There was also a complementary trend of faster responses to dominant associations following anodal stimulation of Wernicke's area. The results support brain asymmetry in processing lexical ambiguity and show that tDCS can enhance complex language processing even in a sample of highly literate individuals.

Cortex; a journal devoted to the study of the nervous system and behavior

Peretz, Y; Lavidor, M


Transcranial direct current stimulation of the affected hemisphere does not accelerate recovery of acute stroke patients.

2012 Mar

Background and purpose:  Transcranial direct current stimulation (TDCS) is a potential tool to improve motor deficits in chronic stroke patients. Safety and efficacy of this procedure in acute stroke patients have not yet been addressed. Methods:  We performed in our stroke unit a single-centre randomized, double-blind, sham-controlled study to investigate safety and efficacy of anodal TDCS of the affected hemisphere in acute stroke patients. The second day from stroke onset, fifty acute stroke patients received either five-daily sessions of anodal (n = 25) at 2 mA for 20 min or sham TDCS (n = 25) to the ipsilesional primary motor cortex (M1). Motor deficit was assessed by the short form of the Fugl-Meyer motor scale (FM) and overall neurological deficit by the National Institute of Health Stroke Scale (NIHSS) at onset, at 5 days after stroke and after 3 months. Results:  No side effects were detected during either TDCS or sham. In both groups, there was a significant improvement in NIHSS and FM scores, which did not significantly differ when comparing TDCS and sham. Conclusions:  Five-daily sessions of anodal TDCS to the ipsilesional M1 appear to be safe in acute stroke patients but do not improve clinical outcome.

European journal of neurology : the official journal of the European Federation of Neurological Societies

Rossi, C; Sallustio, F; Di Legge, S; Stanzione, P; Koch, G


Neuroplasticity in cigarette smokers is altered under withdrawal and partially restituted by nicotine exposition.

2012 Mar

Nicotine improves cognitive functions by modulating neuroplasticity and cortical excitability in nonsmoking subjects. As shown recently, the positive effect of nicotine on cognition might at least partially be caused by a focusing effect of nicotine on neuroplasticity in these subjects. Concordant to this, smokers under nicotine withdrawal show reduced cognitive abilities, which are at least partially restituted by nicotine consumption. We aimed to explore the neurophysiological foundation of these effects by exploring nonfocal and focal plasticity-inducing protocols in human smokers under nicotine withdrawal and exposition. Focal, synapse-specific plasticity was induced by paired associative stimulation (PAS), while nonfocal plasticity was induced by transcranial direct current stimulation (tDCS). Each subject (12) received placebo and nicotine patches combined with one of the stimulation protocols to the primary motor cortex. Corticospinal excitability was monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. In smokers during nicotine withdrawal, facilitatory plasticity induced by tDCS and PAS was abolished, but restituted by nicotine. In contrast, excitability-diminishing plasticity was not affected by nicotine withdrawal. Under nicotine, the inhibitory aftereffects of PAS were delayed and prolonged, while the tDCS-generated excitability reduction was abolished. Thus, absent facilitatory plasticity in smokers during nicotine withdrawal is restituted by nicotine, favoring the deficit-compensating hypothesis of nicotine consumption. These results might shed further light on the proposed mechanism of nicotine on cognition and attention, which might be connected to nicotine addiction and probability of relapse in smokers.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Grundey, J; Thirugnanasambandam, N; Kaminsky, K; Drees, A; Skwirba, AC; Lang, N; Paulus, W; Nitsche, MA


Perceptual Pseudoneglect in Schizophrenia: Candidate Endophenotype and the Role of the Right Parietal Cortex.

2012 Mar

Several contributions have reported an altered expression of pseudoneglect in psychiatric disorders, highlighting the existence of an anomalous brain lateralization in affected subjects. Surprisingly, no studies have yet investigated pseudoneglect in first-degree relatives (FdR) of psychiatric patients. We investigated performance on "paper and pencil" line bisection (LB) tasks in 68 schizophrenic patients (SCZ), 42 unaffected FdR, 41 unipolar depressive patients (UP), and 103 healthy subjects (HS). A subgroup of 20 SCZ and 16 HS underwent computerized LB and mental number line bisection (MNL) tasks requiring judgment of prebisected lines and numerical intervals. Moreover, we evaluated, in a subgroup of 15 SCZ, performance on LB and MNL before and after parietal transcranial direct current stimulation (tDCS). In comparison to HS and UP, SCZ showed a systematic rightward bias on LB, partially corrected by selective right posterior parietal tDCS. Interestingly, even FdR showed a lack of pseudoneglect on LB, expressing a mean error lying in the middle between those of HS and SCZ. On the other hand, our results showed no significant difference between the performance of SCZ and HS on MNL. Both groups showed a comparable leftward bias that could not be significantly altered after left or right parietal tDCS. These findings confirm the existence of reduced lateralization in SCZ, suggesting specific impaired functioning of the right parietal lobule. Notably, we report a lack of pseudoneglect not only in SCZ but also in FdR, raising the hypothesis that an inverted laterality pattern may be considered a concrete marker of schizotypal traits.

Schizophrenia bulletin

Ribolsi, M; Lisi, G; Di Lorenzo, G; Koch, G; Oliveri, M; Magni, V; Pezzarossa, B; Saya, A; Rociola, G; Rubino, IA; Niolu, C; Siracusano, A


Transcranial direct current stimulation does neither modulate results of a quantitative sensory testing protocol nor ratings of suprathreshold heat stimuli in healthy volunteers.

2012 Mar

BACKGROUND: Transcranial direct current stimulation (tDCS) has been shown to effectively modulate cortical excitability. Several studies have suggested clinical efficacy in pain syndromes such as central neuropathic pain or fibromyalgia. However, little is known regarding tDCS effects on nociception in healthy volunteers. METHODS: In the present study, we examined the effects of anodal, cathodal and sham stimulation of the left primary motor cortex in 17 healthy volunteers on modalities of a comprehensive quantitative sensory testing protocol (including thermal and mechanoreceptive detection and pain thresholds) and on a repetitive heat pain paradigm mimicking clinical pain. The study was conducted in a single-blind crossover fashion. tDCS was applied at 1 mA for 15 min. RESULTS: We could not detect any relevant modulation of somatosensory and pain variables in quantitative sensory testing. In addition, no significant alteration of enhanced pain ratings to repetitive noxious heat stimuli (heat hyperalgesia) was found. CONCLUSION: As pain processing in chronic pain patients might differ, tDCS could exert its antinociceptive effects depending on the activation level of the nociceptive system.

European journal of pain (London, England)

Jürgens, TP; Schulte, A; Klein, T; May, A


Low-Frequency Repetitive TMS Plus Anodal Transcranial DCS Prevents Transient Decline in Bimanual Movement Induced by Contralesional Inhibitory rTMS After Stroke.

2012 Mar

BACKGROUND: Low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected motor cortex may improve motor function of the paretic hand after stroke. However, low-frequency rTMS might adversely affect bimanual movement by decreasing transcallosal function. OBJECTIVE: The authors investigated whether combined administration of rTMS and transcranial direct current stimulation (tDCS) prevents deterioration of bimanual movement induced by low-frequency rTMS over the unaffected hemisphere. METHODS: A total of 27 participants with chronic subcortical stroke were randomly assigned to receive either 1 Hz rTMS over the unaffected hemisphere, anodal tDCS over the affected hemisphere, or a combination of rTMS and tDCS. All patients performed a pinching motor-training task after stimulation. Bimanual movement and transcallosal inhibition (TCI) were evaluated after stimulation. RESULTS: rTMS and rTMS-tDCS enhanced the motor training effect on the paretic hand. rTMS decreased bimanual coordination and reduced TCI from the unaffected to the affected hemisphere (TCI(unaff-aff)). rTMS-tDCS changed TCI balance of both hemispheres but did not affect bimanual coordination or TCI(unaff-aff). The change in bimanual coordination was negatively correlated with TCI(unaff-aff). Following stimulation, improvement in the pinch force in the paretic hand was negatively correlated with TCI balance. CONCLUSIONS: Inhibitory rTMS over the unaffected hemisphere transiently caused deterioration of bimanual movements for the current task in stroke patients. This short-term decline was prevented by combined administration of low-frequency rTMS over the unaffected hemisphere and anodal tDCS over the affected hemisphere. These responses to bihemispheric stimulation suggest possible caution and opportunities for the rehabilitation of hand function after stroke.

Neurorehabilitation and neural repair

Takeuchi, N; Tada, T; Matsuo, Y; Ikoma, K


Direct-current-dependent shift of theta-burst-induced plasticity in the human motor cortex.

2012 Mar

Animal studies using polarising currents have shown that induction of synaptic long-term potentiation (LTP) and long-term depression (LTD) by bursts of patterned stimulation is affected by the membrane potential of the postsynaptic neurone. The aim of the present experiments was to test whether it is possible to observe similar phenomena in humans with the aim of improving present protocols of inducing synaptic plasticity for therapeutic purposes. We tested whether the LTP/LTD-like after effects of transcranial theta-burst stimulation (TBS) of human motor cortex, an analogue of patterned electrical stimulation in animals, were affected by simultaneous transcranial direct-current stimulation (tDCS), a non-invasive method of polarising cortical neurones in humans. Nine healthy volunteers were investigated in a single-blind, balanced cross-over study; continuous TBS (cTBS) was used to introduce LTD-like after effects, whereas intermittent TBS (iTBS) produced LTP-like effects. Each pattern was coupled with concurrent application of tDCS (<200 s, anodal, cathodal, sham). Cathodal tDCS increased the response to iTBS and abolished the effects of cTBS. Anodal tDCS changed the effects of cTBS towards facilitation, but had no impact on iTBS. Cortical motor thresholds and intracortical inhibitory/facilitatory networks were not altered by any of the stimulation protocols. We conclude that the after effects of TBS can be modulated by concurrent tDCS. We hypothesise that tDCS changes the membrane potential of the apical dendrites of cortical pyramidal neurones and that this changes the response to patterned synaptic input evoked by TBS. The data show that it may be possible to enhance LTP-like plasticity after TBS in the human cortex.

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Hasan, A; Hamada, M; Nitsche, MA; Ruge, D; Galea, JM; Wobrock, T; Rothwell, JC

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Effect of Stimulation Polarity of Transcranial Direct Current Stimulation on Non-dominant Hand Function.

2012 Feb

To evaluate motor excitability and hand function on the non-dominant side according to the polarity of transcranial direct current stimulation (tDCS) on the motor cortex in a healthy person.tDCS was applied to the hand motor cortex for 15 minutes at an intensity of 1 mA in 28 healthy right-handed adults. Subjects were divided randomly into four groups: an anodal tDCS of the non-dominant hemisphere group, a cathodal tDCS of the non-dominant hemisphere group, an anodal tDCS of the dominant hemisphere group, and a sham group. We measured the motor evoked potential (MEP) in the abductor pollicis brevis and Jabsen-Taylor hand function test (JTT) in the non-dominant hand prior to and following tDCS. All study procedures were done under double-blind design.There was a significant increase in the MEP amplitude and a significant improvement in the JTT in the non-dominant hand following anodal tDCS of the non-dominant hemisphere (p<0.05). But there was no change in JTT and a significant decrease in the MEP amplitude in the non-dominant hand following cathodal tDCS on the non-dominant hemisphere and anodal tDCS of the dominant hemisphere.Non-dominant hand function is improved by increased excitability of the motor cortex. Although motor cortex excitability is decreased in a healthy person, non-dominant hand function is maintained. A homeostatic mechanism in the brain might therefore be involved in preserving this function. Further studies are warranted to examine brain functions to clarify this mechanism.

Annals of rehabilitation medicine

Sohn, MK; Kim, BO; Song, HT

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Effects of transcranial Direct Current Stimulation (tDCS) on cortical activity: A computational modeling study.

2012 Feb

Although it is well-admitted that transcranial Direct Current Stimulation (tDCS) allows for interacting with brain endogenous rhythms, the exact mechanisms by which externally-applied fields modulate the activity of neurons remain elusive. In this study a novel computational model (a neural mass model including subpopulations of pyramidal cells and inhibitory interneurons mediating synaptic currents with either slow or fast kinetics) of the cerebral cortex was elaborated to investigate the local effects of tDCS on neuronal populations based on an in-vivo experimental study. Model parameters were adjusted to reproduce evoked potentials (EPs) recorded from the somatosensory cortex of the rabbit in response to air-puffs applied on the whiskers. EPs were simulated under control condition (no tDCS) as well as under anodal and cathodal tDCS fields. Results first revealed that a feed-forward inhibition mechanism must be included in the model for accurate simulation of actual EPs (peaks and latencies). Interestingly, results revealed that externally-applied fields are also likely to affect interneurons. Indeed, when interneurons get polarized then the characteristics of simulated EPs become closer to those of real EPs. In particular, under anodal tDCS condition, more realistic EPs could be obtained when pyramidal cells were depolarized and, simultaneously, slow (resp. fast) interneurons became de- (resp. hyper-) polarized. Geometrical characteristics of interneurons might provide some explanations for this effect.

Brain stimulation

Molaee-Ardekani, B; Márquez-Ruiz, J; Merlet, I; Leal-Campanario, R; Gruart, A; Sánchez-Campusano, R; Birot, G; Ruffini, G; Delgado-García, JM; Wendling, F


Modulation of verbal fluency networks by transcranial direct current stimulation (tDCS) in Parkinson's disease.

2012 Feb

BACKGROUND: Verbal fluency relies on the coordinated activity between left frontal and temporal areas. Patients with Parkinson's disease (PD) present phonemic and semantic fluency deficits. Recent studies suggest that transcranial direct current stimulation (tDCS) enhances adaptative patterns of brain activity between functionally connected areas. OBJECTIVE: The aim of this study was to assess the differences in the effects induced by tDCS applied to frontal and temporo-parietal areas on phonemic and semantic fluency functional networks in patients with PD. METHOD: Sixteen patients were randomized to receive tDCS to left dorsolateral prefrontal cortex (DLPFC) and left temporo-parietal cortex (TPC) in a counterbalanced order. Immediately following stimulation, patients underwent a verbal fluency paradigm inside a fMRI scanner. Changes induced by tDCS in activation and deactivation task-related pattern networks were studied using free-model independent component analyses (ICA). RESULTS: Functional connectivity in verbal fluency and deactivation task-related networks was significantly more enhanced by tDCS to DLPFC than to TPC. In addition, DLPFC tDCS increased performance on the phonemic fluency task, after adjusting for baseline phonemic performance. CONCLUSIONS: These findings provide evidence that tDCS to specific brain regions induces changes in large scale functional networks that underlay behavioural effects, and suggest that tDCS might be useful to enhance phonemic fluency in PD.

Brain stimulation

Pereira, JB; Junqué, C; Bartrés-Faz, D; Martí, MJ; Sala-Llonch, R; Compta, Y; Falcón, C; Vendrell, P; Pascual-Leone, A; Valls-Solé, J; Tolosa, E


The fade-in - Short stimulation - Fade out approach to sham tDCS - Reliable at 1 mA for naïve and experienced subjects, but not investigators.

2012 Feb

OBJECTIVE: Slowly ramping down initial current intensity after a minimal interval of stimulation is the de facto standard for sham stimulation in transcranial electrical stimulation research. The aim of this study is to further investigate the effectiveness of this method of blinding. METHODS: We have investigated the time course of the cutaneous perception during 10 min of anodal, cathodal, and sham transcranial direct current stimulation, probing the perceived strength and site of the perceived sensation. We have also utilized post-stimulation assessment and measurements of sleepiness prior to and after the intervention. Previous exposure to tDCS has also been taken into account: the experiment has been repeated in naïve and experienced subject groups, and a group consisting of investigators who use tDCS as a research tool. RESULTS: Although we have observed a general reduction in the perceived strength of the stimulation with time, we have not found the complete disappearance of the cutaneous perception during either the verum or the sham conditions. Experienced subjects were more likely to be able to differentiate between trials with stimulation and non-stimulation trials and to correctly identify sham and verum stimulation conditions. CONCLUSION: When taking only naïve and experienced subjects into account, there was no significant difference between the strength of the perceived stimulation in the verum and sham conditions. The fade-in - short stimulation - fade-out sham stimulation can be indistinguishable from verum stimulation, but not because it mimics the disappearance of the cutaneous sensations associated with the verum stimulation, but because these sensations persist also in the sham stimulation. The significance of this finding with potential confounding factors and limitations are discussed.

Brain stimulation

Ambrus, GG; Al-Moyed, H; Chaieb, L; Sarp, L; Antal, A; Paulus, W


Modulating neuronal excitability in the motor cortex with tDCS shows moderate hemispheric asymmetry due to subjects' handedness: A pilot study.

2012 Feb

Purpose: Transcranial direct current stimulation (tDCS) has proven to be a useful tool for fundamental brain research as well as for attempts in therapy of neurological and psychiatric diseases by modulating neuronal plasticity. Little is understood about the effects of tDCS are influenced by hemispheric dominance, even less in terms of handedness. The aim of our pilot study was to investigate whether tDCS induced neuroplastic changes may be different in right- and left-handed individuals due to existing differences in hemispheric lateralisation. Methods: We measured changes in motor evoked potentials (MEPs) after application of tDCS in 8 right-handers, 8 left-handers and 8 mixed-handers according to the Edinburgh Handedness Inventory (EHI). In double-blind sessions, we applied either anodal or cathodal tDCS for 5 minutes for each hemisphere. Results: While motor thresholds (MT) seem to be not influenced by handedness significantly, in right-handed subjects we reproduced the well-known effects of tDCS: anodal stimulation increased while cathodal stimulation decreased MEP amplitudes. However, left-and mixed-handed subjects differed from right-handed subjects. After anodal stimulation of the left hemisphere the increase of the MEP amplitudes was stronger in right handed subjects than in left and mixed handed subjects. Interestingly, after cathodal stimulation of the left hemisphere this difference was less marked. The stimulation of the right hemisphere showed the same tendency, but results were not significant. Conclusions: For the first time, we are able to demonstrate that the modulating effects of tDCS on corticospinal excitability differ moderately in the left-and mixed-handed population compared to right-handed subjects. The shown differences according to handedness should be taken into account in further studies.

Restorative neurology and neuroscience

Schade, S; Moliadze, V; Paulus, W; Antal, A


Temporal Profile of Functional Visual Rehabilitative Outcomes Modulated by Transcranial Direct Current Stimulation.

2012 Feb

Objectives:  We have previously reported that transcranial direct current stimulation (tDCS) delivered to the occipital cortex enhances visual functional recovery when combined with three months of computer-based rehabilitative training in patients with hemianopia. The principal objective of this study was to evaluate the temporal sequence of effects of tDCS on visual recovery as they appear over the course of training and across different indicators of visual function. Methods:  Primary objective outcome measures were 1) shifts in visual field border and 2) stimulus detection accuracy within the affected hemifield. These were compared between patients randomized to either vision restoration therapy (VRT) combined with active tDCS or VRT paired with sham tDCS. Training comprised two half-hour sessions, three times a week for three months. Primary outcome measures were collected at baseline (pretest), monthly interim intervals, and at posttest (three months). As secondary outcome measures, contrast sensitivity and reading performance were collected at pretest and posttest time points only. Results:  Active tDCS combined with VRT accelerated the recovery of stimulus detection as between-group differences appeared within the first month of training. In contrast, a shift in the visual field border was only evident at posttest (after three months of training). tDCS did not affect contrast sensitivity or reading performance. Conclusions:  These results suggest that tDCS may differentially affect the magnitude and sequence of visual recovery in a manner that is task specific to the type of visual rehabilitative training strategy employed.

Neuromodulation : journal of the International Neuromodulation Society

Plow, EB; Obretenova, SN; Jackson, ML; Merabet, LB


The neuroethics of non-invasive brain stimulation.

2012 Feb

Transcranial direct current stimulation (TDCS) is a brain stimulation tool that is portable, painless, inexpensive, apparently safe, and with potential long-term efficacy. Recent results obtained from TDCS experiments offer exciting possibilities for the enhancement and treatment of normal or impaired abilities, respectively. We discuss new neuroethical problems that have emerged from the usage of TDCS, and also focus on one of the most likely future applications of TDCS: enhancing learning and cognition in children with typical and atypical development.

Current biology : CB

Cohen Kadosh, R; Levy, N; O'Shea, J; Shea, N; Savulescu, J


Enhancement of selective attention by tDCS: Interaction with interference in a Sternberg task.

2012 Feb

Transcranial Direct Current Stimulation (tDCS) enhances performance on working memory tasks. However, such effects may be dependent on modulation of specific aspects of working memory. We therefore tested the hypothesis that tDCS improves selective attention in the context of a Sternberg task. Subjects had to maintain a memory set while responding to distracter stimuli. Probes consisted of one item from the memory set, and one item that could have been presented as a distracter. TDCS was found to improve reaction time significantly only when the incorrect choice had been a distracter stimulus. The results thus support the notion that tDCS effects on working memory might be mediated by a specific effect on selective attention.

Neuroscience letters

Gladwin, TE; den Uyl, TE; Fregni, FF; Wiers, RW


Influence of transcranial direct current stimulation of the dorsolateral prefrontal cortex on pain related emotions: A study using electroencephalographic power spectrum analysis.

2012 Feb

Pain is a multidimensional experience with sensory-discriminative, cognitive-evaluative and affective-motivational components. Emotional factors such as unpleasantness or anxiety are known to have influence on pain in humans. The aim of this single-blinded, cross over study was to evaluate the effects of transcranial direct current stimulation (tDCS) on emotional aspects of pain in pain alleviation. Fifteen subjects (5 females, 10 males) volunteered to participate in this study. In an oddball paradigm, three categories of 20 pictures (unpleasant, neutral, and pleasant) served as rare target pictures from the International Affective Picture System (IAPS). The power of the delta (1-4Hz), theta (4-8Hz), alpha (8-12Hz), beta (12-25Hz), and gamma (30-40Hz) frequency bands in the three categories were measured using electroencephalography during an oddball paradigm at pre- and post-anodal or sham tDCS above the left dorsolateral prefrontal cortex (DLPFC). Results showed that the beta band power was significantly increased, and the alpha band power was significantly decreased during unpleasant pictures after anodal tDCS compared with sham tDCS. Furthermore, regarding unpleasant pictures, subjective reports of Self Assessment Manikin (SAM) for emotional valence after anodal tDCS showed a significant decrease of unpleasantness. Therefore, emotional aspects of pain may be effectively alleviated by tDCS of the left DLPFC as was shown not only by subjective evaluation, but also by objective observation of cerebral neural activity. This processing may be mediated by facilitation of the descending pain inhibitory system through enhancing neural activity of the left DLPFC.

Neuroscience letters

Maeoka, H; Matsuo, A; Hiyamizu, M; Morioka, S; Ando, H


Enhanced locomotor adaptation after-effect in the 'broken escalator' phenomenon using anodal tDCS.

2012 Feb

The everyday experience of stepping onto a stationary escalator causes a stumble, despite our full awareness that the escalator is broken. In the laboratory, this 'broken escalator' phenomenon is reproduced when subjects step onto an obviously stationary platform (AFTER trials) that was previously experienced as moving (MOVING trials), and attests to a process of motor adaptation. Given the critical role of M1 in upper limb motor adaptation, and the potential for transcranial direct current stimulation (tDCS) to increase cortical excitability, we hypothesised that anodal tDCS over leg M1 and premotor cortices would increase the size and duration of the locomotor after-effect. Thirty healthy volunteers received either sham or real tDCS (anodal bihemispheric tDCS; 2mA for 15 minutes at rest) to induce excitatory effects over the primary motor and premotor cortex, prior to walking onto the moving platform. The real tDCS group - compared to sham - displayed larger trunk sway, and increased gait velocity in the 1st AFTER trial and a persistence of the trunk sway after-effect into the 2nd AFTER trial. We also used transcranial magnetic stimulation to probe changes in cortical leg excitability using different electrode montages and eyeblink conditioning, before and after tDCS, as well as simulating the current flow of tDCS on the human brain using a computational model of these different tDCS montages. Our data show that anodal tDCS induces excitability changes in lower limb motor cortex, with resultant enhancement of locomotor adaptation after-effects. These findings might encourage the use of tDCS over leg motor and premotor regions to improve locomotor control in patients with neurological gait disorders.

Journal of neurophysiology

Kaski, D; Quadir, S; Patel, M; Yousif, N; Bronstein, AM


Abnormal bihemispheric responses in schizophrenia patients following cathodal transcranial direct stimulation.

2012 Feb

Post-mortem and in vivo studies provide evidence for a link between reduced plasticity and dysconnectivity in schizophrenia patients. It has been suggested that the association between plasticity and connectivity contributes to the pathophysiology and symptomatology of schizophrenia. However, little is known about the impact of glutamate-dependent long-term depression (LTD)-like cortical plasticity on inter-hemispheric connectivity in schizophrenia patients. The aim of the present study was to investigate LTD-like cortical plasticity following excitability-diminishing cathodal transcranial direct current stimulation (tDCS) of the left primary motor cortex (M1) and its effects on the non-stimulated right M1. Eighteen schizophrenia patients and 18 matched (age, gender, handedness, and smoking status) control subjects were investigated in this study. Corticospinal excitability changes following tDCS and intra-cortical inhibitory circuits were monitored with transcranial magnetic stimulation. On the stimulated hemisphere, cathodal tDCS increased resting motor thresholds (RMT) in both groups and decreased motor-evoked potential (MEP) sizes in healthy controls to a greater extent compared to schizophrenia patients. On the non-stimulated hemisphere, RMTs were increased and MEPs were decreased only in the healthy control group. Our results confirm previous findings of reduced LTD-like plasticity in schizophrenia patients and offer hypothetical and indirect in vivo evidence for an association between LTD-like cortical plasticity and inter-hemispheric connectivity in schizophrenia patients. Moreover, our findings highlight the impact of plasticity on connectivity. Dysfunctional N-methyl D: -aspartate receptors or modulation of dopaminergic transmission can explain these findings. Nevertheless, the effects of antipsychotic medication still need to be considered.

European archives of psychiatry and clinical neuroscience

Hasan, A; Aborowa, R; Nitsche, MA; Marshall, L; Schmitt, A; Gruber, O; Falkai, P; Wobrock, T


Transcranial direct current stimulation treatment protocols: should stimulus intensity be constant or incremental over multiple sessions?

2012 Feb

Interest in transcranial direct current stimulation (tDCS) as a new tool in neuropsychiatry has led to the need to establish optimal treatment protocols. In an intra-individual randomized cross-over design, 11 healthy volunteers received five tDCS sessions to the left primary motor cortex on consecutive weekdays at a constant or gradually increasing current intensity, in two separate weeks of testing. Cortical excitability was assessed before and after tDCS at each session through peripheral electromyographic recordings of motor-evoked potentials. Both conditions led to significant cumulative increases in cortical excitability across the week but there were no significant differences between the two groups. Motor thresholds decreased significantly from Monday to Friday in both conditions. This study demonstrated that, in the motor cortex, administration of tDCS five times per week whether at a constant intensity or at a gradually increasing intensity was equally effective in increasing cortical excitability.

The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)

Gálvez, V; Alonzo, A; Martin, D; Loo, CK


Electric field and current density distribution in an anatomical head model during transcranial direct current stimulation for tinnitus treatment.

2012 Feb

Tinnitus is considered an auditory phantom percept. Recently, transcranial direct current stimulation (tDCS) has been proposed as a new approach for tinnitus treatment including, as potential targets of interest, either the temporal and temporoparietal cortex or prefrontal areas. This study investigates and compares the spatial distribution of the magnitude of the electric field and the current density in the brain tissues during tDCS of different brain targets. A numerical method was applied on a realistic human head model to calculate these field distributions in different brain structures, such as the cortex, white matter, cerebellum, hippocampus, medulla oblongata, pons, midbrain, thalamus, and hypothalamus. Moreover, the same distributions were evaluated along the auditory pathways. Results of this study show that tDCS of the left temporoparietal cortex resulted in a widespread diffuse distribution of the magnitude of the electric fields (and also of the current density) on an area of the cortex larger than the target brain region. On the contrary, tDCS of the dorsolateral prefrontal cortex resulted in a stimulation mainly concentrated on the target itself. Differences in the magnitude distribution were also found on the structures along the auditory pathways. A sensitivity analysis was also performed, varying the electrode position and the human head models. Accurate estimation of the field distribution during tDCS in different regions of the head could be valuable to better determine and predict efficacy of tDCS for tinnitus suppression. Bioelectromagnetics. © 2012 Wiley Periodicals, Inc.

Bioelectromagnetics

Parazzini, M; Fiocchi, S; Ravazzani, P


Oppositional transcranial direct current stimulation (tDCS) of parietal substrates of attention during encoding modulates episodic memory.

2012 Feb

Effective learning requires that attentional resources be focused on target information and withheld from irrelevant events in the learner's surroundings. This requires engagement of the brain substrates of selective attention and the concurrent disengagement of brain substrates of orienting toward changes in the environment. In the present study, we attempted to modulate activation of cortical substrates of attention during learning by physiological intervention, using transcranial direct current stimulation (tDCS). To effect adversarial modulation, we applied anodal stimulation directed toward left intraparietal sulcus/superior parietal cortex (IPS/SPL; a substrate of selective attention) and cathodal stimulation directed toward right inferior parietal cortex (IPL; a substrate of orienting). Such stimulation during study of verbal materials led to superior subsequent recognition memory relative to the opposite polarity of stimulation. To our knowledge, this is the first application of direct current stimulation to parietal regions implicated in different forms of attention in an oppositional manner in order to modulate learning in a verbal recognition memory task. Additionally, these results may have practical implications for the development of interventions to benefit persons with various types of attentional deficits.

Brain research

Jacobson, L; Goren, N; Lavidor, M; Levy, DA


Double dissociation of working memory load effects induced by bilateral parietal modulation.

2012 Feb

Transcranial magnetic stimulation and neuroimaging data have revealed bilateral posterior parietal cortex (PPC) involvement during verbal n-back working memory (WM). In this task as n (i.e., WM load) increases, subjects show poorer behavioral performance as well as greater activation of this brain area. Moreover, there is evidence that a brief period of practice or even increased familiarity with the task can improve WM performance and lead to activation changes in the PPC. The aim of this study was to investigate, using transcranial direct current stimulation (tDCS), the effects on WM load performance induced by different PPC modulation after increased familiarity with the task. After a short practice, we tested verbal WM using an n-back task (1-back vs. 2-back) before and after the application of bilateral tDCS over PPCs (left anodal-right cathodal, left cathodal-right anodal or sham). ANOVA showed a significant interaction between tDCS and task. In the 1-back task, left anodal-right cathodal modulation abolished improvement in reaction times observed in the other two modulation conditions. Conversely, in the 2-back task the same effect was observed after left cathodal-right anodal modulation relative to the other two modulation conditions. This double dissociation demonstrates either a differential engagement of each PPC or changes in the interhemispheric balance of activity across this brain region. Neuroimaging studies show parametric activation of the PPC as difficulty increases, but activation does not switch sides. Thus, our observed effects cannot be attributed to increased task difficulty, the stimuli used, or the response requirements. Rather, we suggest that these findings reflect the use of different processing strategies to perform these two tasks. In conclusion, after increased familiarity with the task, different tDCS modulations lead to changes in a task-related region depending on differences in processing strategies in 1-back vs. 2-back.

Neuropsychologia

Sandrini, M; Fertonani, A; Cohen, LG; Miniussi, C


Improving emotional prosody detection in the attending ear by cathodal tDCS suppression of the competing channel.

2012 Feb

Currently it is assumed that cathodal stimulation (in transcranial direct current stimulation, tDCS) degrades the neural firing rate, and thus it is believed to degrade cognitive performance. Here we challenge this assumption by predicting that under high competition the cathodal stimulation might act as a noise filter, leading to an improved performance. We presented auditory targets with different emotional valence using a dichotic listening paradigm. We found that cathodal, but not anodal stimulation of the right IFG generated better prosody comprehension. Cathodal stimulation in competitive situations, such as the dichotic listening paradigm, can act like a noise filter, and may in fact enhance cognitive performance. This study contributes to understanding the way the IFG is engaged with prosody functions, and explains the cathodal effects of tDCS. This might lead to the development of more efficient brain stimulation protocols.

Neuroscience letters

Alexander, T; Avirame, K; Lavidor, M


Prefrontal cortex transcranial direct current stimulation associated with aerobic exercise change aspects of appetite sensation in overweight adults.

2012 Feb

This study investigated whether transcranial direct current stimulation (tDCS) on dorsolateral prefrontal cortex (DLPFC) isolated or combined with aerobic exercise influenced the desire to eat, hunger, and satiety in overweight subjects. Nine volunteers underwent anodal or sham tDCS (2 mA; 20 min) over DLPFC and isocaloric exercise bouts (70%VO(2)R; ~200 kcal). The appetite sensations were evaluated by visual analogue scales at four moments: I - Baseline; II - After tDCS; III - Post-Exercise and IV - 30-min Post-Exercise. The tDCS on left DLPFC decreased the desire to eat at baseline (tDCS -26% vs. -14% Sham). The tDCS associated with exercise had greater suppressing effect in desire to eat compared to either tDCS or exercise alone (tDCS -39% vs. -27% Sham). Moreover, the tDCS associated with exercise decreased hunger (tDCS -48% vs. 36% Sham) and increased satiety (tDCS 28% vs. 7% Sham) immediately after exercise. The post-exercise 30-min recovery elicited an overall increase in appetite. However the increase in desire to eat and hunger after recovery was lower after tDCS (29% and 13%, respectively) compared to sham stimulation (77% and 113%, respectively). These findings in overweight subjects indicate that the combination of tDCS over DLPFC and aerobic exercise induced greater decrease in appetite sensations compared to anodal tDCS or exercise alone.

Appetite

Montenegro, RA; Okano, AH; Cunha, FA; Gurgel, JL; Fontes, EB; Farinatti, PT


A Pilot Study of the Tolerability and Effects of High-Definition Transcranial Direct Current Stimulation (HD-tDCS) on Pain Perception.

2012 Feb

Several brain stimulation technologies are beginning to evidence promise as pain treatments. However, traditional versions of 1 specific technique, transcranial direct current stimulation (tDCS), stimulate broad regions of cortex with poor spatial precision. A new tDCS design, called high definition tDCS (HD-tDCS), allows for focal delivery of the charge to discrete regions of the cortex. We sought to preliminarily test the safety and tolerability of the HD-tDCS technique as well as to evaluate whether HD-tDCS over the motor cortex would decrease pain and sensory experience. Twenty-four healthy adult volunteers underwent quantitative sensory testing before and after 20 minutes of real (n = 13) or sham (n = 11) 2 mA HD-tDCS over the motor cortex. No adverse events occurred and no side effects were reported. Real HD-tDCS was associated with significantly decreased heat and cold sensory thresholds, decreased thermal wind-up pain, and a marginal analgesic effect for cold pain thresholds. No significant effects were observed for mechanical pain thresholds or heat pain thresholds. HD-tDCS appears well tolerated, and produced changes in underlying cortex that are associated with changes in pain perception. Future studies are warranted to investigate HD-tDCS in other applications, and to examine further its potential to affect pain perception. PERSPECTIVE: This article presents preliminary tolerability and efficacy data for a new focal brain stimulation technique called high definition transcranial direct current stimulation. This technique may have applications in the management of pain.

The journal of pain : official journal of the American Pain Society

Borckardt, JJ; Bikson, M; Frohman, H; Reeves, ST; Datta, A; Bansal, V; Madan, A; Barth, K; George, MS


Treatment of chronic tinnitus with repeated sessions of prefrontal transcranial direct current stimulation: outcomes from an open-label pilot study.

2012 Feb

Tinnitus is the perception of sound in the absence of an environmental sound source. Abnormal activity in central auditory pathways is considered as the neuronal correlate of tinnitus. However, there is increasing evidence from neuroimaging studies for an additional involvement of the frontal cortex in the pathophysiology of tinnitus, especially concerning its attentional and emotional aspects. Recently, in a subgroup of tinnitus patients, temporary reduction of tinnitus intensity and tinnitus-related distress has been reported after bifrontal tDCS with the anode over the right and the cathode over the left dorsolateral prefrontal cortex (DLPFC). The aim of this study was to investigate whether repeated application of bifrontal tDCS results in longer-lasting reduction of tinnitus and may represent a potential treatment approach. Thirty-two patients with chronic and treatment-resistant tinnitus received six sessions of bifrontal tDCS (1.5 mA, 30 min, two sessions per week) with the anode over the right and the cathode over the left DLPFC. Treatment outcome was assessed with several standardized tinnitus questionnaires, numeric rating scales, and a depression scale. In the entire group, beneficial effects of bifrontal tDCS on tinnitus were found for numeric rating scores of loudness, unpleasantness, and discomfort, but not in tinnitus or depression scales. Exploratory analysis revealed an effect of gender on treatment effects with female patients demonstrating a better response in several scores. Our open-label pilot study suggests some beneficial effect of bifrontal tDCS (anode right and cathode left) in the treatment of severe tinnitus, warranting further controlled studies.

Journal of neurology

Frank, E; Schecklmann, M; Landgrebe, M; Burger, J; Kreuzer, P; Poeppl, TB; Kleinjung, T; Hajak, G; Langguth, B


Effects of transcranial direct current stimulation on pain perception and working memory.

2012 Jan

Previous studies have shown that non-invasive stimulation of the dorsolateral prefrontal cortex (DLPFC) could modulate experimentally induced pain and working memory (WM) in healthy subjects. However, the two aspects have never been assessed concomitantly. The present study was set up to investigate the effects of transcranial direct current stimulation (tDCS) of the DLPFC on thermal pain and WM in the same population of healthy volunteers. In a randomized and balanced order of different sessions separated by 1 week, 20 min of 2 mA anodal, cathodal or sham tDCS were applied to the left or right DLPFC in two separate experiments. Twelve healthy volunteers were enrolled for each stimulated hemisphere. Warm and cold detection thresholds, heat and cold pain thresholds as well as heat pain tolerance thresholds were measured before, during and following tDCS. WM was assessed by a 2-back task applied once during cortical stimulation. Anodal tDCS of the right DLPFC led to an increase of tolerance to heat pain. The 2-back task revealed fewer outliers during cathodal tDCS of the left DLPFC. The present data show an involvement of the DLPFC in the processing of pain and WM. There was no correlation between these findings, suggesting that the analgesic effects of cortical stimulation are not associated with cognitive processing. However, this conclusion is difficult to affirm because of some limitations of the study regarding the parameters of stimulation or a ceiling effect of the 2-back task for instance.

European journal of pain (London, England)

Mylius, V; Jung, M; Menzler, K; Haag, A; Khader, PH; Oertel, WH; Rosenow, F; Lefaucheur, JP


Comparison of Visual Field Training for Hemianopia With Active Versus Sham Transcranial Direct Cortical Stimulation.

2012 Jan

BACKGROUND: Vision Restoration Therapy (VRT) aims to improve visual field function by systematically training regions of residual vision associated with the activity of suboptimal firing neurons within the occipital cortex. Transcranial direct current stimulation (tDCS) has been shown to modulate cortical excitability. OBJECTIVE: Assess the possible efficacy of tDCS combined with VRT. METHODS: The authors conducted a randomized, double-blind, demonstration-of-concept pilot study where participants were assigned to either VRT and tDCS or VRT and sham. The anode was placed over the occipital pole to target both affected and unaffected lobes. One hour training sessions were carried out 3 times per week for 3 months in a laboratory. Outcome measures included objective and subjective changes in visual field, recording of visual fixation performance, and vision-related activities of daily living (ADLs) and quality of life (QOL). RESULTS: Although 12 participants were enrolled, only 8 could be analyzed. The VRT and tDCS group demonstrated significantly greater expansion in visual field and improvement on ADLs compared with the VRT and sham group. Contrary to expectations, subjective perception of visual field change was greater in the VRT and sham group. QOL did not change for either group. The observed changes in visual field were unrelated to compensatory eye movements, as shown with fixation monitoring. CONCLUSIONS: The combination of occipital cortical tDCS with visual field rehabilitation appears to enhance visual functional outcomes compared with visual rehabilitation alone. TDCS may enhance inherent mechanisms of plasticity associated with training.

Neurorehabilitation and neural repair

Plow, EB; Obretenova, SN; Fregni, F; Pascual-Leone, A; Merabet, LB


Combined Central and Peripheral Stimulation to Facilitate Motor Recovery After Stroke: The Effect of Number of Sessions on Outcome.

2012 Jan

BACKGROUND: . Proof-of-principle studies have demonstrated transient beneficial effects of transcranial direct current stimulation (tDCS) on motor function in stroke patients, mostly after single treatment sessions. OBJECTIVE: . To assess the efficacy of multiple treatment sessions on motor outcome. METHODS: The authors examined the effects of two 5-day intervention periods of bihemispheric tDCS and simultaneous occupational/physical therapy on motor function in a group of 10 chronic stroke patients. RESULTS: . The first 5-day period yielded an increase in Upper-Extremity Fugl-Meyer (UE-FM) scores by 5.9 ± 2.4 points (16.6% ± 10.6%). The second 5-day period resulted in further meaningful, although significantly lower, gains with an additional improvement of 2.3 ± 1.4 points in UE-FM compared with the end of the first 5-day period (5.5% ± 4.2%). The overall mean change after the 2 periods was 8.2 ± 2.2 points (22.9% ± 11.4%). CONCLUSION: . The results confirm the efficacy of bihemispheric tDCS in combination with peripheral sensorimotor stimulation. Furthermore, they demonstrate that the effects of multiple treatment sessions in chronic stroke patients may not necessarily lead to a linear response function, which is of relevance for the design of experimental neurorehabilitation trials.

Neurorehabilitation and neural repair

Lindenberg, R; Zhu, LL; Schlaug, G


Transcranial direct current stimulation in the treatment of major depression: a meta-analysis.

2012 Jan

BACKGROUND: So far, no comprehensive answer has emerged to the question of whether transcranial direct current stimulation (tDCS) can make a clinically useful contribution to the treatment of major depression. We aim to present a systematic review and meta-analysis of tDCS in the treatment of depression.MethodMedline and Embase were searched for open-label and randomized controlled trials of tDCS in depression using the expressions ('transcranial direct current stimulation' or 'tDCS') and ('depression' or 'depressed'). Study data were extracted with a standardized data sheet. For randomized controlled trials, effect size (Hedges' g) was calculated and the relationships between study variables and effect size explored using meta-regression. RESULTS: A total of 108 citations were screened and 10 studies included in the systematic review. Six randomized controlled trials were included in the meta-analysis, with a cumulative sample of 96 active and 80 sham tDCS courses. Active tDCS was found to be more effective than sham tDCS for the reduction of depression severity (Hedges' g=0.743, 95% confidence interval 0.21-1.27), although study results differed more than expected by chance (Q=15.52, df=6, p=0.017, I2=61.35). Meta-regression did not reveal any significant correlations. CONCLUSIONS: Our study was limited by the small number of studies included, which often had small sample size. Future studies should use larger, if possible representative, health service patient samples, and optimized protocols to evaluate the efficacy of tDCS in the treatment of depression further.

Psychological medicine

Kalu, UG; Sexton, CE; Loo, CK; Ebmeier, KP


MODULATION OF LTP AT RAT HIPPOCAMPAL CA3-CA1 SYNAPSES BY DIRECT CURRENT STIMULATION.

2012 Jan

Transcranial direct current stimulation (tDCS) can produce a lasting polarity-specific modulation of cortical excitability in the brain and it is increasingly used in experimental and clinical settings. Recent studies suggest that the after-effects of tDCS are related to molecular mechanisms of activity-dependent synaptic plasticity. Here we investigated the effect of DCS on the induction of one of the most studied N-methyl-D-aspartate (NMDA) receptor-dependent forms of long-term potentiation (LTP) of synaptic activity at CA3-CA1 synapses in the hippocampus. We show that DCS applied to rat brain slices determines a modulation of LTP, that is increased by anodal and reduced by cathodal DCS. Immediate early genes, such as c-fos and zif268 (egr1/NGFI-A/krox24), are rapidly induced following neuronal activation and a specific role of zif268 in the induction and maintenance of LTP has been demonstrated. We found that both anodal and cathodal DCS produce a marked subregion-specific increase in the expression of zif268 protein in the cornus ammonis (CA) region, while the same protocols of stimulation produce a less pronounced increase in c-fos protein expression in the CA and in dentate gyrus (DG) regions of the hippocampus. Brain derived neurotrophic factor (BDNF) expression was also investigated and it was found to be reduced in cathodal stimulated slices. The present data demonstrate that it is possible to modulate LTP by using DCS and provide the rationale for the use of DCS in neurological diseases in order to promote the adaptive and suppress the maladaptive forms of brain plasticity.

Journal of neurophysiology

Ranieri, F; Podda, MV; Riccardi, E; Frisullo, G; Dileone, M; Profice, P; Pilato, F; Di Lazzaro, V; Grassi, C


Induction of visual dream reports after transcranial direct current stimulation (tDCs) during Stage 2 sleep.

2012 Jan

REM sleep is a unique brain state characterized by frontal deactivation alongside activation of the posterior association and limbic cortices. Human brain lesion studies have found that the loss of dreaming is characterized by damage to the frontal and posterior parieto-temporo-occipital association cortex. Therefore, it is reasonable to assume that the function of these brain regions might encapsulate the neural processes of dreaming. The aim of the following two experiments was to investigate the effect of transcranial direct current stimulation (tDCs), applied simultaneously to the frontal and right posterior parietal cortex during Stage 2 sleep, on dreaming. In Experiment 1, 17 healthy participants received tDCs (cathodal-frontal, anodal-parietal) and low-intensity tDCs as well as no tDCs (blank control) during Stage 2 sleep in a counterbalanced order across the night. Dream reports were collected upon awakening after each of the three conditions. In Experiment 2, 10 participants received tDCs (cathodal-frontal, anodal-parietal), no tDCs (blank control) and two additional control conditions (reversed polarity and other-cephalic tDCs). In both experiments a significantly greater number of imagery reports were found on awakening after tDCs (cathodal-frontal, anodal-parietal), compared to the blank control conditions. However, in Experiment 2 the frequency of imagery reports from the tDCs (cathodal-frontal, anodal-parietal) was not significantly different from the other two tDC conditions, suggesting a non-specific effect of tDCs. Overall, it was concluded that tDCs (cathodal-frontal, anodal-parietal) increased the frequency of dream reports with visual imagery, possibly via a general arousing effect and/or recreating specific cortical neural activity involved in dreaming.

Journal of sleep research

Jakobson, AJ; Fitzgerald, PB; Conduit, R


Contribution of axonal orientation to pathway-dependent modulation of excitatory transmission by direct current stimulation in isolated rat hippocampus.

2012 Jan

Transcranial direct current stimulation (tDCS) is a method for modulating cortical excitability by weak constant electrical current that is applied through scalp electrodes. Although often described in terms of anodal or cathodal stimulation, depending on which scalp electrode pole is proximal to the cortical region of interest, it is the orientation of neuronal structures relative to the DC vector that determines the effect of tDCS. To investigate the contribution of neural pathway orientation, we studied DCS-mediated neuromodulation in an in vitro rat hippocampal slice preparation. We examined the contribution of dendritic orientation to the DCS neuromodulatory effect by recording field excitatory postsynaptic potentials (fEPSPs) in apical and basal dendrites of CA1 neurons within a constant DC field. In addition, we assessed the contribution of axonal orientation by recording CA1 and CA3 apical fEPSPs generated by stimulation of oppositely oriented Schaffer collateral and mossy fiber axons, respectively, during DCS. Finally, non-synaptic excitatory signal propagation was measured along antidromically-stimulated CA1 axons at different DCS amplitudes and polarity. We find that modulation of both the fEPSP and population spike depend on axonal orientation relative to the electric field vector. Axonal orientation determines whether the DC field is excitatory or inhibitory and dendritic orientation affects the magnitude, but not the overall direction, of the DC effect. These data suggest that tDCS may oppositely affect neurons in a stimulated cortical volume if these neurons are excited by oppositely orientated axons in a constant electrical field.

Journal of neurophysiology

Kabakov, AY; Muller, PA; Pascual-Leone, A; Jensen, FE; Rotenberg, A


Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial.

2012 Jan

Preliminary evidence suggests transcranial direct current stimulation (tDCS) has antidepressant efficacy.To further investigate the efficacy of tDCS in a double-blind, sham-controlled trial (registered at www.clinicaltrials.gov: NCT00763230).Sixty-four participants with current depression received active or sham anodal tDCS to the left prefrontal cortex (2 mA, 15 sessions over 3 weeks), followed by a 3-week open-label active treatment phase. Mood and neuropsychological effects were assessed.There was significantly greater improvement in mood after active than after sham treatment (P<0.05), although no difference in responder rates (13% in both groups). Attention and working memory improved after a single session of active but not sham tDCS (P<0.05). There was no decline in neuropsychological functioning after 3-6 weeks of active stimulation. One participant with bipolar disorder became hypomanic after active tDCS.Findings confirm earlier reports of the antidepressant efficacy and safety of tDCS. Vigilance for mood switching is advised when administering tDCS to individuals with bipolar disorder.

The British journal of psychiatry : the journal of mental science

Loo, CK; Alonzo, A; Martin, D; Mitchell, PB; Galvez, V; Sachdev, P


Transcranial direct current stimulation preconditioning modulates the effect of high-frequency repetitive transcranial magnetic stimulation in the human motor cortex.

2012 Jan

Experimental studies emphasize the importance of homeostatic plasticity as a mean of stabilizing the properties of neural circuits. In the present work we combined two techniques able to produce short-term (5-Hz repetitive transcranial magnetic stimulation, rTMS) and long-term (transcranial direct current stimulation, tDCS) effects on corticospinal excitability to evaluate whether and how the effects of 5-Hz rTMS can be tuned by tDCS preconditioning. Twelve healthy subjects participated in the study. Brief trains of 5-Hz rTMS were applied to the primary motor cortex at an intensity of 120% of the resting motor threshold, with recording of the electromyograph traces evoked by each stimulus of the train from the contralateral abductor pollicis brevis muscle. This interventional protocol was preconditioned by 15 min of anodal or cathodal tDCS delivered at 1.5 mA intensity. Our results showed that motor-evoked potentials (MEPs) increased significantly in size during trains of 5-Hz rTMS in the absence of tDCS preconditioning. After facilitatory preconditioning with anodal tDCS, 5-Hz rTMS failed to produce progressive MEP facilitation. Conversely, when 5-Hz rTMS was preceded by inhibitory cathodal tDCS, MEP facilitation was not abolished. These findings may give insight into the mechanisms of homeostatic plasticity in the human cerebral cortex, suggesting also more suitable applications of tDCS in a clinical setting.

The European journal of neuroscience

Cosentino, G; Fierro, B; Paladino, P; Talamanca, S; Vigneri, S; Palermo, A; Giglia, G; Brighina, F


tDCS polarity effects in motor and cognitive domains: a meta-analytical review.

2012 Jan

In vivo effects of transcranial direct current stimulation (tDCS) have attracted much attention nowadays as this area of research spreads to both the motor and cognitive domains. The common assumption is that the anode electrode causes an enhancement of cortical excitability during stimulation, which then lasts for a few minutes thereafter, while the cathode electrode generates the opposite effect, i.e., anodal-excitation and cathodal-inhibition effects (AeCi). Yet, this dual-polarity effect has not been observed in all tDCS studies. Here, we conducted a meta-analytical review aimed to investigate the homogeneity/heterogeneity of the effect sizes of the AeCi dichotomy in both motor and cognitive functions. The AeCi effect was found to occur quite commonly with motor investigations and rarely in cognitive studies. When the anode electrode is applied over a non-motor area, in most cases, it will cause an excitation as measured by a relevant cognitive or perceptual task; however, the cathode electrode rarely causes an inhibition. We found homogeneity in motor studies and heterogeneity in cognitive studies with the electrode's polarity serving as a moderator that can explain the source of heterogeneity in cognitive studies. The lack of inhibitory cathodal effects might reflect compensation processes as cognitive functions are typically supported by rich brain networks. Further insights as to the polarity and domain interaction are offered, including subdivision to different classes of cognitive functions according to their likelihood of being affected by stimulation.

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Jacobson, L; Koslowsky, M; Lavidor, M


Modulating the brain at work using noninvasive transcranial stimulation.

2012 Jan

This paper proposes a shift in the way researchers currently view and use transcranial brain stimulation technologies. From a neuroscience perspective, the standard application of both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) has been mainly to explore the function of various brain regions. These tools allow for noninvasive and painless modulation of cortical tissue. In the course of studying the function of an area, many studies often report enhanced performance of a task during or following the stimulation. However, little follow-up research is typically done to further explore these effects. Approaching this growing pool of cognitive neuroscience literature with a neuroergonomics mindset (i.e., studying the brain at work), the possibilities of using these stimulation techniques for more than simply investigating the function of cortical areas become evident. In this paper, we discuss how cognitive neuroscience brain stimulation studies may complement neuroergonomics research on human performance optimization. And, through this discussion, we hope to shift the mindset of viewing transcranial stimulation techniques as solely investigatory basic science tools or possible clinical therapeutic devices to viewing transcranial stimulation techniques as interventional tools to be incorporated in applied science research and systems for the augmentation and enhancement of human operator performance.

NeuroImage

McKinley, RA; Bridges, N; Walters, CM; Nelson, J


Combining transcranial direct current stimulation and neuroimaging: novel insights in understanding neuroplasticity.

2012 Jan

In recent years, noninvasive brain stimulation techniques like transcranial direct current stimulation (tDCS) have gained immense popularity owing to their effects on modulating cortical activity and consequently motor and cognitive performance. However, the neurophysiology underlying such neuroplastic changes is less understood. This article critically evaluates the contemporary approach of combined tDCS and neuroimaging as a means to provide novel insights in understanding the neurophysiological and neuroplastic processes modulated by this brain stimulation technique. We end by briefly suggesting further lines of inquiry.

Journal of neurophysiology

Venkatakrishnan, A; Sandrini, M


TDCS guided using fMRI significantly accelerates learning to identify concealed objects.

2012 Jan

The accurate identification of obscured and concealed objects in complex environments was an important skill required for survival during human evolution, and is required today for many forms of expertise. Here we used transcranial direct current stimulation (tDCS) guided using neuroimaging to increase learning rate in a novel, minimally guided discovery-learning paradigm. Ninety-six subjects identified threat-related objects concealed in naturalistic virtual surroundings used in real-world training. A variety of brain networks were found using functional magnetic resonance imaging (fMRI) data collected at different stages of learning, with two of these networks focused in right inferior frontal and right parietal cortex. Anodal 2.0 mA tDCS performed for 30 min over these regions in a series of single-blind, randomized studies resulted in significant improvements in learning and performance compared with 0.1 mA tDCS. This difference in performance increased to a factor of two after a one-hour delay. A dose-response effect of current strength on learning was also found. Taken together, these brain imaging and stimulation studies suggest that right frontal and parietal cortex are involved in learning to identify concealed objects in naturalistic surroundings. Furthermore, they suggest that the application of anodal tDCS over these regions can greatly increase learning, resulting in one of the largest effects on learning yet reported. The methods developed here may be useful to decrease the time required to attain expertise in a variety of settings.

NeuroImage

Clark, VP; Coffman, BA; Mayer, AR; Weisend, MP; Lane, TD; Calhoun, VD; Raybourn, EM; Garcia, CM; Wassermann, EM


Pharmacological Modulation of the Short-Lasting Effects of Antagonistic Direct Current-Stimulation Over the Human Motor Cortex.

2012

Combined administration of transcranial direct current-stimulation (tDCS) with either pergolide (PER) or d-cycloserine (d-CYC) can prolong the excitability-diminishing effects of cathodal, or the excitability enhancing effect of anodal stimulation for up to 24 h poststimulation. However, it remains unclear whether the potentiation of the observed aftereffects is dominated just by the polarity and duration of the stimulation, or the dual application of combined stimulation and drug administration. The present study looks at whether the aftereffects of oral administration of PER (a D1/D2 agonist) or d-CYC (a partial NMDA receptor agonist), in conjunction with the short-duration antagonistic application of tDCS (either 5 min cathodal followed immediately by 5 min anodal or vice versa), that alone only induces short-lasting aftereffects, can modulate cortical excitability in healthy human subjects, as revealed by a single-pulse MEP (motor-evoked-potential) paradigm. Results indicate that the antagonistic application of tDCS induces short-term neuroplastic aftereffects that are dependent upon the order of the application of short-duration stimulation. The administration of d-CYC resulted in a marked inhibition of cortical excitability under the application of tDCS in both stimulation orders. Intake of PER resulted in an increase in cortical excitability in both stimulation orientations, but was non-significant compared to the placebo condition. These results indicate that the aftereffects of tDCS are dependent upon the order of stimulation applied, and also demonstrate the prolongation of tDCS aftereffects when combined with the administration of CNS active drugs.

Frontiers in psychiatry / Frontiers Research Foundation

Chaieb, L; Antal, A; Terney, D; Paulus, W

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Effects of frontal transcranial direct current stimulation on emotional state and processing in healthy humans.

2012

The prefrontal cortex is involved in mood and emotional processing. In patients suffering from depression, the left dorsolateral prefrontal cortex (DLPFC) is hypoactive, while activity of the right DLPFC is enhanced. Counterbalancing these pathological excitability alterations by repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) improves mood in these patients. In healthy subjects, however, rTMS of the same areas has no major effect, and the effects of tDCS are mixed. We aimed to evaluate the effects of prefrontal tDCS on emotion and emotion-related cognitive processing in healthy humans. In a first study, we administered excitability-enhancing anodal, excitability-diminishing cathodal, and placebo tDCS to the left DLPFC, combined with antagonistic stimulation of the right frontopolar cortex, and tested acute emotional changes by an adjective checklist. Subjective emotions were not influenced by tDCS. Emotional face identification, however, which was explored in a second experiment, was subtly improved by a tDCS-driven excitability modulation of the prefrontal cortex, markedly by anodal tDCS of the left DLPFC for positive emotional content. We conclude that tDCS of the prefrontal cortex improves emotion processing in healthy subjects, but does not influence subjective emotional state.

Frontiers in psychiatry / Frontiers Research Foundation

Nitsche, MA; Koschack, J; Pohlers, H; Hullemann, S; Paulus, W; Happe, S

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Behavioral and electrophysiological effects of transcranial direct current stimulation of the parietal cortex in a visuo-spatial working memory task.

2012

Impairments of working memory (WM) performance are frequent concomitant symptoms in several psychiatric and neurologic diseases. Despite the great advance in treating the reduced WM abilities in patients suffering from, e.g., Parkinson's and Alzheimer's disease by means of transcranial direct current stimulation (tDCS), the exact neurophysiological underpinning subserving these therapeutic tDCS-effects are still unknown. In the present study we investigated the impact of tDCS on performance in a visuo-spatial WM task and its underlying neural activity. In three experimental sessions, participants performed a delayed matching-to-sample WM task after sham, anodal, and cathodal tDCS over the right parietal cortex. The results showed that tDCS modulated WM performance and its underlying electrophysiological brain activity in a polarity-specific way. Parietal tDCS altered event-related potentials and oscillatory power in the alpha band at posterior electrode sites. The present study demonstrates that posterior tDCS can alter visuo-spatial WM performance by modulating the underlying neural activity. This result can be considered an important step toward a better understanding of the mechanisms involved in tDCS-induced modulations of cognitive processing. This is of particular importance for the application of electrical brain stimulation as a therapeutic treatment of neuropsychiatric deficits in clinical populations.

Frontiers in psychiatry / Frontiers Research Foundation

Heimrath, K; Sandmann, P; Becke, A; Müller, NG; Zaehle, T

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Using Transcranial Direct Current Stimulation to Treat Depression in HIV-Infected Persons: The Outcomes of a Feasibility Study.

2012

Transcranial direct current stimulation (tDCS) is a novel non-invasive neuromodulatory method that influences neuronal firing rates and excitability of neuronal circuits in the brain. tDCS has been shown to relieve Major Depressive Disorder (MDD) in the general population, suggesting its potential for other vulnerable populations with high MDD prevalence. Aims: This study evaluated the feasibility, safety, acceptability, and clinical outcomes of a 2-week tDCS antidepressant treatment in HIV-MDD co-diagnosed patients, and the feasibility of collecting serum and saliva for analysis of immunity biomarkers. Methods: Ten enrolled patients underwent baseline evaluation and started the tDCS treatment (Monday-Friday for 2 weeks) delivered with Phoresor II 850 PM for 20 min at 2 mA at each visit, using two saline-soaked sponge electrodes placed over the F3 position of EEG 10-20 system and the contralateral supraorbital region. Outcome measures were collected at baseline, after the last tDCS and 2 weeks later. A quantitative microarray (Ray Bio Tech Inc.) for TH1/TH2 cytokines was used for saliva and plasma analysis. Results: Analyzable outcome-data were obtained from eight subjects. Depression scores significantly decreased (p < 0.0005) after the treatment. No serious adverse events occurred. Several transient minor AEs and occasional changes of blood pressure and heart rate were noted. Mini-mental state examination scores remained unchanged or increased after the treatment. All subjects were highly satisfied with the protocol and treatment results and described the desire to find new treatments for HIV-MDD as motivating participation. Conclusion: Findings support feasibility and clinical potential of tDCS for HIV-MDD patients, and justify larger-sample, sham-controlled trials.

Frontiers in psychiatry / Frontiers Research Foundation

Knotkova, H; Rosedale, M; Strauss, SM; Horne, J; Soto, E; Cruciani, RA; Malaspina, D; Malamud, D

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Action mechanisms of transcranial direct current stimulation in Alzheimer's disease and memory loss.

2012

The pharmacological treatment of Alzheimer's disease (AD) is often limited and accompanied by drug side effects. Thus alternative therapeutic strategies such as non-invasive brain stimulation are needed. Few studies have demonstrated that transcranial direct current stimulation (tDCS), a method of neuromodulation with consecutive robust excitability changes within the stimulated cortex area, is beneficial in AD. There is also evidence that tDCS enhances memory function in cognitive rehabilitation in depressive patients, Parkinson's disease, and stroke. tDCS improves working and visual recognition memory in humans and object-recognition learning in the elderly. AD's neurobiological mechanisms comprise changes in neuronal activity and the cerebral blood flow (CBF) caused by altered microvasculature, synaptic dysregulation from ß-amyloid peptide accumulation, altered neuromodulation via degenerated modulatory amine transmitter systems, altered brain oscillations, and changes in network connectivity. tDCS alters (i) neuronal activity and (ii) human CBF, (iii) has synaptic and non-synaptic after-effects (iv), can modify neurotransmitters polarity-dependently, (v) and alter oscillatory brain activity and (vi) functional connectivity patterns in the brain. It thus is reasonable to use tDCS as a therapeutic instrument in AD as it improves cognitive function in manner based on a disease mechanism. Moreover, it could prove valuable in other types of dementia. Future large-scale clinical and mechanism-oriented studies may enable us to identify its therapeutic validity in other types of demential disorders.

Frontiers in psychiatry / Frontiers Research Foundation

Hansen, N

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Transcranial Direct Current Stimulation of the Frontal Eye Fields during Pro- and Antisaccade Tasks.

2012

Transcranial direct current stimulation (tDCS) has been successfully applied to cortical areas such as the motor cortex and visual cortex. In the present study, we examined whether tDCS can reach and selectively modulate the excitability of the frontal eye field (FEF). In order to assess potential effects of tDCS, we measured saccade latency, landing point, and its variability in a simple prosaccade task and in an antisaccade task. In the prosaccade task, we found that anodal tDCS shortened the latency of saccades to a contralateral visual cue. However, cathodal tDCS did not show a significant modulation of saccade latency. In the antisaccade task, on the other hand, we found that the latency for ipisilateral antisaccades was prolonged during the stimulation, whereas anodal stimulation did not modulate the latency of antisaccades. In addition, anodal tDCS reduced the erroneous saccades toward the contralateral visual cue. These results in the antisaccade task suggest that tDCS modulates the function of FEF to suppress reflexive saccades to the contralateral visual cue. Both in the prosaccade and antisaccade tasks, we did not find any effect of tDCS on saccade landing point or its variability. Our present study is the first to show effects of tDCS over FEF and opens the possibility of applying tDCS for studying the functions of FEF in oculomotor and attentional performance.

Frontiers in psychiatry / Frontiers Research Foundation

Kanai, R; Muggleton, N; Walsh, V

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Anodal transcranial direct current stimulation reduces psychophysically measured surround suppression in the human visual cortex.

2012

Transcranial direct current stimulation (tDCS) is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN), was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex.

PloS one

Spiegel, DP; Hansen, BC; Byblow, WD; Thompson, B

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Transcranial direct current stimulation augments perceptual sensitivity and 24-hour retention in a complex threat detection task.

2012

We have previously shown that transcranial direct current stimulation (tDCS) improved performance of a complex visual perceptual learning task (Clark et al. 2012). However, it is not known whether tDCS can enhance perceptual sensitivity independently of non-specific, arousal-linked changes in response bias, nor whether any such sensitivity benefit can be retained over time. We examined the influence of stimulation of the right inferior frontal cortex using tDCS on perceptual learning and retention in 37 healthy participants, using signal detection theory to distinguish effects on perceptual sensitivity (d') from response bias (ß). Anodal stimulation with 2 mA increased d', compared to a 0.1 mA sham stimulation control, with no effect on ß. On completion of training, participants in the active stimulation group had more than double the perceptual sensitivity of the control group. Furthermore, the performance enhancement was maintained for 24 hours. The results show that tDCS augments both skill acquisition and retention in a complex detection task and that the benefits are rooted in an improvement in sensitivity (d'), rather than changes in response bias (ß). Stimulation-driven acceleration of learning and its retention over 24 hours may result from increased activation of prefrontal cortical regions that provide top-down attentional control signals to object recognition areas.

PloS one

Falcone, B; Coffman, BA; Clark, VP; Parasuraman, R

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Reorganizing the Intrinsic Functional Architecture of the Human Primary Motor Cortex during Rest with Non-Invasive Cortical Stimulation.

2012

The primary motor cortex (M1) is the main effector structure implicated in the generation of voluntary movements and is directly involved in motor learning. The intrinsic horizontal neuronal connections of M1 exhibit short-term and long-term plasticity, which is a strong substrate for learning-related map reorganization. Transcranial direct current stimulation (tDCS) applied for few minutes over M1 has been shown to induce relatively long-lasting plastic alterations and to modulate motor performance. Here we test the hypothesis that the relatively long-lasting synaptic modification induced by tDCS over M1 results in the alteration of associations among populations of M1 neurons which may be reflected in changes of its functional architecture. fMRI resting-state datasets were acquired immediately before and after 10 minutes of tDCS during rest, with the anode/cathode placed over the left M1. For each functional dataset, grey-matter voxels belonging to Brodmann area 4 (BA4) were labelled and afterwards BA4 voxel-based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal network parameters which characterize the architecture of functional networks (connectivity degree, clustering coefficient and characteristic path-length) were computed, transformed to volume maps and compared before and after stimulation. At the dorsolateral-BA4 region cathodal tDCS boosted local connectedness, while anodal-tDCS enhanced long distance functional communication within M1. Additionally, the more efficient the functional architecture of M1 was at baseline, the more efficient the tDCS-induced functional modulations were. In summary, we show here that it is possible to non-invasively reorganize the intrinsic functional architecture of M1, and to image such alterations.

PloS one

Polanía, R; Paulus, W; Nitsche, MA

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Effect of transcranial brain stimulation for the treatment of Alzheimer disease: a review.

2012

Available pharmacological treatments for Alzheimer disease (AD) have limited effectiveness, are expensive, and sometimes induce side effects. Therefore, alternative or complementary adjuvant therapeutic strategies have gained increasing attention. The development of novel noninvasive methods of brain stimulation has increased the interest in neuromodulatory techniques as potential therapeutic tool for cognitive rehabilitation in AD. In particular, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are noninvasive approaches that induce prolonged functional changes in the cerebral cortex. Several studies have begun to therapeutically use rTMS or tDCS to improve cognitive performances in patients with AD. However, most of them induced short-duration beneficial effects and were not adequately powered to establish evidence for therapeutic efficacy. Therefore, TMS and tDCS approaches, seeking to enhance cognitive function, have to be considered still very preliminary. In future studies, multiple rTMS or tDCS sessions might also interact, and metaplasticity effects could affect the outcome.

International journal of Alzheimer's disease

Nardone, R; Bergmann, J; Christova, M; Caleri, F; Tezzon, F; Ladurner, G; Trinka, E; Golaszewski, S

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Finite Element study of skin and fat delineation in an obese subject for transcranial Direct Current Stimulation.

2012

Because of pilot data suggesting the efficacy of transcranial Direct Current Stimulation (tDCS) in treating a range of neuropsychiatric disorders as well as in controlling cravings, there is interest to apply to obese subjects. The abnormal thickness of fat that exist in obese subjects may influence current delivery from scalp electrodes to the brain. MRI-derived Finite Element (FE) models of a morbidly obese subject were created with and without fat delineated. The inclusion of fat to the FE model reduced the effective volume of the relatively conductive skin. This led to greater current penetration to the cortical surface. Electric field was substantially greater (60%) in magnitude and a difference in the spatial profile was noted in the model with fat. Additional models testing the effect of varying fat conductivity revealed an inflection in current penetration as fat conductivity is varied. It was postulated that this may be due to a shunting effect both when the shell of fat surrounding the skull is too resistive for penetration and when the fat is so conductive as to lead current around rather than through the head. Precise FE tDCS model of obese patients requires the precise inclusion of fat.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Truong, DQ; Magerowski, G; Pascual-Leone, A; Alonso-Alonso, M; Bikson, M


Investigation of the electric field components of tDCS via anisotropically conductive gyri-specific finite element head models.

2012

Transcranial Direct Current Stimulation (tDCS) is considered as one of the promising techniques for noninvasive brain stimulation and brain disease therapy. In this study, we have investigated the effect of skull and white matter (WM) anisotropy on the induced electric field (EF) by tDCS in two different montages; one using a pair of clinically used rectangular pad electrodes and the other 4(cathodes)+1(anode) ring electrodes. Using a gyri-specific finite element (FE) head model, we simulated tDCS and investigated the radial and tangential components of the induced EF in terms of their distribution over the cortical surface besides the distribution of the transverse and longitudinal components within WM. The results show that the tangential component of the EF on the cortical surface seems to be the main cause of the cortical stimulation of tDCS. Also WM anisotropy seems to increase the dispersion of the transverse component of the EF that affects the dispersion of the EF magnitude within the WM region.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Metwally, MK; Cho, YS; Park, HJ; Kim, TS


A pipeline for the simulation of transcranial direct current stimulation for realistic human head models using SCIRun/BioMesh3D.

2012

The current work presents a computational pipeline to simulate transcranial direct current stimulation from image based models of the head with SCIRun [15]. The pipeline contains all the steps necessary to carry out the simulations and is supported by a complete suite of open source software tools: image visualization, segmentation, mesh generation, tDCS electrode generation and efficient tDCS forward simulation.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Dannhauer, M; Brooks, D; Tucker, D; MacLeod, R


An automated method for high-definition transcranial direct current stimulation modeling.

2012

Targeted transcranial stimulation with electric currents requires accurate models of the current flow from scalp electrodes to the human brain. Idiosyncratic anatomy of individual brains and heads leads to significant variability in such current flows across subjects, thus, necessitating accurate individualized head models. Here we report on an automated processing chain that computes current distributions in the head starting from a structural magnetic resonance image (MRI). The main purpose of automating this process is to reduce the substantial effort currently required for manual segmentation, electrode placement, and solving of finite element models. In doing so, several weeks of manual labor were reduced to no more than 4 hours of computation time and minimal user interaction, while current-flow results for the automated method deviated by less than 27.9% from the manual method. Key facilitating factors are the addition of three tissue types (skull, scalp and air) to a state-of-the-art automated segmentation process, morphological processing to correct small but important segmentation errors, and automated placement of small electrodes based on easily reproducible standard electrode configurations. We anticipate that such an automated processing will become an indispensable tool to individualize transcranial direct current stimulation (tDCS) therapy.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Huang, Y; Su, Y; Rorden, C; Dmochowski, J; Datta, A; Parra, LC


Axon terminal polarization induced by weak uniform DC electric fields: a modeling study.

2012

Uniform steady state (DC) electric fields, like those generated during transcranial direct current stimulation (tDCS), can affect neuronal excitability depending on field direction and neuronal morphology. In addition to somatic polarization, subthreshold membrane polarization of axon compartments can play a significant role in modulating synaptic efficacy. The aim of this study is to provide an estimation of axon terminal polarization in a weak uniform subthreshold electric field. Simulations based on 3D morphology reconstructions and simplified models indicate that for axons having long final branches compared to the local space constant (L>4λ) the terminal polarization converges to Eλ for electric fields oriented in the same direction as the branch. In particular we determined how and when analytical approximations could be extended to real cases when considering maximal potential polarization during weak DC stimulation.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Arlotti, M; Rahman, A; Minhas, P; Bikson, M


Transcranial direct current stimulation and EEG-based motor imagery BCI for upper limb stroke rehabilitation.

2012

Clinical studies had shown that EEG-based motor imagery Brain-Computer Interface (MI-BCI) combined with robotic feedback is effective in upper limb stroke rehabilitation, and transcranial Direct Current Stimulation (tDCS) combined with other rehabilitation techniques further enhanced the facilitating effect of tDCS. This motivated the current clinical study to investigate the effects of combining tDCS with MI-BCI and robotic feedback compared to sham-tDCS for upper limb stroke rehabilitation. The stroke patients recruited were randomized to receive 20 minutes of tDCS or sham-tDCS prior to 10 sessions of 1-hour MI-BCI with robotic feedback for 2 weeks. The online accuracies of detecting motor imagery from idle condition were assessed and offline accuracies of classifying motor imagery from background rest condition were assessed from the EEG of the evaluation and therapy parts of the 10 rehabilitation sessions respectively. The results showed no evident differences between the online accuracies on the evaluation part from both groups, but the offline analysis on the therapy part yielded higher averaged accuracies for subjects who received tDCS (n=3) compared to sham-tDCS (n=2). The results suggest towards tDCS effect in modulating motor imagery in stroke, but a more conclusive result can be drawn when more data are collected in the ongoing study.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Ang, KK; Guan, C; Phua, KS; Wang, C; Teh, I; Chen, CW; Chew, E


Electrode assembly design for transcranial Direct Current Stimulation: a FEM modeling study.

2012

Despite accelerating progress in transcranial Direct Current Stimulation clinical and cognitive research, there remains remarkably little consistency in the control of electrode design and preparation. Electrode assembly design determines skin sensation and failure at the electrode can lead to skin burns. Though tDCS is generally well tolerated, the desire for rigor in electrode design is motivated by applications in increasingly diverse environments and populations. Generally the tDCS electrode assembly consists of a flat rubber or metal electrode and a saline/water saturated sponge. Here we show using FEM simulations, that each of these factors should be controlled to regulate current flow density across the skin: 1) sponge thickness 2) solution salinity 3) electrode size, 4) electrode placement in the sponge (including surface or pocket configuration) 5) control of excess fluid at the skin surface 6) use of rivets. Two general patterns of current distribution emerge as a result of integrated design: edge concentration or center concentration. Poor control over any of these electrode assembly parameters will result in unpredictable current density at the skin during tDCS.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Kronberg, G; Bikson, M


Transcranial direct current stimulation in pediatric brain: a computational modeling study.

2012

Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation which uses weak electric currents applied on the scalp to modulate activity of underlying brain tissue. In addition to being used as a tool for cognitive neuroscience investigations, tDCS has generated considerable interest for use as a therapeutic modality for neurologic disorders. Though the safety and tolerability of tDCS in adults is well-established, there is little information on the safety of tDCS in children. Because there are differences between children and adults in several key parameters (such as skull thickness and cerebrospinal fluid volume) which affect current flow through the brain, special consideration should be given to the stimulation parameters which are used in a pediatric study population. In this study we present cortical electrical field maps at different stimulation intensities and electrode configurations using a high-resolution-MRI derived finite element model of a typically developing, anatomically normal 12 year old child. The peak electrical fields for a given stimulus intensity in the adolescent brain were twice as high as in the adult brain for conventional tDCS and nearly four times as high for a 4X1 High-Definition tDCS electrode configuration. These data suggest that acceptable tDCS stimulation parameters may be different in children compared to adults, and that further modeling studies are needed to help guide decisions about applied current intensity.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Minhas, P; Bikson, M; Woods, AJ; Rosen, AR; Kessler, SK


Transcranial magnetic stimulation induces current pulses in transcranial direct current stimulation electrodes.

2012

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique where weak direct current is administered through electrodes placed on the subject's head. Transcranial magnetic stimulation (TMS) is a noninvasive method for focal brain stimulation where small intracranial currents are induced by a pulsed magnetic field. TMS can be applied simultaneously with tDCS to probe brain excitability or to effect synergistic neuromodulation. Delivering TMS simultaneously with tDCS can induce electric current pulses in the tDCS electrodes even when the tDCS device is turned off or is set to 0 mA output, as long as the electrodes are connected to the tDCS current source. The output impedance of commercial tDCS devices is in the range of 2-5 kΩ which can allow substantial currents to be induced by TMS. In a rat TMS-tDCS setup, the induced currents are comparable to the tDCS current magnitude. To mitigate the induced currents, the area of the loop formed by the tDCS electrode leads should be minimized and the impedance of the tDCS circuit at TMS pulses frequencies (1-10 kHz) should be maximized.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Peterchev, AV; Dhamne, SC; Kothare, R; Rotenberg, A


Effects of tissue dielectric properties on the electric field induced in tDCS: a sensitivity analysis.

2012

Numerical modeling studies remain the only viable way to accurately predict the electric field (E-field) distribution in transcranial direct current stimulation (tDCS). Despite the existence of multiple studies of this kind, a wide range of different values and properties for the electrical conductivities of the tissues represented is employed. This makes it difficult to predict whether the changes observed between models are due to differences in the geometries of the volume conductors or to the different electrical properties of the tissues. In this study we used the finite element method to calculate the E-field distribution in several spherical head models whose tissues were represented with different isotropic and anisotropic conductivity profiles. Results show that the distribution of the E-field is especially sensitive to the conductivity of the skull, skin and GM. These results might help comparing numerical modeling studies that employ different conductivity values.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Salvador, R; Ramirez, F; V'yacheslavovna, M; Miranda, PC


A pilot study on effects of 4×1 High-Definition tDCS on motor cortex excitability.

2012

High-Definition transcranial Direct Current Stimulation (HD-tDCS) using specialized small electrodes has been proposed as a focal, non-invasive neuromodulatory technique. Here we provide the first evidence of a change in cortical excitability after HD-tDCS of the motor cortex, using TMS motor evoked potential (MEP) as the measure of excitability. Stimulation for 20 minutes at 1 mA with an anode centered over the hand area of the motor cortex and four surrounding return electrodes (anodal 4×1 montage) produced a significant increase in MEP amplitude and variability after stimulation, compared to sham stimulation. Stimulation was well tolerated by all subjects with adverse effects limited to transient sensation under the electrodes. A high-resolution computational model confirmed predictions of increased focality using the 4×1 HD tDCS montage compared to conventional tDCS. Simulations also indicated that variability in placement of the center electrode relative to the location of the target (central sulcus) could account for increasing variability. These results provide support for the careful use of this technique where focal tDCS is desired.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Caparelli-Daquer, EM; Zimmermann, TJ; Mooshagian, E; Parra, LC; Rice, JK; Datta, A; Bikson, M; Wassermann, EM


Dual-tDCS Enhances Online Motor Skill Learning and Long-Term Retention in Chronic Stroke Patients.

2012

Background: Since motor learning is a key component for stroke recovery, enhancing motor skill learning is a crucial challenge for neurorehabilitation. Transcranial direct current stimulation (tDCS) is a promising approach for improving motor learning. The aim of this trial was to test the hypothesis that dual-tDCS applied bilaterally over the primary motor cortices (M1) improves online motor skill learning with the paretic hand and its long-term retention. Methods: Eighteen chronic stroke patients participated in a randomized, cross-over, placebo-controlled, double bind trial. During separate sessions, dual-tDCS or sham dual-tDCS was applied over 30 min while stroke patients learned a complex visuomotor skill with the paretic hand: using a computer mouse to move a pointer along a complex circuit as quickly and accurately as possible. A learning index involving the evolution of the speed/accuracy trade-off was calculated. Performance of the motor skill was measured at baseline, after intervention and 1 week later. Results: After sham dual-tDCS, eight patients showed performance worsening. In contrast, dual-tDCS enhanced the amount and speed of online motor skill learning compared to sham (p < 0.001) in all patients; this superiority was maintained throughout the hour following. The speed/accuracy trade-off was shifted more consistently after dual-tDCS (n = 10) than after sham (n = 3). More importantly, 1 week later, online enhancement under dual-tDCS had translated into superior long-term retention (+44%) compared to sham (+4%). The improvement generalized to a new untrained circuit and to digital dexterity. Conclusion: A single-session of dual-tDCS, applied while stroke patients trained with the paretic hand significantly enhanced online motor skill learning both quantitatively and qualitatively, leading to successful long-term retention and generalization. The combination of motor skill learning and dual-tDCS is promising for improving post-stroke neurorehabilitation.

Frontiers in human neuroscience

Lefebvre, S; Laloux, P; Peeters, A; Desfontaines, P; Jamart, J; Vandermeeren, Y


Neurobiological effects of transcranial direct current stimulation: a review.

2012

Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique that is affordable and easy to operate compared to other neuromodulation techniques. Anodal stimulation increases cortical excitability, while the cathodal stimulation decreases it. Although tDCS is a promising treatment approach for chronic pain as well as for neuropsychiatric diseases and other neurological disorders, several complex neurobiological mechanisms that are not well understood are involved in its effect. The purpose of this systematic review is to summarize the current knowledge regarding the neurobiological mechanisms involved in the effects of tDCS. The initial search resulted in 171 articles. After applying inclusion and exclusion criteria, we screened 32 full-text articles to extract findings about the neurobiology of tDCS effects including investigation of cortical excitability parameters. Overall, these findings show that tDCS involves a cascade of events at the cellular and molecular levels. Moreover, tDCS is associated with glutamatergic, GABAergic, dopaminergic, serotonergic, and cholinergic activity modulation. Though these studies provide important advancements toward the understanding of mechanisms underlying tDCS effects, further studies are needed to integrate these mechanisms as to optimize clinical development of tDCS.

Frontiers in psychiatry / Frontiers Research Foundation

Medeiros, LF; de Souza, IC; Vidor, LP; de Souza, A; Deitos, A; Volz, MS; Fregni, F; Caumo, W; Torres, IL


No effect of a single session of transcranial direct current stimulation on experimentally induced pain in patients with chronic low back pain--an exploratory study.

2012

Transcranial direct current stimulation (tDCS) has been shown to modulate cortical excitability. A small number of studies suggested that tDCS modulates the response to experimental pain paradigms. No trials have been conducted to evaluate the response of patients already suffering from pain, to an additional experimental pain before and after tDCS. The present study investigated the effect of a single session of anodal, cathodal and sham stimulation (15 mins/1 mA) over the primary motor cortex on the perceived intensity of repeated noxious thermal and electrical stimuli and on elements of quantitative sensory testing (thermal pain and perception thresholds) applied to the right hand in 15 patients with chronic low back pain. The study was conducted in a double-blind sham-controlled and cross-over design. No significant alterations of pain ratings were found. Modalities of quantitative sensory testing remained equally unchanged. It is therefore hypothesized that a single 15 mins session of tDCS at 1 mA may not be sufficient to alter the perception of experimental pain and in patients with chronic pain. Further studies applying repetitive tDCS to patients with chronic pain are required to fully answer the question whether experimental pain perception may be influenced by tDCS over the motor cortex.

PloS one

Luedtke, K; May, A; Jürgens, TP


Systematic review of parameters of stimulation, clinical trial design characteristics, and motor outcomes in non-invasive brain stimulation in stroke.

2012

Introduction/Objectives: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation are two powerful non-invasive neuromodulatory therapies that have the potential to alter and evaluate the integrity of the corticospinal tract. Moreover, recent evidence has shown that brain stimulation might be beneficial in stroke recovery. Therefore, investigating and investing in innovative therapies that may improve neurorehabilitative stroke recovery are next steps in research and development. Participants/Materials and Methods: This article presents an up-to-date systematic review of the treatment effects of rTMS and tDCS on motor function. A literary search was conducted, utilizing search terms "stroke" and "transcranial stimulation." Items were excluded if they failed to: (1) include stroke patients, (2) study motor outcomes, or (3) include rTMS/tDCS as treatments. Other exclusions included: (1) reviews, editorials, and letters, (2) animal or pediatric populations, (3) case reports or sample sizes ≤2 patients, and (4) primary outcomes of dysphagia, dysarthria, neglect, or swallowing. Results: Investigation of PubMed English Database prior to 01/01/2012 produced 695 applicable results. Studies were excluded based on the aforementioned criteria, resulting in 50 remaining studies. They included 1314 participants (1282 stroke patients and 32 healthy subjects) evaluated by motor function pre- and post-tDCS or rTMS. Heterogeneity among studies' motor assessments was high and could not be accounted for by individual comparison. Pooled effect sizes for the impact of post-treatment improvement revealed consistently demonstrable improvements after tDCS and rTMS therapeutic stimulation. Most studies provided limited follow-up for long-term effects. Conclusion: It is apparent from the available studies that non-invasive stimulation may enhance motor recovery and may lead to clinically meaningful functional improvements in the stroke population. Only mild to no adverse events have been reported. Though results have been positive results, the large heterogeneity across articles precludes firm conclusions.

Frontiers in psychiatry / Frontiers Research Foundation

Adeyemo, BO; Simis, M; Macea, DD; Fregni, F


Rapid effect of nicotine intake on neuroplasticity in non-smoking humans.

2012

In various studies nicotine has shown to alter cognitive functions in non-smoking subjects. The physiological basis for these effects might be nicotine-generated modulation of cortical structure, excitability, and activity, as mainly described in animal experiments. In accordance, a recently conducted study demonstrated that application of nicotine for hours via nicotine patch in non-smoking humans alters the effects of neuroplasticity-inducing non-invasive brain stimulation techniques on cortical excitability. Specifically, nicotine abolished inhibitory plasticity independent from the focality of the stimulation protocol. While nicotine prevented also the establishment of non-focal facilitatory plasticity, focal synapse-specific facilitatory plasticity was enhanced. These results agree with a focusing effect of prolonged nicotine application on facilitatory plasticity. However, since nicotine induces rapid adaption processes of its receptors, this scenario might differ from the effect of nicotine in cigarette smoking. Thus in this study we aimed to gain further insight in the mechanism of nicotine on plasticity by exploring the effect of nicotine spray on non-focal and focal plasticity-inducing protocols in non-smoking subjects, a fast-acting agent better comparable to cigarette smoking. Focal, synapse-specific plasticity was induced by paired associative stimulation (PAS), while non-focal plasticity was elicited by transcranial direct current stimulation (tDCS). Forty eight non-smokers received nicotine spray respectively placebo combined with one of the following protocols (anodal tDCS, cathodal tDCS, PAS-25, and PAS-10). Corticospinal excitability was monitored via motor-evoked potentials elicited by transcranial magnetic stimulation (TMS). Nicotine spray abolished facilitatory plasticity irrespective of focality and PAS-10-induced excitability diminution, while tDCS-derived excitability reduction was delayed and weakened. Nicotine spray had thus a clear effect on neuroplasticity in non-smoking subjects. However, the effects of nicotine spray differ clearly from those of prolonged nicotine application, which might be due to missing adaptive nicotinic receptor alterations. These results enhance our knowledge about the dynamic impact of nicotine on plasticity, which might be related to its heterogenous effect on cognition.

Frontiers in pharmacology

Grundey, J; Thirugnanasambandam, N; Kaminsky, K; Drees, A; Skwirba, AC; Lang, N; Paulus, W; Nitsche, MA


Transcranial direct current stimulation in tinnitus patients: a systemic review and meta-analysis.

2012

Although transcranial direct current stimulation (tDCS) has already been used to manage tinnitus patients, paucity of reports and variations in protocols preclude a comprehensive understanding. Hence, we conducted a meta-analysis based on systemic review to assess effectiveness of tDCS in tinnitus management and to compare stimulation parameters. PubMed was searched for tDCS studies in tinnitus. For randomized controlled trials (RCTs), a meta-analysis was performed. A total of 17 studies were identified and 6 of them were included in the systemic review and 2 RCTs were included in the meta-analysis. Overall 39.5% responded to active tDCS with a mean tinnitus intensity reduction of 13.5%. Additionally, left temporal area (LTA) and bifrontal tDCS indicated comparable results. Active tDCS was found to be more effective than sham tDCS for tinnitus intensity reduction (Hedges' g = .77, 95% confidence interval 0.23-1.31). The efficacy of tDCS in tinnitus could not be fully confirmed by the current study because of the limited number of studies, but all studies included in the current systemic review and meta-analysis demonstrated significant tinnitus intensity improvement. Therefore, tDCS may be a promising tool for tinnitus management. Future RCTs in a large series regarding the efficacy as well as the comparison between LTA- and bifrontal tDCS are recommended.

TheScientificWorldJournal

Song, JJ; Vanneste, S; Van de Heyning, P; De Ridder, D


Immediate effects of tDCS on the μ-opioid system of a chronic pain patient.

2012

We developed a unique protocol where transcranial direct current stimulation (tDCS) of the motor cortex is performed during positron emission tomography (PET) scan using a μ-opioid receptor (μOR) selective radiotracer, [(11)C]carfentanil. This is one of the most important central neuromechanisms associated with pain perception and regulation. We measured μOR non-displaceable binding potential (μOR BP(ND)) in a trigeminal neuropathic pain patient (TNP) without creating artifacts, or posing risks to the patient (e.g., monitoring of resistance). The active session directly improved in 36.2% the threshold for experimental cold pain in the trigeminal allodynic area, mandibular branch, but not the TNP patient's clinical pain. Interestingly, the single active tDCS application considerably decreased μORBP(ND) levels in (sub)cortical pain-matrix structures compared to sham tDCS, especially in the posterior thalamus. Suggesting that the μ-opioidergic effects of a single tDCS session are subclinical at immediate level, and repetitive sessions are necessary to revert ingrained neuroplastic changes related to the chronic pain. To our knowledge, we provide data for the first time in vivo that there is possibly an instant increase of endogenous μ-opioid release during acute motor cortex neuromodulation with tDCS.

Frontiers in psychiatry / Frontiers Research Foundation

DosSantos, MF; Love, TM; Martikainen, IK; Nascimento, TD; Fregni, F; Cummiford, C; Deboer, MD; Zubieta, JK; Dasilva, AF


Inter-Individual Variation during Transcranial Direct Current Stimulation and Normalization of Dose Using MRI-Derived Computational Models.

2012

Background: Transcranial Direct Current Stimulation (tDCS) is a non-invasive, versatile, and safe neuromodulation technology under investigation for the treatment of neuropsychiatric disorders, adjunct to rehabilitation, and cognitive enhancement in healthy adults. Despite promising results, there is variability in responsiveness. One potential source of variability is the intensity of current delivered to the brain which is a function of both the operator controlled tDCS dose (electrode montage and total applied current) and subject specific anatomy. We are interested in both the scale of this variability across anatomical typical adults and methods to normalize inter-individual variation by customizing tDCS dose. Computational FEM simulations are a standard technique to predict brain current flow during tDCS and can be based on subject specific anatomical MRI. Objective: To investigate this variability, we modeled multiple tDCS montages across three adults (ages 34-41, one female). Results: Conventional pad stimulation led to diffuse modulation with maximum current flow between the pads across all subjects. There was high current flow directly under the pad for one subject while the location of peak induced cortical current flow was variable. The High-Definition tDCS montage led to current flow restricted to within the ring perimeter across all subjects. The current flow profile across all subjects and montages was influenced by details in cortical gyri/sulci. Conclusion: This data suggests that subject specific modeling can facilitate consistent and more efficacious tDCS.

Frontiers in psychiatry / Frontiers Research Foundation

Datta, A; Truong, D; Minhas, P; Parra, LC; Bikson, M


Target optimization in transcranial direct current stimulation.

2012

Transcranial direct current stimulation (tDCS) is an emerging neuromodulation therapy that has been experimentally determined to affect a wide range of behaviors and diseases ranging from motor, cognitive, and memory processes to depression and pain syndromes. The effects of tDCS may be inhibitory or excitatory, depending on the relative polarities of electrodes and their proximity to different brain structures. This distinction is believed to relate to the interaction of current flow with activation thresholds of different neural complexes. tDCS currents are typically applied via a single pair of large electrodes, with one (the active electrode) sited close to brain structures associated with targeted processes. To efficiently direct current toward the areas presumed related to these effects, we devised a method of steering current toward a selected area by reference to a 19-electrode montage applied to a high-resolution finite element model of the head. We used a non-linear optimization procedure to maximize mean current densities inside the left inferior frontal gyrus (IFG), while simultaneously restricting overall current, and median current densities within the accumbens. We found that a distributed current pattern could be found that would indeed direct current toward the IFG in this way, and compared it to other candidate 2-electrode configurations. Further, we found a combination of four anterior-posterior electrodes could direct current densities to the accumbens. We conclude that a similar method using multiple electrodes may be a useful means of directing current toward or away from specific brain regions and also of reducing tDCS side effects.

Frontiers in psychiatry / Frontiers Research Foundation

Sadleir, RJ; Vannorsdall, TD; Schretlen, DJ; Gordon, B


A systematic review of non-invasive brain stimulation therapies and cardiovascular risk: implications for the treatment of major depressive disorder.

2012

Major depressive disorder (MDD) and cardiovascular diseases are intimately associated. Depression is an independent risk factor for mortality in cardiovascular samples. Neuroendocrine dysfunctions in MDD are related to an overactive hypothalamus-pituitary-adrenal (HPA) axis and increased sympathetic activity. Novel intervention strategies for MDD include the non-invasive brain stimulation (NIBS) techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). In fact, although these techniques have being increasingly used as a treatment for MDD, their cardiovascular effects were not sufficiently investigated, which would be important considering the dyad MDD/cardiovascular disorders. We investigated this issue through a systematic review for published articles from the first date available to May 2012 in MEDLINE and other databases, looking for main risk factors and surrogate markers for cardiovascular disease such as: cortisol, heart rate variability (HRV), alcohol, smoking, obesity, hypertension, glucose. We identified 37 articles (981 subjects) according to our eligibility criteria. Our main findings were that NIBS techniques might be effective strategies for down-regulating HPA activity and regulating food, alcohol, and cigarette consumption. NIBS's effects on HRV and blood pressure presented mixed findings, with studies suggesting that HRV values can decrease or remain unchanged after NIBS, while one study found that rTMS increased blood pressure levels. Also, a single study showed that glucose levels decrease after tDCS. However, most studies tested the acute effects after one single session of rTMS/tDCS; therefore further studies are necessary to investigate whether NIBS modifies cardiovascular risk factors in the long-term. In fact, considering the burden of cardiac disease, further trials in cardiovascular, depressed, and non-depressed samples using NIBS should be performed.

Frontiers in psychiatry / Frontiers Research Foundation

Sampaio, LA; Fraguas, R; Lotufo, PA; Benseñor, IM; Brunoni, AR


Rethinking clinical trials of transcranial direct current stimulation: participant and assessor blinding is inadequate at intensities of 2mA.

2012

Many double-blind clinical trials of transcranial direct current stimulation (tDCS) use stimulus intensities of 2 mA despite the fact that blinding has not been formally validated under these conditions. The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding.A randomised double blind crossover trial. 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory. Participants attended for two separate sessions. In each session, they completed a word memory task, then received active or sham tDCS (order randomised) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task. They then judged whether they believed they had received active stimulation and rated their confidence in that judgement. The blinded assessor noted when red marks were observed at the electrode sites post-stimulation.tDCS at 2 mA was not effectively blinded. That is, participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session (kappa level of agreement (κ) 0.28, 95% confidence interval (CI) 0.09 to 0.47 p=0.005) and the second session (κ=0.77, 95%CI 0.64 to 0.90), p=<0.001) indicating inadequate participant blinding. Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation (session one, κ=0.512, 95%CI 0.363 to 0.66, p<0.001; session two, κ=0.677, 95%CI 0.534 to 0.82) indicating inadequate assessor blinding.Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate. Positive results from such studies should be interpreted with caution.

PloS one

O'Connell, NE; Cossar, J; Marston, L; Wand, BM; Bunce, D; Moseley, GL; De Souza, LH


EEG Driven tDCS Versus Bifrontal tDCS for Tinnitus.

2012

Tinnitus is the perception of a sound in the absence of any objective physical sound source. Transcranial Direct Current Stimulation (tDCS) induces shifts in membrane resting potentials depending on the polarity of the stimulation: under the anode gamma band activity increases, whereas under the cathode the opposite occurs. Both single and multiple sessions of tDCS over the dorsolateral prefrontal cortex (DLPFC; anode over right DLPFC) yield a transient improvement in tinnitus intensity and tinnitus distress. The question arises whether optimization of the tDCS protocol can be obtained by using EEG driven decisions on where to place anode and cathode. Using gamma band functional connectivity could be superior to gamma band activity as functional connectivity determines the tinnitus network in many aspects of chronic tinnitus. Six-hundred-seventy-five patients were included in the study: 265 patients received tDCS with cathodal electrode placed over the left DLPFC and the anode placed overlying the right DLPFC, 380 patients received tDCS based on EEG connectivity, and 65 received no tDCS (i.e., waiting list control group). Repeated measures ANOVA revealed a significant main effect for pre versus post measurement. Bifrontal tDCS in comparison to EEG driven tDCS had a larger reduction for both tinnitus distress and tinnitus intensity. Whereas the results of the bifrontal tDCS seem to confirm previous studies, the use of gamma band functional connectivity seems not to bring any advantage to tDCS for tinnitus suppression. Using other potential biomarkers, such as gamma band activity, or theta functional connectivity could theoretically be of use. Further studies will have to elucidate whether brain state based tDCS has any advantages over "blind" bifrontal stimulation.

Frontiers in psychiatry / Frontiers Research Foundation

De Ridder, D; Vanneste, S


Finite-Element Model Predicts Current Density Distribution for Clinical Applications of tDCS and tACS.

2012

Transcranial direct current stimulation (tDCS) has been applied in numerous scientific studies over the past decade. However, the possibility to apply tDCS in therapy of neuropsychiatric disorders is still debated. While transcranial magnetic stimulation (TMS) has been approved for treatment of major depression in the United States by the Food and Drug Administration (FDA), tDCS is not as widely accepted. One of the criticisms against tDCS is the lack of spatial specificity. Focality is limited by the electrode size (35 cm(2) are commonly used) and the bipolar arrangement. However, a current flow through the head directly from anode to cathode is an outdated view. Finite-element (FE) models have recently been used to predict the exact current flow during tDCS. These simulations have demonstrated that the current flow depends on tissue shape and conductivity. To face the challenge to predict the location, magnitude, and direction of the current flow induced by tDCS and transcranial alternating current stimulation (tACS), we used a refined realistic FE modeling approach. With respect to the literature on clinical tDCS and tACS, we analyzed two common setups for the location of the stimulation electrodes which target the frontal lobe and the occipital lobe, respectively. We compared lateral and medial electrode configuration with regard to their usability. We were able to demonstrate that the lateral configurations yielded more focused stimulation areas as well as higher current intensities in the target areas. The high resolution of our simulation allows one to combine the modeled current flow with the knowledge of neuronal orientation to predict the consequences of tDCS and tACS. Our results not only offer a basis for a deeper understanding of the stimulation sites currently in use for clinical applications but also offer a better interpretation of observed effects.

Frontiers in psychiatry / Frontiers Research Foundation

Neuling, T; Wagner, S; Wolters, CH; Zaehle, T; Herrmann, CS


Transcranial direct current stimulation modulates human color discrimination in a pathway-specific manner.

2012

Previous research showed that transcranial direct current stimulation (tDCS) can modulate visual cortex excitability. However, there is no experiment on the effects of tDCS on color perception to date. The present study aimed to investigate the effects of tDCS on color discrimination tasks. Fifteen healthy subjects (mean age of 25.6 ± 4.4 years) were tested with Cambridge Color Test 2.0 (Trivector and ellipses protocols) and a Forced-choice Spatial Color Contrast Sensitivity task (vertical red-green sinusoidal grating) while receiving tDCS. Anodal, cathodal, and sham tDCS were delivered at Oz for 22 min using two square electrodes (25 cm(2) with a current of 1.5 mA) in sessions separated by 7 days. Anodal tDCS significantly increased tritan sensitivity (p < 0.01) and had no significant effect on protan, deutan, or red-green grating discrimination. The effects on the tritan discrimination returned to baseline after 15 min (p < 0.01). Cathodal tDCS reduced the sensitivity in the deutan axis and increased sensitivity in the tritan axis (p < 0.05). The lack of anodal tDCS effects in the protan, deutan, and red-green grating sensitivities could be explained by a "ceiling effect" since adults in this age range tend to have optimal color discrimination performance for these hues. The differential effects of cathodal tDCS on tritan and deutan sensitivities and the absence of the proposed ceiling effects for the tritan axes might be explained by Parvocellular (P) and Koniocellular (K) systems with regard to their functional, physiological, and anatomical differences. The results also support the existence of a systematic segregation of P and K color-coding cells in V1. Future research and possible clinical implications are discussed.

Frontiers in psychiatry / Frontiers Research Foundation

Costa, TL; Nagy, BV; Barboni, MT; Boggio, PS; Ventura, DF


Parietal contributions to visual working memory depend on task difficulty.

2012

The nature of parietal contributions to working memory (WM) remain poorly understood but of considerable interest. We previously reported that posterior parietal damage selectively impaired WM probed by recognition (Berryhill and Olson, 2008a). Recent studies provided support using a neuromodulatory technique, transcranial direct current stimulation (tDCS) applied to the right parietal cortex (P4). These studies confirmed parietal involvement in WM because parietal tDCS altered WM performance: anodal current tDCS improved performance in a change detection task, and cathodal current tDCS impaired performance on a sequential presentation task. Here, we tested whether these complementary results were due to different degrees of parietal involvement as a function of WM task demands, WM task difficulty, and/or participants' WM capacity. In Experiment 1, we applied cathodal and anodal tDCS to the right parietal cortex and tested participants on both previously used WM tasks. We observed an interaction between tDCS (anodal, cathodal), WM task difficulty, and participants' WM capacity. When the WM task was difficult, parietal stimulation (anodal or cathodal) improved WM performance selectively in participants with high WM capacity. In the low WM capacity group, parietal stimulation (anodal or cathodal) impaired WM performance. These nearly equal and opposite effects were only observed when the WM task was challenging, as in the change detection task. Experiment 2 probed the interplay of WM task difficulty and WM capacity in a parametric manner by varying set size in the WM change detection task. Here, the effect of parietal stimulation (anodal or cathodal) on the high WM capacity group followed a linear function as WM task difficulty increased with set size. The low WM capacity participants were largely unaffected by tDCS. These findings provide evidence that parietal involvement in WM performance depends on both WM capacity and WM task demands. We discuss these findings in terms of alternative WM strategies employed by low and high WM capacity individuals. We speculate that low WM capacity individuals do not recruit the posterior parietal lobe for WM tasks as efficiently as high WM capacity individuals. Consequently, tDCS provides greater benefit to individuals with high WM capacity.

Frontiers in psychiatry / Frontiers Research Foundation

Jones, KT; Berryhill, ME


Learning, memory, and transcranial direct current stimulation.

2012

Transcranial direct current stimulation (tDCS) has been the subject of many studies concerning its possible cognitive effects. One of the proposed mechanisms of action for neuromodulatory techniques, such as transcranial magnetic stimulation and tDCS is induction of long-term potentiation (LTP) and long-term depression (LTD)-like phenomena. LTP and LTD are also among the most important neurobiological processes involved in memory and learning. This fact has led to an immediate interest in the study of possible effects of tDCS on memory consolidation, retrieval, or learning of various tasks. This review analyses published articles describing beneficial or disruptive effects of tDCS on memory and learning in normal subjects. The most likely mechanisms underlying these effects are discussed.

Frontiers in psychiatry / Frontiers Research Foundation

Brasil-Neto, JP


Transcranial direct current stimulation and behavioral models of smoking addiction.

2012

While few studies have applied transcranial direct current stimulation (tDCS) to smoking addiction, existing work suggests that the intervention holds promise for altering the complex system by which environmental cues interact with cravings to drive behavior. Imaging and repetitive transcranial magnetic stimulation studies suggest that increased dorsolateral prefrontal cortex (DLPFC) activation and integrity may be associated with increased resistance to smoking cues. Anodal tDCS of the DLPFC, believed to boost activation, reduces cravings in response to these cues. The finding that noninvasive stimulation modifies cue induced cravings has profound implications for understanding the processes underlying addiction and relapse. tDCS can also be applied to probe mechanisms underlying and supporting nicotine addiction, as was done in a pharmacologic study that applied nicotine, tDCS, and TMS paired associative stimulation to find that stopping nicotine after chronic use induces a reduction in plasticity, causing difficulty in breaking free from association between cues and cravings. This mini-review will place studies that apply tDCS to smokers in the context of research involving the neural substrates of nicotine addiction.

Frontiers in psychiatry / Frontiers Research Foundation

Fraser, PE; Rosen, AC


Enhancement of object detection with transcranial direct current stimulation is associated with increased attention.

2012

We previously found that Transcranial Direct Current Stimulation (tDCS) improves learning and performance in a task where subjects learn to detect potential threats indicated by small target objects hidden in a complex virtual environment. In the present study, we examined the hypothesis that these effects on learning and performance are related to changes in attention. The effects of tDCS were tested for three forms of attention (alerting, orienting, and executive attention) using the Attention Network Task (ANT), which were compared with performance on the object-learning task.Participants received either 0.1 mA (N = 10) or 2.0 mA (N = 9) tDCS during training and were tested for performance in object-identification before training (baseline-test) and again immediately after training (immediate test). Participants next performed the Attention Networks Task (ANT), and were later tested for object-identification performance a final time (delayed test). Alerting, but not orienting or executive attention, was significantly higher for participants receiving 2.0 mA compared with 0.1 mA tDCS (p < 0.02). Furthermore, alerting scores were significantly correlated with the proportion of hits (p < 0.01) for participants receiving 2.0 mA.These results indicate that tDCS enhancement of performance in this task may be related in part to the enhancement of alerting attention, which may benefit the initial identification, learning and/or subsequent recognition of target objects indicating potential threats.

BMC neuroscience

Coffman, BA; Trumbo, MC; Clark, VP


Multi-session transcranial direct current stimulation (tDCS) elicits inflammatory and regenerative processes in the rat brain.

2012

Transcranial direct current stimulation (tDCS) is increasingly being used in human studies as an adjuvant tool to promote recovery of function after stroke. However, its neurobiological effects are still largely unknown. Electric fields are known to influence the migration of various cell types in vitro, but effects in vivo remain to be shown. Hypothesizing that tDCS might elicit the recruitment of cells to the cortex, we here studied the effects of tDCS in the rat brain in vivo. Adult Wistar rats (n = 16) were randomized to either anodal or cathodal stimulation for either 5 or 10 consecutive days (500 µA, 15 min). Bromodeoxyuridine (BrdU) was given systemically to label dividing cells throughout the experiment. Immunohistochemical analyses ex vivo included stainings for activated microglia and endogenous neural stem cells (NSC). Multi-session tDCS with the chosen parameters did not cause a cortical lesion. An innate immune response with early upregulation of Iba1-positive activated microglia occurred after both cathodal and anodal tDCS. The involvement of adaptive immunity as assessed by ICAM1-immunoreactivity was less pronounced. Most interestingly, only cathodal tDCS increased the number of endogenous NSC in the stimulated cortex. After 10 days of cathodal stimulation, proliferating NSC increased by ∼60%, with a significant effect of both polarity and number of tDCS sessions on the recruitment of NSC. We demonstrate a pro-inflammatory effect of both cathodal and anodal tDCS, and a polarity-specific migratory effect on endogenous NSC in vivo. Our data suggest that tDCS in human stroke patients might also elicit NSC activation and modulate neuroinflammation.

PloS one

Rueger, MA; Keuters, MH; Walberer, M; Braun, R; Klein, R; Sparing, R; Fink, GR; Graf, R; Schroeter, M


A randomized double-blind sham-controlled study of transcranial direct current stimulation for treatment-resistant major depression.

2012

Objectives: Transcranial direct current stimulation (tDCS) has demonstrated some efficacy in treatment-resistant major depression (TRD). The majority of previous controlled studies have used anodal stimulation to the left dorsolateral prefrontal cortex (DLPFC) and a control location such as the supraorbital region for the cathode. Several open-label studies have suggested effectiveness from anodal stimulation to the left DLPFC combined with cathodal stimulation to the right DLPFC. Thus, this study evaluated the efficacy of tDCS using anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC compared to sham tDCS. Methods: Subjects between the ages of 18 and 65 were recruited from a tertiary care university hospital. Twenty-four subjects with TRD and a 17-item Hamilton Rating Scale for Depression greater than 21 were randomized to receive tDCS or sham tDCS. The rates of remission were compared between the two treatment groups. Results: The remission rates did not differ significantly between the two groups using an intention to treat analysis. More subjects in the active tDCS group had failed a course of electroconvulsive therapy in the current depressive episode. Side effects did not differ between the two groups and in general the treatment was very well tolerated. Conclusion: Anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC was not efficacious in TRD. However, a number of methodological limitations warrant caution in generalizing from this study. Ongoing, controlled studies should provide further clarification on the efficacy of this stimulation configuration in TRD. ClinicalTrials.gov Identifier: NCT01078948.

Frontiers in psychiatry / Frontiers Research Foundation

Blumberger, DM; Tran, LC; Fitzgerald, PB; Hoy, KE; Daskalakis, ZJ


Altering automatic verbal processes with transcranial direct current stimulation.

2012

Background: Word retrieval during verbal fluency tasks invokes both automatic and controlled cognitive processes. A distinction has been made between the generation of words clusters and switches between such clusters on verbal fluency tasks. Clusters, defined by the reporting of contiguous words that constitute semantic or phonemic subcategories, are thought to reflect relatively automatic processing. In contrast, switching from one subcategory to another is thought to require a more controlled, effortful form of cognitive processing. Objective: In this single-blind, sham-controlled experiment, we investigated whether anodal and cathodal transcranial direct current stimulation (tDCS) can differentially modify controlled or automatic processes that support lexical retrieval, as assessed by clustering and switching on verbal fluency tasks, in 24 healthy right-handed adults. Methods: Participants were randomly assigned to receive 1 mA of either anodal (excitatory) or cathodal (inhibitory) active tDCS over the left dorsolateral prefrontal cortex in addition to sham stimulation over the same region in counterbalanced order. Participants engaged in various cognitive activities during the first 23 min of stimulation. Then, during the final segment of each 30-min session, they completed letter- and category-cued word fluency tasks. Results: Participants reported more words on category-cued word fluency tasks during anodal than sham stimulation (25.9 vs. 23.0 words; p = 0.055). They also showed a net increase in the number of clustered words during anodal stimulation compared to a net decrease during cathodal stimulation (1.3 vs. -1.5 words; p = 0.038). Conclusion: tDCS can selectively alter automatic aspects of speeded lexical retrieval in a polarity-dependent fashion during a category-guided fluency task.

Frontiers in psychiatry / Frontiers Research Foundation

Vannorsdall, TD; Schretlen, DJ; Andrejczuk, M; Ledoux, K; Bosley, LV; Weaver, JR; Skolasky, RL; Gordon, B


Enhancing motor skill learning with transcranial direct current stimulation - a concise review with applications to stroke.

2012

In the past few years, there has been a rapid increase in the application of non-invasive brain stimulation to study brain-behavior relations in an effort to potentially increase the effectiveness of neuro-rehabilitation. Transcranial direct current stimulation (tDCS), an emerging technique of non-invasive brain stimulation, has shown to produce beneficial neural effects in consequence with improvements in motor behavior. tDCS has gained popularity as it is economical, simple to use, portable, and increases corticospinal excitability without producing any serious side effects. As tDCS has been increasingly investigated as an effective tool for various disorders, numerous improvements, and developments have been proposed with respect to this technique. tDCS has been widely used to identify the functional relevance of particular brain regions in motor skill learning and also to facilitate activity in specific cortical areas involved in motor learning, in turn improving motor function. Understanding the interaction between tDCS and motor learning can lead to important implications for developing various rehabilitation approaches. This paper provides a concise overview of tDCS as a neuromodulatory technique and its interaction with motor learning. The paper further briefly goes through the application of this priming technique in the stroke population.

Frontiers in psychiatry / Frontiers Research Foundation

Madhavan, S; Shah, B


Contralesional Hemisphere Control of the Proximal Paretic Upper Limb following Stroke.

2011 Dec

Cathodal transcranial direct current stimulation (c-tDCS) can reduce excitability of neurons in primary motor cortex (M1) and may facilitate motor recovery after stroke. However, little is known about the neurophysiological effects of tDCS on proximal upper limb function. We hypothesized that suppression of contralesional M1 (cM1) excitability would produce neurophysiological effects that depended on the severity of upper limb impairment. Twelve patients with varying upper limb impairment after subcortical stroke were assessed on clinical scales of upper limb spasticity, impairment, and function. Magnetic resonance imaging was used to determine lesion size and fractional anisotropy (FA) within the posterior limbs of the internal capsules indicative of corticospinal tract integrity. Excitability within paretic M1 biceps brachii representation was determined from motor-evoked potentials during selective isometric tasks, after cM1 sham stimulation and after c-tDCS. These neurophysiological data indicate that c-tDCS improved selective proximal upper limb control for mildly impaired patients and worsened it for moderate to severely impaired patients. The direction of the neurophysiological after effects of c-tDCS was strongly related to upper limb spasticity, impairment, function, and FA asymmetry between the posterior limbs of the internal capsules. These results indicate systematic variation of cM1 for proximal upper limb control after stroke and that suppression of cM1 excitability is not a "one size fits all" approach.

Cerebral cortex (New York, N.Y. : 1991)

Bradnam, LV; Stinear, CM; Barber, PA; Byblow, WD


A finite element analysis of the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in tDCS.

2011 Dec

We investigated the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in transcranial direct current stimulation (tDCS). For this purpose, we used the finite element method to compute the distribution of the current density in a four-layered spherical head model using various electrode montages, corresponding to a range of electrode sizes and inter-electrode distances. We found that smaller electrodes required slightly less current to achieve a constant value of the current density at a reference point on the brain surface located directly under the electrode center. Under these conditions, smaller electrodes also produced a more focal current density distribution in the brain, i.e. the magnitude of the current density fell more rapidly with distance from the reference point. The combination of two electrodes with different areas produced an asymmetric current distribution that could lead to more effective and localized neural modulation under the smaller electrode than under the larger one. Focality improved rapidly with decreasing electrode size when the larger electrode sizes were considered but the improvement was less marked for the smaller electrode sizes. Also, focality was not affected significantly by inter-electrode distance unless two large electrodes were placed close together. Increasing the inter-electrode distance resulted in decreased shunting of the current through the scalp and the cerebrospinal fluid, and decreasing electrode area resulted in increased current density on the scalp under the edges of the electrode. Our calculations suggest that when working with conventional electrodes (25-35 cm(2)), one of the electrodes should be placed just 'behind' the target relative to the other electrode, for maximum current density on the target. Also electrodes with areas in the range 3.5-12 cm(2) may provide a better compromise between focality and current density in the scalp than the traditional electrodes. Finally, the use of multiple small return electrodes may be more efficient than the use of a single large return electrode.

Journal of neural engineering

Faria, P; Hallett, M; Miranda, PC


Effects of transcranial direct current stimulation (tDCS) on behaviour and electrophysiology of language production.

2011 Dec

Excitatory anodal transcranial direct current stimulation (A-tDCS) over the left dorsal prefrontal cortex (DPFC) has been shown to improve language production. The present study examined neurophysiological underpinnings of this effect. In a single-blinded within-subject design, we traced effects of A-tDCS compared to sham stimulation over the left DPFC using electrophysiological and behavioural correlates during overt picture naming. Online effects were examined during A-tDCS by employing the semantic interference (SI-)Effect - a marker that denotes the functional integrity of the language system. The behavioural SI-Effect was found to be reduced, whereas the electrophysiological SI-Effect was enhanced over left compared to right temporal scalp-electrode sites. This modulation is suggested to reflect a superior tuning of neural responses within language-related generators. After -(offline) effects of A-tDCS were detected in the delta frequency band, a marker of neural inhibition. After A-tDCS there was a reduction in delta activity during picture naming and the resting state, interpreted to indicate neural disinhibition. Together, these findings demonstrate electrophysiological modulations induced by A-tDCS of the left DPFC. They suggest that A-tDCS is capable of enhancing neural processes during and after application. The present functional and oscillatory neural markers could detect positive effects of prefrontal A-tDCS, which could be of use in the neuro-rehabilitation of frontal language functions.

Neuropsychologia

Wirth, M; Rahman, RA; Kuenecke, J; Koenig, T; Horn, H; Sommer, W; Dierks, T


Modulation of motor performance and motor learning by transcranial direct current stimulation.

2011 Dec

Transcranial direct current stimulation (tDCS) has shown preliminary success in improving motor performance and motor learning in healthy individuals, and restitution of motor deficits in stroke patients. This brief review highlights some recent work.Within the past years, behavioural studies have confirmed and specified the timing and polarity specific effects of tDCS on motor skill learning and motor adaptation. There is strong evidence that timely co-application of (hand/arm) training and anodal tDCS to the contralateral M1 can improve motor learning. Improvements in motor function as measured by clinical scores have been described for combined tDCS and training in stroke patients. For this purpose, electrode montages have been modified with respect to interhemispheric imbalance after brain injury. Cathodal tDCS applied to the unlesioned M1 or bihemispheric M1 stimulation appears to be well tolerated and useful to induce improvements in motor function. Mechanistic studies in humans and animals are discussed with regard to physiological motor learning.tDCS is well tolerated, easy to use and capable of inducing lasting improvements in motor function. This method holds promise for the rehabilitation of motor disabilities, although acute studies in patients with brain injury are so far lacking.

Current opinion in neurology

Reis, J; Fritsch, B


Electrical stimulation over the left inferior frontal gyrus (IFG) determines long-term effects in the recovery of speech apraxia in three chronic aphasics.

2011 Dec

A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects the performance of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS for the recovery of apraxia of speech in 3 patients with stroke-induced aphasia. Over 2 weeks, three aphasic subjects participated in a randomized double-blinded experiment involving intensive language training for their articulatory difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation over the left inferior frontal gyrus (referred to as Broca's area) while they performed a repetition task. By the end of each week, a significant improvement was found in both conditions. However, all three subjects showed greater response accuracy in the anodic than in the sham condition. Moreover, results for transfer of treatment effects, although different across subjects, indicate a generalization of the recovery at the language test. Subjects 2 and 3 showed a significant improvement in oral production tasks, such as word repetition and reading, while Subjects 1 and 2 had an unexpected significant recovery in written naming and word writing under dictation tasks. At three follow-ups (1 week, 1 and 2 months after the end of treatment), response accuracy was still significantly better in the anodic than in sham condition, suggesting a long-term effect on the recovery of their articulatory gestures.

Behavioural brain research

Marangolo, P; Marinelli, CV; Bonifazi, S; Fiori, V; Ceravolo, MG; Provinciali, L; Tomaiuolo, F


Improving working memory: exploring the effect of transcranial random noise stimulation and transcranial direct current stimulation on the dorsolateral prefrontal cortex.

2011 Dec

The aim of this study was to determine if working memory (WM) performance is significantly improved after the delivery of transcranial random noise stimulation (tRNS) to the left dorsolateral prefrontal cortex (DLPFC), compared to an active comparator or sham.Ten participants undertook three experimental sessions in which they received 10 min of anodal tDCS (active comparator), tRNS or sham tDCS whilst performing the Sternberg WM task. Intra-stimulation engagement in a WM task was undertaken as this has been previously shown to enhance the effects of tDCS. Experimental sessions were separated by a minimum of 1 week. Immediately prior to and after each stimulation session the participants were measured on speed and accuracy of performance on an n-back task.There was significant improvement in speed of performance following anodal tDCS on the 2-back WM task; this was the only significant finding.The results do not provide support for the hypothesis that tRNS improves WM. However, the study does provide confirmation of previous findings that anodal tDCS enhances some aspects of DLPFC functioning. Methodological limitations that may have contributed to the lack of significant findings following tRNS are discussed.Anodal tDCS may have significant implications for WM remediation in psychiatric conditions, particularly schizophrenia.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Mulquiney, PG; Hoy, KE; Daskalakis, ZJ; Fitzgerald, PB


Abnormal Changes of Synaptic Excitability in Migraine with Aura.

2011 Nov

Migraine patients are characterized by altered cortical excitability and information processing between attacks. The relationship between these abnormalities is still poorly understood. In this study, visual evoked potentials (VEP) and proton magnetic resonance spectroscopy were recorded simultaneously in migraineurs and healthy subjects. In order to investigate the homeostatic-like plasticity in the visual cortex, cortical excitability was modified using transcranial direct current stimulation (tDCS). Before any stimulation, migraineurs showed significantly higher glutamate/creatine ratios (Glx/Cr) than healthy subjects. In healthy subjects, excitatory (anodal) tDCS caused an increase and inhibitory (cathodal) tDCS a decrease in the Glx/Cr ratio. Subsequent photic stimulation (PS) reversed the changes in Glx/Cr ratios, which returned back to baseline, demonstrating homeostatic-like metaplasticity in the control group. In migraine patients, both anodal and cathodal tDCS decreased the Glx/Cr ratio, which did not return to baseline after PS. While healthy subjects showed an increase in VEP amplitude under anodal and a reduction under cathodal tDCS, the modifiability of VEP under tDCS was reduced in migraineurs. The results demonstrate a reduced responsiveness of the occipital cortex to interventions that change cortical excitability in migraine. Moreover, altered glutamatergic neurotransmission seems to mediate the relation between abnormal cortical information processing and excitability in migraineurs.

Cerebral cortex (New York, N.Y. : 1991)

Siniatchkin, M; Sendacki, M; Moeller, F; Wolff, S; Jansen, O; Siebner, H; Stephani, U


Excitability changes induced in the human auditory cortex by transcranial direct current stimulation: direct electrophysiological evidence.

2011 Nov

Transcranial direct current stimulation (tDCS) can systematically modify behavior by inducing changes in the underlying brain function. Objective electrophysiological evidence for tDCS-induced excitability changes has been demonstrated for the visual and somatosensory cortex, while evidence for excitability changes in the auditory cortex is lacking. In the present study, we applied tDCS over the left temporal as well as the left temporo-parietal cortex and investigated tDCS-induced effects on auditory evoked potentials after anodal, cathodal, and sham stimulation. Results show that anodal and cathodal tDCS can modify auditory cortex reactivity. Moreover, auditory evoked potentials were differentially modulated as a function of site of stimulation. While anodal tDCS over the temporal cortex increased auditory P50 amplitudes, cathodal tDCS over the temporo-parietal cortex induced larger N1 amplitudes. The results directly demonstrate excitability changes in the auditory cortex induced by active tDCS over the temporal and temporo-parietal cortex and might contribute to the understanding of mechanisms involved in the successful treatment of auditory disorders like tinnitus via tDCS.

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Zaehle, T; Beretta, M; Jäncke, L; Herrmann, CS; Sandmann, P


Transcranial direct current stimulation in refractory continuous spikes and waves during slow sleep: a controlled study.

2011 Nov

Cathodal transcranial direct current stimulation (tDCS) decreases cortical excitability. The purpose of the study was to investigate whether cathodal tDCS could interrupt the continuous epileptiform activity. Five patients with focal, refractory continuous spikes and waves during slow sleep were recruited. Cathodal tDCS and sham stimulation were applied to the epileptic focus, before sleep (1 mA; 20 min). Cathodal tDCS did not reduce the spike-index in any of the patients.

Epilepsy research

Varga, ET; Terney, D; Atkins, MD; Nikanorova, M; Jeppesen, DS; Uldall, P; Hjalgrim, H; Beniczky, S


Fronto-extracephalic transcranial direct current stimulation as a treatment for major depression: an open-label pilot study.

2011 Nov

Several recent trials have reported transcranial direct current stimulation (tDCS) to be effective in treating depression, though the relative benefits of different electrode montages remain unexplored. Whereas all recent studies have used a bifrontal (BF) electrode montage, studies published in the 1960s and 1970s placed one electrode in an extracephalic position, with some positive reports of efficacy. This study investigated the efficacy and safety of tDCS given with a fronto-extracephalic (F-EX) montage.2 mA tDCS was administered for 20 min every weekday over four weeks in 11 participants with a Major Depressive Episode who had previously shown inadequate response to, or relapsed following, a course of BF tDCS. For F-EX tDCS the anode was placed on the left dorsolateral prefrontal cortex and the cathode on the right upper arm. Depression severity and neuropsychological function were assessed before and after the treatment course. Antidepressant response was compared across an equivalent treatment period for both montages.F-EX tDCS was shown to be safe and well tolerated. Depression ratings improved after acute treatment on the Montgomery Åsberg Depression Rating Scale (p < 0.001). Participants showed greater initial treatment response with F-EX tDCS than with BF tDCS (p < 0.001).This was an open label pilot study. The two comparison treatments were applied consecutively.F-EX tDCS appears to be safe and to have antidepressant effects, and may lead to more rapid improvement than tDCS given with a BF montage.

Journal of affective disorders

Martin, DM; Alonzo, A; Mitchell, PB; Sachdev, P; Gálvez, V; Loo, CK


Short- and long-lasting tinnitus relief induced by transcranial direct current stimulation.

2011 Nov

A significant proportion of the population suffers from tinnitus, a bothersome auditory phantom perception that can severely alter the quality of life. Numerous experimental studies suggests that a maladaptive plasticity of the auditory and limbic cortical areas may underlie tinnitus. Accordingly, repetitive transcranial magnetic stimulation (rTMS) has been repeatedly used with success to reduce tinnitus intensity. The potential of transcranial direct current stimulation (tDCS), another promising method of noninvasive brain stimulation, to relieve tinnitus has not been explored systematically. In a double-blind, placebo-controlled and balanced order design, 20 patients suffering from chronic untreatable tinnitus were submitted to 20 minutes of 1 mA anodal, cathodal and sham tDCS targeting the left temporoparietal area. The primary outcome measure was a change in tinnitus intensity or discomfort assessed with a Visual Analogic Scale (VAS) change-scale immediately after tDCS and 1 hour later. Compared to sham tDCS, anodal tDCS significantly reduced tinnitus intensity immediately after stimulation; whereas cathodal tDCS failed to do so. The variances of the tinnitus intensity and discomfort VAS change-scales increased dramatically after anodal and cathodal tDCS, whereas they remained virtually unchanged after sham tDCS. Moreover, several patients unexpectedly reported longer-lasting effects (at least several days) such as tinnitus improvement, worsening, or changes in tinnitus features, more frequently after real than sham tDCS. Anodal tDCS is a promising therapeutic tool for modulating tinnitus perception. Moreover, both anodal and cathodal tDCS seem able to alter tinnitus perception and could, thus, be used to trigger plastic changes.

Journal of neurology

Garin, P; Gilain, C; Van Damme, JP; de Fays, K; Jamart, J; Ossemann, M; Vandermeeren, Y

Link to full article text


Activation of inhibition: diminishing impulsive behavior by direct current stimulation over the inferior frontal gyrus.

2011 Nov

A common feature of human existence is the ability to reverse decisions after they are made but before they are implemented. This cognitive control process, termed response inhibition, refers to the ability to inhibit an action once initiated and has been localized to the right inferior frontal gyrus (rIFG) based on functional imaging and brain lesion studies. Transcranial direct current stimulation (tDCS) is a brain stimulation technique that can facilitate as well as impair cortical function. To explore whether response inhibition can be improved through rIFG electrical stimulation, we administered focal tDCS before subjects performed the stop signal task (SST), which measures response inhibition. Notably, activation of the rIFG by unilateral anodal stimulation significantly improved response inhibition, relative to a sham condition, whereas the same tDCS protocol did not affect response time in the go trials of the SST and in a control task. Furthermore, the SST was not affected by tDCS at a control site, the right angular gyrus. Our results are the first demonstration of response inhibition improvement with brain stimulation over rIFG and further confirm the rIFG involvement in this task. Although this study was conducted in healthy subjects, present findings with anodal rIFG stimulation support the use of similar paradigms for the treatment of cognitive control impairments in pathological conditions.

Journal of cognitive neuroscience

Jacobson, L; Javitt, DC; Lavidor, M


Treatment of late-life depression: a role of non-invasive brain stimulation techniques.

2011 Oct

Late-life depression (LLD) is a frequent complication of the ageing process, occurring in up to 5% of community-dwelling elderly and in a higher proportion of subjects with coexistent medical illnesses. Its presence has been consistently associated with cognitive impairment, greater disability and increased mortality. Approximately half of patients with LLD have evidence of subcortical ischaemic damage in prefrontal circuits revealed by MRI. This might constitute the biological substrate of the cardinal symptoms of depression and of executive dysfunction. An important proportion of patients with LLD do not achieve remission of their depressive symptoms in spite of adequate pharmacological and psychotherapeutic treatment. In addition, a group of LLD patients progress to further impairment and disability in the form of a dementing disorder. There is an imperative need to develop new treatment strategies for LLD. Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are safe and efficacious interventions that might be used in combination with other therapeutic options to improve treatment outcomes. However, there are still questions regarding the optimal way in which rTMS and dTCS should be delivered as well as to the way in which we may identify the subjects who will benefit the most from these interventions.

International review of psychiatry (Abingdon, England)

Jorge, RE; Robinson, RG


Neglect-like effects induced by tDCS modulation of posterior parietal cortices in healthy subjects.

2011 Oct

Repetitive transcranial magnetic stimulation (rTMS) over right posterior parietal cortex was shown to induce interference on visuospatial perception in healthy subjects. Transcranial direct current stimulation (tDCS) is another noninvasive brain stimulation technique that works modulating cortical activity. It is applied through easy to use, noncostly, and portable devices.The aim of the current study was to investigate if the novel approach of "dual" stimulation over parietal cortices compared with the unilateral (right) cathodal one is able to induce greater and/or longer-lasting neglect-like effects in normal subjects performing a computerized visuospatial task.Eleven healthy subjects underwent a computerized visuospatial task requiring judgments about the symmetry of prebisected lines in baseline condition, during and after tDCS. Right cathodal and left anodal tDCS were simultaneously applied over homologue posterior parietal cortices in the "dual" approach, whereas right cathodal tDCS was used in the traditional unihemisphere stimulation.A significant rightward bias in symmetry judgments as compared with baseline and sham conditions was observed in both the stimulation approaches. With "dual" tDCS compared with cathodal stimulation the effect was stronger and appeared earlier, but no longer-lasting after effects were found.We speculate that the resulting modulation of interhemispheric inhibition mediated the additional rightward bias in task performance for "dual" hemisphere compared with unihemisphere tDCS. If "dual" tDCS may better reproduce mechanisms underlying real lesions, it could provide a more suitable model for rehabilitation of negligent patients.

Brain stimulation

Giglia, G; Mattaliano, P; Puma, A; Rizzo, S; Fierro, B; Brighina, F


Tolerability of transcranial direct current stimulation in childhood-onset schizophrenia.

2011 Oct

In recent years, transcranial direct current stimulation (tDCS) has been used to study and treat many neuropsychiatric conditions. However, information regarding its tolerability in the pediatric population is lacking.This study aims to investigate the tolerability aspects of tDCS in the childhood-onset schizophrenia (COS) population.Twelve participants with COS completed this inpatient study. Participants were assigned to one of two groups: bilateral anodal dorsolateral prefrontal cortex (DLPFC) stimulation (n = 8) or bilateral cathodal superior temporal gyrus (STG) stimulation (n = 5). Patients received either 2 mA of active treatment or sham treatment (with possibility of open active treatment) for 20 minutes, for a total of 10 sessions (2 weeks).tDCS was well tolerated in the COS population with no serious adverse events occurring during the study.This is the first study to demonstrate that a 20-minute duration of 2 mA of bilateral anodal and bilateral cathodal DC polarization to the DLPFC and STG was well tolerated in a pediatric population.

Brain stimulation

Mattai, A; Miller, R; Weisinger, B; Greenstein, D; Bakalar, J; Tossell, J; David, C; Wassermann, EM; Rapoport, J; Gogtay, N


Effects of transcranial direct current stimulation of the primary sensory cortex on somatosensory perception.

2011 Oct

Transcranial direct current stimulation (tDCS) is able to modify cortical excitability and activity in humans.The aim of the present study was to analyze the effects of tDCS of the primary sensory cortex (SI) on thermal and mechanical perception, assessed by quantitative sensory testing (QST).The comprehensive QST protocol encompassing thermal and mechanical detection and pain thresholds as devised by the German Research Network on Neuropathic Pain (DFNS) was applied to skin areas innervated by the radial and median nerve of 12 healthy subjects, who were examined before and after each tDCS stimulation type. Anodal, cathodal, and sham tDCS was applied at a 1 mA current intensity with the active electrode placed over the left primary sensory cortex (SI) and the reference electrode above the right orbit for 15 minutes.After cathodal tDCS cold detection threshold (CDT) significantly increased in the contralateral (P < .01) and ipsilateral hand (P < .05) as compared to baseline condition and sham stimulation, after cathodal stimulation significantly increased warm detection threshold (WDT) was observed in the contralateral hand when compared with the baseline condition (P < .05) but not with sham stimulation. Thermal pain as well as mechanical detection and pain thresholds remained unaltered.Cathodal tDCS of the primary sensory cortex significantly reduced the sensitivity to Aδ-fiber-mediated cold sensation, C-fiber-mediated warm sensation was reduced only compared with baseline, whereas Aß-fiber-mediated somatosensory inputs were less affected. Our results correspond with our previous observations of primary motor cortex tDCS effects on QST parameters.

Brain stimulation

Grundmann, L; Rolke, R; Nitsche, MA; Pavlakovic, G; Happe, S; Treede, RD; Paulus, W; Bachmann, CG


Do tDCS and TMS influence tinnitus transiently via a direct cortical and indirect somatosensory modulating effect? A combined TMS-tDCS and TENS study.

2011 Oct

Tinnitus is usually defined as an intrinsic sound percept that cannot be attributed to an external sound source that tinnitus can be suppressed by neuromodulation techniques such as transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), and transcranial electrical nerve stimulation (TENS). It is thought that TMS and tDCS modulate tinnitus directly by targeting the frontal and/or auditory cortex of the brain, whereas TENS most likely influences tinnitus indirectly via cervical nerve-cochlear nucleus interactions. It is unknown whether part of the tinnitus modulating effect of tDCS and TMS also depends on a somatosensory modulating effect analogous to TENS, via the trigeminal and cervical nerves. We aimed to investigate this question by analyzing to which extent response to one neuromodulation technique predicts the response to another neuromodulation technique. We analyzed 153 patients with chronic tinnitus (> 1 year) who underwent all three neuromodulation techniques (C2 nerve TENS, auditory cortex TMS, and bifrontal tDCS). Our results show that TENS predicts tDCS and TMS better than the opposite, and tDCS predicts TMS response and vice versa. On the basis of these results, it is it is argued that TENS only modulates the tinnitus brain circuit indirectly, whereas TMS and tDCS have a dual working mechanism, a TENS-like mechanism plus a direct brain modulating mechanism.

Brain stimulation

Vanneste, S; Langguth, B; De Ridder, D


Random noise stimulation improves neuroplasticity in perceptual learning.

2011 Oct

Perceptual learning is considered a manifestation of neural plasticity in the human brain. We investigated brain plasticity mechanisms in a learning task using noninvasive transcranial electrical stimulation (tES). We hypothesized that different types of tES would have varying actions on the nervous system, which would result in different efficacies of neural plasticity modulation. Thus, the principal goal of the present study was to verify the possibility of inducing differential plasticity effects using two tES approaches [i.e., direct current stimulation (tDCS) and random noise stimulation (tRNS)] during the execution of a visual perceptual learning task.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Fertonani, A; Pirulli, C; Miniussi, C


Prefrontal transcranial direct current stimulation changes connectivity of resting-state networks during fMRI.

2011 Oct

Transcranial direct current stimulation (tDCS) has been proposed for experimental and therapeutic modulation of regional brain function. Specifically, anodal tDCS of the dorsolateral prefrontal cortex (DLPFC) together with cathodal tDCS of the supraorbital region have been associated with improvement of cognition and mood, and have been suggested for the treatment of several neurological and psychiatric disorders. Although modeled mathematically, the distribution, direction, and extent of tDCS-mediated effects on brain physiology are not well understood. The current study investigates whether tDCS of the human prefrontal cortex modulates resting-state network (RSN) connectivity measured by functional magnetic resonance imaging (fMRI). Thirteen healthy subjects underwent real and sham tDCS in random order on separate days. tDCS was applied for 20 min at 2 mA with the anode positioned over the left DLPFC and the cathode over the right supraorbital region. Patterns of resting-state brain connectivity were assessed before and after tDCS with 3 T fMRI, and changes were analyzed for relevant networks related to the stimulation-electrode localizations. At baseline, four RSNs were detected, corresponding to the default mode network (DMN), the left and right frontal-parietal networks (FPNs) and the self-referential network. After real tDCS and compared with sham tDCS, significant changes of regional brain connectivity were found for the DMN and the FPNs both close to the primary stimulation site and in connected brain regions. These findings show that prefrontal tDCS modulates resting-state functional connectivity in distinct functional networks of the human brain.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Keeser, D; Meindl, T; Bor, J; Palm, U; Pogarell, O; Mulert, C; Brunelin, J; Möller, HJ; Reiser, M; Padberg, F


Top down prefrontal affective modulation of tinnitus with multiple sessions of tDCS of dorsolateral prefrontal cortex.

2011 Oct

Most forms of tinnitus are attributable to reorganization and hyperactivity in the auditory central nervous system with coactivation of nonauditory brain structures. One such nonauditory brain area is the dorsolateral prefrontal cortex (DLPFC), which is important for the integration of sensory and emotional aspects of tinnitus. Based on extensive evidence that transcranial direct current stimulation can induce significant effects on DLPFC-related cognitive function, we aimed to investigate whether left or right anodal DLFPC tDCS is associated with modulation of tinnitus. We conducted a double-blind, placebo-controlled cross-over study in which 15 subjects with tinnitus were randomly assigned to receive active and sham anodal tDCS over left (n = 8) or right DLPFC (n = 7) for six sessions in a counterbalanced order; the cathode electrode was placed in the contralateral DLPFC. The results demonstrate that both active conditions-irrespective of the anodal position-can decrease tinnitus annoyance but it is not associated with improvements in tinnitus intensity when comparing pre-tDCS versus post-tDCS as well as comparing sham-tDCS versus real tDCS. Also, we show that the anode electrode placed over the left DLPFC modulates depression when comparing pre-tDCS versus post-tDCS as well as comparing sham-tDCS versus real tDCS. In addition, we also show that the anode electrode placed over the right DLPFC modulates anxiety when comparing pre-tDCS versus post-tDCS. This latter effect does not remain when we compare sham-tDCS versus real tDCS. This study further supports the involvement of the prefrontal cortex in the neural network associated with tinnitus, and also provides initial evidence for a potential brain stimulation site for tinnitus treatment in association with other treatments that can reduce tinnitus intensity.

Brain stimulation

Faber, M; Vanneste, S; Fregni, F; De Ridder, D


Effects of anodal tDCS on lumbar propriospinal system in healthy subjects.

2011 Oct

OBJECTIVE: It has recently been shown that transcranial direct current stimulation (tDCS) (1) can modify lumbar spinal network excitability and (2) decreases cervical propriospinal system excitability. Thus the purpose of this series of experiments was to determine if anodal tDCS applied over the leg motor cortex area induces changes in lumbar propriospinal system excitability. To that end, the effects of anodal tDCS and sham tDCS on group I and group II propriospinal facilitation of quadriceps motoneurones were studied in healthy subjects. METHODS: Common peroneal nerve group I and group II quadriceps H-reflex facilitation was assessed in 15 healthy subjects in two randomised conditions: anodal tDCS condition and sham tDCS condition. Recordings were performed before, during and after the end of the cortical stimulation. RESULTS: Compared to sham, anodal tDCS decreases significantly CPN-induced group I and II quadriceps H-reflex facilitation during and also after the end of the cortical stimulation. CONCLUSIONS: Anodal tDCS induces (1) modulation of lumbar propriospinal system excitability (2) post-effects on spinal network. SIGNIFICANCE: These results open a new vista to regulate propriospinal lumbar system excitability in patients and suggest that anodal tDCS would be interesting for neuro-rehabilitation of patients with central nervous system lesions.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Roche, N; Lackmy, A; Achache, V; Bussel, B; Katz, R


Anomia training and brain stimulation in chronic aphasia.

2011 Oct

Recent studies have reported enhanced performance on language tasks induced by non-invasive brain stimulation, i.e., repetitive transcranial magnetic stimulation (rTMS), or transcranial direct current stimulation (tDCS), in patients with aphasia due to stroke or Alzheimer's disease (AD). The first part of this article reviews brain stimulation studies related to language recovery in aphasic patients. The second part reports results from a pilot study with three chronic stroke patients who had non-fluent aphasia, where real or placebo rTMS was immediately followed by 25 minutes of individualised speech therapy. Real rTMS consisted of high-frequency rTMS over the left dorsolateral prefrontal cortex (BA 8/9) for 25 minutes. Each patient underwent a total of four weeks of intervention. P1 underwent four weeks of real rTMS (5 days/week) where individualised speech therapy was provided for 25 minutes immediately following each rTMS session. P2 and P3 each underwent two weeks of placebo rTMS, followed immediately by individualised speech therapy; then two weeks of real rTMS, followed immediately by individualised speech therapy. Assessments took place at 2, 4, 12, 24 and 48 weeks post-entry/baseline testing. Relative to entry/baseline testing, a significant improvement in object naming was observed at all testing times, from two weeks post-intervention in real rTMS plus speech therapy, or placebo rTMS plus speech therapy. Our findings suggest beneficial effects of targeted behavioural training in combination with brain stimulation in chronic aphasic patients. However, further work is required in order to verify whether optimal combination parameters (rTMS alone or speech therapy alone) and length of rTMS treatment may be found.

Neuropsychological rehabilitation

Cotelli, M; Fertonani, A; Miozzo, A; Rosini, S; Manenti, R; Padovani, A; Ansaldo, AI; Cappa, SF; Miniussi, C


Modulating oscillatory brain activity correlates of behavioral inhibition using transcranial direct current stimulation.

2011 Oct

OBJECTIVE: Studies have mainly documented behavioral changes induced by transcranial direct current stimulation (tDCS), but recently cortical modulations of tDCS have also been investigated. Our previous work revealed behavioral inhibition modulation by anodal tDCS over the right inferior frontal gyrus (rIFG); however, the electrophysiological correlates underlying this stimulation montage have yet to be established. The current work aimed to evaluate the distribution of neuronal oscillations changes following anodal tDCS over rIFG coupled with cathodal tDCS over left orbitofrontal cortex (lOFC) using spectral power analysis. METHODS: Healthy subjects underwent sham and real tDCS (15min, 1.5mA, anodal rIFG; cathodal lOFC) stimulation conditions in a single-blind, placebo-controlled cross-over trial. Following tDCS session, resting EEG recordings were collected during 15min. RESULTS: Analysis showed a significant and selective diminution of the power of theta band. The theta diminution was observed in the rIFG area (represented the anode electrode), and was not found in the lOFC area (represented the cathode electrode). A significant effect was observed only in the theta but not in other bands. CONCLUSIONS: These results are the first demonstration of modulating oscillatory activity as measured by EEG with tDCS over rIFG in general, and documenting theta band reduction with this montage in particular. SIGNIFICANCE: Our results may explain the improvement in behavioral inhibition reported in our previous work, and although this study was conducted with healthy subjects, the findings suggest that tDCS may also modulate electrophysiological changes among ADHD patients, where decreasing theta activity is the target of neuro-feedback methods aimed to improve cognitive control.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Jacobson, L; Ezra, A; Berger, U; Lavidor, M


Evaluation of differentiated neurotherapy programs for a patient after severe TBI and long term coma using event-related potentials.

2011 Oct

This article examines the effectiveness of differentiated rehabilitation programs for a patient with frontal syndrome after severe TBI and long-term coma. We hypothesized that there would be a small response to relative beta training, and a good response to rTMS, applied to regulate the dynamics of brain function.M. L-S, age 26, suffered from anosognosia, executive dysfunction, and behavioral changes, after a skiing accident and prolonged coma, rendering him unable to function independently in many situations of everyday life. Only slight progress was made after traditional rehabilitation. The patient took part in 20 sessions of relative beta training (program A) and later in 20 sessions of rTMS (program B); both programs were combined with behavioral training. We used standardized neuropsychological testing, as well as ERPs before the experiment, after the completion of program A, and again after the completion of program B. As hypothesized, patient M.L-S showed small improvements in executive dysfunction and behavioral disorders after the conclusion of program A, and major improvement after program B. Similarly, in physiological changes the patient showed small improvement after relative beta training and a significant improvement of the P300 NOGO component after the rTMS program.The rTMS program produced larger physiological and behavioral changes than did relative beta training. A combination of different neurotherapeutical approaches (such as neurofeedback, rTMS, tDCS) can be suggested for similar severe cases of TBI. ERPs can be used to assess functional brain changes induced by neurotherapeutical programs.

Medical science monitor : international medical journal of experimental and clinical research

Pachalska, M; Łukowicz, M; Kropotov, JD; Herman-Sucharska, I; Talar, J


Modulation of motor learning and memory formation by non-invasive cortical stimulation of the primary motor cortex.

2011 Oct

Transcranial magnetic (TMS) and direct current (tDCS) stimulation are non-invasive brain stimulation techniques that allow researchers to purposefully modulate cortical excitability in focal areas of the brain. Recent work has provided preclinical evidence indicating that TMS and tDCS can facilitate motor performance, motor memory formation, and motor skill learning in healthy subjects and possibly in patients with brain lesions. Although the optimal stimulation parameters to accomplish these goals remain to be determined, and controlled multicentre clinical studies are lacking, these findings suggest that cortical stimulation techniques could become in the future adjuvant strategies in the rehabilitation of motor deficits. The aim of this article is to critically review these findings and to discuss future directions regarding the possibility of combining these techniques with other interventions in neurorehabilitation.

Neuropsychological rehabilitation

Tanaka, S; Sandrini, M; Cohen, LG


Non-invasive brain stimulation to assess and modulate neuroplasticity in Alzheimer's disease.

2011 Oct

Alzheimer's disease (AD) is a neurodegenerative and progressive disease related to a gradual decline in cognitive functions such as memory, attention, perceptual-spatial abilities, language, and executive functions. Recent evidence has suggested that interventions promoting neural plasticity can induce significant cognitive gains especially in subjects at risk of or with mild AD. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques that can induce significant and long-lasting changes in focal and non-focal neuroplasticity. In this review, we present initial preliminary evidence that TMS and tDCS can enhance performance in cognitive functions typically impaired in AD. Also, we reviewed the initial six studies on AD that presented early findings showing cognitive gains such as in recognition memory and language associated with TMS and tDCS treatment. In addition, we showed that TMS has also been used to assess neuroplasticity changes in AD supporting the notion that cortical excitability is changed in AD due to the neurodegenerative process. Due to the safe profile, cost of these tools, and initial clinical trials results, further studies are warranted in order to replicate and extend the initial findings of rTMS and tDCS as cognitive enhancers in AD. Further trials should explore different targets of stimulation along with different paradigms of stimulation including combination with behavioural interventions.

Neuropsychological rehabilitation

Boggio, PS; Valasek, CA; Campanhã, C; Giglio, AC; Baptista, NI; Lapenta, OM; Fregni, F


Ameliorating spatial neglect with non-invasive brain stimulation: from pathophysiological concepts to novel treatment strategies.

2011 Oct

Neglect is a multifaceted, complex syndrome, in which patients fail to detect or respond to stimuli or parts thereof located contralesionally. Non-invasive brain stimulation by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) may not only be useful as diagnostic research tools to explore the pathophysiology of neglect, but also for ameliorating its symptoms. Current approaches for modulating neglect non-invasively are mainly based on the neurophysiological concept of interhemispheric inhibition, which suggests a pathological overactivation of the contralesional hemisphere due to reduced inhibitory influences from the lesioned one. Within this framework, non-invasive brain stimulation mainly aims to inhibit the contralesional hemisphere to allow for rebalancing the system. However, facilitatory protocols for enhancing the ipsilesional neural circuitry might also prove useful. In this review, we discuss the contribution of non-invasive brain stimulation to current pathological concepts of neglect, the promising results of the proof-of-principle studies currently available as well as the specific aspects to be systematically investigated before broader clinical trials may eventually suggest a routine clinical application.

Neuropsychological rehabilitation

Hesse, MD; Sparing, R; Fink, GR


Transcranial electrical stimulation (tES - tDCS; tRNS, tACS) methods.

2011 Oct

Weak transcranial direct current stimulation (tDCS) with a homogenous DC field at intensities of around 1 mA induces long-lasting changes in the brain. tDCS can be used to manipulate brain excitability via membrane polarisation: cathodal stimulation hyperpolarises, while anodal stimulation depolarises the resting membrane potential, whereby the induced after-effects depend on polarity, duration and intensity of the stimulation. A variety of other parameters influence tDCS effects; co-application of neuropharmacologically active drugs may most impressively prolong or even reverse stimulation effects. Transcranial alternating stimulation (tACS) and random noise stimulation (tRNS) are used to interfere with ongoing neuronal oscillations and also finally produce neuroplastic effects if applied with appropriate parameters.

Neuropsychological rehabilitation

Paulus, W


Cumulative benefits of frontal transcranial direct current stimulation on visuospatial working memory training and skill learning in rats.

2011 Oct

Transcranial direct current stimulation (tDCS) of the prefrontal cortex, which non-invasively alters cortical activity, has been established to affect executive functions in humans. We hypothesized that changes in excitability by tDCS, found to improve cognitive functions dependent on moderate prefrontal cortex activity, would operate similarly in animals as in humans. To verify this we performed experiments using a rat behavioral model of visuospatial working memory and skill learning paired with tDCS of the frontal cortex. The effect of anodal/cathodal tDCS was examined in three sessions using the allothetic place avoidance alternation task (APAAT) and later re-examined without stimulation. Stimulation had no measurable short term effect on on-going place avoidance learning. However, in the follow-up session on day 21 the rats previously treated with cathodal tDCS showed significantly more efficient place avoidance and skill retention in comparison to the controls. This demonstrates a long-term benefit of diminished excitability by frontal tDCS when paired with training on working memory and skill learning in a novel task. The presented behavioral model provides a tool to evaluate the underlying mechanisms of how tDCS modulates neural network function to support successful behavior.

Neurobiology of learning and memory

Dockery, CA; Liebetanz, D; Birbaumer, N; Malinowska, M; Wesierska, MJ


Brain energy consumption induced by electrical stimulation promotes systemic glucose uptake.

2011 Oct

Controlled transcranial stimulation of the brain is part of clinical treatment strategies in neuropsychiatric diseases such as depression, stroke, or Parkinson's disease. Manipulating brain activity by transcranial stimulation, however, inevitably influences other control centers of various neuronal and neurohormonal feedback loops and therefore may concomitantly affect systemic metabolic regulation. Because hypothalamic adenosine triphosphate-sensitive potassium channels, which function as local energy sensors, are centrally involved in the regulation of glucose homeostasis, we tested whether transcranial direct current stimulation (tDCS) causes an excitation-induced transient neuronal energy depletion and thus influences systemic glucose homeostasis and related neuroendocrine mediators.In a crossover design testing 15 healthy male volunteers, we increased neuronal excitation by anodal tDCS versus sham and examined cerebral energy consumption with ³¹phosphorus magnetic resonance spectroscopy. Systemic glucose uptake was determined by euglycemic-hyperinsulinemic glucose clamp, and neurohormonal measurements comprised the parameters of the stress systems.We found that anodic tDCS-induced neuronal excitation causes an energetic depletion, as quantified by ³¹phosphorus magnetic resonance spectroscopy. Moreover, tDCS-induced cerebral energy consumption promotes systemic glucose tolerance in a standardized euglycemic-hyperinsulinemic glucose clamp procedure and reduces neurohormonal stress axes activity.Our data demonstrate that transcranial brain stimulation not only evokes alterations in local neuronal processes but also clearly influences downstream metabolic systems regulated by the brain. The beneficial effects of tDCS on metabolic features may thus qualify brain stimulation as a promising nonpharmacologic therapy option for drug-induced or comorbid metabolic disturbances in various neuropsychiatric diseases.

Biological psychiatry

Binkofski, F; Loebig, M; Jauch-Chara, K; Bergmann, S; Melchert, UH; Scholand-Engler, HG; Schweiger, U; Pellerin, L; Oltmanns, KM


Cathodal transcranial direct current stimulation of the right Wernicke's area improves comprehension in subacute stroke patients.

2011 Oct

Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and tDCS have been found to improve naming in non-fluent post-stroke aphasic patients. Here, we investigated the effect of tDCS on the comprehension of aphasic patients with subacute stroke. We hypothesized that tDCS applied to the left superior temporal gyrus (Wernicke's area) or the right Wernicke's area might be associated with recovery of comprehension ability in aphasic patients with subacute stroke. Participants included right-handed subacute stroke patients with global aphasia due to ischemic infarct of the left M1 or M2 middle cerebral artery. Patients were randomly divided into three groups: patients who received anodal tDCS applied to the left superior temporal gyrus, patients who received cathodal tDCS applied to the right superior temporal gyrus, and patients who received sham tDCS. All patients received conventional speech and language therapy during each period of tDCS application. The Korean-Western Aphasia Battery (K-WAB) was used to assess all patients before and after tDCS sessions. After intervention, all patients had significant improvements in aphasia quotients, spontaneous speech, and auditory verbal comprehension. However, auditory verbal comprehension improved significantly more in patients treated with a cathode, as compared to patients in the other groups. These results are consistent with the role of Wernicke's area in language comprehension and the therapeutic effect that cathodal tDCS has on aphasia patients with subacute stroke, suggesting that tDCS may be an adjuvant treatment approach for aphasia rehabilitation therapy in patients in an early stage of stroke.

Brain and language

You, DS; Kim, DY; Chun, MH; Jung, SE; Park, SJ


Behavioural facilitation following brain stimulation: implications for neurorehabilitation.

2011 Oct

Studies showing facilitation of behavioural performance by transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS) in sensory and perceptual domains, spatial attention, working memory, and executive and emotional tasks are reviewed. In these domains the performance of neurologically unimpaired participants may be modulated, with behavioural facilitation or interference, by TMS, and by tDCS. The mapping of the frequency-dependent effects of TMS, and of the polarity-dependent effects of tDCS on behaviour does not systematically and mechanistically result in an increase or decrease of behavioural performance. Factors such as the parameters of the cerebral stimulation (localisation, duration, intensity), and the features of the task (complexity, phase of training) contribute to determine the final net effect on the participants' performance. Non-invasive brain stimulation (NIBS), which modulates learning, and appears to have, under some conditions, long lasting effects, is a promising tool to be used in the rehabilitation of a variety of neurological and cognitive disorders, that typically involve repeated behavioural training sessions.

Neuropsychological rehabilitation

Vallar, G; Bolognini, N


Bilateral transcranial direct current stimulation modulates activation-induced regional blood flow changes during voluntary movement.

2011 Oct

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that induces changes in cortical excitability: anodal stimulation increases while cathodal stimulation reduces excitability. Imaging studies performed after unilateral stimulation have shown conflicting results regarding the effects of tDCS on surrogate markers of neuronal activity. The aim of this study was to directly measure these effects on activation-induced changes in regional cerebral blood flow (ΔrCBF) using positron emission tomography (PET) during bilateral tDCS. Nine healthy subjects underwent repeated rCBF measurements with (15)O-water and PET during a simple motor task while receiving tDCS or sham stimulation over the primary motor cortex (M1). Motor evoked potentials (MEPs) were also assessed before and after real and sham stimulation. During tDCS with active movement, ΔrCBF in M1 was significantly lower on the cathodal than the anodal side when compared with sham stimulation. This decrease in ΔrCBF was accompanied by a decrease in MEP amplitude on the cathodal side. No effect was observed on resting or activated rCBF relative to sham stimulation. We thus conclude that it is the interaction of cathodal tDCS with activation-induced ΔrCBF rather than the effect on resting or activated rCBF itself which constitutes the physiological imaging correlate of tDCS.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Paquette, C; Sidel, M; Radinska, BA; Soucy, JP; Thiel, A


Brain stimulation: new vistas for the exploration and treatment of tinnitus.

2011 Oct

Tinnitus, the perception of sounds or noise in the absence of auditory stimuli, is a frequent and often severely disabling symptom of different disorders of the auditory system. Attempts to develop evidence-based therapies have been thwarted by a poor understanding of the underlying pathophysiology. However, recent work points toward a pivotal role of maladaptive cortical reorganization in the generation and perpetuation of tinnitus. Changes in the representation of sounds, abnormalities of oscillatory activity, and hyperactivity in higher order areas of auditory processing have been linked with the perception of tinnitus. Brain stimulation techniques have entered the field and have opened exciting new perspectives for the modulation of dysfunctional brain activity. In this review, a comprehensive overview on the use of brain-stimulation techniques in the exploration and experimental treatment of tinnitus is provided.Noninvasive and invasive brain stimulation techniques, for example, transcranial magnetic stimulation (TMS), direct current stimulation (tDCS), and direct electrical cortical stimulation gave rise to a new line of investigation in tinnitus research. First, it has been shown that focal interference with presumably pathological cortical function can reduce tinnitus at least transiently. Second, the reduction of tinnitus-associated enhancement of cortical activity by neuronavigated TMS has been demonstrated to ameliorate tinnitus. Third, preliminary data suggest that repeated application of TMS or continuous cortical stimulation may lead to a longer lasting suppression of tinnitus.These proof of principle studies point toward a new option for the investigation and neurophysiology based treatment of tinnitus. Based on these findings, larger scale randomized clinical trials are needed to explore the efficacy of different brain stimulation techniques and parameters as well as the optimal target sites and treatment schedules. Particularly, a careful evaluation of clinical relevance under consideration of an adequate sham control and attention to possible unwanted side effects of these new interventions are indispensable.

CNS neuroscience & therapeutics

Plewnia, C


Modulation of large-scale brain networks by transcranial direct current stimulation evidenced by resting-state functional MRI.

2011 Sep

BACKGROUND: Brain areas interact mutually to perform particular complex brain functions such as memory or language. Furthermore, under resting-state conditions several spatial patterns have been identified that resemble functional systems involved in cognitive functions. Among these, the default-mode network (DMN), which is consistently deactivated during task periods and is related to a variety of cognitive functions, has attracted most attention. In addition, in resting-state conditions some brain areas engaged in focused attention (such as the anticorrelated network, AN) show a strong negative correlation with DMN; as task demand increases, AN activity rises, and DMN activity falls. OBJECTIVE: We combined transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) to investigate these brain network dynamics. METHODS: Ten healthy young volunteers underwent four blocks of resting-state fMRI (10-minutes), each of them immediately after 20 minutes of sham or active tDCS (2 mA), on two different days. On the first day the anodal electrode was placed over the left dorsolateral prefrontal cortex (DLPFC) (part of the AN) with the cathode over the contralateral supraorbital area, and on the second day, the electrode arrangement was reversed (anode right-DLPFC, cathode left-supraorbital). RESULTS: After active stimulation, functional network connectivity revealed increased synchrony within the AN components and reduced synchrony in the DMN components. CONCLUSIONS: Our study reveals a reconfiguration of intrinsic brain activity networks after active tDCS. These effects may help to explain earlier reports of improvements in cognitive functions after anodal-tDCS, where increasing cortical excitability may have facilitated reconfiguration of functional brain networks to address upcoming cognitive demands.

Brain stimulation

Peña-Gómez, C; Sala-Lonch, R; Junqué, C; Clemente, IC; Vidal, D; Bargalló, N; Falcón, C; Valls-Solé, J; Pascual-Leone, A; Bartrés-Faz, D


Transcranial direct current stimulation in treatment resistant depression: a randomized double-blind, placebo-controlled study.

2011 Sep

BACKGROUND: Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has been proposed as therapeutic intervention in major depression. According to clinical needs, this study addresses the question whether tDCS is effective in treatment resistant major depressive episodes. METHODS: Twenty-two patients with a major depressive episode were randomly assigned to a cross-over protocol comparing tDCS and placebo stimulation add-on to a stable antidepressant medication. The parameters of active tDCS were: 1 or 2 mA for 20 minutes/day, anode over the left dorsolateral prefrontal cortex, cathode over the contralateral supraorbital region. Active and placebo tDCS was applied for 2 weeks using indistinguishable DC stimulators. Patients, raters, and operators were blinded to treatment conditions. RESULTS: There was no significant difference in depression scores after 2 weeks of real compared with 2 weeks of sham tDCS. Scores on the Hamilton Depression Rating Scale were reduced from baseline by 14.7% for active tDCS and 10% for placebo tDCS. In contrast, subjective mood ratings showed an increase in positive emotions after real tDCS compared with sham tDCS. CONCLUSIONS: Anodal tDCS, applied for 2 weeks, was not superior to placebo treatment in patients with treatment resistant depression. However, secondary outcome measures are pointing to a positive effect of tDCS on emotions. Therefore, modified and improved tDCS protocols should be carried out in controlled pilot trials to develop tDCS towards an efficacious antidepressant intervention in therapy-resistant depression.

Brain stimulation

Palm, U; Schiller, C; Fintescu, Z; Obermeier, M; Keeser, D; Reisinger, E; Pogarell, O; Nitsche, MA; Möller, HJ; Padberg, F


Impaired long-term depression in schizophrenia: a cathodal tDCS pilot study.

2011 Sep

BACKGROUND: Neural plasticity involves the reorganization of synaptic connections and represents the ability of the brain to adjust its function in response to challenge. Disturbed cortical plasticity has been linked to the pathophysiology of schizophrenia, with indirect evidence for disturbed plasticity in the disease state having been provided by postmortem studies and various animal models. However, glutamate-dependent long-term depression (LTD)-like cortical plasticity has not yet been investigated. OBJECTIVE: To investigate LTD-like cortical plasticity after transcranial direct current stimulation (tDCS) in schizophrenia patients. METHODS: Using excitability-diminishing cathodal tDCS, we performed the first in vivo assessment of glutamate-dependent LTD-like cortical plasticity in 21 schizophrenia patients and 21 matched healthy control subjects. To reveal the physiologic basis of the hypothesized plasticity deficits, we tested different inhibitory and excitatory neuronal circuits with transcranial magnetic stimulation (TMS). RESULTS: Cathodal tDCS failed to reduce motor-evoked potential amplitudes in schizophrenia patients, indicating abolished LTD-like plasticity. Furthermore, schizophrenia patients had a prolonged GABA(B)-dependent cortical silent period (CSP) at baseline and tDCS failed to modulate the duration of CSP in the patient group. Finally, schizophrenia patients presented an elevated resting-motor threshold at baseline in comparison to healthy controls. CONCLUSIONS: The pattern of our results provides evidence for a specific plasticity deficit in schizophrenia patients, which might be associated with a hyperglutamatergic state. These findings may reflect a reduced signal-to-noise ratio and a disturbed filter function in schizophrenia patients. An increase of GABA(B)-activity may be a compensatory mechanism to dysfunctional LTD-like plasticity in schizophrenia.

Brain stimulation

Hasan, A; Nitsche, MA; Herrmann, M; Schneider-Axmann, T; Marshall, L; Gruber, O; Falkai, P; Wobrock, T


Combining visual rehabilitative training and noninvasive brain stimulation to enhance visual function in patients with hemianopia: a comparative case study.

2011 Sep

To standardize a protocol for promoting visual rehabilitative outcomes in post-stroke hemianopia by combining occipital cortical transcranial direct current stimulation (tDCS) with Vision Restoration Therapy (VRT).A comparative case study assessing feasibility and safety.A controlled laboratory setting.Two patients, both with right hemianopia after occipital stroke damage. METHODS AND OUTCOME MEASUREMENTS: Both patients underwent an identical VRT protocol that lasted 3 months (30 minutes, twice a day, 3 days per week). In patient 1, anodal tDCS was delivered to the occipital cortex during VRT training, whereas in patient 2 sham tDCS with VRT was performed. The primary outcome, visual field border, was defined objectively by using high-resolution perimetry. Secondary outcomes included subjective characterization of visual deficit and functional surveys that assessed performance on activities of daily living. For patient 1, the neural correlates of visual recovery were also investigated, by using functional magnetic resonance imaging.Delivery of combined tDCS with VRT was feasible and safe. High-resolution perimetry revealed a greater shift in visual field border for patient 1 versus patient 2. Patient 1 also showed greater recovery of function in activities of daily living. Contrary to the expectation, patient 2 perceived greater subjective improvement in visual field despite objective high-resolution perimetry results that indicated otherwise. In patient 1, visual function recovery was associated with functional magnetic resonance imaging activity in surviving peri-lesional and bilateral higher-order visual areas.Results of preliminary case comparisons suggest that occipital cortical tDCS may enhance recovery of visual function associated with concurrent VRT through visual cortical reorganization. Future studies may benefit from incorporating protocol refinements such as those described here, which include global capture of function, control for potential confounds, and investigation of underlying neural substrates of recovery.

PM & R : the journal of injury, function, and rehabilitation

Plow, EB; Obretenova, SN; Halko, MA; Kenkel, S; Jackson, ML; Pascual-Leone, A; Merabet, LB


Modulating cortico-striatal and thalamo-cortical functional connectivity with transcranial direct current stimulation.

2011 Sep

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has been shown to alter cortical excitability and activity via application of weak direct currents. Beyond intracortical effects, functional imaging as well as behavioral studies are suggesting additional tDCS-driven alterations of subcortical areas, however, direct evidence for such effects is scarce. We aimed to investigate the impact of tDCS on cortico-subcortical functional networks by seed functional connectivity analysis of different striatal and thalamic regions to prove tDCS-induced alterations of the cortico-striato-thalamic circuit. fMRI resting state data sets were acquired immediately before and after 10 min of bipolar tDCS during rest, with the anode/cathode placed over the left primary motor cortex (M1) and the cathode/anode over the contralateral frontopolar cortex. To control for possible placebo effects, an additional sham stimulation session was carried out. Functional coupling between the left thalamus and the ipsilateral primary motor cortex (M1) significantly increased following anodal stimulation over M1. Additionally, functional connectivity between the left caudate nucleus and parietal association cortices was significantly strengthened. In contrast, cathodal tDCS over M1 decreased functional coupling between left M1 and contralateral putamen. In summary, in this study, we show for the first time that tDCS modulates functional connectivity of cortico-striatal and thalamo-cortical circuits. Here we highlight that anodal tDCS over M1 is capable of modulating elements of the cortico-striato-thalamo-cortical functional motor circuit. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc.

Human brain mapping

Polanía, R; Paulus, W; Nitsche, MA


The use of non-invasive brain stimulation techniques to facilitate recovery from post-stroke aphasia.

2011 Sep

Aphasia is a common symptom after left hemispheric stroke. Neuroimaging techniques over the last 10-15 years have described two general trends: Patients with small left hemisphere strokes tend to recruit perilesional areas, while patients with large left hemisphere lesions recruit mainly homotopic regions in the right hemisphere. Non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been employed to facilitate recovery by stimulating lesional and contralesional regions. The majority of these brain stimulation studies have attempted to block homotopic regions in the right posterior inferior frontal gyrus (IFG) to affect a presumed disinhibited right IFG (triangular portion). Other studies have used anodal or excitatory tDCS to stimulate the contralesional (right) fronto-temporal region or parts of the intact left IFG and perilesional regions to improve speech-motor output. It remains unclear whether the interhemispheric disinhibition model, which is the basis for motor cortex stimulation studies, also applies to the language system. Future studies could address a number of issues, including: the effect of lesion location on current density distribution, timing of the intervention with regard to stroke onset, whether brain stimulation should be combined with behavioral therapy, and whether multiple brain sites should be stimulated. A better understanding of the predictors of recovery from natural outcome studies would also help to inform study design, and the selection of clinically meaningful outcome measures in future studies.

Neuropsychology review

Schlaug, G; Marchina, S; Wan, CY

Link to full article text


Transcranial direct current stimulation influences probabilistic association learning in schizophrenia.

2011 Sep

Schizophrenia is associated with heterogeneity in symptoms, cognition and treatment response. Probabilistic association learning, involving a gradual learning of cue-outcome associations, activates a frontal-striatal network in healthy adults. Studies of probabilistic association learning in schizophrenia have shown frontal-striatal dysfunction although considerable heterogeneity in performance has also been reported. Anodal transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex has been shown to improve probabilistic association learning in healthy adults. The aim of the current study was to determine the extent to which anodal tDCS to the left dorsolateral prefrontal cortex would reverse probabilistic association learning deficits in schizophrenia. Prior to tDCS, 20 people with schizophrenia performed an initial baseline assessment without stimulation. Anodal tDCS was administered continuously for 20 min at an intensity of 2.0 mA to the left dorsolateral prefrontal cortex in a single-blind, counterbalanced, sham-controlled, cross-over design while participants performed 150 trials of a probabilistic association learning test. Although anodal tDCS failed to improve probabilistic association learning based on the whole sample performance, greater variance in the active relative to the sham conditions suggested a subset of people may respond to treatment. Further correlation, regression and cluster analyses revealed differential effects of baseline performance on active tDCS and sham treatment and that there was a subset of people with schizophrenia who displayed improvement with tDCS suggesting that anodal tDCS to the dorsolateral prefrontal cortex may facilitate access to existing prefrontal cortex neural reserves in people with schizophrenia who show adequate capacity to learn at baseline.

Schizophrenia research

Vercammen, A; Rushby, JA; Loo, C; Short, B; Weickert, CS; Weickert, TW


Effects of transcranial direct current stimulation (tDCS) on human regional cerebral blood flow.

2011 Sep

Transcranial direct current stimulation (tDCS) can up- and down-regulate cortical excitability depending on current direction, however our abilities to measure brain-tissue effects of the stimulation and its after-effects have been limited so far. We used regional cerebral blood flow (rCBF), a surrogate measure of brain activity, to examine regional brain-tissue and brain-network effects during and after tDCS. We varied the polarity (anodal and cathodal) as well as the current strength (0.8 to 2.0mA) of the stimulation. Fourteen healthy subjects were randomized into receiving either anodal or cathodal stimulation (two subjects received both, one week apart) while undergoing Arterial Spin Labeling (ASL) in the MRI scanner with an alternating off-on sampling paradigm. The stimulating, MRI-compatible electrode was placed over the right motor region and the reference electrode over the contralateral supra-orbital region. SPM5 was used to process and extract the rCBF data using a 10mm spherical volume of interest (VOI) placed in the motor cortex directly underneath the stimulating scalp electrode. Anodal stimulation induced a large increase (17.1%) in rCBF during stimulation, which returned to baseline after the current was turned off, but exhibited an increase in rCBF again in the post-stimulation period. Cathodal stimulation induced a smaller increase (5.6%) during stimulation, a significant decrease compared to baseline (-6.5%) after cessation, and a continued decrease in the post-stimulation period. These changes in rCBF were all significant when compared to the pre-stimulation baseline or to a control region. Furthermore, for anodal stimulation, there was a significant correlation between current strength and the increase in rCBF in the on-period relative to the pre-stimulation baseline. The differential rCBF after-effects of anodal (increase in resting state rCBF) and cathodal (decrease in resting state rCBF) tDCS support findings of behavioral and cognitive after-effects after cathodal and anodal tDCS. We also show that tDCS not only modulates activity in the brain region directly underlying the stimulating electrode but also in a network of brain regions that are functionally related to the stimulated area. Our results indicate that ASL may be an excellent tool to investigate the effects of tDCS and its stimulation parameters on brain activity.

NeuroImage

Zheng, X; Alsop, DC; Schlaug, G


D2 receptor block abolishes theta burst stimulation-induced neuroplasticity in the human motor cortex.

2011 Sep

Dopamine (DA) is a neurotransmitter with an important influence on learning and memory, which is thought to be due to its modulatory effect on plasticity at central synapses, which in turn depends on activation of D1 and D2 receptors. Methods of brain stimulation (transcranial direct current stimulation, tDCS; paired associative stimulation, PAS) lead to after-effects on cortical excitability that are thought to resemble long-term potentization (LTP)/long-term depression (LTD) in reduced preparations. In a previous study we found that block of D2 receptors abolished plasticity induced by tDCS but had no effect on the facilitatory plasticity induced by PAS. We postulated that the different effect of D2 receptor block on tDCS- and PAS-induced plasticity may be due to the different focality and associativity of the stimulation techniques. However, alternative explanations for this difference could not be ruled out. tDCS also differs from PAS in other aspects, as tDCS induces plasticity by subthreshold neuronal activation, modulating spontaneous activity, whereas PAS induces plasticity via phasic suprathreshold stimulation. The present study in 12 volunteers examined effects of D2 receptor blockade (sulpiride (SULP) 400 mg), on the LTP/LTD-like effects of theta burst transcranial magnetic stimulation (TBS), which has less restricted effects on cortical synapses than that of PAS, and does not induce associative plasticity, similar to tDCS, but on the other hand induces cortical excitability shifts by suprathreshold (rhythmic) activation of cortical neurons similarly to PAS. Administration of SULP blocked both the excitatory and inhibitory effects of intermittent (iTBS) and continuous TBS (cTBS), respectively. As the reduced response to TBS following SULP resembles its effect on tDCS, the results support an effect of DA on plasticity, which might be related to the focality and associativity of the plasticity induced.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Monte-Silva, K; Ruge, D; Teo, JT; Paulus, W; Rothwell, JC; Nitsche, MA


Transcranial direct current stimulation modulates the spinal plasticity induced with patterned electrical stimulation.

2011 Sep

Patterned sensory electrical stimulation (PES) has been shown to induce plasticity in spinal reciprocal Ia inhibition of the calf muscles. To study the cortical modulation of spinal plasticity, we examined the effects of giving transcranial direct current stimulation (tDCS) to the motor cortex before PES.Seven healthy volunteers participated in this study. PES involved stimulating the left common peroneal nerve at the fibular head with a train of 10 pulses at 100 Hz every 1.5s for 20 min using an intensity equal to the motor threshold of the tibialis anterior. tDCS was applied for 10 min before PES. For anodal stimulation, the electrode was placed over the motor cortex, and the cathodal electrode over the contralateral supraorbital area. For cathodal stimulation, the electrodes were reversed. Reciprocal inhibition was assessed using a soleus H reflex conditioning-test paradigm.PES increased disynaptic reciprocal inhibition from the peroneal nerve to the soleus H reflex. When cathodal tDCS was applied before PES, PES no longer increased reciprocal inhibition.Applying tDCS before PES modulated the effects of PES on spinal reciprocal inhibition in a polarity specific manner.We suggest that the motor cortex may play a role in spinal plasticity.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Fujiwara, T; Tsuji, T; Honaga, K; Hase, K; Ushiba, J; Liu, M


A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation.

2011 Sep

Transcranial direct current stimulation (tDCS) is a non-invasive method of brain stimulation that has been intensively investigated in clinical and cognitive neuroscience. Although the general impression is that tDCS is a safe technique with mild and transient adverse effects (AEs), human data on safety and tolerability are largely provided from single-session studies in healthy volunteers. In addition the frequency of AEs and its relationship with clinical variables is unknown. With the aim of assessing tDCS safety in different conditions and study designs, we performed a systematic review and meta-analysis of tDCS clinical trials. We assessed Medline and other databases and reference lists from retrieved articles, searching for articles from 1998 (first trial with contemporary tDCS parameters) to August 2010. Animal studies, review articles and studies assessing other neuromodulatory techniques were excluded. According to our eligibility criteria, 209 studies (from 172 articles) were identified. One hundred and seventeen studies (56%) mentioned AEs in the report. Of these studies, 74 (63%) reported at least one AE and only eight studies quantified AEs systematically. In the subsample reporting AEs, the most common were, for active vs. sham tDCS group, itching (39.3% vs. 32.9%, p>0.05), tingling (22.2% vs. 18.3%, p>0.05), headache (14.8% vs. 16.2%, p>0.05), burning sensation (8.7% vs. 10%, p>0.05) and discomfort (10.4% vs. 13.4%, p>0.05). Meta-analytical techniques could be applied in only eight studies for itching, but no definite results could be obtained due to between-study heterogeneity and low number of studies. Our results suggested that some AEs such as itching and tingling were more frequent in the tDCS active group, although this was not statistically significant. Although results suggest that tDCS is associated with mild AEs only, we identified a selective reporting bias for reporting, assessing and publishing AEs of tDCS that hinders further conclusions. Based on our findings, we propose a revised adverse effects questionnaire to be applied in tDCS studies in order to improve systematic reporting of tDCS-related AEs.

The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)

Brunoni, AR; Amadera, J; Berbel, B; Volz, MS; Rizzerio, BG; Fregni, F


Hypomania induction in a patient with bipolar II disorder by transcranial direct current stimulation (tDCS).

2011 Sep

To report a case of hypomania induced by transcranial direct current stimulation (tDCS) given with an extracephalic reference electrode. Transcranial direct current stimulation is a noninvasive brain stimulation technique in which a weak current is applied through the scalp to produce changes in neuronal excitability in the underlying cerebral tissue. Recent clinical trials have shown promising results with left anodal prefrontal tDCS in treating depression. When the reference cathodal electrode in tDCS is moved from the cranium to an extracephalic position, larger areas of both cerebral hemispheres are stimulated, with potential implications for both efficacy and safety.We report the case of a 33-year-old female with bipolar II disorder, on mood stabilizer medication, who had previously participated in a clinical trial of tDCS given with a bifrontal electrode montage for the treatment of major depression without incident, but became hypomanic when she received a later course of tDCS given with a frontoextracephalic configuration. Factors contributing to the development of hypomania in the second course of tDCS are examined.No substantial differences were found in the patient's clinical presentation between the 2 tDCS courses to explain the emergence of hypomania only after the second course. The different montage used in the second course appeared to be the main contributory factor in the induction of hypomania.The reported case suggests that frontoextracephalic tDCS has antidepressant properties and the potential to induce hypomanic symptoms. In particular, it raises the question of whether frontoextracephalic tDCS requires additional precautions when administered to bipolar patients compared to bifrontal tDCS.

The journal of ECT

Gálvez, V; Alonzo, A; Martin, D; Mitchell, PB; Sachdev, P; Loo, CK


Transcranial direct current stimulation improves word retrieval in healthy and nonfluent aphasic subjects.

2011 Sep

A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects performances of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS to enhance associative verbal learning in 10 healthy individuals and to improve word retrieval deficits in three patients with stroke-induced aphasia. In healthy individuals, tDCS (20 min, 1 mA) was applied over Wernicke's area (position CP5 of the International 10-20 EEG System) while they learned 20 new "words" (legal nonwords arbitrarily assigned to 20 different pictures). The healthy subjects participated in a randomized counterbalanced double-blind procedure in which they were subjected to one session of anodic tDCS over left Wernicke's area, one sham session over this location and one session of anodic tDCS stimulating the right occipito-parietal area. Each experimental session was performed during a different week (over three consecutive weeks) with 6 days of intersession interval. Over 2 weeks, three aphasic subjects participated in a randomized double-blind experiment involving intensive language training for their anomic difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation over Wernicke's area while they performed a picture-naming task. By the end of each week, anodic tDCS had significantly improved their accuracy on the picture-naming task. Both normal subjects and aphasic patients also had shorter naming latencies during anodic tDCS than during sham condition. At two follow-ups (1 and 3 weeks after the end of treatment), performed only in two aphasic subjects, response accuracy and reaction times were still significantly better in the anodic than in the sham condition, suggesting a long-term effect on recovery of their anomic disturbances.

Journal of cognitive neuroscience

Fiori, V; Coccia, M; Marinelli, CV; Vecchi, V; Bonifazi, S; Ceravolo, MG; Provinciali, L; Tomaiuolo, F; Marangolo, P


Independent component analysis of resting brain activity reveals transient modulation of local cortical processing by transcranial direct current stimulation.

2011 Aug

Neuroplasticity induced by transcranial direct current stimulation (tDCS) contributes to motor learning although the underlying mechanisms are incompletely understood. Here, we investigated the effects of tDCS on resting brain dynamics recorded by whole-head magnetoencephalography (MEG) pre- and up to 35 minutes post-tDCS or sham over the left primary motor cortex (M1) in healthy adults. Owing to superior temporal and spatial resolution of MEG, we sought to apply a robust, blind and data-driven analytic approach such as independent component analysis (ICA) and statistical clustering to these data to investigate potential neuroplastic effects of tDCS during resting state conditions. We found decreased alpha and increased gamma band power that outlasted the real tDCS stimulation period in a fronto-parietal motor network relative to sham. However, this method could not find differences between anodal and cathodal polarities of tDCS. These results suggest that tDCS over M1 modulates resting brain dynamics in a fronto-parietal motor network (that includes the stimulated location), indicative of within-network enhanced localized cortical processing.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Venkatakrishnan, A; Contreras-Vidal, JL; Sandrini, M; Cohen, LG


Effect of transcranial direct current stimulation on cortico-muscular coherence and standing postural steadiness.

2011 Aug

Non-invasive brain stimulation is a promising tool for inducing cortico-spinal excitability and facilitating motor function. The objective of this study was to investigate the effect of transcranial DC stimulation (tDCS) on cortico-spinal excitability of leg area, cortico-muscular coherence of tibialis anterior muscle, and standing postural steadiness there from. In single-blind, sham-controlled, crossover study, five healthy subjects were evaluated under two conditions - with 10min anodal tDCS and with 10min sham tDCS. Anodal tDCS induced statistically significant (P=0.001, N=20) cortico-spinal excitability, 45min and 60min after the end of tDCS as revealed by single pulse transcranial magnetic stimulation (TMS) of resting tibialis anterior muscle. Furthermore, anodal tDCS induced statistically significant (P=0.001, N=20) cortico-muscular coherence in tibialis anterior muscle during quiet standing with eyes closed, 45min and 60min after the end of tDCS. The % change in the stabilogram metrics after anodal tDCS during quiet standing with eyes closed showed that anodal tDCS strongly (P=0.0000) affected the change in centroid of CoP data-points in medio-lateral direction (%CoP(ML)) at 45min and 60min after tDCS session. Anodal tDCS had moderate effect (P=0.0113) on the change (decrease) in the path length of CoP trajectory (%CoP(PL)) at 60min after tDCS. Also, anodal tDCS had a strong (P=0.0000) effect on the change (decrease) in sway area (%CoP(EA)) at 45min and 60min after tDCS session.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Dutta, A; Chugh, S


Effect of electrode profile and conductivity on current density and cutaneous sensation during transcranial DC stimulation.

2011 Aug

Non-invasive brain stimulation (NIBS) such as transcranial direct current stimulation (tDCS) involves passing low currents through the brain and is a promising tool for inducing cortical excitability. However tDCS presents challenges in terms of discomfort due to painful cutaneous sensation and reduced efficacy in stimulating deeper cortical structures. This warrants design optimization of the stimulation electrode that interfaces with the tissue and injects the electrical current. In this study we investigated the effect of electrode profile and conductivity on current density at depths below the center of the electrode as well as along the electrode-skin interface. We also investigated cutaneous sensation during tDCS with electrodes having different conductivities. We found from Finite Element Analysis that lower conductivity as well as concave-top sponge electrode can reduce edge-effects. Furthermore, concave-top sponge electrode in conjunction with lower electrode conductivity can improve current density at shallow depths below the center of the electrode. Two-way ANOVA revealed a significant effect of electrode conductivity (p=0.0000) and hair/bald condition (p=0.0029) as well as their synergistic effect (p=0.0000) on the cutaneous sensation. Moreover, a lower conductivity sponge electrode reduced prickle sensation at the edges during tDCS.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Dutta, A; Mudaliar, A; Chugh, S


Computational study of subdural and epidural cortical stimulation of the motor cortex.

2011 Aug

Cortical stimulation (CS) has gained wide attention for its use in augmenting neurological recovery in various conditions. Noninvasive cortical stimulations using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are less invasive when delivering the electrical current to the patient's brain, but have several limitations. Direct cortical stimulation (DCS) using an implantable stimulation system consisting of epidurally or subdurally placed electrodes and pulse generators, provides cortical stimulation and concurrent rehabilitative training in a stable fashion without limiting a patient's activities. The effectiveness of these two types of DCS - epidural cortical stimulation (ECS) and subdural cortical stimulation (SCS) - has not been compared. In this work, a computer simulation study was conducted to predict the current density distributions (CDD) through cortical stimulations using subdurally or epidurally placed electrodes. The simulation study is based on the human motor cortex model with a three-dimensional finite element model (FEM). The change in CDD depending on the shape of the electrode (disc or ring) is discussed. The output current induced by SCS was about four times larger than that of ECS when voltage stimulations with the same magnitude were regulated. Thus, SCS showed substantially better penetration of the current into gray or white matter. Further, the ring electrode performed comparably or slightly inferior to the disc electrode in both cortical stimulations.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Kim, D; Jun, SC; Kim, HI


On handling the layered structure of the skull in transcranial direct current stimulation models.

2011 Aug

In a tDCS model study, the accuracy of isotropic and anisotropic single-layer approximations to the actual three-layered skull is evaluated. For both approximation models, the average difference in brain current density with respect to the layered skull model are shown to be small. We conclude that both approximations can be used to accurately compute the current density in the brain, provided that the radial conductivity in the model matches the effective radial conductivity of the three-layered skull.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Rampersad, S; Stegeman, D; Oostendorp, T


Anodal transcranial direct current stimulation relieves the unilateral bias of a rat model of Parkinson's disease.

2011 Aug

The unilaterally lesioned rat model of Parkinson's disease which fails to orient to the food stimuli presented on the contralateral side of its preferential side of body could be induced by the injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB). We employed transcranial direct current stimulation (tDCS, current intensity: 80 μA, and 40 μA; anodal electrode area: 3.14 mm(2); stimulation time: 30 minutes) over the M1 area to relieve the ipsilateral bias in the rat model. A corridor test was set to count the ipsilateral bias of the rats. In this experiment, 30 Sprague-Dawley rats (80 μA: n = 8, 40 μA: n = 8, sham: n = 7, healthy control: n = 7) were chosen for the corridor test and the tDCS session. The lesioned rats exhibited increased ipsilateral bias 4 weeks after the lesion surgery (P < 0.01), and the anodal tDCS with the active electrode on the lesioned side relieved the ipsilateral bias significantly (P < 0.01) immediately after the surgery and the improvement lasted for nearly 1 day. The rats in the group of 80 μA exhibited more significant changes than the 40 μA group after one day. After all the experiments, the histological process showed no neurotrauma led by the tDCS. In conclusion, the modulatory function of the cortical excitability of the tDCS may awaken the compensatory mechanisms and the response mechanisms which modulate the loss of the brain function. Further studies should be done to provide more evidence about the assumption.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Li, Y; Tian, X; Qian, L; Yu, X; Jiang, W


Modulation of cortical activity after anodal transcranial direct current stimulation of the lower limb motor cortex: a functional MRI study.

2011 Aug

BACKGROUND AND OBJECTIVES: Functional magnetic resonance imaging (fMRI) has shown that transcranial direct current stimulation (tDCS) of the hand motor cortex modulates cortical activity of the healthy human brain. However, few studies have assessed the effects of tDCS on the leg motor cortex. We therefore used fMRI to examine the modulating effects of tDCS on lower limb motor cortex responses. METHODS: In this sham-controlled case-control study, 11 subjects were exposed to active anodal (n = 6) or sham (n = 5) stimulation, with the anode being positioned on the leg motor cortex of the right hemisphere. Each tDCS was delivered for 15 minutes at 2 mA, with each subject receiving a total of four stimulatory sessions on consecutive days. Cortical activity was measured before the first and after the fourth session by fMRI, and changes in cortical activity were calculated. RESULTS: Anodal tDCS increased activation of the ipsilateral supplementary motor area and lowered the extent of activation of both anterior cingulate gyri, the right middle and superior temporal gyri, the middle and superior frontal gyri, and the primary and secondary somatosensory cortices. CONCLUSIONS: Anodal tDCS increased corticospinal excitability of the lower limb motor cortex in healthy subjects, suggesting that multiple brain cortical areas may be associated with leg motor performance via involvement of variable corticocortical connections.

Brain stimulation

Kim, CR; Kim, DY; Kim, LS; Chun, MH; Kim, SJ; Park, CH


Bifrontal and bioccipital transcranial direct current stimulation (tDCS) does not induce mood changes in healthy volunteers: a placebo controlled study.

2011 Aug

Transcranial direct current stimulation (tDCS) is the application of a weak electrical direct current (1.5 mA), which has the ability to modulate spontaneous firing rates of the cortical neurons by depolarizing or hyperpolarizing the neural resting membrane potential. tDCS in patients with depressive disorders has been proven to be an interesting therapeutic method potentially influencing pathologic mood states. Except one study, no alterations in mood could be confirmed applying tDCS in healthy participants. In this study, bifrontal or bioccipital stimulation was applied in 17 healthy subjects during 20 minutes with 1.5 mA in a placebo-controlled manner. Bifrontal stimulation consisted of both anodal and cathodal placement on right and left dorsolateral prefrontal cortex (DLPFC) in two separate sessions. Using a set of self-reported moodscales (SUDS, POMS-32, PANAS, BISBAS) no significant mood changes could be observed, neither with bifrontal nor bioccipital tDCS. As already demonstrated by previous studies, we confirmed the minimal side effects and the safety of this neuromodulation technique.

Brain stimulation

Plazier, M; Joos, K; Vanneste, S; Ost, J; De Ridder, D


Short duration transcranial direct current stimulation (tDCS) modulates verbal memory.

2011 Aug

Transcranial direct current stimulation (tDCS) is a noninvasive method of modulating cortical excitability. The aim of this study was to investigate the effects of short-duration tDCS (1.6 seconds per trial) on memory performance, and whether the effects were affected by stimulation administered early or late in a trial. Participants memorize words under anodal and cathodal tDCS to the left dorsolateral prefrontal cortex (DLPFC) in two separate sessions in no-stimulation, early stimulation, and late stimulation trials. Early stimulation occurred during word presentation, whereas late stimulation occurred after word presentation. Early anodal tDCS led to significantly better accuracy and speed in a subsequent recognition test compared to anodal late or no-stimulation conditions. Early cathodal tDCS, on the other hand, led to significantly worse accuracy and speed in a subsequent recognition test compared with cathodal late or no-stimulation conditions. The results of this study suggest that short-duration tDCS can modulate memory performance and highlight the importance of period of stimulation.

Brain stimulation

Javadi, AH; Cheng, P; Walsh, V


Speech facilitation by left inferior frontal cortex stimulation.

2011 Aug

Electrophysiological studies in humans and animals suggest that noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting [1], polarity-dependent [2] changes in neocortical excitability. Application of tDCS can have significant and selective behavioral consequences that are associated with the cortical location of the stimulation electrodes and the task engaged during stimulation [3-8]. However, the mechanism by which tDCS affects human behavior is unclear. Recently, functional magnetic resonance imaging (fMRI) has been used to determine the spatial topography of tDCS effects [9-13], but no behavioral data were collected during stimulation. The present study is unique in this regard, in that both neural and behavioral responses were recorded using a novel combination of left frontal anodal tDCS during an overt picture-naming fMRI study. We found that tDCS had significant behavioral and regionally specific neural facilitation effects. Furthermore, faster naming responses correlated with decreased blood oxygen level-dependent (BOLD) signal in Broca's area. Our data support the importance of Broca's area within the normal naming network and as such indicate that Broca's area may be a suitable candidate site for tDCS in neurorehabilitation of anomic patients, whose brain damage spares this region.

Current biology : CB

Holland, R; Leff, AP; Josephs, O; Galea, JM; Desikan, M; Price, CJ; Rothwell, JC; Crinion, J


Bifrontal transcranial direct current stimulation modulates tinnitus intensity and tinnitus-distress-related brain activity.

2011 Aug

Bifrontal transcranial direct current stimulation (tDCS), with the anodal electrode overlying the right and the cathodal electrode overlying the left dorsolateral prefrontal cortex, has been shown to suppress tinnitus significantly in 30% of patients. The source localized resting-state electrical activity is recorded before and after bifrontal tDCS in patients who respond to tDCS to unravel the mechanism by which tDCS suppresses tinnitus. The present electroencephalography study (N = 12) provides support for the ability of bifrontal tDCS to suppress tinnitus intensity and tinnitus-related distress by modulation of the pregenual anterior cingulate cortex, parahippocampal area and right primary auditory cortex in resting-state spontaneous brain activity. These findings provide direct support for tDCS having an impact not only directly on the underlying dorsolateral prefrontal cortex but also indirectly on functionally connected brain areas relevant for tinnitus distress and tinnitus intensity, respectively.

The European journal of neuroscience

Vanneste, S; De Ridder, D


[The use of noninvasive brain stimulation in childhood psychiatric disorders: new diagnostic and therapeutic opportunities and challenges].

2011 Aug

Novel diagnostic and therapeutic approaches based on noninvasive brain stimulation offer some promise in the field of childhood psychiatric disorders. There are two primary methods of noninvasive brain stimulation currently available: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Both noninvasive neuromodulation techniques appear to rely on modulating brain plasticity and thus open new hopes in the treatment of brain circuit and plasticity disorders. Since many childhood psychiatric disorders involve disturbances in the timing or mechanisms of plasticity within frontostriatal circuits, and the developing brain shows a greater capacity of brain plasticity, noninvasive brain stimulation might induce greater benefits in this population than in adults. Although the utilization of TMS and tDCS remains limited in children, there is enough evidence for their rational, safe use in this population. In this paper, we review the principles of noninvasive brain stimulation and the diagnostic and therapeutic applications in child-hood psychiatric disorders in order to inform its development into safe and reliable diagnostic and effective therapeutic approaches in pediatric psychiatry.

Revista de neurologia

Rubio-Morell, B; Rotenberg, A; Hernández-Expósito, S; Pascual-Leone, Á


Transcranial direct current stimulation's effect on novice versus experienced learning.

2011 Aug

Transcranial direct current stimulation (TDCS) is a non-invasive form of brain stimulation applied via a weak electrical current passed between electrodes on the scalp. In recent studies, TDCS has been shown to improve learning when applied to the prefrontal cortex (e.g., Kincses et al. in Neuropsychologia 42:113-117, 2003; Clark et al. Neuroimage in 2010). The present study examined the effects of TDCS delivered at the beginning of training (novice) or after an hour of training (experienced) on participants' ability to detect cues indicative of covert threats. Participants completed two 1-h training sessions. During the first 30 min of each training session, either 0.1 mA or 2.0 mA of anodal TDCS was delivered to the participant. The anode was positioned near F8, and the cathode was placed on the upper left arm. Testing trials immediately followed training. Accuracy in classification of images containing and not-containing threat stimuli during the testing sessions indicated: (1) that mastery of threat detection significantly increased with training, (2) that anodal TDCS at 2 mA significantly enhanced learning, and (3) TDCS was significantly more effective in enhancing test performance when applied in novice learners than in experienced learners. The enhanced performance following training with TDCS persisted into the second session when TDCS was delivered early in training.

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Bullard, LM; Browning, ES; Clark, VP; Coffman, BA; Garcia, CM; Jung, RE; van der Merwe, AJ; Paulson, KM; Vakhtin, AA; Wootton, CL; Weisend, MP


Transcranial direct current stimulation (tDCS) produces localized and specific alterations in neurochemistry: a ¹H magnetic resonance spectroscopy study.

2011 Aug

Transcranial direct current stimulation (tDCS) has been found to produce significant changes in behavior, including a large increase of learning and performance for a difficult visual perceptual task (Clark et al., NeuroImage 2010). The mechanisms by which tDCS produces these behavioral effects are currently uncertain. One hypothesis is that anodal tDCS leads to increased metabolic activity in the brain, which enhances cognitive and memory processes. Here we examined the neuronal mechanisms by which tDCS influences learning by measuring changes in brain metabolite concentrations using proton magnetic resonance spectroscopy (¹H MRS). As perception and learning can also influence neurochemistry, here we applied tDCS during rest. MRS data was obtained before and after 2.0 mA of anodal tDCS was applied for 30 min over electrode site P4, with the cathode placed on the contralateral arm. MRS data were acquired from the right parietal lobe beneath the anodal tDCS electrode, and from the homologous regions of the left hemisphere once before and once after tDCS. Significantly higher combined glutamate and glutamine levels were found in right parietal cortex, beneath the stimulating electrode, with non-significant increases in homologous regions of the opposite hemisphere. In addition, a significant interaction between hemispheres was found for tDCS effects on tNAA. These results suggest that changes in glutamatergic activity and tNAA may be related to the mechanisms by which tDCS influences learning and behavior.

Neuroscience letters

Clark, VP; Coffman, BA; Trumbo, MC; Gasparovic, C


Optimized multi-electrode stimulation increases focality and intensity at target.

2011 Aug

Transcranial direct current stimulation (tDCS) provides a non-invasive tool to elicit neuromodulation by delivering current through electrodes placed on the scalp. The present clinical paradigm uses two relatively large electrodes to inject current through the head resulting in electric fields that are broadly distributed over large regions of the brain. In this paper, we present a method that uses multiple small electrodes (i.e. 1.2 cm diameter) and systematically optimize the applied currents to achieve effective and targeted stimulation while ensuring safety of stimulation. We found a fundamental trade-off between achievable intensity (at the target) and focality, and algorithms to optimize both measures are presented. When compared with large pad-electrodes (approximated here by a set of small electrodes covering 25 cm(2)), the proposed approach achieves electric fields which exhibit simultaneously greater focality (80% improvement) and higher target intensity (98% improvement) at cortical targets using the same total current applied. These improvements illustrate the previously unrecognized and non-trivial dependence of the optimal electrode configuration on the desired electric field orientation and the maximum total current (due to safety). Similarly, by exploiting idiosyncratic details of brain anatomy, the optimization approach significantly improves upon prior un-optimized approaches using small electrodes. The analysis also reveals the optimal use of conventional bipolar montages: maximally intense tangential fields are attained with the two electrodes placed at a considerable distance from the target along the direction of the desired field; when radial fields are desired, the maximum-intensity configuration consists of an electrode placed directly over the target with a distant return electrode. To summarize, if a target location and stimulation orientation can be defined by the clinician, then the proposed technique is superior in terms of both focality and intensity as compared to previous solutions and is thus expected to translate into improved patient safety and increased clinical efficacy.

Journal of neural engineering

Dmochowski, JP; Datta, A; Bikson, M; Su, Y; Parra, LC


Neuroplastic changes following rehabilitative training correlate with regional electrical field induced with tDCS.

2011 Aug

Transcranial direct current stimulation (tDCS) has recently emerged as a promising approach to enhance neurorehabilitative outcomes. However, little is known about how the local electrical field generated by tDCS relates to underlying neuroplastic changes and behavior. To address this question, we present a case study analysis of an individual with hemianopia due to stroke and who benefited from a combined visual rehabilitation training and tDCS treatment program. Activation associated with a visual motion perception task (obtained by functional magnetic resonance imaging; fMRI) was used to characterize local changes in brain activity at baseline and after training. Individualized, high-resolution electrical field modeling reproducing precise cerebral and lesioned tissue geometry, predicted distortions of current flow in peri-lesional areas and diffuse clusters of peak electric fields. Using changes in fMRI signal as an index of cortical recovery, correlations to the electrical field map were determined. Significant correlations between the electrical field and change in fMRI signal were region specific including cortical areas under the anode electrode and peri-lesional visual areas. These patterns were consistent with effective tDCS facilitated rehabilitation. We describe the methodology used to analyze tDCS mechanisms through combined fMRI and computational modeling with the ultimate goal of developing a rationale for individualized therapy.

NeuroImage

Halko, MA; Datta, A; Plow, EB; Scaturro, J; Bikson, M; Merabet, LB


Probing for hemispheric specialization for motor skill learning: a transcranial direct current stimulation study.

2011 Aug

Convergent findings point to a left-sided specialization for the representation of learned actions in right-handed humans, but it is unknown whether analogous hemispheric specialization exists for motor skill learning. In the present study, we explored this question by comparing the effects of anodal transcranial direct current stimulation (tDCS) over either left or right motor cortex (M1) on motor skill learning in either hand, using a tDCS montage to better isolate stimulation to one hemisphere. Results were compared with those previously found with a montage more commonly used in the field. Six groups trained for three sessions on a visually guided sequential pinch force modulation task with their right or left hand and received right M1, left M1, or sham tDCS. A linear mixed-model analysis for motor skill showed a significant main effect for stimulation group (left M1, right M1, sham) but not for hand (right, left) or their interaction. Left M1 tDCS induced significantly greater skill learning than sham when hand data were combined, a result consistent not only with the hypothesized left hemisphere specialization for motor skill learning but also with possible increased left M1 responsiveness to tDCS. The unihemispheric montage effect size was one-half that of the more common montage, and subsequent power analysis indicated that 75 subjects per group would be needed to detect differences seen with only 12 subjects with the customary bihemispheric montage.

Journal of neurophysiology

Schambra, HM; Abe, M; Luckenbaugh, DA; Reis, J; Krakauer, JW; Cohen, LG


Noninvasive brain stimulation in Alzheimer's disease: systematic review and perspectives for the future.

2011 Aug

A number of studies have applied transcranial magnetic stimulation (TMS) to physiologically characterize Alzheimer's disease (AD) and to monitor effects of pharmacological agents, while others have begun to therapeutically use TMS and transcranial direct current stimulation (tDCS) to improve cognitive function in AD. These applications are still very early in development, but offer the opportunity of learning from them for future development.We performed a systematic search of all studies using noninvasive stimulation in AD and reviewed all 29 identified articles. Twenty-four focused on measures of motor cortical reactivity and (local) plasticity and functional connectivity, with eight of these studies assessing also effects of pharmacological agents. Five studies focused on the enhancement of cognitive function in AD.Short-latency afferent inhibition (SAI) and resting motor threshold are significantly reduced in AD patients as compared to healthy elders. Results on other measures of cortical reactivity, e.g. intracortical inhibition (ICI), are more divergent. Acetylcholine-esterase inhibitors and dopaminergic drugs may increase SAI and ICI in AD. Motor cortical plasticity and connectivity are impaired in AD. TMS/tDCS can induce acute and short-duration beneficial effects on cognitive function, but the therapeutic clinical significance in AD is unclear. Safety of TMS/tDCS is supported by studies to date.TMS/tDCS appears safe in AD, but longer-term risks have been insufficiently considered. TMS holds promise as a physiologic biomarker in AD to identify therapeutic targets and monitor pharmacologic effects. In addition, TMS/tDCS may have therapeutic utility in AD, though the evidence is still very preliminary and cautious interpretation is warranted.

Experimental gerontology

Freitas, C; Mondragón-Llorca, H; Pascual-Leone, A


Mood and cognitive effects of transcranial direct current stimulation in post-stroke depression.

2011 Aug

Depression following stroke (PSD) affects up to 33% of patients and is associated with increased mortality. Antidepressant drugs have several side effects; therefore novel treatments are needed. Transcranial direct current stimulation (tDCS) has induced mood and cognitive gain in several neuropsychiatric conditions but has not been tested for PSD to date. Here, we report a patient with significant mood and cognitive impairment who showed marked amelioration of these symptoms following anodal stimulation (2 mA per 30 minutes per 10 days) over the left dorsolateral prefrontal cortex. We discuss the possible mechanisms of tDCS in improving PSD. This initial preliminary data is useful to encourage further controlled trials on the field.

Neurocase

Bueno, VF; Brunoni, AR; Boggio, PS; Bensenor, IM; Fregni, F


Dissociating the roles of the cerebellum and motor cortex during adaptive learning: the motor cortex retains what the cerebellum learns.

2011 Aug

Adaptation to a novel visuomotor transformation has revealed important principles regarding learning and memory. Computational and behavioral studies have suggested that acquisition and retention of a new visuomotor transformation are distinct processes. However, this dissociation has never been clearly shown. Here, participants made fast reaching movements while unexpectedly a 30-degree visuomotor transformation was introduced. During visuomotor adaptation, subjects received cerebellar, primary motor cortex (M1) or sham anodal transcranial direct current stimulation (tDCS), a noninvasive form of brain stimulation known to increase excitability. We found that cerebellar tDCS caused faster adaptation to the visuomotor transformation, as shown by a rapid reduction of movement errors. These findings were not present with similar modulation of visual cortex excitability. In contrast, tDCS over M1 did not affect adaptation, but resulted in a marked increase in retention of the newly learnt visuomotor transformation. These results show a clear dissociation in the processes of acquisition and retention during adaptive motor learning and demonstrate that the cerebellum and primary motor cortex have distinct functional roles. Furthermore, they show that is possible to enhance cerebellar function using tDCS.

Cerebral cortex (New York, N.Y. : 1991)

Galea, JM; Vazquez, A; Pasricha, N; de Xivry, JJ; Celnik, P


Modulating functional connectivity patterns and topological functional organization of the human brain with transcranial direct current stimulation.

2011 Aug

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that alters cortical excitability and activity in a polarity-dependent way. Stimulation for few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be caused by stimulation-induced alterations of functional cortical network connectivity. We aimed to investigate the impact of tDCS on cortical network function through functional connectivity and graph theoretical analysis. Single recordings in healthy volunteers with 62 electroencephalography channels were acquired before and after 10 min of facilitatory anodal tDCS over the primary motor cortex (M1), combined with inhibitory cathodal tDCS of the contralateral frontopolar cortex, in resting state and during voluntary hand movements. Correlation matrices containing all 62 pairwise electrode combinations were calculated with the synchronization likelihood (SL) method and thresholded to construct undirected graphs for the θ, α, β, low-γ and high-γ frequency bands. SL matrices and undirected graphs were compared before and after tDCS. Functional connectivity patterns significantly increased within premotor, motor, and sensorimotor areas of the stimulated hemisphere during motor activity in the 60-90 Hz frequency range. Additionally, tDCS-induced significant intrahemispheric and interhemispheric connectivity changes in all the studied frequency bands. In summary, we show for the first time evidence for tDCS-induced changes in brain synchronization and topological functional organization.

Human brain mapping

Polanía, R; Nitsche, MA; Paulus, W


Prolonged visual memory enhancement after direct current stimulation in Alzheimer's disease.

2011 Jul

BACKGROUND: Immediately after patients with Alzheimer's disease (AD) receive a single anodal transcranial direct current stimulation (tDCS) session their memory performance improves. Whether multiple tDCS sessions improve memory performance in the longer term remains unclear. OBJECTIVE: In this study we aimed to assess memory changes after five consecutive sessions of anodal tDCS applied over the temporal cortex in patients with AD. METHODS: A total of 15 patients were enrolled in two centers. Cognitive functions were evaluated before and after therapeutic tDCS. tDCS was delivered bilaterally through two scalp anodal electrodes placed over the temporal regions and a reference electrode over the right deltoid muscle. The stimulating current was set at 2 mA intensity and was delivered for 30 minutes per day for 5 consecutive days. RESULTS: After patients received tDCS, their performance in a visual recognition memory test significantly improved. We found a main effect of tDCS on memory performance, i.e., anodal stimulation improved it by 8.99% from baseline, whereas sham stimulation decreased it by 2.62%. tDCS failed to influence differentially general cognitive performance measures or a visual attention measure. CONCLUSIONS: Our findings show that after patients with AD receive anodal tDCS over the temporal cerebral cortex in five consecutive daily sessions their visual recognition memory improves and the improvement persists for at least 4 weeks after therapy. These encouraging results provide additional support for continuing to investigate anodal tDCS as an adjuvant treatment for patients with AD.

Brain stimulation

Boggio, PS; Ferrucci, R; Mameli, F; Martins, D; Martins, O; Vergari, M; Tadini, L; Scarpini, E; Fregni, F; Priori, A


Transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex modulates declarative memory.

2011 Jul

BACKGROUND: Previous studies have claimed that weak transcranial direct current stimulation (tDCS) induces persisting activity changes in the human motor cortex and working memory, but to date no studies have evaluated the effects of tDCS on declarative memory. OBJECTIVE: Our aim was to determine whether anodal and cathodal transcranial direct current stimulation would differentially modify performance in a word memorization task during encoding or recognition when administered over the left dorsolateral prefrontal cortex (DLPFC). METHODS: In two experiments, 32 participants underwent a series of word memorization tasks. This task was performed during sham, anodal, and cathodal stimulation applied over the left DLPFC. Moreover, participants in the first experiment performed the same task with anodal tDCS of the primary motor cortex (M1). RESULTS: During encoding, anodal stimulation of the left DLPFC improved memory, whereas cathodal stimulation of the same area impaired memory performance in later recognition. Anodal stimulation of M1 had no effect on later recognition. During recognition cathodal stimulation of the left DLPFC impaired recognition compared with sham stimulation of the same area and anodal stimulation had a trend toward improving the recognition. CONCLUSIONS: The results indicated that active stimulation of the left DLPFC leads to an enhancement or impairment of verbal memorization depending on the polarity of the stimulation. Furthermore, this effect was specific to the site of stimulation.

Brain stimulation

Javadi, AH; Walsh, V


Auditory event-related potentials (P3) and cognitive changes induced by frontal direct current stimulation in alcoholics according to Lesch alcoholism typology.

2011 Jul

Frontal lobe dysfunction is a hallmark of alcohol dependence. Recent studies have shown that a simple but powerful technique of cortical modulation - transcranial direct current stimulation (tDCS) - can induce significant cognitive changes. We therefore aimed to assess the clinical and electrophysiological (as indexed by P3) effects of tDCS of left dorsolateral prefrontal cortex (DLPFC) in different types of alcoholic patients according to Lesch's typology. We enrolled 49 alcoholic subjects, aged between 18 and 75 yr, during the subacute abstinence period to participate in this study. Subjects underwent event-related potential (ERP) registration of alcohol-related and neutral sounds before, during and after active tDCS (1 mA, 35 cm2, during 10 min) or sham procedure in a counterbalanced and randomized order. Frontal assessment battery (FAB) and five items of the Obsessive Compulsive Drinking Scale were applied at the beginning and at the end of each experimental session. ERP analysis showed an increase in the mean amplitude of P3 associated with alcohol-related sounds after tDCS. This effect was not seen for neutral sounds. This change was more pronounced in Lesch IV alcoholics. Secondary exploratory analysis showed a significant improvement of FAB performance after active tDCS compared to sham tDCS in Lesch IV alcoholics only. We showed clinical and electrophysiological evidence of tDCS-induced frontal activity enhancement that was specific for Lesch IV alcoholics. Given that frontal dysfunction may contribute to the loss of control over drinking behaviour, local increase in frontal activity induced by tDCS might have a beneficial clinical impact in the future.

The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)

Nakamura-Palacios, EM; de Almeida Benevides, MC; da Penha Zago-Gomes, M; de Oliveira, RW; de Vasconcellos, VF; de Castro, LN; da Silva, MC; Ramos, PA; Fregni, F


Individualized model predicts brain current flow during transcranial direct-current stimulation treatment in responsive stroke patient.

2011 Jul

Although numerous published reports have demonstrated the beneficial effects of transcranial direct-current stimulation (tDCS) on task performance, fundamental questions remain regarding the optimal electrode configuration on the scalp. Moreover, it is expected that lesioned brain tissue will influence current flow and should therefore be considered (and perhaps leveraged) in the design of individualized tDCS therapies for stroke. The current report demonstrates how different electrode configurations influence the flow of electrical current through brain tissue in a patient who responded positively to a tDCS treatment targeting aphasia. The patient, a 60-year-old man, sustained a left hemisphere ischemic stroke (lesion size = 87.42 mL) 64 months before his participation. In this study, we present results from the first high-resolution (1 mm(3)) model of tDCS in a brain with considerable stroke-related damage; the model was individualized for the patient who received anodal tDCS to his left frontal cortex with the reference cathode electrode placed on his right shoulder. We modeled the resulting brain current flow and also considered three additional reference electrode positions: right mastoid, right orbitofrontal cortex, and a "mirror" configuration with the anode over the undamaged right cortex. Our results demonstrate the profound effect of lesioned tissue on resulting current flow and the ability to modulate current pattern through the brain, including perilesional regions, through electrode montage design. The complexity of brain current flow modulation by detailed normal and pathologic anatomy suggest: (1) That computational models are critical for the rational interpretation and design of individualized tDCS stroke-therapy; and (2) These models must accurately reproduce head anatomy as shown here.

Brain stimulation

Datta, A; Baker, JM; Bikson, M; Fridriksson, J


Non-invasive electrical stimulation of the brain (ESB) modifies the resting-state network connectivity of the primary motor cortex: a proof of concept fMRI study.

2011 Jul

An innovative method to obtain fMRI resting-state network maps during non-invasive electrical stimulation of the brain (ESB) was developed and tested. Five healthy volunteers participated in 2 fMRI sessions. In session one, a transcranial direct current stimulator (tDCS) was applied placing the positive electrode (31.5 cm(2)) over the right M1 of the cortex and the negative electrode (31.5 cm(2)) over the left supra-orbital area of the head. In session two, a monophasic pulsed current stimulator (tPCS) was applied using the identical electrode placement. Imaging was performed on a Siemens 3T Tim Trio scanner with a 12-channel head coil. At each session, five consecutive functional scans were obtained: 1) resting-state without stimulation (Rest-1), 2) a motor scan consisting of self-paced, bilateral finger-thumb opposition task, 3) resting-state with ESB (Stim-1), 4) resting-state without stimulation (Rest-2), and 5) resting-state with ESB, replicating Stim-1 (Stim-2). Data were analyzed using AFNI and MATLAB. For motor task fMRI analysis, a general linear model (GLM) determined the voxels in the right and left M1 that were significantly correlated with the motor task paradigm. The resting-state time series from the voxels in the R-M1 were averaged and the resulting time series used as a regressor in a GLM analysis to identify M1 connectivity maps. Connectivity maps were quantified as R(2) values, and then combined to give overlap maps for each of the experimental conditions. Fourier analysis determined the energy in the normalized signal average time courses extracted from L-M1 and R-M1 for each of the resting-state scans. Both tDCS and tPCS lowered the R(2) values and energy of the averaged time course in the right and left M1 ROI. The effect of the tPCS appeared more pronounced and less variable among subjects. Applying non-invasive ESB during fMRI scanning may down regulate the motor cortex's resting-state network connectivity.

Brain research

Alon, G; Roys, SR; Gullapalli, RP; Greenspan, JD


Transcranial direct current stimulation does not modulate motor cortex excitability in patients with amyotrophic lateral sclerosis.

2011 Jul

Amyotrophic lateral sclerosis (ALS) is a progressive disease caused by the degeneration of upper and lower motor neurons. The etiology of ALS is unclear, but there is evidence that loss of cortical inhibition could be related to motor neuron degeneration. We sought to determine whether cathodal transcranial direct current stimulation (tDCS) can reduce cortical excitability in patients with ALS.Three sessions of cathodal tDCS, lasting 7, 11, or 15 minutes, were performed in 10 patients and 10 healthy controls. Corticospinal excitability was measured before and after the tDCS.Cathodal tDCS induced a consistent decrease in corticospinal excitability in healthy controls, but not in ALS patients.The failure of tDCS to produce an excitability shift in the patients supports the potential diagnostic value of tDCS as a marker of upper motor neuron involvement. However, variation in corticospinal excitability measurements both inter- and intraindividually will limit its usefulness.

Muscle & nerve

Munneke, MA; Stegeman, DF; Hengeveld, YA; Rongen, JJ; Schelhaas, HJ; Zwarts, MJ


Increased short latency afferent inhibition after anodal transcranial direct current stimulation.

2011 Jul

Transcranial direct current stimulation (tDCS), a technique for central neuromodulation, has been recently proposed as possible treatment in several neurological and psychiatric diseases. Although shifts on focal brain excitability have been proposed to explain the clinical effects of tDCS, how tDCS-induced functional changes influence cortical interneurones is still largely unknown. The assessment of short latency afferent inhibition (SLAI) of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS), provides the opportunity to test non-invasively interneuronal cholinergic circuits in the human motor cortex. The aim of the present study was to assess whether anodal tDCS can modulate interneuronal circuits involved in SLAI. Resting motor threshold (RMT), amplitude of unconditioned MEPs and SLAI were assessed in the dominant hemisphere of 12 healthy subjects (aged 21-37) before and after anodal tDCS (primary motor cortex, 13min, 1mA). SLAI was assessed delivering electrical conditioning stimuli to the median nerve at the wrist prior to test TMS given at the interstimulus interval (ISI) of 2ms. Whereas RMT and the amplitude of unconditioned MEPs did not change after anodal tDCS, SLAI significantly increased. In conclusion, anodal tDCS-induced effects depend also on the modulation of cortical interneuronal circuits. The enhancement of cortical cholinergic activity assessed by SLAI could be an important mechanism explaining anodal tDCS action in several pathological conditions.

Neuroscience letters

Scelzo, E; Giannicola, G; Rosa, M; Ciocca, M; Ardolino, G; Cogiamanian, F; Ferrucci, R; Fumagalli, M; Mameli, F; Barbieri, S; Priori, A


Mechanisms of aphasia recovery after stroke and the role of noninvasive brain stimulation.

2011 Jul

One of the most frequent symptoms of unilateral stroke is aphasia, the impairment or loss of language functions. Over the past few years, behavioral and neuroimaging studies have shown that rehabilitation interventions can promote neuroplastic changes in aphasic patients that may be associated with the improvement of language functions. Following left hemisphere strokes, the functional reorganization of language in aphasic patients has been proposed to involve both intrahemispheric interactions between damaged left hemisphere and perilesional sites and transcallosal interhemispheric interactions between the lesioned left hemisphere language areas and homotopic regions in the right hemisphere. A growing body of evidence for such reorganization comes from studies using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), two safe and noninvasive procedures that can be applied clinically to modulate cortical excitability during post-stroke language recovery. We discuss a hierarchical model for the plastic changes in language representation that occur in the setting of dominant hemisphere stroke and aphasia. We further argue that TMS and tDCS are potentially promising tools for enhancing functional recovery of language and for further elucidating mechanisms of plasticity in patients with aphasia.

Brain and language

Hamilton, RH; Chrysikou, EG; Coslett, B


Effects of simultaneous bilateral tDCS of the human motor cortex.

2011 Jun

BACKGROUND: Transcranial direct current stimulation (tDCS) is a noninvasive technique that has been investigated as a therapeutic tool for different neurologic disorders. Neuronal excitability can be modified by application of DC in a polarity-specific manner: anodal tDCS increases excitability, while cathodal tDCS decreases excitability. Previous research has shown that simultaneous bilateral tDCS of the human motor cortex facilitates motor performance in the anodal stimulated hemisphere much more than when the same hemisphere is stimulated using unilateral anodal motor cortex tDCS. OBJECTIVE: The main purpose of this study was to determine whether simultaneous bilateral tDCS is able to increase cortical excitability in one hemisphere whereas decreasing cortical excitability in the contralateral hemisphere. To test our hypothesis, cortical excitability before and after bilateral motor cortex tDCS was evaluated. Moreover, the effects of bilateral tDCS were compared with those of unilateral motor cortex tDCS. METHODS: We evaluated cortical excitability in healthy volunteers before and after unilateral or bilateral tDCS using transcranial magnetic stimulation. RESULTS: We demonstrated that simultaneous application of anodal tDCS over the motor cortex and cathodal tDCS over the contralateral motor cortex induces an increase in cortical excitability on the anodal-stimulated side and a decrease in the cathodal stimulated side. We also used the electrode montage (motor cortex-contralateral orbit) method to compare the bilateral tDCS montage with unilateral tDCS montage. The simultaneous bilateral tDCS induced similar effects to the unilateral montage on the cathode-stimulated side. On the anodal tDCS side, the simultaneous bilateral tDCS seems to be a slightly less robust electrode arrangement compared with the placement of electrodes in the motor cortex-contralateral orbit montage. We also found that intersubject variability of the excitability changes that were induced by the anodal motor cortex tDCS using the bilateral montage was lower than that with the unilateral montage. CONCLUSIONS: This is the first study in which cortical excitability before and after bilateral motor cortex tDCS was extensively evaluated, and the effects of bilateral tDCS were compared with unilateral motor cortex tDCS. Simultaneous bilateral tDCS seems to be a useful tool to obtain increases in cortical excitability of one hemisphere whereas causing decreases of cortical excitability in the contralateral hemisphere (e.g.,to treat stroke).

Brain stimulation

Mordillo-Mateos, L; Turpin-Fenoll, L; Millán-Pascual, J; Núñez-Pérez, N; Panyavin, I; Gómez-Argüelles, JM; Botia-Paniagua, E; Foffani, G; Lang, N; Oliviero, A


Non-invasive brain stimulation improves object-location learning in the elderly.

2011 Jun

Remembering the location of objects, an integral part of everyday life, is known to decline with advancing age and early in the course of neurodegenerative dementia. Here, we aimed to test if object-location learning and its retention could be modified by noninvasive brain stimulation. In a group of 20 elderly (mean age 62.1 years) right-handed individuals, we applied transcranial direct current stimulation (tDCS; 20 minutes, 1 mA) over the right temporoparietal cortex, while subjects acquired the correct position of buildings on a street map using an associative learning paradigm. Each subject participated in a randomized and balanced order in 1 session of anodal tDCS and 1 session of sham stimulation, in a double-blind design with 2 parallel versions of the task. Outcome measures were learning success at the end of each session, and immediate as well as delayed (1 week) free recall. We found that subjects performed comparably in the learning task in the 2 conditions, but showed improved recall 1 week after learning with anodal tDCS compared with learning with sham stimulation. In conclusion, retention of object-location learning in the elderly may be modulated by noninvasive brain stimulation, a finding of potential relevance not only for normal aging but also for memory deficits in pathological aging.

Neurobiology of aging

Flöel, A; Suttorp, W; Kohl, O; Kürten, J; Lohmann, H; Breitenstein, C; Knecht, S


The use of the Bilingual Aphasia Test for assessment and transcranial direct current stimulation to modulate language acquisition in minimally verbal children with autism.

2011 Jun

Minimally verbal children with autism commonly demonstrate language dysfunction, including immature syntax acquisition. We hypothesised that transcranial direct current stimulation (tDCS) should facilitate language acquisition in a cohort (n = 10) of children with immature syntax. We modified the English version of the Bilingual Aphasia Test (BAT) to test only basic canonical subject-verb-object sentences. We tested syntactic accuracy after teaching then testing all vocabulary from the subsequent syntax test to ensure validity of syntactic scoring. We used scaffolding sentences for syntax training. All procedures were performed both before and after tDCS. Results demonstrated a large effect size of the difference between pre-/post-tDCS groups (p < 0.0005, d = 2.78), indicating syntax acquisition. Combining a modified BAT with tDCS constitutes effective modalities for assessment and treatment of immature syntax in children with autism. Future studies should explore the BAT for patients with an inability to use or understand language, in particular bilingual children with autism.

Clinical linguistics & phonetics

Schneider, HD; Hopp, JP


Clinical trial design in non-invasive brain stimulation psychiatric research.

2011 Jun

Major depressive disorder (MDD) trials - investigating either non-pharmacological or pharmacological interventions - have shown mixed results. Many reasons explain this heterogeneity, but one that stands out is the trial design due to specific challenges in the field. We aimed therefore to review the methodology of non-invasive brain stimulation (NIBS) trials and provide a framework to improve clinical trial design. We performed a systematic review for randomized, controlled MDD trials whose intervention was transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in MEDLINE and other databases from April 2002 to April 2008. We created an unstructured checklist based on CONSORT guidelines to extract items such as power analysis, sham method, blinding assessment, allocation concealment, operational criteria used for MDD, definition of refractory depression and primary study hypotheses. Thirty-one studies were included. We found that the main methodological issues can be divided in to three groups: (1) issues related to phase II/small trials, (2) issues related to MDD trials and, (3) specific issues of NIBS studies. Taken together, they can threaten study validity and lead to inconclusive results. Feasible solutions include: estimating the sample size a priori; measuring the degree of refractoriness of the subjects; specifying the primary hypothesis and statistical tests; controlling predictor variables through stratification randomization methods or using strict eligibility criteria; adjusting the study design to the target population; using adaptive designs and exploring NIBS efficacy employing biological markers. In conclusion, our study summarizes the main methodological issues of NIBS trials and proposes a number of alternatives to manage them.

International journal of methods in psychiatric research

Brunoni, AR; Fregni, F


Transcranial direct current stimulation influences the cardiac autonomic nervous control.

2011 Jun

To investigate whether the manipulation of brain excitability by transcranial direct current stimulation (tDCS) modulates the heart rate variability (HRV), the effect of tDCS applied at rest on the left temporal lobe in athletes (AG) and non-athletes (NAG) was evaluated. The HRV parameters (natural logarithms of LF, HF, and LF/HF) was assessed in 20 healthy men before, and immediately after tDCS and sham stimulation. After anodal tDCS in AG the parasympathetic activity (HF(log)) increased (P<0.01) and the sympathetic activity (LF(log)) and sympatho-vagal balance (LF/HF(log)) decreased (P<0.01), whereas no significant effects were detected in NAG (P>0.05). No significant changes in HRV indexes were provoked by sham stimulation in both AG and NAG (P>0.05). In conclusion, tDCS applied on the left temporal lobe significantly increased the overall HRV in AG, enhancing the parasympathetic and decreasing the sympathetic modulation of heart rate. Consequently the sympatho-vagal balance decreased at rest in AG but not in NAG. Releasing a weak electric current to stimulate selected brain areas may induce favorable effects on the autonomic control to the heart in highly fit subjects.

Neuroscience letters

Montenegro, RA; Farinatti, Pde T; Fontes, EB; Soares, PP; Cunha, FA; Gurgel, JL; Porto, F; Cyrino, ES; Okano, AH


Flash visual evoked potentials in mice can be modulated by transcranial direct current stimulation.

2011 Jun

Transcranial direct current stimulation (tDCS) in humans has been shown to affect the size of visual evoked potentials (VEPs) in a polarity-dependent way. VEPs have been widely employed in mice to study the visual system in physiological and pathological conditions and are extensively used as animal models of neurological and visual disorders. The present study was performed to evaluate whether mice VEPs could be modulated by tDCS in the same manner as in humans. We describe here the effects of 10 min tDCS (anodal, cathodal or no stimulation) on flash-VEPs in C57BL/6 mice under sevoflurane anesthesia. VEP amplitudes of the first major peak (P1) were analyzed before, at 0, 5 and 10 min after tDCS. Compared with no stimulation condition, anodal tDCS increased P1 amplitude slightly more than 25%, while cathodal stimulation had opposite effects, with a decrease of P1 amplitude by about 30%. After-effects tended to reverse toward basal levels within 10 min after tDCS. These results, suggesting polarity-dependent modulation similar to what described in humans of tDCS effects on VEPs, encourage the use of mice models to study tDCS mechanisms of action and explore therapeutic applications on neurological models of disease.

Neuroscience

Cambiaghi, M; Teneud, L; Velikova, S; Gonzalez-Rosa, JJ; Cursi, M; Comi, G; Leocani, L


Cathodal transcranial direct current stimulation of the primary motor cortex improves selective muscle activation in the ipsilateral arm.

2011 Jun

Proximal upper limb muscles are represented bilaterally in primary motor cortex. Goal-directed upper limb movement requires precise control of proximal and distal agonist and antagonist muscles. Failure to suppress antagonist muscles can lead to abnormal movement patterns, such as those commonly experienced in the proximal upper limb after stroke. We examined whether noninvasive brain stimulation of primary motor cortex could be used to improve selective control of the ipsilateral proximal upper limb. Thirteen healthy participants performed isometric left elbow flexion by contracting biceps brachii (BB; agonist) and left forearm pronation (BB antagonist) before and after 20 min of cathodal transcranial direct current stimulation (c-tDCS) or sham tDCS of left M1. During the tasks, motor evoked potentials (MEPs) in left BB were acquired using single-pulse transcranial magnetic stimulation of right M1 150-270 ms before muscle contraction. As expected, left BB MEPs were facilitated before flexion and suppressed before pronation. After c-tDCS, left BB MEP amplitudes were reduced compared with sham stimulation, before pronation but not flexion, indicating that c-tDCS enhanced selective muscle activation of the ipsilateral BB in a task-specific manner. The potential for c-tDCS to improve BB antagonist control correlated with BB MEP amplitude for pronation relative to flexion, expressed as a selectivity ratio. This is the first demonstration that selective muscle activation in the proximal upper limb can be improved after c-tDCS of ipsilateral M1 and that the benefits of c-tDCS for selective muscle activation may be most effective in cases where activation strategies are already suboptimal. These findings may have relevance for the use of tDCS in rehabilitation after stroke.

Journal of neurophysiology

McCambridge, AB; Bradnam, LV; Stinear, CM; Byblow, WD


Effects of anodal transcranial direct current stimulation over the leg motor area on lumbar spinal network excitability in healthy subjects.

2011 Jun

In recent years, two techniques have become available for the non-invasive stimulation of human motor cortex: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). The effects of TMS and tDCS when applied over motor cortex should be considered with regard not only to cortical circuits but also to spinal motor circuits. The different modes of action and specificity of TMS and tDCS suggest that their effects on spinal network excitability may be different from that in the cortex. Until now, the effects of tDCS on lumbar spinal network excitability have never been studied. In this series of experiments, on healthy subjects, we studied the effects of anodal tDCS over the lower limb motor cortex on (i) reciprocal Ia inhibition projecting from the tibialis anterior muscle (TA) to the soleus (SOL), (ii) presynaptic inhibition of SOL Ia terminals, (iii) homonymous SOL recurrent inhibition, and (iv) SOL H-reflex recruitment curves. The results show that anodal tDCS decreases reciprocal Ia inhibition, increases recurrent inhibition and induces no modification of presynaptic inhibition of SOL Ia terminals and of SOL-H reflex recruitment curves. Our results indicate therefore that the effects of tDCS are the opposite of those previously described for TMS on spinal network excitability. They also indicate that anodal tDCS induces effects on spinal network excitability similar to those observed during co-contraction suggesting that anodal tDCS activates descending corticospinal projections mainly involved in co-contractions.

The Journal of physiology

Roche, N; Lackmy, A; Achache, V; Bussel, B; Katz, R


Non-invasive brain stimulation techniques for chronic pain. A report of a Cochrane systematic review and meta-analysis.

2011 Jun

Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES) and transcranial direct current stimulation (tDCS).To evaluate the efficacy of non-invasive brain stimulation techniques in chronic pain.A Cochrane systematic review with meta-analyses.We employed a comprehensive search strategy. Randomised and quasi-randomised studies of rTMS, CES or tDCS were included if they employed a sham stimulation control group, recruited patients over the age of 18 with pain of three months duration or more and measured pain as a primary outcome. Where possible we entered data into meta-analyses.We included 33 trials in the review (19 rTMS, eight CES and six tDCS). Only one study was judged as being at low risk of bias. Studies of rTMS demonstrated significant heterogeneity. Pre-specified subgroup analyses suggest that low-frequency stimulation is ineffective. A short-term effect on pain of active high-frequency stimulation of the motor cortex in single-dose studies was suggested (standardised mean difference (SMD) -0.40, 95% confidence interval (CI) -0.26 to -0.54, P < 0.00001). This equates to a 15% (95% CI 10% to 20%) reduction in pain which does not clearly exceed the pre-established criteria for a minimally clinically important difference (> 15%). For CES (four studies, 133 participants) no statistically significant difference was found between active stimulation and sham. Analysis of tDCS studies (five studies, 83 people) demonstrated significant heterogeneity and did not find a significant difference between active and sham stimulation. Pre-specified subgroup analysis of tDCS applied to the motor cortex suggested superiority of active stimulation over sham (SMD -0.59, 95% CI -1.10 to -0.08). Non-invasive brain stimulation appears to be associated with minor and transient side effects.Single doses of high-frequency rTMS of the motor cortex may have small short-term effects on chronic pain. The effects do not clearly exceed the predetermined threshold of minimal clinical significance. Low-frequency rTMS is not effective in the treatment of chronic pain. There is insufficient evidence from which to draw firm conclusions regarding the efficacy of CES or tDCS. The available evidence suggests that tDCS applied to the motor cortex may have short-term effects on chronic pain and that CES may be ineffective. There is a need for further, rigorously designed studies of all types of stimulation.

European journal of physical and rehabilitation medicine

O'Connell, NE; Wand, BM; Marston, L; Spencer, S; Desouza, LH

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Transcranial direct current stimulation over Broca's region improves phonemic and semantic fluency in healthy individuals.

2011 Jun

Previous studies have demonstrated that transcranial direct current stimulation (tDCS) can be proficiently used to modulate attentional and cognitive functions. For instance, in the language domain there is evidence that tDCS can fasten picture naming in both healthy individuals and aphasic patients, or improve grammar learning. In this study, we investigated whether tDCS can be used to increase healthy subjects' performance in phonemic and semantic fluency tasks, that are typically used in clinical assessment of language. Ten healthy individuals performed a semantic and a phonemic fluency task following anodal tDCS applied over Broca's region. Each participant underwent a real and a sham tDCS session. Participants were found to produce more words following real anodal tDCS both in the phonemic and in the semantic fluency. Control experiments ascertained that this finding did not depend upon unspecific effects of tDCS over levels of general arousal or attention or upon participants' expectations. These data confirm the efficacy of tDCS in transiently improving language functions by showing that anodal stimulation of Broca's region can enhance verbal fluency. Implications of these results for the treatment of language functions in aphasia are considered.

Neuroscience

Cattaneo, Z; Pisoni, A; Papagno, C


Feasibility, safety, and effectiveness of transcranial direct current stimulation for decreasing post-ERCP pain: a randomized, sham-controlled, pilot study.

2011 Jun

Emerging evidence shows that transcranial direct current stimulation (tDCS), a minimally invasive brain stimulation technique, has analgesic effects in chronic pain patients and in healthy volunteers with experimental pain. No studies have examined the analgesic effects of tDCS immediately after surgical/endoscopic procedures. Endoscopy investigating abdominal pain, especially ERCP, can cause significant postprocedural pain.To test the feasibility, efficacy, and safety of tDCS on post-ERCP pain and analgesia use.Randomized, sham-controlled, pilot study.Tertiary-care medical center.This study involved 21 patients who were hospitalized overnight for ERCP for unexplained right upper quadrant pain.Twenty minutes of real 2.0 mA tDCS or sham (anode over left prefrontal cortex; cathode over gut-representation of right sensory cortex) immediately after ERCP.Pain (visual analogue scale, McGill pain questionnaire, brief pain inventory), patient-controlled analgesia use, adverse events.Real tDCS was associated with 22% less total hydromorphone use, versus sham. The slope of the cumulative patient-controlled analgesia usage curve was significantly steeper in the sham tDCS group (F [2,13] = 15.96; P = .0003). Real tDCS patients reported significantly less pain interference with sleep (t [17] = 3.70; P = .002) and less throbbing pain (t [16] = 2.37; P = .03). Visual analogue scale pain and mood scores (4 hours post-ERCP) suggested a nonsignificant advantage for real tDCS, despite less hydromorphone use. Side effects of tDCS were limited to mild, self-limited tingling, itching, and stinging under electrodes.Small sample size, variability in chronic pain, and chronic opioid use.In this pilot study, tDCS appears to be safe, has minimal side effects, and may reduce postprocedural analgesia requirements and subjective pain ratings. Future studies appear warranted.

Gastrointestinal endoscopy

Borckardt, JJ; Romagnuolo, J; Reeves, ST; Madan, A; Frohman, H; Beam, W; George, MS


Modulating inhibitory control with direct current stimulation of the superior medial frontal cortex.

2011 Jun

The executive control of voluntary action involves not only choosing from a range of possible actions but also the inhibition of responses as circumstances demand. Recent studies have demonstrated that many clinical populations, such as people with attention-deficit hyperactivity disorder, exhibit difficulties in inhibitory control. One prefrontal area that has been particularly associated with inhibitory control is the pre-supplementary motor area (Pre-SMA). Here we applied non-invasive transcranial direct current stimulation (tDCS) over Pre-SMA to test its role in this behavior. tDCS allows for current to be applied in two directions to selectively excite or suppress the neural activity of Pre-SMA. Our results showed that anodal tDCS improved efficiency of inhibitory control. Conversely, cathodal tDCS showed a tendency towards impaired inhibitory control. To our knowledge, this is the first demonstration of non-invasive intervention tDCS altering subjects' inhibitory control. These results further our understanding of the neural bases of inhibitory control and suggest a possible therapeutic intervention method for clinical populations.

NeuroImage

Hsu, TY; Tseng, LY; Yu, JX; Kuo, WJ; Hung, DL; Tzeng, OJ; Walsh, V; Muggleton, NG; Juan, CH


The enhancement of cortical excitability over the DLPFC before and during training impairs categorization in the prototype distortion task.

2011 Jun

The present study investigated the effects of transcranial weak electrical stimulation techniques applied to the right and left dorsolateral prefrontal cortex (DLPFC) on categorization learning measured using a variant of the prototype distortion task. During the training phase of this task subjects saw low- and high distortions of a prototype dot-pattern. 60 participants received 10min of either anodal or cathodal transcranial direct current (tDCS), transcranial random noise (tRNS) or sham stimulation before and during the training. We have assessed the effects of the intervention during a test phase, where the subjects had to decide whether the consecutive high- and low-distortion versions of the prototype or random patterns that were presented belonged to the category established in the training phase. Our results show that the categorization of prototypes is significantly impaired by the application of anodal tDCS and tRNS to the DLPFC. The prototype-effect, observable in the case of the sham stimulation group, was severed in all active stimulation conditions.

Neuropsychologia

Ambrus, GG; Zimmer, M; Kincses, ZT; Harza, I; Kovács, G; Paulus, W; Antal, A


Transcranial direct current stimulation effects on I-wave activity in humans.

2011 Jun

Transcranial direct current stimulation (tDCS) of the human cerebral cortex modulates cortical excitability noninvasively in a polarity-specific manner: anodal tDCS leads to lasting facilitation and cathodal tDCS to inhibition of motor cortex excitability. To further elucidate the underlying physiological mechanisms, we recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation of the primary motor cortex before and after a 5-min period of anodal or cathodal tDCS in eight conscious patients who had electrodes implanted in the cervical epidural space for the control of pain. The effects of anodal tDCS were evaluated in six subjects and the effects of cathodal tDCS in five subjects. Three subjects were studied with both polarities. Anodal tDCS increased the excitability of cortical circuits generating I waves in the corticospinal system, including the earliest wave (I1 wave), whereas cathodal tDCS suppressed later I waves. The motor evoked potential (MEP) amplitude changes immediately following tDCS periods were in agreement with the effects produced on intracortical circuitry. The results deliver additional evidence that tDCS changes the excitability of cortical neurons.

Journal of neurophysiology

Lang, N; Nitsche, MA; Dileone, M; Mazzone, P; De Andrés-Arés, J; Diaz-Jara, L; Paulus, W; Di Lazzaro, V; Oliviero, A


Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces food cravings and increases the self-reported ability to resist food in adults with frequent food craving.

2011 Jun

This study examined whether a 20-min session of prefrontal transcranial direct current stimulation (tDCS) (anode over the right prefrontal cortex and cathode over the left prefrontal cortex) would reduce food cravings and increase the self-reported ability to resist foods in 19 healthy individuals who reported frequent food cravings. Participants viewed computerized images of food and used computerized visual analogue scales to rate food cravings and inability to resist foods before, during, and after receiving either real or sham tDCS. This study employed a randomized within-subject crossover design; participants received both real and sham tDCS and were blind to the condition. Food cravings ratings were reduced in both conditions, however, the percent change in cravings ratings from pre- to post-stimulation was significantly greater for real stimulation than for sham. The percent change in inability to resist food from pre- to post-stimulation also showed a greater decrease in the real condition than for sham. Post hoc analyses suggest that active prefrontal tDCS acutely and significantly decreased food cravings ratings for sweet foods and carbohydrates more so than sham tDCS. No significant differences were seen in the amount of food ingested between real and sham tDCS. These findings in healthy subjects indicate that tDCS is able to temporarily reduce food cravings and improve the self-reported ability to resist foods.

Appetite

Goldman, RL; Borckardt, JJ; Frohman, HA; O'Neil, PM; Madan, A; Campbell, LK; Budak, A; George, MS


Left lateralizing transcranial direct current stimulation improves reading efficiency.

2011 May

BACKGROUND: Poor reading efficiency is the most persistent problem for adults with developmental dyslexia. Previous research has demonstrated a relationship between left posterior temporal cortex (pTC) function and reading ability, regardless of dyslexia status. OBJECTIVE/HYPOTHESIS: In this study, we tested whether enhancing left lateralization of pTC using transcranial direct current stimulation (tDCS) improves reading efficiency in adults without dyslexia. METHOD: Twenty-five right-handed adults with no history of learning disorder participated. Real and sham "Left lateralizing" tDCS were applied to the pTC in separate sessions. Standardized word and nonword reading tests were given immediately after stimulation. RESULTS: Modeling of the induced electrical field confirmed that tDCS was likely to increase left pTC excitability and reduce right pTC excitability as intended. Relative to sham, real tDCS induced improvements in word reading efficiency in below average readers. CONCLUSIONS: Enhancing left lateralization of the pTC using tDCS improves word reading efficiency in below-average readers. This demonstrates that left lateralization of the pTC plays a role in reading ability, and provides stimulation parameters that could be used for a trial of tDCS in adults with developmental dyslexia. Such short-term gains could amplify the effect of appropriate reading interventions when performed in conjunction with them.

Brain stimulation

Turkeltaub, PE; Benson, J; Hamilton, RH; Datta, A; Bikson, M; Coslett, HB


Daily transcranial direct current stimulation (tDCS) leads to greater increases in cortical excitability than second daily transcranial direct current stimulation.

2011 May

BACKGROUND: Evidence from recent clinical trials suggests that transcranial direct current stimulation (tDCS) may have potential in treating neuropsychiatric disorders. However, the optimal frequency at which tDCS sessions should be administered is unknown. OBJECTIVE/HYPOTHESIS: This study investigated the effects of daily or second daily tDCS sessions on motor cortical excitability, over a 5-day period. METHODS: Twelve healthy volunteers received daily or second daily sessions of tDCS to the left primary motor cortex over the study period, in a randomized, intraindividual crossover design. Motor cortical excitability was assessed before and after tDCS at each session through responses to transcranial magnetic stimulation. RESULTS: Over a fixed 5-day period, tDCS induced greater increases in MEP amplitude when given daily rather than second daily. Analyses showed that this difference reflected greater cumulative effects between sessions rather than a greater response to each individual tDCS session. CONCLUSIONS: These results demonstrate that in the motor cortex of healthy volunteers, tDCS alters cortical excitability more effectively when given daily rather than second daily over a 5-day period.

Brain stimulation

Alonzo, A; Brassil, J; Taylor, JL; Martin, D; Loo, CK


Transcranial direct current stimulation for the outpatient treatment of poor-responder depressed patients.

2011 May

Transcranial direct current stimulation (tDCS) is a selective, painless, brain stimulation technique that allows the electric stimulation of specific cortical regions. TDCS has been recently used as investigational intervention for major depression and treatment resistant depression (TRD) with encouraging results. The present study was aimed to investigate the efficacy and tolerability of tDCS in major depressives with poor response to pharmacological treatment. Twenty-three depressed patients, with a diagnosis of major depressive disorder or bipolar disorder, were treated with augmentative tDCS for 5 days, two sessions per day in a blind-rater trial. The course of depressive symptoms was analyzed using repeated measures ANOVA for HAM-D and MADRS total scores. A qualitative analysis on the basis of the HAM-D response was performed as well. Both analyses were conducted at three time-points: T0 (baseline), T1 (endpoint tDCS) and T2 (end of the first week of follow-up). All patients completed the trial without relevant side-effects. A significant reduction of HAM-D and MADRS total scores was observed during the study (P<0.0001). Treatment response (endpoint HAM-D reduction ≥50%) was obtained by four patients (17.4%) at T1 and by seven patients (30.4%) at T2 and remission (endpoint HAM-D<8) by three patients (13.0%) at T1 and by four subjects (17.4%) at T2. Present findings support the efficacy and good tolerability of tDCS in the acute treatment of patients with TRD with clinical benefit being progressive and extended to the first week of follow-up. Further sham-controlled trials with longer follow-up are needed to confirm present results.

European psychiatry : the journal of the Association of European Psychiatrists

Dell'osso, B; Zanoni, S; Ferrucci, R; Vergari, M; Castellano, F; D'Urso, N; Dobrea, C; Benatti, B; Arici, C; Priori, A; Altamura, AC


Stimulation of the human motor cortex alters generalization patterns of motor learning.

2011 May

It has been hypothesized that the generalization patterns that accompany learning carry the signatures of the neural systems that are engaged in that learning. Reach adaptation in force fields has generalization patterns that suggest primary engagement of a neural system that encodes movements in the intrinsic coordinates of joints and muscles, and lesser engagement of a neural system that encodes movements in the extrinsic coordinates of the task. Among the cortical motor areas, the intrinsic coordinate system is most prominently represented in the primary sensorimotor cortices. Here, we used transcranial direct current stimulation (tDCS) to alter mechanisms of synaptic plasticity and found that when it was applied to the motor cortex, it increased generalization in intrinsic coordinates but not extrinsic coordinates. However, when tDCS was applied to the posterior parietal cortex, it had no effects on learning or generalization in the force field task. The results suggest that during force field adaptation, the component of learning that produces generalization in intrinsic coordinates depends on the plasticity in the sensorimotor cortex.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Orban de Xivry, JJ; Marko, MK; Pekny, SE; Pastor, D; Izawa, J; Celnik, P; Shadmehr, R

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Transcranial DC stimulation in fibromyalgia: optimized cortical target supported by high-resolution computational models.

2011 May

In this study we aimed to determine current distribution and short-term analgesic effects of transcranial direct current stimulation (tDCS) in fibromyalgia using different electrode montages. For each electrode montage, clinical effects were correlated with predictions of induced cortical current flow using magnetic resonance imaging-derived finite element method head model. Thirty patients were randomized into 5 groups (Cathodal-M1 [primary motor cortex], Cathodal-SO [supra-orbital area], Anodal-M1, Anodal-SO, and Sham) to receive tDCS application (2 mA, 20 minutes) using an extracephalic montage. Pain was measured using a visual numerical scale (VNS), pressure pain threshold (PPT), and a body diagram (BD) evaluating pain area. There was significant pain reduction in cathodal-SO and anodal-SO groups indexed by VNS. For PPT there was a trend for a similar effect in anodal-SO group. Computer simulation indicated that the M1-extracephalic montage produced dominantly temporo-parietal current flow, consistent with lack of clinical effects with this montage. Conversely, the SO-extracephalic montage produced current flow across anterior prefrontal structures, thus supporting the observed analgesic effects. Our clinical and modeling findings suggest that electrode montage, considering both electrodes, is critical for the clinical effects of M1-tDCS as electric current needs to be induced in areas associated with the pain matrix. These results should be taken into consideration for the design of pain tDCS studies. PERSPECTIVE: Results in this article support that electrode montage is a critical factor to consider for the clinical application of tDCS for pain control, as there is an important correlation between the location of induced electrical current and tDCS-induced analgesic effects.

The journal of pain : official journal of the American Pain Society

Mendonca, ME; Santana, MB; Baptista, AF; Datta, A; Bikson, M; Fregni, F; Araujo, CP


Cathodal transcranial direct current stimulation of the visual cortex in the prophylactic treatment of migraine.

2011 May

The purpose of this study was to determine whether transcranial direct current stimulation (tDCS) can be an effective prophylactic therapy for migraine and migraine-associated pain.This painless and non-invasive method was applied for 6 weeks over the visual cortex (V1), delivered three times per week. Thirty patients were assigned to cathodal or to sham stimulation, and 26 patients participated in the final analyses (cathodal: n = 13, sham: n = 13). During the first 3 weeks both groups received only placebo stimulation. Measures of attack frequency and duration, intensity of pain and number of migraine-related days were recorded 2 months before, during and 2 months post-treatment.Patients treated by cathodal tDCS showed a significant reduction in the duration of attacks, the intensity of pain and the number of migraine-related days post-treatment as compared to the baseline period, but not in the frequency of the attacks. However, compared to the sham group, only the intensity of the pain was significantly reduced post-stimulation. No patients experienced severe adverse effects.Our results suggest that the application of cathodal stimulation over the V1 might be an effective prophylactic therapy in migraine, at least with regard to pain control.

Cephalalgia : an international journal of headache

Antal, A; Kriener, N; Lang, N; Boros, K; Paulus, W


Cathodal transcranial direct current stimulation suppresses ipsilateral projections to presumed propriospinal neurons of the proximal upper limb.

2011 May

This study investigated whether cathodal transcranial direct current stimulation (c-tDCS) of left primary motor cortex (M1) modulates excitability of ipsilateral propriospinal premotoneurons (PNs) in healthy humans. Transcranial magnetic stimulation (TMS) of the right motor cortex was used to obtain motor evoked potentials (MEPs) from the left biceps brachii (BB) while participants maintained contraction of the left BB. To examine presumed PN excitability, left BB MEPs were compared with those conditioned by median nerve stimulation (MNS) at the left elbow. Interstimulus intervals between TMS and MNS were set to produce summation at the C3-C4 level of the spinal cord. MNS facilitated BB MEPs elicited at TMS intensities near active motor threshold but inhibited BB MEPs at slightly higher intensities, indicative of putative PN modulation. c-tDCS suppressed the facilitatory and inhibitory effects of MNS. Sham tDCS did not alter either component. There was no effect of c-tDCS and sham tDCS on nonconditioned left BB MEPs or on the ipsilateral silent period of left BB. Right first dorsal interosseous MEPs were suppressed by c-tDCS. These results indicate that M1 c-tDCS can be used to modulate excitability of ipsilateral projections to presumed PNs controlling the proximal arm muscle BB. This technique may hold promise for promoting motor recovery of proximal upper limb function after stroke.

Journal of neurophysiology

Bradnam, LV; Stinear, CM; Byblow, WD


Clinical research with transcranial direct current stimulation (tDCS): Challenges and future directions.

2011 Apr

BACKGROUND: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past 10 years, tDCS physiologic mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodologic, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. METHODS: We convened a workgroup of researchers in the field to review, discuss, and provide updates and key challenges of tDCS use in clinical research. MAIN FINDINGS/DISCUSSION: We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (1) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (2) methodologic aspects related to the clinical research of tDCS as divided according to study phase (ie, preclinical, phase I, phase II, and phase III studies); (3) ethical and regulatory concerns; and (4) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS.

Brain stimulation

Brunoni, AR; Nitsche, MA; Bolognini, N; Bikson, M; Wagner, T; Merabet, L; Edwards, DJ; Valero-Cabre, A; Rotenberg, A; Pascual-Leone, A; Ferrucci, R; Priori, A; Boggio, PS; Fregni, F


Lack of clinically detectable acute changes on autonomic or thermoregulatory functions in healthy subjects after transcranial direct current stimulation (tDCS).

2011 Apr

BACKGROUND: Neuromodulatory techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have been increasingly studied as possible treatments for many neurological and psychiatric disorders. tDCS is capable of inducing changes in regional cerebral blood flow in both cortical and subcortical structures, as shown by positron emission tomography studies, and might conceivably affect hypothalamic and autonomic nervous system functions. However, it remains unknown whether acute changes in autonomic or hypothalamic functions may be triggered by conventional tDCS protocols. OBJECTIVE/HYPOTHESIS: To verify whether tDCS, when performed with a bipolar cephalic montage, is capable of inducing acute changes in autonomic or hypothalamic functions in healthy subjects. METHODS: Fifty healthy volunteers were studied. tDCS was performed with the anode over the C3 position and the cathode over the right supraorbital region. Subjects received either real or sham tDCS. Parameters assessed before and after a 20-minute session included blood pressure, tympanic thermometry, hand skin temperature, heart rate and ventilatory rate. Plasma concentrations of cortisol were also measured in a sub-set of 10 participants. RESULTS: A repeated-measures, mixed-design ANOVA showed significant changes in hand skin temperature (p=0.005) and cortisol levels (p < 0.001) after both real and sham stimulation. There were no statistically significant changes in any of the other measurements. CONCLUSIONS: The changes in hand temperature and cortisol levels, having occurred in both the sham and experimental groups, probably reflect a non-specific stress response to a new procedure. There were no significant changes in autonomic functions, ventilation rate or core body temperature that can be attributed to conventional tDCS applied to healthy volunteers.

Brain stimulation

Raimundo, RJ; Uribe, CE; Brasil-Neto, JP


Basic knowledge of transcranial direct current stimulation.

2011 Apr

Transcranial direct current stimulation (tDCS) was a neurophysiologic technique using weak electrical currents (1-2 mA) to modulate the activity of neurons in the brain. It was discovered in the 1960s, and then reintroduced by the reasonably well-controlled experiments 12 years ago. They suggested that electrodes placed on the head can produce noticeable neurological changes depended on the current direction.To review a basic technique of the instrument, mechanism of action, and application in clinical researches of tDCS.The tDCS studies were thoroughly reviewed in MEDLINE database using the key words "Transcranial direct current stimulation, tDCS, noninvasive brain stimulation, neurophysiologic technique" from 1998 to 2010.The basic technique of the instrument, mechanism of action, application in clinical researches such as stroke, pain syndrome and craving; safety, side effect, and precaution of tDCS are described.tDCS study is rapidly increasing and accepted as a noninvasive technique. It is easy to use and safe. The outcomes of tDCS in clinical researches are preferable with very little side effects.

Journal of the Medical Association of Thailand = Chotmaihet thangphaet

Auvichayapat, P; Auvichayapat, N


A case of refractory orofacial pain treated by transcranial direct current stimulation applied over hand motor area in combination with NMDA agonist drug intake.

2011 Apr

A female patient presented with persistent orofacial pain on the right side for 3 years, attributed to a viral infection. The pain had remained largely pharmacoresistant, reaching a value of 8/10 on the visual analogue scale.The patient underwent varying three different conditions of trancranial direct current stimulation (tDCS). First, the contralateral representational field of the face area of the primary motor cortex (M1) was anodally stimulated for 5 consecutive days for 20 minutes at 1 mA. During the second stimulation condition, 20 minutes cathodal stimulation was applied for 5 consecutive days at 2 mA intensity over the contralateral representational field the face area of primary somatosensory cortex (SI). In the third condition, the hand area of the left M1 was anodally stimulated for 20 minutes at 1 mA intensity for 8 days combined with the oral administration of D-cycloserine.With regard the third stimulation condition, a 60% reduction in pain perception was observed toward the end of the stimulation. The patient reported a significant pain relief sensation for up to 6 weeks poststimulation.Although this is a pilot exploratory trial in a single patient, our study is a further step toward clinical application of tDCS over the M1 using pharmacologic intervention, to prolong the induced after effect. Furthermore, it demonstrates the potential for repetitive daily stimulation therapy for chronic pain patients.

Brain stimulation

Antal, A; Paulus, W


Improving working memory: the effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex.

2011 Apr

Transcranial direct current stimulation (tDCS), applied to the left dorsolateral prefrontal cortex (DLPFC) has been found to improve working memory (WM) performance in both healthy and clinical participants. However, whether this effect can be enhanced by cognitive activity undertaken during tDCS has not yet been explored.This study aimed to explore whether tDCS applied to the left DLPFC during the persistent performance of one WM task would improve performance on a subsequent WM task, to a greater extent than either tDCS or cognitive activity alone.Ten healthy participants took part in three counterbalanced conditions. The conditions involved 10 minutes of either anodal tDCS while completing an n-back task, anodal tDCS while at rest, or sham tDCS while completing an n-back task. The n-back that was used in this study was a computer-based letter WM task that involved 5 minutes of two-back, followed by 5 minutes of three-back. Digit span forward and backward was administered immediately before and after each treatment, and performance change (pre- to posttreatment) calculated and compared across conditions. The digit span tasks involved a series of numbers being read to the participant, and the participant was required to repeat them back, either in the same order (Digits forward) or in the reverse order (Digits backward).tDCS applied during completion of the n-back task was found to result in greater improvement in performance on digit span forward, compared with tDCS applied while at rest and sham tDCS during the n-back task. This finding was not evident with digit span backward.These results indicate that there may be potential for the use of adjunctive cognitive remediation techniques to enhance the effects of tDCS. However, further research needs to be undertaken in this area to replicate and extend this finding.

Brain stimulation

Andrews, SC; Hoy, KE; Enticott, PG; Daskalakis, ZJ; Fitzgerald, PB


Noninvasive brain stimulation may improve stroke-related dysphagia: a pilot study.

2011 Apr

Treatment options for stroke-related dysphagia are currently limited. In this study, we investigated whether noninvasive brain stimulation in combination with swallowing maneuvers facilitates swallowing recovery in dysphagic stroke patients during early stroke convalescence.Fourteen patients with subacute unilateral hemispheric infarction were randomized to anodal transcranial direct current stimulation (tDCS) versus sham stimulation to the sensorimotor cortical representation of swallowing in the unaffected hemisphere over the course of 5 consecutive days with concurrent standardized swallowing maneuvers. Severity of dysphagia was measured using a validated swallowing scale, Dysphagia Outcome and Severity scale, before the first and after the last session of tDCS or sham. The effect of tDCS was analyzed in a multivariate linear regression model using changes in Dysphagia Outcome and Severity Scale as the outcome variable after adjusting for the effects of other potential confounding variables such as the National Institutes of Health Stroke Scale and Dysphagia Outcome and Severity scale scores at baseline, acute ischemic lesion volumes, patient age, and time from stroke onset to stimulation.Patients who received anodal tDCS gained 2.60 points of improvement in Dysphagia Outcome and Severity scale scores compared to patients in the sham stimulation group who showed an improvement of 1.25 points (P=0.019) after controlling for the effects of other aforementioned variables. Six out 7 (86%) patients in tDCS stimulation group gained at least 2 points of improvement compared with 3 out 7 (43%) patients in the sham group (P=0.107).Because brain stem swallowing centers have bilateral cortical innervations, measures that enhance cortical input and sensorimotor control of brain stem swallowing may be beneficial for dysphagia recovery.

Stroke; a journal of cerebral circulation

Kumar, S; Wagner, CW; Frayne, C; Zhu, L; Selim, M; Feng, W; Schlaug, G


Different resting state brain activity and functional connectivity in patients who respond and not respond to bifrontal tDCS for tinnitus suppression.

2011 Apr

Tinnitus is an ongoing phantom percept. It has been demonstrated that bifrontal transcranial direct current stimulation (tDCS) can reduce tinnitus. In this study, one group of patients reported a substantial improvement in their tinnitus perception, whereas another group described minor or no beneficial effect at all. The objective was to verify whether the activity and connectivity of the resting brain is different for people who will respond to bifrontal tDCS for tinnitus in comparison with non-responders. Higher gamma band activity was demonstrated in right primary and secondary auditory cortex and right parahippocampus for responders. It has been shown that gamma band activity in the auditory cortex is correlated with tinnitus loudness and that the anterior cingulate is involved in tinnitus distress. People who were going to respond to bifrontal tDCS also demonstrated an increased functional connectivity in the gamma band between the right dorsolateral prefrontal cortex (DLPFC) and the right parahippocampus as well as the right DLPFC and subgenual anterior cingulate cortex (sgACC). An analysis revealed that responders to bifrontal tDCS also experienced a larger suppression effect on TMS placed over the right temporal cortex (i.e. auditory cortex) than non-responders. Responders to bifrontal tDCS seem to differ in resting brain activity compared to non-responders in the right auditory cortex and parahippocampal area. They also have a different functional connectivity between DLPFC and, respectively, the sgACC and parahippocampal area. These connectivities might explain the suppression effect for both tinnitus loudness and tinnitus-related distress.

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Vanneste, S; Focquaert, F; Van de Heyning, P; De Ridder, D


Polarity and timing-dependent effects of transcranial direct current stimulation in explicit motor learning.

2011 Apr

Transcranial direct current stimulation (tDCS) is attracting increasing interest as a therapeutic tool for neurorehabilitation, particularly after stroke, because of its potential to modulate local excitability and therefore promote functional plasticity. Previous studies suggest that timing is important in determining the behavioural effects of brain stimulation. Regulatory metaplastic mechanisms exist to modulate the effects of a stimulation intervention in a manner dependent on prior cortical excitability, thereby preventing destabilization of existing cortical networks. The importance of such timing dependence has not yet been fully explored for tDCS. Here, we describe the results of a series of behavioural experiments in healthy controls to determine the importance of the relative timing of tDCS for motor performance. Application of tDCS during an explicit sequence-learning task led to modulation of behaviour in a polarity specific manner: relative to sham stimulation, anodal tDCS was associated with faster learning and cathodal tDCS with slower learning. Application of tDCS prior to performance of the sequence-learning task led to slower learning after both anodal and cathodal tDCS. By contrast, regardless of the polarity of stimulation, tDCS had no significant effect on performance of a simple reaction time task. These results are consistent with the idea that anodal tDCS interacts with subsequent motor learning in a metaplastic manner and suggest that anodal stimulation modulates cortical excitability in a manner similar to motor learning.

Neuropsychologia

Stagg, CJ; Jayaram, G; Pastor, D; Kincses, ZT; Matthews, PM; Johansen-Berg, H

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The enhanced cortical activation induced by transcranial direct current stimulation during hand movements.

2011 Apr

The aim of this study is to evaluate whether tDCS applied on the primary motor cortex (M1) in company with hand movements could enhance cortical activation, using functional MRI (fMRI). Twelve right-handed normal subjects were recruited. Real tDCS and sham tDCS with hand movements were applied during fMRI scanning. Subjects performed grasp-release hand movements at a metronome-guided frequency of 1Hz, while direct current with 1.0mA was delivered to the primary motor cortex. The averaged cortical map and the intensity index were compared between real tDCS with hand movements and sham tDCS with hand movements. Our result showed that cortical activation on the primary sensorimotor cortex was observed under both of two conditions; real tDCS with hand movements and sham tDCS with hand movements. Voxel count and peak intensity were 365.10±227.23 and 5.66±1.97, respectively, in the left primary sensorimotor cortex during real tDCS with right hand movements; in contrast, those were 182.20±117.88 and 4.12±0.88, respectively, during sham tDCS with right hand movements. Significant differences in voxel count and peak intensity were observed between real tDCS and sham tDCS (p<0.05). We found that anodal tDCS application during motor task enhanced cortical activation on the underlying targeted motor cortex, compared with the same motor task without tDCS. Therefore, it seemed that tDCS induced more cortical activity and modulated brain function when concurrently applied with motor task.

Neuroscience letters

Kwon, YH; Jang, SH


Modulation of human trigeminal and extracranial nociceptive processing by transcranial direct current stimulation of the motor cortex.

2011 Apr

The study was conducted to investigate the after-effect of transcranial direct current stimulation (tDCS) applied over the human primary motor cortex (M1) on trigeminal and extracranial nociceptive processing.Nineteen healthy volunteers were stimulated using cathodal, anodal (both 1 mA) or sham tDCS for 20 minutes. Pain processing was assessed by recording trigeminal and extracranial pain-related evoked potentials (PREPs) following electrical stimulation of the contralateral forehead and hand at baseline, 0, 20 and 50 minutes post-tDCS.Cathodal tDCS resulted in decreased peak-to-peak amplitudes (PPAs) by 18% while anodal tDCS lead to increased PPAs of PREPs by 35% (p < .05).The decreased PPAs suggest an inhibition and the increased PPAs of PREPs suggest an excitation of trigeminal and extracranial pain processing induced by tDCS of the M1. These results may provide evidence for the effectiveness of tDCS as a therapeutic instrument in treating headache disorders.

Cephalalgia : an international journal of headache

Hansen, N; Obermann, M; Poitz, F; Holle, D; Diener, HC; Antal, A; Paulus, W; Katsarava, Z


Transcranial direct current stimulation over the motor association cortex induces plastic changes in ipsilateral primary motor and somatosensory cortices.

2011 Apr

This study was performed to elucidate whether transcranial direct current stimulation (tDCS) over the motor association cortex modifies the excitability of primary motor (M1) and somatosensory (S1) cortices via neuronal connectivity.Anodal, cathodal, and sham tDCS (1 mA) over the left motor association cortex was applied to 10 subjects for 15 min using electrodes of two sizes (9 and 18 cm(2)). Both motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) were recorded before, immediately after, and 15 min after tDCS. Electrode positions were confirmed by overlaying them on MRI anatomical surface images of two individuals.After applying anodal tDCS using the large electrode, amplitudes of MEP components significantly decreased, whereas those of early SEP components (N20 and P25) increase. Opposite effects were observed on MEPs and SEPs after cathodal tDCS. However, a small electrode did not significantly influence either MEPs or SEPs, irrespective of polarity. The small electrode covered mainly the dorsal premotor cortex (PMd) while the large electrode involved the supplementary motor area (SMA) in addition to PMd.These results suggest that anodal tDCS over PMd together with SMA enhanced the inhibitory input to M1 and excitatory input to S1, and that cathodal tDCS might lead to an opposite effect.The finding that only the large electrode modulated M1 and S1 implies that activation of PMd together with SMA by tDCS can induce plastic changes in primary sensorimotor areas.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Kirimoto, H; Ogata, K; Onishi, H; Oyama, M; Goto, Y; Tobimatsu, S


Functional connectivity between non-primary motor cortex and primary motor and sensory areas investigated in humans with TDCS and rTMS.

2011 Apr

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Suppa, A; Berardelli, A


Comparing cutaneous perception induced by electrical stimulation using rectangular and round shaped electrodes.

2011 Apr

We have investigated the cutaneous perception differences for anodal and cathodal transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS) between two electrode configurations: a standard, rectangle-shaped, and a circle-shaped, round geometry with the same surface area, and thus, same nominal current distribution. We have aimed to find whether a smaller perimeter length and the absence of corners in the case of the round configuration would lead to altered skin perception characteristics when compared to the rectangular geometry.Twelve subjects were tested for tDCS and tRNS skin perception characteristics in the intensity range of 200-2000 μA using round and rectangular electrode configurations.We have not found any substantial differences between detection thresholds, detection rates, false positive rates or consistent alterations in the sites of perceived stimulation.We conclude that there is no difference between the round and the rectangular electrode configurations regarding their blinding potentials.The results of this investigation indicate that the altering of the electrode geometry to a round configuration is unwarranted for better blinding purposes in future studies using tDCS and tRNS.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Ambrus, GG; Antal, A; Paulus, W


Differences in the experience of active and sham transcranial direct current stimulation.

2011 Mar

BACKGROUND: A limited number of studies have shown that modulation of cortical excitability using transcranial direct current stimulation (tDCS) is safe and tolerable. Few have directly evaluated whether sham and active stimulation are indistinguishable. OBJECTIVE: We aimed to demonstrate tDCS safety and tolerability in a large cohort, and to compare the occurrence and severity of side effects between sham and active stimulation sessions. METHODS: One hundred thirty-one healthy subjects undergoing 277 tDCS sessions rated on a 1 to 5 scale the perception of side effects during and after stimulation. Proportions of active and sham sessions associated with side effects were compared using Fisher exact test, and distributions of severity ratings were compared using the Kruskal-Wallis test. RESULTS: No serious adverse effects occurred. Side effects most commonly reported were tingling (76%), itching (68%), burning (54%), and pain (25%). Side effect severity was mild, with fewer than 2% of responses indicating a severity > 3 on all questions except tingling (15%), itching (20%), burning (7%), pain (5%), and fatigue (3%) during stimulation. Rates of sensory side effects were statistically significantly higher in active stimulation sessions compared with sham sessions. No other stimulation parameters had a statistically significant impact on side effect occurrence. CONCLUSIONS: TDCS is a safe well-tolerated technique with no evidence of risk for serious adverse effects. Sensory side effects are common, but the severity is typically low. Because sensory side effects are more frequent and more severe in active compared with sham tDCS, the current method of sham stimulation may not be an adequate control condition for some studies.

Brain stimulation

Kessler, SK; Turkeltaub, PE; Benson, JG; Hamilton, RH


When anger leads to aggression: induction of relative left frontal cortical activity with transcranial direct current stimulation increases the anger-aggression relationship.

2011 Mar

The relationship between anger and aggression is imperfect. Based on work on the neuroscience of anger, we predicted that anger associated with greater relative left frontal cortical activation would be more likely to result in aggression. To test this hypothesis, we combined transcranial direct current stimulation (tDCS) over the frontal cortex with interpersonal provocation. Participants received insulting feedback after 15 min of tDCS and were able to aggress by administering noise blasts to the insulting participant. Individuals who received tDCS to increase relative left frontal cortical activity behaved more aggressively when they were angry. No relation between anger and aggression was observed in the increase relative right frontal cortical activity or sham condition. These results concur with the motivational direction model of frontal asymmetry, in which left frontal activity is associated with anger. We propose that anger with approach motivational tendencies is more likely to result in aggression.

Social cognitive and affective neuroscience

Hortensius, R; Schutter, DJ; Harmon-Jones, E


The role of GABA in human motor learning.

2011 Mar

GABA modification plays an important role in motor cortical plasticity. We therefore hypothesized that interindividual variation in the responsiveness of the GABA system to modification influences learning capacity in healthy adults. We assessed GABA responsiveness by transcranial direct current stimulation (tDCS), an intervention known to decrease GABA. The magnitude of M1 GABA decrease induced by anodal tDCS correlated positively with both the degree of motor learning and the degree of fMRI signal change within the left M1 during learning. This study therefore suggests that the responsiveness of the GABAergic system to modification may be relevant to short-term motor learning behavior and learning-related brain activity.

Current biology : CB

Stagg, CJ; Bachtiar, V; Johansen-Berg, H

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Transcranial direct current stimulation improves naming reaction time in fluent aphasia: a double-blind, sham-controlled study.

2011 Mar

Previous evidence suggests that anodal transcranial direct current stimulation (A-tDCS) applied to the left hemisphere can improve aphasic participants' ability to name common objects. The current study further examined this issue in a more tightly controlled experiment in participants with fluent aphasia.We examined the effect of A-tDCS on reaction time during overt picture naming in 8 chronic stroke participants. Anode electrode placement targeted perilesional brain regions that showed the greatest activation on a pretreatment functional MRI scan administered during overt picture naming with the reference cathode electrode placed on the contralateral forehead. A-tDCS (1 mA; 20-minute) was compared with sham tDCS (S-tDCS) in a crossover design. Participants received 10 sessions of computerized anomia treatment; 5 sessions included A-tDCS and 5 included S-tDCS.Coupling A-tDCS with behavioral language treatment reduced reaction time during naming of trained items immediately posttreatment (Z=1.96, P=0.025) and at subsequent testing 3 weeks later (Z=2.52, P=0.006).A-tDCS administered during language treatment decreased processing time during picture naming by fluent aphasic participants. Additional studies combining A-tDCS, an inexpensive method with no reported serious side effects, with behavioral language therapy are recommended.

Stroke; a journal of cerebral circulation

Fridriksson, J; Richardson, JD; Baker, JM; Rorden, C

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A rat model for measuring the effectiveness of transcranial direct current stimulation using fMRI.

2011 Mar

Transcranial direct current stimulation (tDCS) is one of the noteworthy noninvasive brain stimulation techniques, but the mechanism of its action remains unclear. With the aim of clarifying the mechanism, we developed a rat model and measured its effectiveness using fMRI. Carbon fiber electrodes were placed on the top of the head over the frontal cortex as the anode and on the neck as the cathode. The stimulus was 400- or 40-μA current applied for 10 min after a baseline recording under an anesthetized condition. The 400-μA stimulation significantly increased signal intensities in the frontal cortex and nucleus accumbens. This suggests anodal tDCS over the frontal cortex induces neuronal activation in the frontal cortex and in its connected brain region.

Neuroscience letters

Takano, Y; Yokawa, T; Masuda, A; Niimi, J; Tanaka, S; Hironaka, N


Transcranial direct current stimulation over the primary motor cortex during fMRI.

2011 Mar

Measurements of motor evoked potentials (MEPs) have shown that anodal and cathodal transcranial direct current stimulations (tDCS) have facilitatory or inhibitory effects on corticospinal excitability in the stimulated area of the primary motor cortex (M1). Here, we investigated the online effects of short periods of anodal and cathodal tDCS on human brain activity of healthy subjects and associated hemodynamics by concurrent blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) at 3T. Using a block design, 20s periods of tDCS at 1 mA intensity over the left M1 altered with 20s periods without tDCS. In different fMRI runs, the effect of anodal or cathodal tDCS was assessed at rest or during finger tapping. A control experiment was also performed, in which the electrodes were placed over the left and right occipito-temporo-parietal junction. Neither anodal nor cathodal tDCS over the M1 for 20s stimulation duration induced a detectable BOLD signal change. However, in comparison to a voluntary finger tapping task without stimulation, anodal tDCS during finger tapping resulted in a decrease in the BOLD response in the supplementary motor area (SMA). Cathodal stimulation did not result in significant change in BOLD response in the SMA, however, a tendency toward decreased activity could be seen. In the control experiment neither cathodal nor anodal stimulation resulted in a significant change of BOLD signal during finger tapping in any brain area including SMA, PM, and M1. These findings demonstrate that the well-known polarity-dependent shifts in corticospinal excitability that have previously been demonstrated using measurements of MEPs after M1 stimulation are not paralleled by analogous changes in regional BOLD signal. This difference implies that the BOLD signal and measurements of MEPs probe diverse physiological mechanisms. The MEP amplitude reflects changes in transsynaptic excitability of large pyramidal neurons while the BOLD signal is a measure of net synaptic activity of all cortical neurons.

NeuroImage

Antal, A; Polania, R; Schmidt-Samoa, C; Dechent, P; Paulus, W


Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex.

2011 Mar

Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent "homeostatic-like" rule governing the response of the human motor cortex to plasticity probing protocols.

Journal of neurophysiology

Fricke, K; Seeber, AA; Thirugnanasambandam, N; Paulus, W; Nitsche, MA; Rothwell, JC

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Non-invasive brain stimulation enhances fine motor control of the hemiparetic ankle: implications for rehabilitation.

2011 Mar

We set out to answer two questions with this study: 1. Can stroke patients improve voluntary control of their paretic ankle by practising a visuo-motor ankle-tracking task? 2. Are practice effects enhanced with non-invasive brain stimulation? A carefully selected sample of chronic stroke patients able to perform the experimental task attended three data collection sessions. Facilitatory transcranial direct current stimulation (tDCS) was applied in a random order over the lower limb primary motor cortex of the lesioned hemisphere or the non-lesioned hemisphere or sham stimulation was delivered over the lesioned hemisphere. In each session, tDCS was applied as patients practiced tracking a sinusoidal waveform for 15 min using dorsiflexion-plantarflexion movements of their paretic ankle. The difference in tracking error prior to, and after, the 15 min of practice was calculated. A practice effect was revealed following sham stimulation, and this effect was enhanced with tDCS applied over the lesioned hemisphere. The practice effect observed following sham stimulation was eliminated by tDCS applied over the non-lesioned hemisphere. The study provides the first evidence that non-invasive brain stimulation applied to the lesioned motor cortex of moderate- to well-recovered stroke patients enhances voluntary control of the paretic ankle. The results provide a basis for examining whether this enhanced ankle control can be induced in patients with greater impairments and whether enhanced control of a single or multiple lower limb joints improves hemiparetic gait patterns.

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Madhavan, S; Weber, KA; Stinear, JW


Nicotinergic impact on focal and non-focal neuroplasticity induced by non-invasive brain stimulation in non-smoking humans.

2011 Mar

Nicotine improves cognitive performance and modulates neuroplasticity in brain networks. The neurophysiological mechanisms underlying nicotine-induced behavioral changes have been sparsely studied, especially in humans. Global cholinergic activation focuses on plasticity in humans. However, the specific contribution of nicotinic receptors to these effects is unclear. Henceforth, we explored the impact of nicotine on non-focal neuroplasticity induced by transcranial direct current stimulation (tDCS) and focal, synapse-specific plasticity induced by paired associative stimulation (PAS) in healthy non-smoking individuals. Forty-eight subjects participated in the study. Each subject received placebo and nicotine patches combined with one of the stimulation protocols to the primary motor cortex in different sessions. Transcranial magnetic stimulation (TMS)-elicited motor-evoked potential (MEP) amplitudes were recorded as a measure of corticospinal excitability until the evening of the second day following the stimulation. Nicotine abolished or reduced both PAS- and tDCS-induced inhibitory neuroplasticity. Non-focal facilitatory plasticity was also abolished, whereas focal facilitatory plasticity was slightly prolonged by nicotine. Thus, nicotinergic influence on facilitatory, but not inhibitory plasticity mimics that of global cholinergic enhancement. Therefore, activating nicotinic receptors has clearly discernable effects from global cholinergic activation. These nicotine-generated plasticity alterations might be important for the effects of the drug on cognitive function.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Thirugnanasambandam, N; Grundey, J; Adam, K; Drees, A; Skwirba, AC; Lang, N; Paulus, W; Nitsche, MA

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Prefrontal direct current stimulation modulates resting EEG and event-related potentials in healthy subjects: a standardized low resolution tomography (sLORETA) study.

2011 Mar

Prefrontal transcranial direct current stimulation (tDCS) with the anode placed on the left dorsolateral prefrontal cortex (DLPFC) has been reported to enhance working memory in healthy subjects and to improve mood in major depression. However, its putative antidepressant, cognitive and behavior action is not well understood. Here, we evaluated the distribution of neuronal electrical activity changes after anodal tDCS of the left DLPFC and cathodal tDCS of the right supraorbital region using spectral power analysis and standardized low resolution tomography (sLORETA). Ten healthy subjects underwent real and sham tDCS on separate days in a double-blind, placebo-controlled cross-over trial. Anodal tDCS was applied for 20 min at 2 mA intensity over the left DLPFC, while the cathode was positioned over the contralateral supraorbital region. After tDCS, EEG was recorded during an eyes-closed resting state followed by a working memory (n-back) task. Statistical non-parametric mapping showed reduced left frontal delta activity in the real tDCS condition. Specifically, a significant reduction of mean current densities (sLORETA) for the delta band was detected in the left subgenual PFC, the anterior cingulate and in the left medial frontal gyrus. Moreover, the effect was strongest for the first 5 min (p<0.01). The following n-back task revealed a positive impact of prefrontal tDCS on error rate, accuracy and reaction time. This was accompanied by increased P2- and P3- event-related potentials (ERP) component-amplitudes for the 2-back condition at the electrode Fz. A source localization using sLORETA for the time window 250-450 ms showed enhanced activity in the left parahippocampal gyrus for the 2-back condition. These results suggest that anodal tDCS of the left DLPFC and/or cathodal tDCS of the contralateral supraorbital region may modulate regional electrical activity in the prefrontal and anterior cingulate cortex in addition to improving working memory performance.

NeuroImage

Keeser, D; Padberg, F; Reisinger, E; Pogarell, O; Kirsch, V; Palm, U; Karch, S; Möller, HJ; Nitsche, MA; Mulert, C


Physiological basis of transcranial direct current stimulation.

2011 Feb

Since the rediscovery of transcranial direct current stimulation (tDCS) about 10 years ago, interest in tDCS has grown exponentially. A noninvasive stimulation technique that induces robust excitability changes within the stimulated cortex, tDCS is increasingly being used in proof-of-principle and stage IIa clinical trials in a wide range of neurological and psychiatric disorders. Alongside these clinical studies, detailed work has been performed to elucidate the mechanisms underlying the observed effects. In this review, the authors bring together the results from these pharmacological, neurophysiological, and imaging studies to describe their current knowledge of the physiological effects of tDCS. In addition, the theoretical framework for how tDCS affects motor learning is proposed.

The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry

Stagg, CJ; Nitsche, MA


Transcranial direct current stimulation induces polarity-specific changes of cortical blood perfusion in the rat.

2011 Feb

Transcranial direct current stimulation (tDCS) induces changes in cortical excitability and improves hand-motor function in chronic stroke. These effects depend on polarity, duration of stimulation and current intensity applied. Towards evaluating the therapeutic potential of tDCS in acute stroke, we investigated tDCS-effects on cerebral blood flow (CBF) in a tDCS rat model adapted for this purpose.In a randomised crossover design eight Sprague-Dawley rats received three single cathodal and anodal tDCS for 15 min every other day. At each polarity, current intensities of 25, 50 and 100 μA were applied. CBF was measured prior and after tDCS for at least 30 min with laser Doppler flowmetry (LDF).At higher intensities (50 and 100 μA) anodal tDCS increased CBF up to 30 min. At 100 μA CBF was increased by about 25%, at 50 μA by about 18%. In contrast, cathodal tDCS led to a decrease of CBF, likewise depending on the current intensity applied. At 100 μA the effects were about 25% of baseline levels and persisted for at least 30 min. At 25 and 50 μA, baseline-levels were mostly re-established within 30 min.tDCS modulates CBF in a polarity specific way, the extent of modulation depending on the stimulation parameters applied. Because of its polarity-specificity, we assume that CBF-alterations are causally related to tDCS-induced alterations in cortical excitability via neuro-vascular coupling. tDCS may constitute a therapeutic option in acute stroke patients or in patients at risk for vasospasm-induced ischemia after subarachnoid hemorrhage.

Experimental neurology

Wachter, D; Wrede, A; Schulz-Schaeffer, W; Taghizadeh-Waghefi, A; Nitsche, MA; Kutschenko, A; Rohde, V; Liebetanz, D


Introducing graph theory to track for neuroplastic alterations in the resting human brain: a transcranial direct current stimulation study.

2011 Feb

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability and activity in a polarity-dependent way. Stimulation for a few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be related to stimulation-induced alterations of functional cortical network connectivity. We aimed to investigate the impact of tDCS on cortical network function by functional connectivity and graph theoretical analysis of the BOLD fMRI spontaneous activity. fMRI resting-state datasets were acquired immediately before and after 10-min bipolar tDCS during rest, with the anode placed over the left primary motor cortex (M1) and the cathode over the contralateral frontopolar cortex. For each dataset, grey matter voxel-based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal connectivity degree and minimum path length maps were calculated and compared before and after tDCS. Nodal minimum path lengths significantly increased in the left somatomotor (SM1) cortex after anodal tDCS, which means that the number of direct functional connections from the left SM1 to topologically distant grey matter voxels significantly decreased. In contrast, functional coupling between premotor and superior parietal areas with the left SM1 significantly increased. Additionally, the nodal connectivity degree in the left posterior cingulate cortex (PCC) area as well as in the right dorsolateral prefrontal cortex (right DLPFC) significantly increased. In summary, we provide initial support that tDCS-induced neuroplastic alterations might be related to functional connectivity changes in the human brain. Additionally, we propose our approach as a powerful method to track for neuroplastic changes in the human brain.

NeuroImage

Polanía, R; Paulus, W; Antal, A; Nitsche, MA


Transcranial direct current stimulation decreases convulsions and spatial memory deficits following pilocarpine-induced status epilepticus in immature rats.

2011 Feb

Transcranial direct current stimulation (tDCS) is a recently available, noninvasive brain stimulation technique. The effects of cathodal tDCS on convulsions and spatial memory after status epilepticus (SE) in immature animals were investigated.Rats underwent lithium-pilocarpine-induced SE at postnatal day (P) 20-21 and received daily 30-min cathodal tDCS for 2 weeks at P23-36 through a unilateral epicranial electrode at 200μA. After tDCS, convulsions over 2 weeks were estimated by 20-h/day video monitoring. The rats were tested in a water maze for spatial learning at P50-53 and the brains were examined for cell loss and mossy fiber sprouting.Long-term treatment with weak cathodal tDCS reduced SE-induced hippocampal cell loss, supragranular and CA3 mossy fiber sprouting, and convulsions (reduction of 21%) in immature rats. The tDCS treatment also rescued cognitive impairment following SE.These findings suggested that cathodal tDCS has neuroprotective effects on the immature rat hippocampus after pilocarpine-induced SE, including reduced sprouting and subsequent improvements in cognitive performance. Such treatment might also have an antiepileptic effect.

Behavioural brain research

Kamida, T; Kong, S; Eshima, N; Abe, T; Fujiki, M; Kobayashi, H


Assessment and treatment of pain with non-invasive cortical stimulation.

2011 Jan

There remains an unmet clinical need for the development of new therapeutic approaches for the treatment of pain. Recent findings have confirmed significant changes in the pain-related neural networks among patients with chronic pain, opening novel possibilities for investigation. Two non-invasive techniques (transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS)) have emerged as interesting, effective, and promising modalities for pain relief.Here we review the clinical efficacy of these techniques for the treatment of pain through an updated systematic meta-analysis on the effects of primary motor cortex stimulation on pain and we discuss potential mechanisms of action based on insights from brain stimulation studies. Our meta-analysis includes 18 studies, which together show that non-invasive brain stimulation is associated with an effect size of -0.86 (95% C.I., -1.54, -0.19) on a standardized pain scale ranging from 0 (no pain) to 10 (worst pain possible).Besides its use as a therapeutic tool, non-invasive brain stimulation can also be used to measure cortical reactivity and plasticity in chronic pain. Such measurements could potentially be used as biomarkers for the dysfunctional chronic pain-related neural network and might be helpful in measuring the efficacy of interventions designed for chronic pain.

Restorative neurology and neuroscience

Zaghi, S; Thiele, B; Pimentel, D; Pimentel, T; Fregni, F


Noninvasive brain stimulation in the treatment of aphasia: exploring interhemispheric relationships and their implications for neurorehabilitation.

2011 Jan

Aphasia is a common consequence of unilateral stroke, typically involving perisylvian regions of the left hemisphere. The course of recovery from aphasia after stroke is variable, and relies on the emergence of neuroplastic changes in language networks. Recent evidence suggests that rehabilitation interventions may facilitate these changes. Functional reorganization of language networks following left-hemisphere stroke and aphasia has been proposed to involve multiple mechanisms, including intrahemispheric recruitment of perilesional left-hemisphere regions and transcallosal interhemispheric interactions between lesioned left-hemisphere language areas and homologous regions in the right hemisphere. Moreover, it is debated whether interhemispheric interactions are beneficial or deleterious to recovering language networks. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are two safe and noninvasive procedures that can be applied clinically to modulate cortical excitability during poststroke language recovery. Intervention with these noninvasive brain stimulation techniques also allows for inferences to be made regarding mechanisms of recovery, including the role of intrahemispheric and interhemispheric interactions. Here we review recent evidence that suggests that TMS and tDCS are promising tools for facilitating language recovery in aphasic patients, and examine evidence that indicates that both right and left hemisphere mechanisms of plasticity are instrumental in aphasia recovery.

Restorative neurology and neuroscience

Chrysikou, EG; Hamilton, RH


Modifying somatosensory processing with non-invasive brain stimulation.

2011 Jan

Purposeful manipulation of cortical plasticity and excitability within somatosensory regions may have therapeutic potential. Non-invasive brain stimulation (NBS) techniques such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) have shown promise towards this end with certain NBS protocols augmenting somatosensory processing and others down-regulating it. Here, we review NBS protocols which, when applied to primary somatosensory cortex, facilitate cortical excitability and tactile acuity (i.e., high-frequency repetitive TMS (rTMS), intermittent theta burst stimulation (TBS), paired associative stimulation (PAS) N20-5 to 0, anodal tDCS), and protocols that inhibit the same (i.e., low-frequency rTMS, continuous TBS, PAS N20-20, cathodal tDCS). Other studies have targeted multisensory regions of the brain to modulate somatosensory processing. These studies in full present a wide array of strategies in which NBS can be utilized to influence somatosensory processing in a behaviorally and clinically relevant capacity.

Restorative neurology and neuroscience

Song, S; Sandrini, M; Cohen, LG


Electrical stimulation and visual network plasticity.

2011 Jan

The visual system has the most complex circuitry of all the sensory systems and it also possesses the ability to undergo induced and spontaneous neuroplastic changes. Most of what we know about the functional organization of the visual system is derived from animal experiments or by correlating circumscribed anatomical lesions in patients and their visual perceptual deficits or dysfunctions. However, in the past years, significant achievements have been made in characterizing visual information processing in the human using non-invasive neurophysiological techniques, such as electrical stimulation of the brain. Transcranial direct (tDCS) and alternating current stimulation (tACS) applied through the skull was shown to directly modulate the excitability of the motor and visual cortices in human subjects. This review article focuses on these stimulation methods and summarizes the latest results with regard to the application of these method over the visual areas in healthy subjects and clinical populations.

Restorative neurology and neuroscience

Antal, A; Paulus, W; Nitsche, MA


Optimizing recovery potential through simultaneous occupational therapy and non-invasive brain-stimulation using tDCS.

2011 Jan

It is thought that following a stroke the contralesional motor region exerts an undue inhibitory influence on the lesional motor region which might limit recovery. Pilot studies have shown that suppressing the contralesional motor region with cathodal transcranial Direct Current Stimulation (tDCS) can induce a short lasting functional benefit; greater and longer lasting effects might be achieved with combining tDCS with simultaneous occupational therapy (OT) and applying this intervention for multiple sessions.We carried out a randomized, double blind, sham controlled study of chronic stroke patients receiving either 5 consecutive days of cathodal tDCS (for 30 minutes) applied to the contralesional motor region and simultaneous OT, or sham tDCS+OT.we showed that cathodal tDCS+OT resulted in significantly more improvement in Range-Of-Motion in multiple joints of the paretic upper extremity and in the Upper-Extremity Fugl-Meyer scores than sham tDCS+OT, and that the effects lasted at least one week post-stimulation. Improvement in motor outcome scores was correlated with decrease in fMRI activation in the contralesional motor region exposed to cathodal stimulation.This suggests that cathodal tDCS combined with OT leads to significant motor improvement after stroke due to a decrease in the inhibitory effect that the contralesional hemisphere exerts onto the lesional hemisphere.

Restorative neurology and neuroscience

Nair, DG; Renga, V; Lindenberg, R; Zhu, L; Schlaug, G


Transcranial direct current stimulation--update 2011.

2011 Jan

Non-invasive brain stimulation with weak direct currents (transcranial direct current stimulation (tDCS)) has emerged as one of the major tools to induce neuroplastic cortical excitability alterations in humans since its (re-) introduction to the arsenal of plasticity-inducing brain stimulation tools. In this review, we gather newly emerged knowledge about the effect of tDCS on brain function in both, basic and applied research. This overview will deliver an update of the last two years of research, because especially during this time numerous important studies were published covering the above-mentioned fields.

Restorative neurology and neuroscience

Nitsche, MA; Paulus, W


Isometric contraction interferes with transcranial direct current stimulation (tDCS) induced plasticity: evidence of state-dependent neuromodulation in human motor cortex.

2011 Jan

Neuroplastic alterations of cortical excitability and activity represent the likely neurophysiological foundation of learning and memory formation. Beyond their induction, alterations of these processes by subsequent modification of cortical activity, termed metaplasticity, came into the focus of interest recently. Animal slice experiments demonstrated that neuroplastic excitability enhancements, or diminutions, can be abolished by consecutive subthreshold stimulation. These processes, termed de-potentiation, and de-depression, have so far not been explored in humans.We combined neuroplasticity induction by transcranial direct current stimulation (tDCS) applied to the hand area of primary motor cortex (M1), which can be used to induce long-lasting excitability enhancements or reductions, dependent on the polarity of stimulation, with short-lasting voluntary muscle contraction (VMC), which itself does not induce plastic cortical excitability changes. Corticospinal and intra-cortical M1 excitability were monitored by different transcranial magnetic stimulation (TMS) protocols.VMC reduced or tended to reverse the anodal tDCS-driven motor cortical excitability enhancement and the cathodal tDCS-induced excitability diminution. Our findings thus demonstrate de-potentiation- and de-depression-like phenomena at the system level in the human motor cortex.This neurophysiological study may contribute to a better understanding of the balance between induction and reversal of plasticity associated with motor learning and rehabilitation processes.

Restorative neurology and neuroscience

Thirugnanasambandam, N; Sparing, R; Dafotakis, M; Meister, IG; Paulus, W; Nitsche, MA; Fink, GR


Reducing procedural pain and discomfort associated with transcranial direct current stimulation.

2011 Jan

Transcranial direct current stimulation (tDCS) appears to have modulatory effects on the excitability of cortical brain tissue. Though tDCS as presently applied causes no apparent harm to brain structure or function, a number of uncomfortable sensations can occur beneath the electrodes during stimulation, including tingling, pain, itching, and burning sensations. Therefore, we investigated the effect of topically applied Eutectic mixture of local anesthetics (EMLA) on tDCS-related discomfort.Nine healthy adults received both anodal and cathodal 2.0 mA tDCS for 5 minutes over the prefrontal cortex with the skin pretreated for 20 minutes with either EMLA or placebo cream. Participants rated procedural discomfort six times across eight dimensions of sensation.On average, the mean sensation ratings for EMLA-associated tDCS stimulation were significantly lower than placebo-associated stimulation for every cutaneous sensation evaluated. Cathodal stimulation was associated with higher ratings of "sharpness" and intolerability than anodal stimulation.Topical EMLA may reduce tDCS-related discomfort.

Brain stimulation

McFadden, JL; Borckardt, JJ; George, MS; Beam, W

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Enhancement of precise hand movement by transcranial direct current stimulation.

2011 Jan

The effect of transcranial direct current stimulation (tDCS) on the precise nondominant hand movement was investigated by applying anodal stimulation over the right primary motor cortex. We recruited 14 healthy participants for this single-blind, sham-controlled crossover trial. A circle-drawing task was performed before, immediately after, and at 30 min after 20 min of 1 mA anodal or sham tDCS. Anodal tDCS, compared with sham stimulation, significantly improved the circle-drawing task compared with sham stimulation. The deviation area and path length of the task were significantly decreased after anodal tDCS application and were further enhanced at 30 min after stimulation. These results suggest that anodal tDCS over the primary motor cortex enhances the precise movement of the nondominant hand for 30 min in healthy participants.

Neuroreport

Matsuo, A; Maeoka, H; Hiyamizu, M; Shomoto, K; Morioka, S; Seki, K


Sertraline vs. ELectrical Current Therapy for Treating Depression Clinical Trial--SELECT TDCS: design, rationale and objectives.

2011 Jan

Despite significant advancements in psychopharmacology, treating major depressive disorder (MDD) is still a challenge considering the efficacy, tolerability, safety, and economical costs of most antidepressant drugs. One approach that has been increasingly investigated is modulation of cortical activity with tools of non-invasive brain stimulation - such as transcranial magnetic stimulation and transcranial direct current stimulation (tDCS). Due to its profile, tDCS seems to be a safe and affordable approach.The SELECT TDCS trial aims to compare sertraline vs. tDCS in a double-blinded, randomized, factorial trial enrolling 120 participants to be allocated to four groups to receive sertraline+tDCS, sertraline, tDCS or placebo. Eligibility criteria are moderate-to-severe unipolar depression (Hamilton Depression Rating Scale >17) not currently on sertraline treatment. Treatment will last 6weeks and the primary outcome is depression change in the Montgomery-Asberg Depression Rating Score (MADRS). Potential biological markers that mediate response, such as BDNF serum levels, Val66Met BDNF polymorphism, and heart rate variability will also be examined. A neuropsychological battery with a focus on executive functioning will be administered.With this design we will be able to investigate whether tDCS is more effective than placebo in a sample of patients free of antidepressants and in addition, we will be able to secondarily compare the effect sizes of sertraline vs. tDCS and also the comparison between tDCS and combination of tDCS and sertraline.

Contemporary clinical trials

Brunoni, AR; Valiengo, L; Baccaro, A; Zanao, TA; de Oliveira, JF; Vieira, GP; Bueno, VF; Goulart, AC; Boggio, PS; Lotufo, PA; Bensenor, IM; Fregni, F


Transcranial direct current stimulation (tDCS) in unipolar vs. bipolar depressive disorder.

2011 Jan

Transcranial direct current stimulation (tDCS) is a non-invasive method for brain stimulation. Although pilot trials have shown that tDCS yields promising results for major depressive disorder (MDD), its efficacy for bipolar depressive disorder (BDD), a condition with high prevalence and poor treatment outcomes, is unknown. In a previous study we explored the effectiveness of tDCS for MDD. Here, we expanded our research, recruiting patients with MDD and BDD. We enrolled 31 hospitalized patients (24 women) aged 30-70 years 17 with MDD and 14 with BDD (n = 14). All patients received stable drug regimens for at least two weeks before enrollment and drug dosages remained unchanged throughout the study. We applied tDCS over the dorsolateral prefrontal cortex (anodal electrode on the left and cathodal on the right) using a 2 mA-current for 20 min, twice-daily, for 5 consecutive days. Depression was measured at baseline, after 5 tDCS sessions, one week later, and one month after treatment onset. We used the scales of Beck (BDI) and Hamilton-21 items (HDRS). All patients tolerated treatment well without adverse effects. After the fifth tDCS session, depressive symptoms in both study groups diminished, and the beneficial effect persisted at one week and one month. In conclusion, our preliminary study suggests that tDCS is a promising treatment for patients with MDD and BDD.2.

Progress in neuro-psychopharmacology & biological psychiatry

Brunoni, AR; Ferrucci, R; Bortolomasi, M; Vergari, M; Tadini, L; Boggio, PS; Giacopuzzi, M; Barbieri, S; Priori, A


[New neurostimulation techniques in adicctions].

2011

Addiction is associated with changes in brain activation patterns. In recent years new techniques of neurostimulation that can alter the activity of brain circuits have been developed, and are being explored in the treatment of addictions. The most important of these techniques are Transcranial Magnetic Stimulation (TMS), Transcranial Direct Electrical Stimulation (tDCS), Vagus Nerve Stimulation (VNS) and Deep Brain Stimulation (DBS). The findings reported are clearly still insufficient for them to be considered as therapeutic alternatives in substance use disorders.

Adicciones

García-Toro, M; Gili, M; Roca, M


Modulation of event-related desynchronization during motor imagery with transcranial direct current stimulation in a patient with severe hemiparetic stroke: a case report.

2011

Recently, surface electroencephalogram (EEG)-based brain-machine interfaces (BMI) have been used for people with disabilities. As a BMI signal source, event-related desynchronization of alpha-band EEG (8-13 Hz) during motor imagery (mu ERD), which is interpreted as desynchronized activities of the activated neurons, is commonly used. However, it is often difficult for patients with severe hemiparesis to produce mu ERD of sufficient strength to activate BMI. Therefore, whether it is possible to modulate mu ERD during motor imagery with anodal transcranial direct-current stimulation (tDCS) was assessed in a severe left hemiparetic stroke patient. EEG was recorded over the primary motor cortex (M1), and mu ERD during finger flexion imagery was measured before and after a 5-day course of tDCS applied to M1. The ERD recorded over the affected M1 increased significantly after tDCS intervention. Anodal tDCS may increase motor cortex excitability and potentiate ERD during motor imagery in patients with severe hemiparetic stroke.

The Keio journal of medicine

Tohyama, T; Fujiwara, T; Matsumoto, J; Honaga, K; Ushiba, J; Tsuji, T; Hase, K; Liu, M

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Efficacy of transcranial direct current stimulation coupled with a multidisciplinary rehabilitation program for the treatment of fibromyalgia.

2011

Pain control in fibromyalgia patients is limited no matter the therapeutic regimens used. Recent data have shown that daily sessions of anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) in patients with fibromyalgia (FM) are associated with reduction of pain perception.We aimed to test whether active tDCS, as compared with sham tDCS, combined with multidisciplinary rehabilitation is associated with significant clinical gains in fibromyalgia.This was a randomized, double-blinded controlled trial.23 patients were randomized to receive weekly sessions of multidisciplinary rehabilitation approach combined with sham or anodal tDCS of M1. Patients were evaluated for pain with VAS and for quality of life with SF-36, fibromyalgia pain questionnaire and health assessment questionnaire by a blinded rater before and after the 4 month period of rehabilitation.Patients tolerated tDCS treatment well, without adverse effects. Patients who received active treatment had a significantly greater reduction of SF-36 pain domain scores (F((2,21))=6.57; p=0.006) and a tendency of higher improvement in Fibromyalgia Impact Questionnaire (FIQ) scores after (p=0.056) as compared with sham tDCS/standard treatment, but no differences were observed in the other domains.Although active tDCS was associated with superior results in one domain (SF-36 pain domain), the lack of significance in the other domains does not fully support this strategy (weekly tDCS) combined with a multidisciplinary approach.

The open rheumatology journal

Riberto, M; Marcon Alfieri, F; Monteiro de Benedetto Pacheco, K; Dini Leite, V; Nemoto Kaihami, H; Fregni, F; Rizzo Battistella, L

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Improved proper name recall in aging after electrical stimulation of the anterior temporal lobes.

2011

Evidence from neuroimaging and neuropsychology suggests that portions of the anterior temporal lobes (ATLs) play a critical role in proper name retrieval. We previously found that anodal transcranial direct current stimulation (tDCS) to the ATLs improved retrieval of proper names in young adults (Ross et al., 2010). Here we extend that finding to older adults who tend to experience greater proper-naming deficits than young adults. The task was to look at pictures of famous faces or landmarks and verbally recall the associated proper name. Our results show a numerical improvement in face naming after left or right ATL stimulation, but a statistically significant effect only after left-lateralized stimulation. The magnitude of the enhancing effect was similar in older and younger adults but the lateralization of the effect differed depending on age. The implications of these findings for the use of tDCS as tool for rehabilitation of age-related loss of name recall are discussed.

Frontiers in aging neuroscience

Ross, LA; McCoy, D; Coslett, HB; Olson, IR; Wolk, DA

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Non-invasive brain stimulation enhances the effects of melodic intonation therapy.

2011

Research has suggested that a fronto-temporal network in the right hemisphere may be responsible for mediating melodic intonation therapy's (MIT) positive effects on speech recovery. We investigated the potential for a non-invasive brain stimulation technique, transcranial direct current stimulation (tDCS), to augment the benefits of MIT in patients with non-fluent aphasia by modulating neural activity in the brain during treatment with MIT. The polarity of the current applied to the scalp determines the effects of tDCS on the underlying tissue: anodal-tDCS increases excitability, whereas cathodal tDCS decreases excitability. We applied anodal-tDCS to the posterior inferior frontal gyrus of the right hemisphere, an area that has been shown both to contribute to singing through the mapping of sounds to articulatory actions and to serve as a key region in the process of recovery from aphasia, particularly in patients with large left hemisphere lesions. The stimulation was applied while patients were treated with MIT by a trained therapist. Six patients with moderate to severe non-fluent aphasia underwent three consecutive days of anodal-tDCS + MIT, and an equivalent series of sham-tDCS + MIT. The two treatment series were separated by 1 week, and the order in which the treatments were administered was randomized. Compared to the effects of sham-tDCS + MIT, anodal-tDCS + MIT led to significant improvements in fluency of speech. These results support the hypothesis that, as the brain seeks to reorganize and compensate for damage to left hemisphere language centers, combining anodal-tDCS with MIT may further recovery from post-stroke aphasia by enhancing activity in a right hemisphere sensorimotor network for articulation.

Frontiers in psychology

Vines, BW; Norton, AC; Schlaug, G

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Polarity-dependent transcranial direct current stimulation effects on central auditory processing.

2011

Given the polarity dependent effects of transcranial direct current stimulation (tDCS) in facilitating or inhibiting neuronal processing, and tDCS effects on pitch perception, we tested the effects of tDCS on temporal aspects of auditory processing. We aimed to change baseline activity of the auditory cortex using tDCS as to modulate temporal aspects of auditory processing in healthy subjects without hearing impairment. Eleven subjects received 2mA bilateral anodal, cathodal and sham tDCS over auditory cortex in a randomized and counterbalanced order. Subjects were evaluated by the Random Gap Detection Test (RGDT), a test measuring temporal processing abilities in the auditory domain, before and during the stimulation. Statistical analysis revealed a significant interaction effect of time vs. tDCS condition for 4000 Hz and for clicks. Post-hoc tests showed significant differences according to stimulation polarity on RGDT performance: anodal improved 22.5% and cathodal decreased 54.5% subjects' performance, as compared to baseline. For clicks, anodal also increased performance in 29.4% when compared to baseline. tDCS presented polarity-dependent effects on the activity of the auditory cortex, which results in a positive or negative impact in a temporal resolution task performance. These results encourage further studies exploring tDCS in central auditory processing disorders.

PloS one

Ladeira, A; Fregni, F; Campanhã, C; Valasek, CA; De Ridder, D; Brunoni, AR; Boggio, PS

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Task-specific effects of tDCS-induced cortical excitability changes on cognitive and motor sequence set shifting performance.

2011

In this study, we tested the effects of transcranial Direct Current Stimulation (tDCS) on two set shifting tasks. Set shifting ability is defined as the capacity to switch between mental sets or actions and requires the activation of a distributed neural network. Thirty healthy subjects (fifteen per site) received anodal, cathodal and sham stimulation of the dorsolateral prefrontal cortex (DLPFC) or the primary motor cortex (M1). We measured set shifting in both cognitive and motor tasks. The results show that both anodal and cathodal single session tDCS can modulate cognitive and motor tasks. However, an interaction was found between task and type of stimulation as anodal tDCS of DLPFC and M1 was found to increase performance in the cognitive task, while cathodal tDCS of DLPFC and M1 had the opposite effect on the motor task. Additionally, tDCS effects seem to be most evident on the speed of changing sets, rather than on reducing the number of errors or increasing the efficacy of irrelevant set filtering.

PloS one

Leite, J; Carvalho, S; Fregni, F; Gonçalves, ÓF

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Cortico-Cortical Connectivity between Right Parietal and Bilateral Primary Motor Cortices during Imagined and Observed Actions: A Combined TMS/tDCS Study.

2011

Previous transcranial magnetic stimulation (TMS) studies showed functional connections between the parietal cortex (PC) and the primary motor cortex (M1) during tasks of different reaching-to-grasp movements. Here, we tested whether the same network is involved in cognitive processes such as imagined or observed actions. Single pulse TMS of the right and left M1 during rest and during a motor imagery and an action observation task (i.e., an index-thumb pinch grip in both cases) was used to measure corticospinal excitability changes before and after conditioning of the right PC by 10 min of cathodal, anodal, or sham transcranial direct current stimulation (tDCS). Corticospinal excitability was indexed by the size of motor-evoked potentials (MEPs) from the contralateral first dorsal interosseous (FDI; target) and abductor digiti minimi muscle (control) muscles. Results showed selective ipsilateral effects on the M1 excitability, exclusively for motor imagery processes: anodal tDCS enhanced the MEPs' size from the FDI muscle, whereas cathodal tDCS decreased it. Only cathodal tDCS impacted corticospinal facilitation induced by action observation. Sham stimulation was always uneffective. These results suggest that motor imagery, differently from action observation, is sustained by a strictly ipsilateral parieto-motor cortex circuits. Results might have implication for neuromodulatory rehabilitative purposes.

Frontiers in neural circuits

Feurra, M; Bianco, G; Polizzotto, NR; Innocenti, I; Rossi, A; Rossi, S

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Down-regulation of negative emotional processing by transcranial direct current stimulation: effects of personality characteristics.

2011

Evidence from neuroimaging and electrophysiological studies indicates that the left dorsolateral prefrontal cortex (DLPFC) is a core region in emotional processing, particularly during down-regulation of negative emotional conditions. However, emotional regulation is a process subject to major inter-individual differences, some of which may be explained by personality traits. In the present study we used transcranial direct current stimulation (tDCS) over the left DLPFC to investigate whether transiently increasing the activity of this region resulted in changes in the ratings of positive, neutral and negative emotional pictures. Results revealed that anodal, but not cathodal, tDCS reduced the perceived degree of emotional valence for negative stimuli, possibly due to an enhancement of cognitive control of emotional expression. We also aimed to determine whether personality traits (extraversion and neuroticism) might condition the impact of tDCS. We found that individuals with higher scores on the introversion personality dimension were more permeable than extraverts to the modulatory effects of the stimulation. The present study underlines the role of the left DLPFC in emotional regulation, and stresses the importance of considering individual personality characteristics as a relevant variable, although replication is needed given the limited sample size of our study.

PloS one

Peña-Gómez, C; Vidal-Piñeiro, D; Clemente, IC; Pascual-Leone, Á; Bartrés-Faz, D

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Translational research in transcranial direct current stimulation (tDCS): a systematic review of studies in animals.

2011

Recent therapeutic human studies testing transcranial direct current stimulation (tDCS) has shown promising results, although many questions remain unanswered. Translational research with experimental animals is an appropriate framework for investigating its mechanisms of action that are still undetermined. Nevertheless, animal and human studies are often discordant. Our aim was to review tDCS animal studies, examining and comparing their main findings with human studies. We performed a systematic review in Medline and other databases, screening for animal studies in vivo that delivered tDCS. Studies in vitro and using other neuromodulatory techniques were excluded. We extracted data according to Animal Research: Reporting In Vivo Experiments (ARRIVE) guidelines for reporting in vivo animal research. Thus, we collected data on sample characteristics (size, gender, weight and specimen) and methodology (experimental procedures, experimental animals, housing and husbandry, as well as analysis). We also collected data on methods for delivering tDCS (location, size, current and current density of electrodes and electrode montage), experimental effects (polarity-, intensity- and after-effects) and safety. Only 12 of 48 potentially eligible studies met our inclusion criteria and were reviewed. Quality assessment reporting was only moderate and studies were heterogeneous regarding tDCS montage methodology, position of active and reference electrodes, and current density used. Nonetheless, almost all studies demonstrated that tDCS had positive immediate and long-lasting effects. Vis-à-vis human trials, animal studies applied higher current densities (34.2 vs. 0.4 A/m(2), respectively), preferred extra-cephalic positions for reference electrodes (60% vs. 10%, respectively) and used electrodes with different sizes more often. Potential implications for translational tDCS research are discussed.

Reviews in the neurosciences

Brunoni, AR; Fregni, F; Pagano, RL


Investigating the Role of Current Strength in tDCS Modulation of Working Memory Performance in Healthy Controls.

2011

Transcranial direct current stimulation (tDCS) is a brain stimulation technique that has the potential to improve working memory (WM) deficits in many clinical disorders. The aim of this study was to investigate the role of current strength on the ability of anodal tDCS to improve WM, and secondly to investigate the time course of effects. Twelve healthy participants underwent three stimulation sessions consisting of 20 min of either 1 mA anodal tDCS, 2 mA anodal tDCS, or sham tDCS to the left dorsolateral prefrontal cortex (DLPFC) localized via F3, all whilst completing a WM task. Intra-stimulation and post-stimulation WM performances were measured using the n-back and Sternberg tasks respectively. Results revealed no significant improvements in participants' accuracy, but a significant interaction was found with respect to current strength and time for accurate reaction time. The finding provides partial support for the hypothesis, in that it appears current strength may affect aspects of WM performance. However, more research is needed, and a higher difficulty level of WM tasks is one of the suggestions discussed for future research.

Frontiers in psychiatry / Frontiers Research Foundation

Teo, F; Hoy, KE; Daskalakis, ZJ; Fitzgerald, PB

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Errorless and errorful learning modulated by transcranial direct current stimulation.

2011

Errorless learning is advantageous over trial and error learning (errorful learning) as errors are avoided during learning resulting in increased memory performance. Errorful learning challenges the executive control system of memory processes as the erroneous items compete with the correct items during retrieval. The left dorsolateral prefrontal cortex (DLPFC) is a core region involved in this executive control system. Transcranial direct current stimulation (tDCS) can modify the excitability of underlying brain functioning.In a single blinded tDCS study one group of young healthy participants received anodal and another group cathodal tDCS of the left DLPFC each compared to sham stimulation. Participants had to learn words in an errorless and an errorful manner using a word stem completion paradigm. The results showed that errorless compared to errorful learning had a profound effect on the memory performance in terms of quality. Anodal stimulation of the left DLPFC did not modulate the memory performance following errorless or errorful learning. By contrast, cathodal stimulation hampered memory performance after errorful learning compared to sham, whereas there was no modulation after errorless learning.Concluding, the study further supports the advantages of errorless learning over errorful learning. Moreover, cathodal stimulation of the left DLPFC hampered memory performance following the conflict-inducing errorful learning as compared to no modulation after errorless learning emphasizing the importance of the left DLPFC in executive control of memory.

BMC neuroscience

Hammer, A; Mohammadi, B; Schmicker, M; Saliger, S; Münte, TF

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Single-session tDCS-supported retraining does not improve fine motor control in musician's dystonia.

2011

Focal dystonia in musicians (MD) is a task-specific movement disorder with a loss of voluntary motor control during instrumental playing. Defective inhibition on different levels of the central nervous system is involved in the pathophysiology. Sensorimotor retraining is a therapeutic approach to MD and aims to establish non-dystonic movements. Transcranial direct current stimulation (tDCS) modulates cortical excitability and alters motor performance. In this study, tDCS of the motor cortex was expected to assist retraining at the instrument.Nine professional pianists suffering from MD were included in a placebo-controlled double-blinded study. Retraining consisted of slow, voluntarily controlled movements on the piano and was combined with tDCS. Patients were treated with three stimulation protocols: anodal tDCS, cathodal tDCS and placebo stimulation.No beneficial effects of single-session tDCS-supported sensorimotor retraining on fine motor control in pianists with MD were found in all three conditions.The main cause of the negative result of this study may be the short intervention time. One retraining session with a duration of 20 min seems not sufficient to improve symptoms of MD. Additionally, a single tDCS session might not be sufficient to modify sensorimotor learning of a highly skilled task in musicians with dystonia.

Restorative neurology and neuroscience

Buttkus, F; Baur, V; Jabusch, HC; de la Cruz Gomez-Pellin, M; Paulus, W; Nitsche, MA; Altenmüller, E


Electrode positioning and montage in transcranial direct current stimulation.

2011

Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a non-invasive and safe alternative to change cortical excitability. The effects of one session of tDCS can last for several minutes, and its effects depend on polarity of stimulation, such as that cathodal stimulation induces a decrease in cortical excitability, and anodal stimulation induces an increase in cortical excitability that may last beyond the duration of stimulation. These effects have been explored in cognitive neuroscience and also clinically in a variety of neuropsychiatric disorders--especially when applied over several consecutive sessions. One area that has been attracting attention of neuroscientists and clinicians is the use of tDCS for modulation of pain-related neural networks. Modulation of two main cortical areas in pain research has been explored: primary motor cortex and dorsolateral prefrontal cortex. Due to the critical role of electrode montage, in this article, we show different alternatives for electrode placement for tDCS clinical trials on pain; discussing advantages and disadvantages of each method of stimulation.

Journal of visualized experiments : JoVE

DaSilva, AF; Volz, MS; Bikson, M; Fregni, F


Improved picture naming in aphasia patients treated with cathodal tDCS to inhibit the right Broca's homologue area.

2011

Previous reports have suggested that noninvasive cortical stimulation could influence speech production in patients with chronic stroke. Here, we evaluated the hypothesis that cathodal transcranial DC stimulation (ctDCS), a technique that decreases excitability of stimulated cortical sites, applied over a healthy right Broca's homologue area could improve picture naming in patients with post-stroke aphasia.Ten right-handed patients with post-stroke aphasia were enrolled in this double blind, counterbalanced sham-controlled, crossover study. Each patient received an intervention of ctDCS (2 mA for 20 min) and of sham tDCS (2 mA for 1 min) daily for 5 consecutive days in a randomized crossover manner with a minimum interval of one week between interventions, over a healthy right Broca's homologue area using a left supraorbital anode and simultaneous daily sessions of conventional word-retrieval training. The primary endpoint measure of this study was a standardized, validated Korean version of the Boston Naming Test, which is a measure of picture naming skills.ctDCS was not found to have any adverse effects. Furthermore, significantly improved picture naming (p = 0.02) was observed at 1 hour following the last (5th) ctDCS treatment session, but no changes were observed after sham tDCS.These results demonstrate that cathodal tDCS over the right healthy Broca's homologue area with a left supraorbital anodal location can improve picture naming task performance in post-stroke aphasia.

Restorative neurology and neuroscience

Kang, EK; Kim, YK; Sohn, HM; Cohen, LG; Paik, NJ


Effect of a tDCS electrode montage on implicit motor sequence learning in healthy subjects.

2011

This study was undertaken to test the hypothesis that a combination of excitatory anodal transcranial direct current stimulation (tDCS) to the contralateral motor cortex and inhibitory cathodal tDCS to the ipsilateral motor cortex of the motor performing hand (Bi-tDCS) would elicit more implicit motor sequence learning than anodal tDCS applied to the contralateral motor cortex alone (Uni-tDCS).Eleven healthy right-handed adults underwent a randomized crossover experiment of Uni-tDCS, Bi-tDCS, or sham stimulation. Subjects performed a 12-digit finger sequence serial reaction time task with the right hand at baseline (Pre), at immediately (Post 1), and 24 hours after stimulation (Post 2). The ratios of reaction times of predetermined repeating sequence versus random sequence were subjected to statistical analysis.The paired t test showed that reaction time ratios were significant decreased by all stimulation types at Post 1 versus Pre (P < 0.01). However, mean reaction time ratios showed a significant decrease after Uni-tDCS (P < 0.01) and Bi-tDCS (P < 0.01), but only a marginal decreased after Sham (P = 0.05) at Post 2, which suggests that motor sequence learning is consolidated by Uni-tDCS and Bi-tDCS, but only partially consolidated by sham stimulation. No significant differences were observed between Uni-tDCS and Bi-tDCS in terms of in reaction time ratios at Post 1 or 2.No significant difference was found between Uni-tDCS and Bi-tDCS in terms of induced implicit motor sequence learning, but tDCS led to greater consolidation of the learned motor sequence than sham stimulation. These findings need to be tested in the context of stroke hand motor rehabilitation.

Experimental & translational stroke medicine

Kang, EK; Paik, NJ

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Transcranial electrical currents to probe EEG brain rhythms and memory consolidation during sleep in humans.

2011

Previously the application of a weak electric anodal current oscillating with a frequency of the sleep slow oscillation (∼0.75 Hz) during non-rapid eye movement sleep (NonREM) sleep boosted endogenous slow oscillation activity and enhanced sleep-associated memory consolidation. The slow oscillations occurring during NonREM sleep and theta oscillations present during REM sleep have been considered of critical relevance for memory formation. Here transcranial direct current stimulation (tDCS) oscillating at 5 Hz, i.e., within the theta frequency range (theta-tDCS) is applied during NonREM and REM sleep. Theta-tDCS during NonREM sleep produced a global decrease in slow oscillatory activity conjoint with a local reduction of frontal slow EEG spindle power (8-12 Hz) and a decrement in consolidation of declarative memory, underlining the relevance of these cortical oscillations for sleep-dependent memory consolidation. In contrast, during REM sleep theta-tDCS appears to increase global gamma (25-45 Hz) activity, indicating a clear brain state-dependency of theta-tDCS. More generally, results demonstrate the suitability of oscillating-tDCS as a tool to analyze functions of endogenous EEG rhythms and underlying endogenous electric fields as well as the interactions between EEG rhythms of different frequencies.

PloS one

Marshall, L; Kirov, R; Brade, J; Mölle, M; Born, J

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Facilitate insight by non-invasive brain stimulation.

2011

Our experiences can blind us. Once we have learned to solve problems by one method, we often have difficulties in generating solutions involving a different kind of insight. Yet there is evidence that people with brain lesions are sometimes more resistant to this so-called mental set effect. This inspired us to investigate whether the mental set effect can be reduced by non-invasive brain stimulation. 60 healthy right-handed participants were asked to take an insight problem solving task while receiving transcranial direct current stimulation (tDCS) to the anterior temporal lobes (ATL). Only 20% of participants solved an insight problem with sham stimulation (control), whereas 3 times as many participants did so (p = 0.011) with cathodal stimulation (decreased excitability) of the left ATL together with anodal stimulation (increased excitability) of the right ATL. We found hemispheric differences in that a stimulation montage involving the opposite polarities did not facilitate performance. Our findings are consistent with the theory that inhibition to the left ATL can lead to a cognitive style that is less influenced by mental templates and that the right ATL may be associated with insight or novel meaning. Further studies including neurophysiological imaging are needed to elucidate the specific mechanisms leading to the enhancement.

PloS one

Chi, RP; Snyder, AW

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Respective implications of glutamate decarboxylase antibodies in stiff person syndrome and cerebellar ataxia.

2011

To investigate whether Stiff-person syndrome (SPS) and cerebellar ataxia (CA) are associated with distinct GAD65-Ab epitope specificities and neuronal effects.Purified GAD65-Ab from neurological patients and monoclonal GAD65-Ab with distinct epitope specificities (b78 and b96.11) were administered in vivo to rat cerebellum. Effects of intra-cerebellar administration of GAD65-Ab were determined using neurophysiological and neurochemical methods.Intra-cerebellar administration of GAD65-Ab from a SPS patient (Ab SPS) impaired the NMDA-mediated turnover of glutamate, but had no effect on NMDA-mediated turnover of glycerol. By contrast, GAD65-Ab from a patient with cerebellar ataxia (Ab CA) markedly decreased the NMDA-mediated turnover of glycerol. Both GAD65-Ab increased the excitability of the spinal cord, as assessed by the F wave/M wave ratios. The administration of BFA, an inhibitor of the recycling of vesicles, followed by high-frequency stimulation of the cerebellum, severely impaired the cerebello-cortical inhibition only when Ab CA was used. Moreover, administration of transcranial direct current stimulation (tDCS) of the motor cortex revealed a strong disinhibition of the motor cortex with Ab CA. Monoclonal antibodies b78 and b96.11 showed distinct effects, with greater effects of b78 in terms of increase of glutamate concentrations, impairment of the adaptation of the motor cortex to repetitive peripheral stimulation, disinhibition of the motor cortex following tDCS, and increase of the F/M ratios. Ab SPS shared antibody characteristics with b78, both in epitope recognition and ability to inhibit enzyme activity, while Ab CA had no effect on GAD65 enzyme activity.These results suggest that, in vivo, neurological impairments caused by GAD65-Ab could vary according to epitope specificities. These results could explain the different neurological syndromes observed in patients with GAD65-Ab.

Orphanet journal of rare diseases

Manto, MU; Hampe, CS; Rogemond, V; Honnorat, J

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Transcranial direct current stimulation of the prefrontal cortex modulates working memory performance: combined behavioural and electrophysiological evidence.

2011

Transcranial direct current stimulation (tDCS) is a technique that can systematically modify behaviour by inducing changes in the underlying brain function. In order to better understand the neuromodulatory effect of tDCS, the present study examined the impact of tDCS on performance in a working memory (WM) task and its underlying neural activity. In two experimental sessions, participants performed a letter two-back WM task after sham and either anodal or cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC).Results showed that tDCS modulated WM performance by altering the underlying oscillatory brain activity in a polarity-specific way. We observed an increase in WM performance and amplified oscillatory power in the theta and alpha bands after anodal tDCS whereas cathodal tDCS interfered with WM performance and decreased oscillatory power in the theta and alpha bands under posterior electrode sides.The present study demonstrates that tDCS can alter WM performance by modulating the underlying neural oscillations. This result can be considered an important step towards a better understanding of the mechanisms involved in tDCS-induced modulations of WM performance, which is of particular importance, given the proposal to use electrical brain stimulation for the therapeutic treatment of memory deficits in clinical settings.

BMC neuroscience

Zaehle, T; Sandmann, P; Thorne, JD; Jäncke, L; Herrmann, CS

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Transcranial direct current stimulation: electrode montage in stroke.

2011

Neurophysiological and computer modelling studies have shown that electrode montage is a critical parameter to determine the neuromodulatory effects of transcranial direct current stimulation (tDCS). We tested these results clinically by systematically investigating optimal tDCS electrode montage in stroke. Ten patients received in a counterbalanced and randomised order the following conditions of stimulation (i) anodal stimulation of affected M1 (primary motor cortex) and cathodal stimulation of unaffected M1 ('bilateral tDCS'); (ii) anodal stimulation of affected M1 and cathodal stimulation of contralateral supraorbital area ('anodal tDCS'); (iii) cathodal stimulation of unaffected M1 and anodal stimulation of contralateral supraorbital area ('cathodal tDCS'); (iv) anodal stimulation of affected M1 and cathodal stimulation of contralateral deltoid muscle ('extra-cephalic tDCS') and (v) sham stimulation. We used the Jebsen-Taylor Test (JTT) as a widely accepted measure of upper limb function. Bilateral tDCS, anodal tDCS and cathodal tDCS were shown to be associated with significant improvements on the JTT. Placing the reference electrode in an extracephalic position and use of sham stimulation did not induce any significant effects. This small sham controlled cross-over clinical trial is important to provide additional data on the clinical effects of tDCS in stroke and for planning and designing future large tDCS trials in patients with stroke.

Disability and rehabilitation

Mahmoudi, H; Borhani Haghighi, A; Petramfar, P; Jahanshahi, S; Salehi, Z; Fregni, F


Bihemispheric brain stimulation facilitates motor recovery in chronic stroke patients.

2010 Dec

Motor recovery after stroke depends on the integrity of ipsilesional motor circuits and interactions between the ipsilesional and contralesional hemispheres. In this sham-controlled randomized trial, we investigated whether noninvasive modulation of regional excitability of bilateral motor cortices in combination with physical and occupational therapy improves motor outcome after stroke.Twenty chronic stroke patients were randomly assigned to receive 5 consecutive sessions of either 1) bihemispheric transcranial direct current stimulation (tDCS) (anodal tDCS to upregulate excitability of ipsilesional motor cortex and cathodal tDCS to downregulate excitability of contralesional motor cortex) with simultaneous physical/occupational therapy or 2) sham stimulation with simultaneous physical/occupational therapy. Changes in motor impairment (Upper Extremity Fugl-Meyer) and motor activity (Wolf Motor Function Test) assessments were outcome measures while functional imaging parameters were used to identify neural correlates of motor improvement.The improvement of motor function was significantly greater in the real stimulation group (20.7% in Fugl-Meyer and 19.1% in Wolf Motor Function Test scores) when compared to the sham group (3.2% in Fugl-Meyer and 6.0% in Wolf Motor Function Test scores). The effects outlasted the stimulation by at least 1 week. In the real-stimulation group, stronger activation of intact ipsilesional motor regions during paced movements of the affected limb were found postintervention whereas no significant activation changes were seen in the control group.The combination of bihemispheric tDCS and peripheral sensorimotor activities improved motor functions in chronic stroke patients that outlasted the intervention period. This novel approach may potentiate cerebral adaptive processes that facilitate motor recovery after stroke. Classification of evidence: This study provides Class I evidence that for adult patients with ischemic stroke treated at least 5 months after their first and only stroke, bihemispheric tDCS and simultaneous physical/occupational therapy given over 5 consecutive sessions significantly improves motor function as measured by the Upper Extremity Fugl-Meyer assessment (raw change treated 6.1 ± 3.4, sham 1.2 ± 1.0).

Neurology

Lindenberg, R; Renga, V; Zhu, LL; Nair, D; Schlaug, G

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Transcranial direct current stimulation affects visual perception measured by threshold perimetry.

2010 Dec

In this study, we aimed to characterize the effect of anodal and cathodal direct current stimulation (tDCS) on contrast sensitivity inside the central 10 degrees of the visual field in healthy subjects. Distinct eccentricities were investigated separately, since at the cortical level, more central regions of the visual field are represented closer to the occipital pole, i.e. closer to the polarizing electrodes, than are the more peripheral regions. Using a double-blind and sham-controlled within-subject design, we measured the effect of stimulation and potential learning effect separately across testing days. Anodal stimulation of the visual cortex compared to sham stimulation yielded a significant increase in contrast sensitivity within 8° of the visual field. A significant increase in contrast sensitivity between the conditions "pre" and "post" anodal stimulation was only obtained for the central positions at eccentricities smaller than 2°. Cathodal stimulation of the visual cortex did not affect contrast sensitivity at either eccentricity. Perceptual learning across testing days was only observed for threshold perimetry before stimulation. Measuring contrast sensitivity changes after tDCS with a standard clinical tool such as threshold perimetry may provide an interesting perspective in assessing therapeutic effects of tDCS in ophthalmological or neurological defects (e.g. with foveal sparing vs. foveal splitting).

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Kraft, A; Roehmel, J; Olma, MC; Schmidt, S; Irlbacher, K; Brandt, SA


Electrode montages for tDCS and weak transcranial electrical stimulation: role of "return" electrode's position and size.

2010 Dec

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Bikson, M; Datta, A; Rahman, A; Scaturro, J

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Modulation of risk-taking in marijuana users by transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC).

2010 Dec

Cognitive deficits that are reported in heavy marijuana users (attention, memory, affect perception, decision-making) appear to be completely reversible after a prolonged abstinence period of about 28 days. However, it remains unclear whether the reversibility of these cognitive deficits indicates that (1) chronic marijuana use is not associated with long-lasting changes in cortical networks or (2) that such changes occur but the brain adapts to and compensates for the drug-induced changes. Therefore, we examined whether chronic marijuana smokers would demonstrate a differential pattern of response in comparison to healthy volunteers on a decision-making paradigm (Risk Task) while undergoing sham or active transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). Twenty-five chronic marijuana users who were abstinent for at least 24h were randomly assigned to receive left anodal/right cathodal tDCS of DLPFC (n=8), right anodal/left cathodal tDCS of DLPFC (n=9), or sham stimulation (n=8); results on Risk Task during sham/active tDCS were compared to healthy volunteers from a previously published dataset. Chronic marijuana users demonstrated more conservative (i.e. less risky) decision-making during sham stimulation. While right anodal stimulation of the DLPFC enhanced conservative decision-making in healthy volunteers, both right anodal and left anodal DLPFC stimulation increased the propensity for risk-taking in marijuana users. These findings reveal alterations in the decision-making neural networks among chronic marijuana users. Finally, we also assessed the effects of tDCS on marijuana craving and observed that right anodal/left cathodal tDCS of DLPFC is significantly associated with a diminished craving for marijuana.

Drug and alcohol dependence

Boggio, PS; Zaghi, S; Villani, AB; Fecteau, S; Pascual-Leone, A; Fregni, F


Transcranial direct current stimulation of the motor cortex induces distinct changes in thermal and mechanical sensory percepts.

2010 Dec

The aim of this single-blinded, complete crossover study was to evaluate the effects of tDCS on thermal and mechanical perception, as assessed by quantitative sensory testing (QST).QST was performed upon the radial part of both hands of eight healthy subjects (3 female, 5 male, 25-41years of age). These subjects were examined before and after cathodal, anodal or sham tDCS, applied in a random order. TDCS was administered for 15min at a 1mA current intensity, with the active electrode placed over the left primary motor cortex and the reference electrode above the right orbit.After cathodal tDCS, cold detection thresholds (CDT), mechanical detection thresholds (MDT), and mechanical pain thresholds (MPT) significantly increased in the contralateral hand, when compared to the baseline condition.Cathodal tDCS temporarily reduced the sensitivity to A-fiber mediated somatosensory inputs.Impairment of these somatosensory percepts suggests a short-term suppression of lemniscal or suprathalamic sensory pathways following motor cortex stimulation by cathodal tDCS.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Bachmann, CG; Muschinsky, S; Nitsche, MA; Rolke, R; Magerl, W; Treede, RD; Paulus, W; Happe, S


Electrode-distance dependent after-effects of transcranial direct and random noise stimulation with extracephalic reference electrodes.

2010 Dec

To evaluate the importance of the distance between stimulation electrodes, in various montages, on the ability to induce sustained cortical excitability changes using transcranial direct and random noise stimulation.Twelve healthy subjects participated in four different experimental conditions. The stimulation electrode was always placed over the primary motor cortex; the reference electrode was placed at the contralateral orbit or at the ipsilateral/contralateral arm. MEPs were recorded in order to measure changes in cortical excitability over time.The distance between the two electrodes correlates negatively with the duration and magnitude of induced after-effects.In particular when using extracephalic reference electrodes with transcranial electric stimulation techniques, the stimulation intensity has to be adapted to account for interelectrode distance.Electrode distance plays a critical role in the induction for stimulation after-effects in tDCS and tRNS studies, and must be taken into account in future studies and also when making comparisons with the published literature.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Moliadze, V; Antal, A; Paulus, W


Recovery of motor function after stroke.

2010 Nov

The human brain possesses a remarkable ability to adapt in response to changing anatomical (e.g., aging) or environmental modifications. This form of neuroplasticity is important at all stages of life but is critical in neurological disorders such as amblyopia and stroke. This review focuses upon our new understanding of possible mechanisms underlying functional deficits evidenced after adult-onset stroke. We review the functional interactions between different brain regions that may contribute to motor disability after stroke and, based on this information, possible interventional approaches to motor stroke disability. New information now points to the involvement of non-primary motor areas and their interaction with the primary motor cortex as areas of interest. The emergence of this new information is likely to impact new efforts to develop more effective neurorehabilitative interventions using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) that may be relevant to other neurological disorders such as amblyopia. © 2010 Wiley Periodicals, Inc. Dev Psychobiol.

Developmental psychobiology

Sharma, N; Cohen, LG


Modulating neuronal activity produces specific and long-lasting changes in numerical competence.

2010 Nov

Around 20% of the population exhibits moderate to severe numerical disabilities [1-3], and a further percentage loses its numerical competence during the lifespan as a result of stroke or degenerative diseases [4]. In this work, we investigated the feasibility of using noninvasive stimulation to the parietal lobe during numerical learning to selectively improve numerical abilities. We used transcranial direct current stimulation (TDCS), a method that can selectively inhibit or excitate neuronal populations by modulating GABAergic (anodal stimulation) and glutamatergic (cathodal stimulation) activity [5, 6]. We trained subjects for 6 days with artificial numerical symbols, during which we applied concurrent TDCS to the parietal lobes. The polarity of the brain stimulation specifically enhanced or impaired the acquisition of automatic number processing and the mapping of number into space, both important indices of numerical proficiency [7-9]. The improvement was still present 6 months after the training. Control tasks revealed that the effect of brain stimulation was specific to the representation of artificial numerical symbols. The specificity and longevity of TDCS on numerical abilities establishes TDCS as a realistic tool for intervention in cases of atypical numerical development or loss of numerical abilities because of stroke or degenerative illnesses.

Current biology : CB

Cohen Kadosh, R; Soskic, S; Iuculano, T; Kanai, R; Walsh, V

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Contribution of the premotor cortex to consolidation of motor sequence learning in humans during sleep.

2010 Nov

Motor learning and memory consolidation require the contribution of different cortices. For motor sequence learning, the primary motor cortex is involved primarily in its acquisition. Premotor areas might be important for consolidation. In accordance, modulation of cortical excitability via transcranial DC stimulation (tDCS) during learning affects performance when applied to the primary motor cortex, but not premotor cortex. We aimed to explore whether premotor tDCS influences task performance during motor memory consolidation. The impact of excitability-enhancing, -diminishing, or placebo premotor tDCS during rapid eye movement (REM) sleep on recall in the serial reaction time task (SRTT) was explored in healthy humans. The motor task was learned in the evening. Recall was performed immediately after tDCS or the following morning. In two separate control experiments, excitability-enhancing premotor tDCS was performed 4 h after task learning during daytime or immediately before conduction of a simple reaction time task. Excitability-enhancing tDCS performed during REM sleep increased recall of the learned movement sequences, when tested immediately after stimulation. REM density was enhanced by excitability-increasing tDCS and reduced by inhibitory tDCS, but did not correlate with task performance. In the control experiments, tDCS did not improve performance. We conclude that the premotor cortex is involved in motor memory consolidation during REM sleep.

Journal of neurophysiology

Nitsche, MA; Jakoubkova, M; Thirugnanasambandam, N; Schmalfuss, L; Hullemann, S; Sonka, K; Paulus, W; Trenkwalder, C; Happe, S

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Cutaneous perception thresholds of electrical stimulation methods: comparison of tDCS and tRNS.

2010 Nov

Controlled blinded studies using transcranial electrical stimulation (tES) paradigms need a validated sham stimulation paradigm since an itching or tingling sensation on the skin surface under the electrode can be associated with current flow.Here we investigated the skin perception thresholds of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS) for current intensities ranging from 200 to 2000μA and additional non-stimulation trials using a motor cortex-contralateral orbit montage in three different healthy subject groups: subjects naïve to tES methods, subjects with previous experience with these techniques and investigators, who use these methods in their research.Taking the whole sample into consideration the 50% perception threshold for both tDCS conditions was at 400μA while this threshold was at 1200μA in the case of tRNS. Anodal and cathodal tDCS are indistinguishable regarding sites of perception. Experienced investigators show a significantly higher anodal stimulation detection rate when compared to the naïve group, furthermore investigators performed significantly better than naïve subjects in non-stimulation discrimination.tRNS has the advantage of higher cutaneous perception thresholds and lower response rates in when compared with tDCS. Further investigation in blinding methods (such as placebo itching) is warranted in order to improve sham control.As tRNS has been shown to have similar aftereffects as anodal tDCS, this finding points to the application of tRNS as a possible alternative with a better blinding control.

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Ambrus, GG; Paulus, W; Antal, A


Electrical stimulation of Broca's area enhances implicit learning of an artificial grammar.

2010 Nov

Artificial grammar learning constitutes a well-established model for the acquisition of grammatical knowledge in a natural setting. Previous neuroimaging studies demonstrated that Broca's area (left BA 44/45) is similarly activated by natural syntactic processing and artificial grammar learning. The current study was conducted to investigate the causal relationship between Broca's area and learning of an artificial grammar by means of transcranial direct current stimulation (tDCS). Thirty-eight healthy subjects participated in a between-subject design, with either anodal tDCS (20 min, 1 mA) or sham stimulation, over Broca's area during the acquisition of an artificial grammar. Performance during the acquisition phase, presented as a working memory task, was comparable between groups. In the subsequent classification task, detecting syntactic violations, and specifically, those where no cues to superficial similarity were available, improved significantly after anodal tDCS, resulting in an overall better performance. A control experiment where 10 subjects received anodal tDCS over an area unrelated to artificial grammar learning further supported the specificity of these effects to Broca's area. We conclude that Broca's area is specifically involved in rule-based knowledge, and here, in an improved ability to detect syntactic violations. The results cannot be explained by better tDCS-induced working memory performance during the acquisition phase. This is the first study that demonstrates that tDCS may facilitate acquisition of grammatical knowledge, a finding of potential interest for rehabilitation of aphasia.

Journal of cognitive neuroscience

de Vries, MH; Barth, AC; Maiworm, S; Knecht, S; Zwitserlood, P; Flöel, A


Brain-derived neurotrophic factor (BDNF) gene polymorphisms shape cortical plasticity in humans.

2010 Oct

The brain-derived neurotrophic factor (BDNF) gene is involved in mechanisms of synaptic plasticity in the adult brain. It has been demonstrated that BDNF also plays a significant role in shaping externally induced human brain plasticity. Plasticity induced in the human motor cortex by intermittent theta-burst stimulation (iTBS) was impaired in individuals expressing the Val66Met polymorphism.To explore whether this polymorphism is also important for other neuroplasticity-inducing tools in humans with modes of action differing from that of iTBS, namely, transcranial direct current (tDCS) and random noise stimulation (tRNS), we retrospectively analyzed the data of 64 subjects studied in our laboratory with regard to BDNF genotype.Fifteen subjects with the Val66Met allele, 46 subjects with the Val66Val allele, and 3 Met66Met carriers were identified. The response of the Val66Met allele carriers to stimulation differed in two protocols compared with the response of Val66Val individuals. For iTBS (15 subjects, 5 heterozygotes), plasticity could be only induced in the Val66Val allele carriers. However, for facilitatory tDCS (24 subjects, 10 heterozygotes), as well as for inhibitory tDCS, (19 subjects, 8 heterozygotes), carriers of the Val66Met allele displayed enhanced plasticity, whereas for transcranial random noise stimulation (29 subjects, 8 heterozygotes), the difference between groups was not so pronounced.BDNF polymorphism has a definite impact on plasticity in humans, which might differ according to the mechanism of plasticity induction. This impact of BDNF on plasticity should be taken into account for future studies, as well as having wider ranging implications for the treatment of neuropsychiatric disorders with transcranial stimulation tools, as it may predetermine their efficacy for the treatment of disease and rehabilitation.

Brain stimulation

Antal, A; Chaieb, L; Moliadze, V; Monte-Silva, K; Poreisz, C; Thirugnanasambandam, N; Nitsche, MA; Shoukier, M; Ludwig, H; Paulus, W


Functional and histologic changes after repeated transcranial direct current stimulation in rat stroke model.

2010 Oct

Transcranial direct current stimulation (tDCS) is associated with enhancement or weakening of the NMDA receptor activity and change of the cortical blood flow. Therefore, repeated tDCS of the brain with cerebrovascular injury will induce the functional and histologic changes. Sixty-one Sprague-Dawley rats with cerebrovascular injury were used. Twenty rats died during the experimental course. The 41 rats that survived were allocated to the exercise group, the anodal stimulation group, the cathodal stimulation group, or the control group according to the initial motor function. Two-week treatment schedules started from 2 days postoperatively. Garcia, modified foot fault, and rota-rod performance scores were checked at 2, 9, and 16 days postoperatively. After the experiments, rats were sacrificed for the evaluation of histologic changes (changes of the white matter axon and infarct volume). The anodal stimulation and exercise groups showed improvement of Garcia's and modified foot fault scores at 16 days postoperatively. No significant change of the infarct volume happened after exercise and tDCS. Neuronal axons at the internal capsule of infarct hemispheres showed better preserved axons in the anodal stimulation group. From these results, repeated tDCS might have a neuroprotective effect on neuronal axons in rat stroke model.

Journal of Korean medical science

Kim, SJ; Kim, BK; Ko, YJ; Bang, MS; Kim, MH; Han, TR

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The involvement of the left motor cortex in learning of a novel action word lexicon.

2010 Oct

Current theoretical positions assume that action-related word meanings are established by functional connections between perisylvian language areas and the motor cortex (MC) according to Hebb's associative learning principle. To test this assumption, we probed the functional relevance of the left MC for learning of a novel action word vocabulary by disturbing neural plasticity in the MC with transcranial direct current stimulation (tDCS). In combination with tDCS, subjects learned a novel vocabulary of 76 concrete, body-related actions by means of an associative learning paradigm. Compared with a control condition with "sham" stimulation, cathodal tDCS reduced success rates in vocabulary acquisition, as shown by tests of novel action word translation into the native language. The analysis of learning behavior revealed a specific effect of cathodal tDCS on the ability to associatively couple actions with novel words. In contrast, we did not find these effects in control experiments, when tDCS was applied to the prefrontal cortex or when subjects learned object-related words. The present study lends direct evidence to the proposition that the left MC is causally involved in the acquisition of novel action-related words.

Current biology : CB

Liuzzi, G; Freundlieb, N; Ridder, V; Hoppe, J; Heise, K; Zimerman, M; Dobel, C; Enriquez-Geppert, S; Gerloff, C; Zwitserlood, P; Hummel, FC


Transcranial direct current stimulation for the treatment of Parkinson's disease.

2010 Oct

Progression of Parkinson's disease (PD) is characterised by motor deficits which eventually respond less to dopaminergic therapy and thus pose a therapeutic challenge. Deep brain stimulation has proven efficacy but carries risks and is not possible in all patients. Non-invasive brain stimulation has shown promising results and may provide a therapeutic alternative.To investigate the efficacy of transcranial direct current stimulation (tDCS) in the treatment of PD.Randomised, double blind, sham controlled study.Research institution.The efficacy of anodal tDCS applied to the motor and prefrontal cortices was investigated in eight sessions over 2.5 weeks. Assessment over a 3 month period included timed tests of gait (primary outcome measure) and bradykinesia in the upper extremities, Unified Parkinson's Disease Rating Scale (UPDRS), Serial Reaction Time Task, Beck Depression Inventory, Health Survey and self-assessment of mobility.Twenty-five PD patients were investigated, 13 receiving tDCS and 12 sham stimulation. tDCS improved gait by some measures for a short time and improved bradykinesia in both the on and off states for longer than 3 months. Changes in UPDRS, reaction time, physical and mental well being, and self-assessed mobility did not differ between the tDCS and sham interventions.tDCS of the motor and prefrontal cortices may have therapeutic potential in PD but better stimulation parameters need to be established to make the technique clinically viable. This study was publicly registered (clinicaltrials.org: NCT00082342).

Journal of neurology, neurosurgery, and psychiatry

Benninger, DH; Lomarev, M; Lopez, G; Wassermann, EM; Li, X; Considine, E; Hallett, M


Improved proper name recall by electrical stimulation of the anterior temporal lobes.

2010 Oct

People's names have an embarrassing propensity to be forgotten. This problem is exacerbated by normal aging and by some kinds of dementia. As evidence from neuroimaging and neuropsychology suggest that portions of the anterior temporal lobes play a role in proper name retrieval, we hypothesized that transcranial direct current stimulation (tDCS), a technique that modulates neural transmission, to the anterior temporal lobes would alter the retrieval of proper names. Fifteen young adults received left anodal, right anodal, or sham stimulation of the anterior temporal lobes while naming pictures of famous individuals and landmarks. Right anterior temporal lobe stimulation significantly improved naming for people but not landmarks. These findings are consistent with the notion that the anterior temporal lobes are critically involved in the retrieval of people's names.

Neuropsychologia

Ross, LA; McCoy, D; Wolk, DA; Coslett, HB; Olson, IR


Transcranial direct current stimulation in patients with skull defects and skull plates: high-resolution computational FEM study of factors altering cortical current flow.

2010 Oct

Preliminary positive results of transcranial direct current stimulation (tDCS) in enhancing the effects of cognitive and motor training indicate that this technique might also be beneficial in traumatic brain injury or patients who had decompressive craniectomy for trauma and cerebrovascular disease. One perceived hurdle is the presence of skull defects or skull plates in these patients that would hypothetically alter the intensity and location of current flow through the brain. We aimed to model tDCS using a magnetic resonance imaging (MRI)-derived finite element head model with several conceptualized skull injuries. Cortical electric field (current density) peak intensities and distributions were compared with the healthy (skull intact) case. The factors of electrode position (C3-supraorbital or O1-supraorbital), electrode size skull defect size, skull defect state (acute and chronic) or skull plate (titanium and acrylic) were analyzed. If and how electric current through the brain was modulated by defects was found to depend on a specific combination of factors. For example, the condition that led to largest increase in peak cortical electric field was when one electrode was placed directly over a moderate sized skull defect. In contrast, small defects midway between electrodes did not significantly change cortical currents. As the conductivity of large skull defects/plates was increased (chronic to acute to titanium), current was shunted away from directly underlying cortex and concentrated in cortex underlying the defect perimeter. The predictions of this study are the first step to assess safety of transcranial electrical therapy in subjects with skull injuries and skull plates.

NeuroImage

Datta, A; Bikson, M; Fregni, F

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Visual memory improved by non-invasive brain stimulation.

2010 Sep

Our visual memories are susceptible to errors, but less so in people who have a more literal cognitive style. This inspired us to attempt to improve visual memory with non-invasive brain stimulation. We applied 13 min of bilateral transcranial direct current stimulation (tDCS) to the anterior temporal lobes. Our stimulation protocol included 3 conditions, each with 12 neurotypical participants: (i) left cathodal stimulation together with right anodal stimulation, (ii) left anodal stimulation together with right cathodal stimulation, and (iii) sham (control) stimulation. Only participants who received left cathodal stimulation (decrease in excitability) together with right anodal stimulation (increase in excitability) showed an improvement in visual memory. This 110% improvement in visual memory was similar to the advantage people with autism, who are known to be more literal, show over normal people in the identical visual task. Importantly, participants receiving stimulation of the opposite polarity (left anodal together with right cathodal stimulation) failed to show any change in memory performance. This is the first demonstration that visual memory can be enhanced in healthy people using non-invasive brain stimulation.

Brain research

Chi, RP; Fregni, F; Snyder, AW


Cortical neuromodulation modifies cerebral vasomotor reactivity.

2010 Sep

Cerebral vasomotor reactivity (VMR) is a capability of cerebral vessels to dilate in response to hypercapnia. Transcranial direct current stimulation (tDCS) effects on cerebral hemodynamics have been poorly studied.Ten healthy subjects underwent anodal/cathodal tDCS on the left motor cortex. Before and after tDCS, VMR assessment by transcranial Doppler and an electrocardiogram were performed. Normalized low-frequency band power of heart rate variability and its reactivity from basal to VMR condition (LFN(react)) were estimated as relative markers of sympathetic activation. tDCS exerted a polarity-specific effect on both VMR (P=0.0001) and LFN(react) (P=0.001). Anodal tDCS decreased VMR by 3.4%/mm Hg CO(2) bilaterally and increased LFN(react), whereas cathodal tDCS increased VMR by 0.8%/mm Hg CO(2) bilaterally and reduced LFN(react).Cerebral VMR is modified by tDCS. Based on the consensual changes with heart rate variability, we can hypothesize that the sympathetic nervous system could modulate the bihemispheric modification of VMR. Further studies are needed to confirm this hypothesis.

Stroke; a journal of cerebral circulation

Vernieri, F; Assenza, G; Maggio, P; Tibuzzi, F; Zappasodi, F; Altamura, C; Corbetto, M; Trotta, L; Palazzo, P; Ercolani, M; Tecchio, F; Rossini, PM

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Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.

2010 Sep

The neuromodulator dopamine affects learning and memory formation and their likely physiological correlates, long-term depression and potentiation, in animals and humans. It is known from animal experiments that dopamine exerts a dosage-dependent, inverted U-shaped effect on these functions. However, this has not been explored in humans so far. In order to reveal a non-linear dose-dependent effect of dopamine on cortical plasticity in humans, we explored the impact of 25, 100 and 200 mg of L-dopa on transcranial direct current (tDCS)-induced plasticity in twelve healthy human subjects. The primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential amplitudes elicited by transcranial magnetic stimulation. As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition. Thus the results show clear non-linear, dosage-dependent effects of dopamine on both facilitatory and inhibitory plasticity, and support the assumption of the importance of a specific dosage of dopamine optimally suited to improve plasticity. This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies.

The Journal of physiology

Monte-Silva, K; Liebetanz, D; Grundey, J; Paulus, W; Nitsche, MA

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Brain polarization of parietal cortex augments training-induced improvement of visual exploratory and attentional skills.

2010 Aug

Recent evidence suggests that behavioural gains induced by behavioural training are maximized when combined with techniques of cortical neuromodulation, such as transcranial Direct Current Stimulation (tDCS). Here we address the validity of this appealing approach by investigating the effect of coupling a multisensory visual field exploration training with tDCS of the posterior parietal cortex (PPC). The multisensory visual field exploration training consisted in the practice of visual search through the systematic audio-visual stimulation of the visual field. Neurologically unimpaired participants performed a bimodal exploration training for 30 min, while simultaneously receiving anodal-excitatory PPC tDCS or sham tDCS. In two different experiments, the left and the right hemisphere were stimulated. Outcome measures included visual exploration speed at different time intervals during the training, and the post-training effects on tests assessing visual scanning and visuo-spatial orienting. Results show that PPC tDCS applied to the right, but not to the left, hemisphere increases the training-induced behavioural improvement of visual exploration, as compared to sham tDCS. In addition, right PPC tDCS brings about an improvement of covert visual orienting, in a task different from the visual search practice. In an additional experiment, we confirm that right parietal tDCS by itself, even without the associated training, can lead to enhancement of visual search. Overall, anodal PPC tDCS is a promising technique to enhance visuo-spatial abilities, when combined to a visual field exploration training task.

Brain research

Bolognini, N; Fregni, F; Casati, C; Olgiati, E; Vallar, G


A selective working memory impairment after transcranial direct current stimulation to the right parietal lobe.

2010 Aug

The role of the posterior parietal cortex in working memory (WM) is poorly understood. We previously found that patients with parietal lobe damage exhibited a selective WM impairment on recognition but not recall tasks. We hypothesized that this dissociation reflected strategic differences in the utilization of attention. One concern was that these findings, and our subsequent interpretation, would not generalize to normal populations because of the patients' older age, progressive disease processes, and/or possible brain reorganization following injury. To test whether our findings extended to a normal population we applied transcranial direct current stimulation (tDCS) to right inferior parietal cortex. tDCS is a technique by which low electric current applied to the scalp modulates the resting potentials of underlying neural populations and can be used to test structure-function relationships. Eleven normal young adults received cathodal, anodal, or sham stimulation over right inferior posterior parietal cortex and then performed separate blocks of an object WM task probed by recall or recognition. The results showed that cathodal stimulation selectively impaired WM on recognition trials. These data replicate and extend our previous findings of preserved WM recall and impaired WM recognition in patients with parietal lobe lesions.

Neuroscience letters

Berryhill, ME; Wencil, EB; Branch Coslett, H; Olson, IR

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Electrified minds: transcranial direct current stimulation (tDCS) and galvanic vestibular stimulation (GVS) as methods of non-invasive brain stimulation in neuropsychology--a review of current data and future implications.

2010 Aug

Transcranial direct current stimulation (tDCS) is a noninvasive, low-cost and easy-to-use technique that can be applied to modify cerebral excitability. This is achieved by weak direct currents to shift the resting potential of cortical neurons. These currents are applied by attaching two electrodes (usually one anode and one cathode) to distinct areas of the skull. Galvanic Vestibular Stimulation (GVS) is a variant of tDCS where the electrodes are attached to the mastoids behind the ears in order to stimulate the vestibular system. tDCS and GVS are safe when standard procedures are used. We describe the basic physiological mechanisms and application of these procedures. We also review current data on the effects of tDCS and GVS in healthy subjects as well as clinical populations. Significant effects of such stimulation have been reported for motor, visual, somatosensory, attentional, vestibular and cognitive/emotional function as well as for a range of neurological and psychiatric disorders. Moreover, both techniques may induce neuroplastic changes which make them promising techniques in the field of neurorehabilitation. A number of open research questions that could be addressed with tDCS or GVS are formulated in the domains of sensory and motor processing, spatial and nonspatial attention including neglect, spatial cognition and body cognition disorders, as well as novel treatments for various neuropsychological disorders. We conclude that the literature suggests that tDCS and GVS are exciting and easily applicable research tools for neuropsychological as well as clinical-therapeutic investigations.

Neuropsychologia

Utz, KS; Dimova, V; Oppenländer, K; Kerkhoff, G


Anodal transcranial direct current stimulation enhances procedural consolidation.

2010 Aug

The primary motor cortex (M1) area recruitment enlarges while learning a finger tapping sequence. Also M1 excitability increases during procedural consolidation. Our aim was to investigate whether increasing M1 excitability by anodal transcranial DC stimulation (AtDCS) when procedural consolidation occurs was able to induce an early consolidation improvement. Forty-seven right-handed healthy participants were trained in a nine-element serial finger tapping task (SFTT) executed with the left hand. Random series blocks were interspersed with training series blocks. Anodal or sham tDCS was administered over the right M1 after the end of the training session. After stimulation, the motor skills of both trained and a new untrained sequential series blocks were tested again. For each block, performance was estimated as the median execution time of correct series. Early consolidation of the trained series, assessed by the performance difference between the first block after and the last block before stimulation normalized by the random, was enhanced by anodal and not by sham tDCS. Stimulation did not affect random series execution. No stimulation effect was found on the on-line learning of the trained and new untrained series. Our results suggest that AtDCS applied on M1 soon after training improves early consolidation of procedural learning. Our data highlight the importance of neuromodulation procedures for understanding learning processes and support their use in the motor rehabilitation setting, focusing on the timing of the application.

Journal of neurophysiology

Tecchio, F; Zappasodi, F; Assenza, G; Tombini, M; Vollaro, S; Barbati, G; Rossini, PM

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Dorsolateral prefrontal cortex specifically processes general - but not personal - knowledge deception: Multiple brain networks for lying.

2010 Aug

Despite intensive research into ways of detecting deception in legal, moral and clinical contexts, few experimental data are available on the neural substrate for the different types of lies. We used transcranial direct current stimulation (tDCS) to modulate dorsolateral prefrontal cortex (DLPFC) function and to assess its influence on various types of lies. Twenty healthy volunteers were tested before and after tDCS (anodal and sham). In each session the Guilty Knowledge Task and Visual Attention Task were administered at baseline and immediately after tDCS ended. A computer-controlled task was used to evaluate truthful responses and lie responses to questions referring to personal information and general knowledge. Dependent variables collected were reaction times (RTs) and accuracy. At baseline the RTs were significantly longer for lies than for truthful responses. After sham stimulation, lie responses remained unchanged (p = 0.24) but after anodal tDCS, RTs decreased significantly only for lies involving general knowledge (p = 0.02). tDCS left the Visual Attention Task unaffected. These findings show that manipulating DLPFC function with tDCS specifically modulates deceptive responses for general information leaving those on personal information unaffected. Multiple cortical networks intervene in deception involving general and personal knowledge. Deception referring to general and personal knowledge probably involves multiple cortical networks.

Behavioural brain research

Mameli, F; Mrakic-Sposta, S; Vergari, M; Fumagalli, M; Macis, M; Ferrucci, R; Nordio, F; Consonni, D; Sartori, G; Priori, A


Direct current brain polarization: a simple, noninvasive technique for human neuromodulation.

2010 Jul

Objectives:  It has been known for decades that neurons in vitro and in vivo respond in a polarity-specific manner to changes in their electrical environment. Likewise, investigators have passed direct current (DC) across the human head for decades in attempts to alter brain function and behavior. Recent human data, however, have put this technique on a more solid empirical footing and it has re-emerged from obscurity as a "new," noninvasive means of neuromodulation, called transcranial direct current stimulation (TDCS). Materials and Methods:  Here, we offer a selective literature review together with our own research on the basic mechanisms and human applications of TDCS in neurophysiologic, cognitive, and behavioral research. We discuss a possible role for TDCS in enhancing normal brain function and treating neurologic and behavioral disorders. Results:  While there are uncertainties about how TDCS produces behavioral effects and how the current is distributed in the human brain, TDCS has safely produced a variety effects on human brain function in small studies. Conclusions:  The field is very young and many findings will require replication. Nevertheless, TDCS appears to have the potential to be a simple and safe means of neuromodulation.

Neuromodulation : journal of the International Neuromodulation Society

Ukueberuwa, D; Wassermann, EM


Electrodes for high-definition transcutaneous DC stimulation for applications in drug delivery and electrotherapy, including tDCS.

2010 Jul

Transcutaneous electrical stimulation is applied in a range of biomedical applications including transcranial direct current stimulation (tDCS). tDCS is a non-invasive procedure where a weak direct current (<2 mA) is applied across the scalp to modulate brain function. High-definition tDCS (HD-tDCS) is a technique used to increase the spatial focality of tDCS by passing current across the scalp using <12 mm diameter electrodes. The purpose of this study was to design and optimize "high-definition" electrode-gel parameters for electrode durability, skin safety and subjective pain. Anode and cathode electrode potential, temperature, pH and subjective sensation over time were assessed during application of 2 mA direct current, for up to 22 min on agar gel or subject forearms. A selection of five types of solid-conductors (Ag pellet, Ag/AgCl pellet, rubber pellet, Ag/AgCl ring and Ag/AgCl disc) and seven conductive gels (Signa, Spectra, Tensive, Redux, BioGel, Lectron and CCNY-4) were investigated. The Ag/AgCl ring in combination with CCNY-4 gel resulted in the most favorable outcomes. Under anode stimulations, electrode potential and temperature rises were generally observed in all electrode-gel combinations except for Ag/AgCl ring and disc electrodes. pH remained constant for all solid-conductors except for both Ag and rubber pellet electrodes with Signa and CCNY-4 gels. Sensation ratings were independent of stimulation polarity. Ag/AgCl ring electrodes were found to be the most comfortable followed by Ag, rubber and Ag/AgCl pellet electrodes across all gels.

Journal of neuroscience methods

Minhas, P; Bansal, V; Patel, J; Ho, JS; Diaz, J; Datta, A; Bikson, M

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Transcranial direct current stimulation (tDCS) in a realistic head model.

2010 Jul

Distributions of current produced by transcranial direct current stimulation (tDCS) in humans were predicted by a finite-element model representing several individual and collective refinements over prior efforts. A model of the entire human head and brain was made using a finely meshed (1.1x1.1x1.4mm(3) voxel) tissue dataset derived from the MRI data set of a normal human brain. The conductivities of ten tissues were simulated (bone, scalp, blood, CSF, muscle, white matter, gray matter, sclera, fat, and cartilage). We then modeled the effect of placing a "stimulating" electrode with a saline-like conductivity over F3, and a similar "reference" electrode over a right supraorbital (RS) location, as well as the complements of these locations, to compare expectations derived from the simulation with experimental data also using these locations in terms of the presence or absence of subjective and objective effects. The sensitivity of the results to changes in conductivity values were examined by varying white matter conductivity over a factor of ten. Our simulations established that high current densities were found directly under the stimulating and reference electrodes, but values of the same order of magnitude occurred in other structures, and many areas of the brain that might be behaviorally active were also subjected to what may be substantial amounts of current. The modeling also suggests that more targeted stimulations might be achieved by different electrode topologies.

NeuroImage

Sadleir, RJ; Vannorsdall, TD; Schretlen, DJ; Gordon, B


Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting.

2010 Jun

The use of neuromodulation as a treatment for major depressive disorder (MDD) has recently attracted renewed interest due to development of other non-pharmacological therapies besides electroconvulsive therapy (ECT) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS).We convened a working group of researchers to discuss the updates and key challenges of neuromodulation use for the treatment of MDD.The state-of-art of neuromodulation techniques was reviewed and discussed in four sections: [1] epidemiology and pathophysiology of MDD; [2] a comprehensive overview of the neuromodulation techniques; [3] using neuromodulation techniques in MDD associated with non-psychiatric conditions; [4] the main challenges of neuromodulation research and alternatives to overcome them.ECT is the first-line treatment for severe depression. TMS and tDCS are strategies with a relative benign profile of side effects; however, while TMS effects are comparable to antidepressant drugs for treating MDD; further research is needed to establish the role of tDCS. DBS and VNS are invasive strategies with a possible role in treatment-resistant depression. In summary, MDD is a chronic and incapacitating condition with a high prevalence; therefore clinicians should consider all the treatment options including invasive and non-invasive neuromodulation approaches.

Arquivos de neuro-psiquiatria

Brunoni, AR; Teng, CT; Correa, C; Imamura, M; Brasil-Neto, JP; Boechat, R; Rosa, M; Caramelli, P; Cohen, R; Del Porto, JA; Boggio, PS; Fregni, F

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Using transcranial direct-current stimulation to treat stroke patients with aphasia.

2010 Jun

Recent research suggests that increased left hemisphere cortical activity, primarily of the left frontal cortex, is associated with improved naming performance in stroke patients with aphasia. Our aim was to determine whether anodal transcranial direct-current stimulation (tDCS), a method thought to increase cortical excitability, would improve naming accuracy in stroke patients with aphasia when applied to the scalp overlying the left frontal cortex.Ten patients with chronic stroke-induced aphasia received 5 days of anodal tDCS (1 mA for 20 minutes) and 5 days of sham tDCS (for 20 minutes, order randomized) while performing a computerized anomia treatment. tDCS positioning was guided by a priori functional magnetic resonance imaging results for each individual during an overt naming task to ensure that the active electrode was placed over structurally intact cortex.Results revealed significantly improved naming accuracy of treated items (F[1,9]=5.72, P<0.040) after anodal tDCS compared with sham tDCS. Patients who demonstrated the most improvement were those with perilesional areas closest to the stimulation site. Crucially, this treatment effect persisted at least 1 week after treatment.Our findings suggest that anodal tDCS over the left frontal cortex can lead to enhanced naming accuracy in stroke patients with aphasia and, if proved to be effective in larger studies, may provide a supplementary treatment approach for anomia.

Stroke; a journal of cerebral circulation

Baker, JM; Rorden, C; Fridriksson, J

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Transcranial direct current stimulation in the treatment of anorexia.

2010 Jun

Transcranial direct current stimulation (tDCS) is a non-invasive technique for brain stimulation and it increasingly being used in the treatments of some neurological/psychiatric conditions (e.g. chronic pain, epilepsy, depression, motor rehabilitation after stroke and Parkinson's disease). With tDCS, cortical neurons excitability increases in the vicinity of the anodal electrode and suppressed near the cathodal electrode. There is evidence that anorexia is associated with hyperactivity in right-hemisphere frontal regions. tDCS, therefore has a promising potential in facilitating inter-hemispheric balance. A tDCS protocol is proposed: the anode electrode placed over the left prefrontal cortex and the cathode electrode located, either on the right homotopic region for non-SSRI-medicated anorexics, or on a non-cephalic site for SSRI-medicated anorexics. Together with nutritional supplements, psychotherapy and other treatments, tDCS have a good potential, as a complementary tool, in the treatment of anorexia.

Medical hypotheses

Hecht, D


Enhancing multisensory spatial orienting by brain polarization of the parietal cortex.

2010 May

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that induces polarity-specific excitability changes in the human brain, therefore altering physiological, perceptual and higher-order cognitive processes. Here we investigated the possibility of enhancing attentional orienting within and across different sensory modalities, namely visual and auditory, by polarization of the posterior parietal cortex (PPC), given the putative involvement of this area in both unisensory and multisensory spatial processing. In different experiments, we applied anodal or sham tDCS to the right PPC and, for control, anodal stimulation of the right occipital cortex. Using a redundant signal effect (RSE) task, we found that anodal tDCS over the right PPC significantly speeded up responses to contralateral targets, regardless of the stimulus modality. Furthermore, the effect was dependant on the nature of the audiovisual enhancement, being stronger when subserved by a probabilistic mechanism induced by blue visual stimuli, which probably involves processing in the PPC. Hence, up-regulating the level of excitability in the PPC by tDCS appears a successful approach for enhancing spatial orienting to unisensory and crossmodal stimuli. Moreover, audiovisual interactions mostly occurring at a cortical level can be selectively enhanced by anodal PPC tDCS, whereas multisensory integration of stimuli, which is also largely mediated at a subcortical level, appears less susceptible to polarization of the cortex.

The European journal of neuroscience

Bolognini, N; Olgiati, E; Rossetti, A; Maravita, A


Anodal transcranial direct current stimulation of the motor cortex ameliorates chronic pain and reduces short intracortical inhibition.

2010 May

Consecutive sessions of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) may be a suitable therapy to treat chronic pain, as it can modulate neural activities in the stimulated and interconnected regions.The present study investigated the analgesic effect of five consecutive days of anodal/sham tDCS using subjective (visual analog scale [VAS]) and objective (cortical excitability measured by transcranial magnetic stimulation [TMS]) measurements.Patients with therapy-resistant chronic pain syndromes (trigeminal neuralgia, poststroke pain syndrome, back pain, fibromyalgia) participated. As this clinical trial was an exploratory study, statistical analyses implemented exploratory methods. Twelve patients, who underwent both anodal and sham tDCS, were analyzed using a crossover design. An additional nine patients had only anodal or sham stimulation. tDCS was applied over the hand area of the M1 for 20 minutes, at 1mA for five consecutive days, using a randomized, double-blind design. Pain was assessed daily using a VAS rating for one month before, during, and one month post-stimulation. M1 excitability was determined using paired-pulse TMS.Anodal tDCS led to a greater improvement in VAS ratings than sham tDCS, evident even three to four weeks post-treatment. Decreased intracortical inhibition was demonstrated after anodal stimulation, indicating changes in cortico-cortical excitability. No patient experienced severe adverse effects; seven patients suffered from light headache after anodal and six after sham stimulation.Results confirm that five daily sessions of tDCS over the hand area of the M1 can produce long-lasting pain relief in patients with chronic pain.

Journal of pain and symptom management

Antal, A; Terney, D; Kühnl, S; Paulus, W


Task-dependent modulation of inputs to proximal upper limb following transcranial direct current stimulation of primary motor cortex.

2010 May

Cathodal transcranial DC stimulation (c-tDCS) suppresses excitability of primary motor cortex (M1) controlling contralateral hand muscles. This study assessed whether c-tDCS would have similar effects on ipsi- and contralateral M1 projections to a proximal upper limb muscle. Transcranial magnetic stimulation (TMS) of left M1 was used to elicit motor evoked potentials (MEPs) in the left and right infraspinatus (INF) muscle immediately before and after c-tDCS of left M1, and at 20 and 40 min, post-c-tDCS. TMS was delivered as participants preactivated each INF in isolation (left, right) or both INF together (bilateral). After c-tDCS, ipsilateral MEPs in left INF and contralateral MEPs in right INF were suppressed in the left task but not in the bilateral or right tasks, indicative of task-dependent modulation. Ipsilateral silent period duration in the left INF was reduced after c-tDCS, indicative of altered transcallosal inhibition. These findings may have implications for the use of tDCS as an adjunct to therapy for the proximal upper limb after stroke.

Journal of neurophysiology

Bradnam, LV; Stinear, CM; Lewis, GN; Byblow, WD

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Bilateral dorsolateral prefrontal cortex modulation for tinnitus by transcranial direct current stimulation: a preliminary clinical study.

2010 May

Tinnitus is considered as an auditory phantom percept. Preliminary evidence indicates that transcranial direct current stimulation (tDCS) of the temporo-parietal area might reduce tinnitus. tDCS studies of the prefrontal cortex have been successful in reducing depression, impulsiveness and pain. Recently, it was shown that the prefrontal cortex is important for the integration of sensory and emotional aspects of tinnitus. As such, frontal tDCS might suppress tinnitus as well. In an open label study, a total of 478 tinnitus patients received bilateral tDCS on dorsolateral prefrontal cortex (448 patients anode right, cathode left and 30 anode left, cathode right) for 20 min. Treatment effects were assessed with visual analogue scale for tinnitus intensity and distress. No tinnitus-suppressing effect was found for tDCS with left anode and right cathode. Analyses show that tDCS with right anode and left cathode modulates tinnitus perception in 29.9% of the tinnitus patients. For these responders a significant reduction was found for both tinnitus-related distress and tinnitus intensity. In addition, the amount of suppression for tinnitus-related distress is moderated by an interaction between tinnitus type and tinnitus laterality. This was, however, not the case for tinnitus intensity. Our study supports the involvement of the prefrontal cortex in the pathophysiology of tinnitus.

Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale

Vanneste, S; Plazier, M; Ost, J; van der Loo, E; Van de Heyning, P; De Ridder, D


Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis.

2010 May

Neuropathic pain in patients with MS is frequent and is associated with a great interference with daily life activities. In the present study, we investigated whether anodal transcranial direct current stimulation (tDCS) may be effective in reducing central chronic pain in MS patients. Patients received sham tDCS or real tDCS in a 5-day period of treatment in a randomized, double blind, sham-controlled study. Pain was measured using visual analog scale (VAS) for pain and the short form McGill questionnaire (SF-MPQ). Quality of life was measured using the Multiple Sclerosis Quality of Life-54 scale (MSQoL-54). Depressive symptoms and anxiety were also evaluated as confounding factors using the Beck Depression Inventory (BDI) and VAS for anxiety. Evaluations were performed at baseline, immediately after the end of treatment, and once a week during a 3-week follow-up period. Following anodal but not sham tDCS over the motor cortex, there was a significant pain improvement as assessed by VAS for pain and McGill questionnaire, and of overall quality of life. No depression or anxiety changes were observed. Our results show that anodal tDCS is able to reduce pain-scale scores in MS patients with central chronic pain and that this effect outlasts the period of stimulation, leading to long-lasting clinical effects. PERSPECTIVE: This article presents a new, noninvasive therapeutic approach to chronic, central neuropathic pain in multiple sclerosis, poorly responsive to current conventional medications. tDCS is known to cause long-lasting changes of neuronal excitability at the site of stimulation and in the connected areas in healthy subjects. This led us to hypothesize that pain decrease may be the result of functional plastic changes in brain structures involved in the pathogenesis of chronic neuropathic pain.

The journal of pain : official journal of the American Pain Society

Mori, F; Codecà, C; Kusayanagi, H; Monteleone, F; Buttari, F; Fiore, S; Bernardi, G; Koch, G; Centonze, D


Inducing Disorders in Pitch Perception and Production: a Reverse-Engineering Approach.

2010 Apr

To perceive and produce music accurately, the brain must represent, categorize, plan, and execute pitched information in response to environmental stimuli. Convergent methods from psychophysics, voxel-based morphometry, and diffusion tensor imaging with normal and tone-deaf (TD) subjects have shown that neural networks controlling pitch perception and production systems include bilateral frontotemporal networks. Although psychophysical and neuroimaging results are suggestive of a superior temporal and inferior frontal network responsible for pitch perception and production, active intervention of these areas is necessary to establish a causal connection between superior temporal and inferior frontal areas and pitch production ability. We sought to reverse-engineer the pitch perception-production network by noninvasive brain stimulation. Transcranial direct current stimulation (tDCS), a noninvasive brain-stimulation technique that is optimal for auditory research, was applied over superior temporal and inferior frontal regions. Pitch matching ability was assessed using an individually optimized pitch matching task administered after each stimulation session. Results showed diminished accuracy in pitch matching after cathodal stimulation over inferior frontal and superior temporal areas compared to sham control. Results demonstrate that intact function and connectivity of a distributed cortical network, centered around bilateral superior temporal and inferior frontal regions, are required for efficient neural interactions with musical sounds.

Proceedings of meetings on acoustics Acoustical Society of America

Loui, P; Hohmann, A; Schlaug, G

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Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning.

2010 Apr

Despite its increasing use in experimental and clinical settings, the cellular and molecular mechanisms underlying transcranial direct current stimulation (tDCS) remain unknown. Anodal tDCS applied to the human motor cortex (M1) improves motor skill learning. Here, we demonstrate in mouse M1 slices that DCS induces a long-lasting synaptic potentiation (DCS-LTP), which is polarity specific, NMDA receptor dependent, and requires coupling of DCS with repetitive low-frequency synaptic activation (LFS). Combined DCS and LFS enhance BDNF-secretion and TrkB activation, and DCS-LTP is absent in BDNF and TrkB mutant mice, suggesting that BDNF is a key mediator of this phenomenon. Moreover, the BDNF val66met polymorphism known to partially affect activity-dependent BDNF secretion impairs motor skill acquisition in humans and mice. Motor learning is enhanced by anodal tDCS, as long as activity-dependent BDNF secretion is in place. We propose that tDCS may improve motor skill learning through augmentation of synaptic plasticity that requires BDNF secretion and TrkB activation within M1.

Neuron

Fritsch, B; Reis, J; Martinowich, K; Schambra, HM; Ji, Y; Cohen, LG; Lu, B

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[Transcranial magnetic and direct current stimulation in the therapy of pain].

2010 Apr

Neuroplasticity is the ability of the central nervous system to induce functional and microstructural changes in order to adapt to a new environment. However, so-called maladaptive neuroplasticity can also bring disadvantages, such as reduced inhibition of input signals, one of the suspected causes of chronic pain. With the method of repetitive transcranial magnetic stimulation (rTMS) a technique has been developed that makes it possible to study cortical excitability changes in the human brain non-invasively over a long time. Electrophysiological studies have shown that the application of rTMS over the primary motor cortex induces a facilitatory or inhibitory effect on the corticospinal and cortico-cortical excitability depending on the protocol used. The results of the clinical studies published suggest that rTMS can inhibit pain perception with regard to chronic pain and in experimentally induced pain conditions. An alternative method to induce neuroplastic changes is transcranial direct current stimulation (tDCS). tDCS acts primarily on the membrane potential, by hyper- or depolarizing it. The induced after-effects are NMDA receptor dependent. The effectiveness of tDCS is currently being explored in migraine research as well as experimentally induced and chronic pain conditions. In phase II trials its efficacy has been demonstrated. Ongoing studies are focusing on management of the placebo effect; however, it is easier to control this effect in tDCS compared to rTMS. Phase III trials are currently in preparation.

Schmerz (Berlin, Germany)

Antal, A; Paulus, W


Shaping the optimal repetition interval for cathodal transcranial direct current stimulation (tDCS).

2010 Apr

Transcranial DC stimulation (tDCS) is a plasticity-inducing noninvasive brain stimulation tool with various potential therapeutic applications in neurological and psychiatric diseases. Currently, the duration of the aftereffects of stimulation is restricted. For future clinical applications, stimulation protocols are required that produce aftereffects lasting for days or weeks. Options to prolong the effects of tDCS are further prolongation or repetition of tDCS. Nothing is known thus far about optimal protocols in this behalf, although repetitive stimulation is already performed in clinical applications. Thus we explored the effects of different break durations on cathodal tDCS-induced cortical excitability alterations. In 12 subjects, two identical periods of cathodal tDCS (9-min duration; 1 mA) with an interstimulation interval of 0 (no break), 3, or 20 min or 3 or 24 h were performed. The results indicate that doubling stimulation duration without a break prolongs the aftereffects from 60 to 90 min after tDCS. When the second stimulation was performed during the aftereffects of the first, a prolongation and enhancement of tDCS-induced effects for ≤ 120 min after stimulation was observed. In contrast, when the second stimulation followed the first one after 3 or 24 h, the aftereffects were initially attenuated, or abolished, but afterwards re-established for up to 120 min after tDCS in the 24-h condition. These results suggest that, for prolonging the aftereffects of cathodal tDCS, stimulation interval might be important.

Journal of neurophysiology

Monte-Silva, K; Kuo, MF; Liebetanz, D; Paulus, W; Nitsche, MA

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Slow-oscillatory transcranial direct current stimulation can induce bidirectional shifts in motor cortical excitability in awake humans.

2010 Apr

Constant transcranial direct stimulation (c-tDCS) of the primary motor hand area (M1(HAND)) can induce bidirectional shifts in motor cortical excitability depending on the polarity of tDCS. Recently, anodal slow oscillation stimulation at a frequency of 0.75 Hz has been shown to augment intrinsic slow oscillations during sleep and theta oscillations during wakefulness. To embed this new type of stimulation into the existing tDCS literature, we aimed to characterize the after effects of slowly oscillating stimulation (so-tDCS) on M1(HAND) excitability and to compare them to those of c-tDCS. Here we show that so-tDCS at 0.8 Hz can also induce lasting changes in corticospinal excitability during wakefulness. Experiment 1. In 10 healthy awake individuals, we applied c-tDCS or so-tDCS to left M1(HAND) on separate days. Each tDCS protocol lasted for 10 min. Measurements of motor evoked potentials (MEPs) confirmed previous work showing that anodal c-tDCS at an intensity of 0.75 mA (maximal current density 0.0625 mA/cm2) enhanced corticospinal excitability, while cathodal c-tDCS at 0.75 mA reduced it. The polarity-specific shifts in excitability persisted for at least 20 min after c-tDCS. Using a peak current intensity of 0.75 mA, neither anodal nor cathodal so-tDCS had consistent effects on corticospinal excitability. Experiment 2. In a separate group of ten individuals, peak current intensity of so-tDCS was raised to 1.5 mA (maximal current density 0.125 mA/cm2) to match the total amount of current applied with so-tDCS to the amount of current that had been applied with c-tDCS at 0.75 mA in Experiment 1. At peak intensity of 1.5 mA, anodal and cathodal so-tDCS produced bidirectional changes in corticospinal excitability comparable to the after effects that had been observed after c-tDCS at 0.75 mA in Experiment 1. The results show that so-tDCS can induce bidirectional shifts in corticospinal excitability in a similar fashion as c-tDCS if the total amount of applied current during the tDCS session is matched.

Neuroscience

Groppa, S; Bergmann, TO; Siems, C; Mölle, M; Marshall, L; Siebner, HR


Naming facilitation induced by transcranial direct current stimulation.

2010 Apr

Transcranial direct current stimulation (tDCS) is able to generate a long-term increase or decrease in the neuronal excitability that can modulate cognitive tasks, similar to repetitive transcranial magnetic stimulation. The aim of this study was to explore the effects of tDCS on a language task in young healthy subjects. Anodal, cathodal and sham tDCS were applied to the left dorsolateral prefrontal cortex (DLPFC) before two picture naming experiments, a preliminary study (i.e., experiment 1) and a main study (i.e., experiment 2). The results show that anodal tDCS of the left DLPFC improves naming performance, speeding up verbal reaction times after the end of the stimulation, whereas cathodal stimulation had no effect. We hypothesize that the cerebral network dedicated to lexical retrieval processing is facilitated by anodal tDCS to the left DLPFC. Although the mechanisms responsible for facilitation are not yet clear, the results presented herein implicate a facilitation lasting beyond the end of the stimulation that imply cortical plasticity mechanisms. The opportunity to non-invasively interact with the functioning of these plasticity mechanisms will surely open new and promising scenarios in language studies in basic and clinical neuroscience fields.

Behavioural brain research

Fertonani, A; Rosini, S; Cotelli, M; Rossini, PM; Miniussi, C


Transcranial direct current stimulation facilitates decision making in a probabilistic guessing task.

2010 Mar

In a random sequence of binary events where one alternative occurs more often than the other, humans tend to guess which of the two alternatives will occur next by trying to match the frequencies of previous occurrences. Based on split-brain and unilaterally damaged patients' performances, it has been proposed that the left hemisphere (LH) tends to match the frequencies, while the right hemisphere (RH) tends toward maximizing and always choosing the most frequent alternative. The current study used transcranial direct current stimulation (tDCS) to test this hemispheric asymmetry hypothesis by stimulating the dorsolateral prefrontal cortex of each hemisphere and simultaneously inhibiting the corresponding region in the homotopic hemisphere, while participants were engaged in a probabilistic guessing task. Results showed no difference in strategy between the three groups (RH anodal/LH cathodal, LH anodal/RH cathodal, no stimulation) as participants predominantly matched the frequencies of the two alternatives. However, when anodal tDCS was applied to the LH and cathodal tDCS applied to the RH, participants became quicker to select the most frequent alternative. This finding is in line with previous evidence on the involvement of the LH in probabilistic learning and reasoning and adds to a number of demonstrations of anodal tDCS leading to some behavioral enhancement or change in bias.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Hecht, D; Walsh, V; Lavidor, M

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Interhemispheric modulation induced by cortical stimulation and motor training.

2010 Mar

Interhemispheric inhibition might be a beneficial cortico-cortical interaction, but also might be maladaptive in people with neurological disorders. One recently revisited technique that has been shown to be effective in improving motor function in people with stroke using interhemispheric modulation is transcranial direct current stimulation (tDCS).The aim of this study was to investigate the effects of tDCS combined with unilateral motor training with contralateral hand restraint on interhemispheric inhibition between the dominant and nondominant hemispheres of the brain and on motor performance in participants who were healthy.This was a double-blind, prospective, single-center study with participants who were healthy.Twenty participants who were healthy were randomly assigned to receive either active or sham tDCS of the primary motor cortex (M1) bilaterally combined with unilateral motor training and contralateral hand restraint. A blinded rater assessed motor function and cortical excitability, including assessment of transcallosal inhibition (TCI).There was a larger increase in motor performance in the nondominant hand for the active tDCS group compared with the sham tDCS group. In addition, a decrease in cortical excitability in the dominant hemisphere and a decrease in TCI from the dominant to nondominant hemisphere were observed for the active tDCS group only. The TCI decrease in the active tDCS group was correlated with motor performance improvement for the nondominant hand. Limitations Limitations of this study included missing the effect of intracortical inhibition due to a floor effect, not using the optimal tDCS montage, and not being able to assess the effects of other variables such as gender due to the small sample size.The results indicate that tDCS enhances the effects of unilateral motor training and contralateral hand restraint on motor function, and this benefit is associated with a different mechanism of action characterized by bihemispheric modulation in which TCI from the dominant to the nondominant hemisphere is decreased. Transcranial direct current stimulation might be a useful tool to enhance the motor effects of constraint-induced movement therapy.

Physical therapy

Williams, JA; Pascual-Leone, A; Fregni, F

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Brain stimulation in the study and treatment of addiction.

2010 Mar

Addiction is a devastating and chronically relapsing disorder. Repeated drug administration induces neuroadaptations associated with abnormal dopaminergic activity in the mesocorticolimbic circuitry, resulting in altered cortical neurotransmission and excitability. Electrical stimulation of specific brain regions can be used in animal models and humans to induce local activation or disruption of specific circuitries or alter neuronal excitability and cause neuroadaptations. Non-surgical stimulation of specific brain regions in human addicts can be achieved by transcranial magnetic stimulation (TMS). TMS is used for transient stimulation or disruption of neural activity in specific cortical regions, which can be used to assess cortical excitability, and to induce changes in cortical excitability. Moreover, it is suggested that repeated stimulation can cause long-lasting neuroadaptations. Therefore, TMS paradigms were used in some studies to assess the presence of altered cortical excitability associated with chronic drug consumption, while other studies have begun to assess the therapeutic potential of repetitive TMS. Similarly, transcranial direct current stimulation (tDCS) is used to modulate neuronal resting membrane potential in humans and alter cortical excitability. The current review describes how these brain stimulation techniques have recently been used for the study and treatment of addiction in animal models and humans.

Neuroscience and biobehavioral reviews

Feil, J; Zangen, A


Brain transcranial direct current stimulation modulates motor excitability in mice.

2010 Feb

Shortly after the application of weak transcranial direct current stimulation (tDCS) to the animal and human brain, changes in corticospinal excitability, which mainly depend on polarity, duration and current density of the stimulation protocol, have been reported. In humans, anodal tDCS has been reported to enhance motor-evoked potentials (MEPs) elicited by transcranial brain stimulation while cathodal tDCS has been shown to decrease them. Here we investigated the effects produced by tDCS on mice motor cortex. MEPs evoked by transcranial electric stimulation were recorded from forelimbs of 12 C57BL/6 mice, under sevofluorane anaesthesia, before and after (0, 5 and 10 min) anodal and cathodal tDCS (tDCS duration 10 min). With respect to sham condition stimulation (anaesthesia), MEP size was significantly increased immediately after anodal tDCS, and was reduced after cathodal tDCS (approximately 20% vs. sham). Both effects declined towards basal levels in the following 10 min. Although the site and mechanisms of action of tDCS need to be more clearly identified, the directionality of effects of tDCS on mice MEPs is consistent with previous findings in humans. The feasibility of tDCS in mice suggests the potential applicability of this technique to assess the potential therapeutic options of brain polarization in animal models of neurological and neuropsychiatric diseases.

The European journal of neuroscience

Cambiaghi, M; Velikova, S; Gonzalez-Rosa, JJ; Cursi, M; Comi, G; Leocani, L


Modulation of decision-making in a gambling task in older adults with transcranial direct current stimulation.

2010 Feb

Cognitive performance usually declines in older adults as a result of neurodegenerative processes. One of the cognitive domains usually affected is decision-making. Based on our recent findings suggesting that non-invasive brain stimulation can improve decision-making in young participants, we studied whether bifrontal transcranial direct current stimulation (tDCS) applied over the right and left prefrontal cortex of older adult subjects can change balance of risky and safe responses as it can in younger individuals. Twenty-eight subjects (age range from 50 to 85 years) performed a gambling risk task while receiving either anodal tDCS over the right and cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC), anodal tDCS over the left with cathodal tDCS over the right DLPFC, or sham stimulation. Our main finding was a significant group effect showing that participants receiving left anodal/right cathodal stimulation chose more often high-risk prospects as compared with participants receiving sham or those receiving right anodal/left cathodal stimulation. This result is contrary to previous findings in young subjects, suggesting that modulation of cortical activity in young and elderly results in opposite behavioral effects; thus supporting fundamental changes in cognitive processing in the elderly.

The European journal of neuroscience

Boggio, PS; Campanhã, C; Valasek, CA; Fecteau, S; Pascual-Leone, A; Fregni, F


1 Hz rTMS preconditioned by tDCS over the primary motor cortex in Parkinson's disease: effects on bradykinesia of arm and hand.

2010 Feb

To investigate whether a period of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over M1 preconditioned by tDCS improves bradykinesia of the upper limb in Parkinson's disease (PD). Fifteen patients with PD performed index finger, hand tapping and horizontal pointing movements as well as reach-to-grasp movements with either hand before (baseline conditions) and after a period of 1 Hz rTMS preconditioned by (1) sham, (2) anodal or (3) cathodal tDCS over the primary motor cortex contralateral to the more affected body side. Movement kinematics was analysed using an ultrasound-based motion analyser at baseline, immediately after and 30 min after each stimulation session. Dopaminergic medication was continued. Compared to baseline, 1 Hz rTMS significantly increased the frequency of index finger and hand tapping as well as horizontal pointing movements performed with the contralateral hand. Movement frequency increased up to 40% over 30 min after cessation of the stimulation. Preconditioning with cathodal tDCS, but not with anodal tDCS, reduced the effectiveness of 1 Hz rTMS to improve tapping and pointing movements. There was no significant increase of movement frequencies of the ipsilateral hand induced by 1 Hz rTMS preconditioned by either tDCS session. Movement kinematics of reach-to-grasp movements were not significantly influenced by either stimulation session. In PD the beneficial effects of 1 Hz rTMS over the primary motor cortex on bradykinesia of simple finger, hand and pointing movements is reduced by preconditioning with cathodal tDCS, but not with anodal tDCS. Preconditioning with tDCS is a powerful tool to modulate the behavioural effect of 1 Hz rTMS over the primary motor cortex in PD.

Journal of neural transmission (Vienna, Austria : 1996)

Grüner, U; Eggers, C; Ameli, M; Sarfeld, AS; Fink, GR; Nowak, DA


Prefrontal hemodynamic changes produced by anodal direct current stimulation.

2010 Feb

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has been investigated for the treatment of many neurological or neuropsychiatric disorders. Its main effect is to modulate the cortical excitability depending on the polarity of the current applied. However, understanding the mechanisms by which these modulations are induced and persist is still an open question. A possible marker indicating a change in cortical activity is the subsequent variation in regional blood flow and metabolism. These variations can be effectively monitored using functional near-infrared spectroscopy (fNIRS), which offers a noninvasive and portable measure of regional blood oxygenation state in cortical tissue. We studied healthy volunteers at rest and evaluated the changes in cortical oxygenation related to tDCS using fNIRS. Subjects were tested after active stimulation (12 subjects) and sham stimulation (10 subjects). Electrodes were applied at two prefrontal locations; stimulation lasted 10 min and fNIRS data were then collected for 20 min. The anodal stimulation induced a significant increase in oxyhemoglobin (HbO(2)) concentration compared to sham stimulation. Additionally, the effect of active 10-min tDCS was localized in time and lasted up to 8-10 min after the end of the stimulation. The cathodal stimulation manifested instead a negligible effect. The changes induced by tDCS on HbO(2), as captured by fNIRS, agreed with the results of previous studies. Taken together, these results help clarify the mechanisms underlying the regional alterations induced by tDCS and validate the use of fNIRS as a possible noninvasive method to monitor the neuromodulation effect of tDCS.

NeuroImage

Merzagora, AC; Foffani, G; Panyavin, I; Mordillo-Mateos, L; Aguilar, J; Onaral, B; Oliviero, A


Non-invasive brain stimulation for the management of arterial hypertension.

2010 Feb

The neural control of the cardiovascular system is a complex process that involves many structures at different levels of nervous system. Several cortical areas are involved in the control of systemic blood pressure, such as the sensorimotor cortex, the medial prefrontal cortex and the insular cortex. Non-invasive brain stimulation techniques - repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) - induce sustained and prolonged functional changes of the human cerebral cortex. rTMS and tDCS has led to positive results in the treatment of some neurological and psychiatric disorders. Because experiments in animals show that cortical modulation can be an effective method to regulate the cardiovascular system, non-invasive brain stimulation might be a novel tool in the therapeutics of human arterial hypertension. We here review the experimental evidence that non-invasive brain stimulation can influence the autonomic nervous system and discuss the hypothesis that focal modulation of cortical excitability by rTMS or tDCS can influence sympathetic outflow and, eventually, blood pressure, thus providing a novel therapeutic tool for human arterial hypertension.

Medical hypotheses

Cogiamanian, F; Brunoni, AR; Boggio, PS; Fregni, F; Ciocca, M; Priori, A


A double-blind, sham-controlled trial of transcranial direct current stimulation for the treatment of depression.

2010 Feb

Two recent sham-controlled studies found that transcranial direct current stimulation (tDCS) was an effective treatment for depression. As tDCS is painless, relatively safe and inexpensive, its efficacy in treating depression warrants further investigation. This double-blind, randomized study tested tDCS at the same stimulation parameters as a previous positive study (1 mA current strength, five treatment sessions, active or sham, given on alternate days) in 40 depressed participants. Anodal stimulation was centred over the left dorsolateral prefrontal cortex, with the cathode placed on the lateral aspect of the contralateral orbit. tDCS was continued up to a total of ten active sessions per participant. Mood outcomes were measured by psychiatrist raters blind to treatment condition using the Montgomery-Asberg and other depression rating scales. Psychomotor speed was assessed immediately before and after a single tDCS session and attention, frontal executive function, working memory and verbal learning were assessed after each group of five sessions. Overall depression scores improved significantly over ten tDCS treatments, but there was no between-group difference in the five-session, sham-controlled phase. tDCS was found to be safe, with no adverse effects on neuropsychological function, and only minor side-effects. It is recommended that the efficacy of tDCS in depression be further evaluated over a longer treatment period, using enhanced stimulation parameters.

The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)

Loo, CK; Sachdev, P; Martin, D; Pigot, M; Alonzo, A; Malhi, GS; Lagopoulos, J; Mitchell, P


Focal and bi-directional modulation of lower limb motor cortex using anodal transcranial direct current stimulation.

2010 Jan

Because we are interested in non-invasive transcranial brain stimulation as an adjuvant to post-stroke walking therapy, we applied direct current stimulation (tDCS) preferentially to either the left or right lower limb motor cortex (M1) in two separate sessions and assessed the resulting modulation in both cortices.We hypothesized that tDCS applied preferentially to one lower limb M1 of healthy subjects would induce between-hemisphere opposite sign modulation.Transcranial magnetic stimulation (TMS) with the coil offset 2 cm either side of vertex was used to assess the percent change in rectified motor evoked potential (MEP) area recorded bilaterally from vastus lateralis (VL) and tibialis anterior (TA) of 10 subjects during weak tonic contraction.ANOVA revealed an up-regulation of the target cortex and a down-regulation of the non-target cortex (p = 0.001) and no effects of hemisphere (left, right) or muscle (TA, VL). Significant modulation was evident in 78% of VL and TA muscles (all p < 0.05). Excitability increased in 60%, but decreased in 18%. For 43% when excitability increased, a simultaneous decrease in excitability was evident in homologous muscle responses providing support for our hypothesis.The results indicate a modest effectiveness and focality of anodal tDCS when applied to lower limb M1, suggesting in a human model that the strength and depth of polarizing cortical currents induced by tDCS likely depend on inter-individual differences in the electrical properties of superficial brain structures.

Brain stimulation

Madhavan, S; Stinear, JW

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Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS).

2010 Jan

Although the preceding chapters discuss much of the new knowledge of neurocircuitry of neuropsychiatric diseases, and an invasive approach to treatment, this chapter describes and reviews the noninvasive methods of testing circuit-based theories and treating neuropsychiatric diseases that do not involve implanting electrodes into the brain or on its surface. These techniques are transcranial magnetic stimulation, vagus nerve stimulation, and transcranial direct current stimulation. Two of these approaches have FDA approval as therapies.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

George, MS; Aston-Jones, G

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The truth about lying: inhibition of the anterior prefrontal cortex improves deceptive behavior.

2010 Jan

Recent neuroimaging studies have indicated a predominant role of the anterior prefrontal cortex (aPFC) in deception and moral cognition, yet the functional contribution of the aPFC to deceptive behavior remains unknown. We hypothesized that modulating the excitability of the aPFC by transcranial direct current stimulation (tDCS) could reveal its functional contribution in generating deceitful responses. Forty-four healthy volunteers participated in a thief role-play in which they were supposed to steal money and then to attend an interrogation with the Guilty Knowledge Test. During the interrogation, participants received cathodal, anodal, or sham tDCS. Remarkably, inhibition of the aPFC by cathodal tDCS did not lead to an impairment of deceptive behavior but rather to a significant improvement. This effect manifested in faster reaction times in telling lies, but not in telling the truth, a decrease in sympathetic skin-conductance response and feelings of guilt while deceiving the interrogator and a significantly higher lying quotient reflecting skillful lying. Increasing the excitability of the aPFC by anodal tDCS did not affect deceptive behavior, confirming the specificity of the stimulation polarity. These findings give causal support to recent correlative data obtained by functional magnetic resonance imaging studies indicating a pivotal role of the aPFC in deception.

Cerebral cortex (New York, N.Y. : 1991)

Karim, AA; Schneider, M; Lotze, M; Veit, R; Sauseng, P; Braun, C; Birbaumer, N

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Transcranial alternating current stimulation enhances individual alpha activity in human EEG.

2010

Non-invasive electrical stimulation of the human cortex by means of transcranial direct current stimulation (tDCS) has been instrumental in a number of important discoveries in the field of human cortical function and has become a well-established method for evaluating brain function in healthy human participants. Recently, transcranial alternating current stimulation (tACS) has been introduced to directly modulate the ongoing rhythmic brain activity by the application of oscillatory currents on the human scalp. Until now the efficiency of tACS in modulating rhythmic brain activity has been indicated only by inference from perceptual and behavioural consequences of electrical stimulation. No direct electrophysiological evidence of tACS has been reported. We delivered tACS over the occipital cortex of 10 healthy participants to entrain the neuronal oscillatory activity in their individual alpha frequency range and compared results with those from a separate group of participants receiving sham stimulation. The tACS but not the sham stimulation elevated the endogenous alpha power in parieto-central electrodes of the electroencephalogram. Additionally, in a network of spiking neurons, we simulated how tACS can be affected even after the end of stimulation. The results show that spike-timing-dependent plasticity (STDP) selectively modulates synapses depending on the resonance frequencies of the neural circuits that they belong to. Thus, tACS influences STDP which in turn results in aftereffects upon neural activity.The present findings are the first direct electrophysiological evidence of an interaction of tACS and ongoing oscillatory activity in the human cortex. The data demonstrate the ability of tACS to specifically modulate oscillatory brain activity and show its potential both at fostering knowledge on the functional significance of brain oscillations and for therapeutic application.

PloS one

Zaehle, T; Rach, S; Herrmann, CS

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Non-invasive brain stimulation techniques for chronic pain.

2010

Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES) and transcranial direct current stimulation (tDCS).To evaluate the efficacy of non-invasive brain stimulation techniques in chronic pain.We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, the Cochrane PaPaS Group Trials Register and clinical trials registers.Randomised and quasi-randomised studies of rTMS, CES or tDCS if they employed a sham stimulation control group, recruited patients over the age of 18 with pain of three months duration or more and measured pain as a primary outcome.Two authors independently extracted and verified data. Where possible we entered data into meta-analyses. We excluded studies judged as being at high risk of bias from the analysis.We included 33 trials in the review (involving 937 people)(19 rTMS, eight CES and six tDCS). Only one study was judged as being at low risk of bias.Studies of rTMS (involving 368 participants ) demonstrated significant heterogeneity. Pre-specified subgroup analyses suggest that low-frequency stimulation is ineffective. A short-term effect on pain of active high-frequency stimulation of the motor cortex in single-dose studies was suggested (standardised mean difference (SMD) -0.40, 95% confidence interval (CI) -0.26 to -0.54, P < 0.00001). This equates to a 15% (95% CI 10% to 20%) reduction in pain which does not clearly exceed the pre-established criteria for a minimally clinically important difference (> 15%).For CES (four studies, 133 participants) no statistically significant difference was found between active stimulation and sham. Analysis of tDCS studies (five studies, 83 people) demonstrated significant heterogeneity and did not find a significant difference between active and sham stimulation. Pre-specified subgroup analysis of tDCS applied to the motor cortex suggested superiority of active stimulation over sham (SMD -0.59, 95% CI -1.10 to -0.08).Non-invasive brain stimulation appears to be associated with minor and transient side effects.Single doses of high-frequency rTMS of the motor cortex may have small short-term effects on chronic pain. The effects do not clearly exceed the predetermined threshold of minimal clinical significance. Low-frequency rTMS is not effective in the treatment of chronic pain. There is insufficient evidence from which to draw firm conclusions regarding the efficacy of CES or tDCS. The available evidence suggests that tDCS applied to the motor cortex may have short-term effects on chronic pain and that CES may be ineffective. There is a need for further, rigorously designed studies of all types of stimulation.

Cochrane database of systematic reviews (Online)

O'Connell, NE; Wand, BM; Marston, L; Spencer, S; Desouza, LH


Modulation of mu rhythm desynchronization during motor imagery by transcranial direct current stimulation.

2010

The mu event-related desynchronization (ERD) is supposed to reflect motor preparation and appear during motor imagery. The aim of this study is to examine the modulation of ERD with transcranial direct current stimulation (tDCS).Six healthy subjects were asked to imagine their right hand grasping something after receiving a visual cue. Electroencephalograms (EEGs) were recorded near the left M1. ERD of the mu rhythm (mu ERD) by right hand motor imagery was measured. tDCS (10 min, 1 mA) was used to modulate the cortical excitability of M1. Anodal, cathodal, and sham tDCS were tested in each subject with a randomized sequence on different days. Each condition was separated from the preceding one by more than 1 week in the same subject. Before and after tDCS, mu ERD was assessed. The motor thresholds (MT) of the left M1 were also measured with transcranial magnetic stimulation.Mu ERD significantly increased after anodal stimulation, whereas it significantly decreased after cathodal stimulation. There was a significant correlation between mu ERD and MT.Opposing effects on mu ERD based on the orientation of the stimulation suggest that mu ERD is affected by cortical excitability.

Journal of neuroengineering and rehabilitation

Matsumoto, J; Fujiwara, T; Takahashi, O; Liu, M; Kimura, A; Ushiba, J

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Effects of Transcranial Direct Current Stimulation on episodic memory related to emotional visual stimuli.

2010

The present study investigated emotional memory following bilateral transcranial electrical stimulation (direct current of 1 mA, for 20 minutes) over fronto-temporal cortical areas of healthy participants during the encoding of images that differed in affective arousal and valence. The main result was a significant interaction between the side of anodal stimulation and image emotional valence. Specifically, right anodal/left cathodal stimulation selectively facilitated the recall of pleasant images with respect to both unpleasant and neutral images whereas left anodal/right cathodal stimulation selectively facilitated the recall of unpleasant images with respect to both pleasant and neutral images. From a theoretical perspective, this double dissociation between the side of anodal stimulation and the advantage in the memory performance for a specific type of stimulus depending on its pleasantness supported the specific-valence hypothesis of emotional processes, which assumes a specialization of the right hemisphere in processing unpleasant stimuli and a specialization of the left hemisphere in processing pleasant stimuli. From a methodological point of view, first we found tDCS effects strictly dependent on the stimulus category, and second a pattern of results in line with an interfering and inhibitory account of anodal stimulation on memory performance. These findings need to be carefully considered in applied contexts, such as the rehabilitation of altered emotional processing or eye-witness memory, and deserve to be further investigated in order to understand their underlying mechanisms of action.

PloS one

Penolazzi, B; Di Domenico, A; Marzoli, D; Mammarella, N; Fairfield, B; Franciotti, R; Brancucci, A; Tommasi, L

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Non-invasive transcranial direct current stimulation for the study and treatment of neuropathic pain.

2010

In the last decade, radiological neuroimaging techniques have enhanced the study of mechanisms involved in the development and maintenance of neuropathic pain. Recent findings suggest that neuropathic pain in certain pain syndromes (e.g., complex regional pain syndrome/reflex sympathic dystrophy, phantom-limb pain) is associated with a functional reorganization and hyperexitability of the somatosensory and motor cortex. Studies showing that the reversal of cortical reorganization in patients with spontaneous or provoked pain is accompanied by pain relief stimulated the search for novel alternatives how to modulate the cortical excitability as a strategy to relieve pain. Recently, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) were proposed as suitable methods for modulation of cortical excitability. Both techniques (TMS and tDCS) have been clinically investigated in healthy volunteers as well as in patients with various clinical pathologies and variety of pain syndromes. Although there is less evidence on tDCS as compared with TMS, the findings on tDCS in patients with pain are promising, showing an analgesic effect of tDCS, and observations up to date justify the use of tDCS for the treatment of pain in selected patient populations. tDCS has been shown to be very safe if utilized within the current protocols. In addition, tDCS has been proven to be easy to apply, portable and not expensive, which further enhances great clinical potential of this technique.

Methods in molecular biology (Clifton, N.J.)

Knotkova, H; Cruciani, RA


Effect of tDCS with an extracephalic reference electrode on cardio-respiratory and autonomic functions.

2010

Transcranial direct current stimulation (tDCS) is used in human physiological studies and for therapeutic trials in patients with abnormalities of cortical excitability. Its safety profile places tDCS in the pole-position for translating in real-world therapeutic application. However, an episode of transient respiratory depression in a subject receiving tDCS with an extracephalic electrode led to the suggestion that such an electrode montage could modulate the brainstem autonomic centres. We investigated whether tDCS applied over the midline frontal cortex in 30 healthy volunteers (sham n = 10, cathodal n = 10, anodal n = 10) with an extracephalic reference electrode would modulate brainstem activity as reflected by the monitoring and stringent analysis of vital parameters: heart rate (variability), respiratory rate, blood pressure and sympatho-vagal balance. We reasoned that this study could lead to two opposite but equally interesting outcomes: 1) If tDCS with an extracephalic electrode modulated vital parameters, it could be used as a new tool to explore the autonomic nervous system and, even, to modulate its activity for therapeutic purposes. 2) On the opposite, if applying tDCS with an extracephalic electrode had no effect, it could thus be used safely in healthy human subjects. This outcome would significantly impact the field of non-invasive brain stimulation with tDCS. Indeed, on the one hand, using an extracephalic electrode as a genuine neutral reference (as opposed to the classical "bi-cephalic" tDCS montages which deliver bi-polar stimulation of the brain) would help to comfort the conclusions of several modern studies regarding the spatial location and polarity of tDCS. On the other hand, using an extracephalic reference electrode may impact differently on a given cortical target due to the change of direct current flow direction; this may enlarge the potential interventions with tDCS.Whereas the respiratory frequency decreased mildly over time and the blood pressure increased steadily, there was no differential impact of real (anodal or cathodal) versus sham tDCS. The heart rate remained stable during the monitoring period. The parameters reflecting the sympathovagal balance suggested a progressive shift over time favouring the sympathetic tone, again without differential impact of real versus sham tDCS.Applying tDCS with an extracephalic reference electrode in healthy volunteers did not significantly modulate the activity of the brainstem autonomic centres. Therefore, using an extracephalic reference electrode for tDCS appears safe in healthy volunteers, at least under similar experimental conditions.

BMC neuroscience

Vandermeeren, Y; Jamart, J; Ossemann, M

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Brain switches utilitarian behavior: does gender make the difference?

2010

Decision often implies a utilitarian choice based on personal gain, even at the expense of damaging others. Despite the social implications of utilitarian behavior, its neurophysiological bases remain largely unknown. To assess how the human brain controls utilitarian behavior, we delivered transcranial direct current stimulation (tDCS) over the ventral prefrontal cortex (VPC) and over the occipital cortex (OC) in 78 healthy subjects. Utilitarian judgment was assessed with the moral judgment task before and after tDCS. At baseline, females provided fewer utilitarian answers than males for personal moral dilemmas (p = .007). In males, VPC-tDCS failed to induce changes and in both genders OC-tDCS left utilitarian judgments unchanged. In females, cathodal VPC-tDCS tended to decrease whereas anodal VPC-tDCS significantly increased utilitarian responses (p = .005). In males and females, reaction times for utilitarian responses significantly decreased after cathodal (p<.001) but not after anodal (p = .735) VPC-tDCS. We conclude that ventral prefrontal tDCS interferes with utilitarian decisions, influencing the evaluation of the advantages and disadvantages of each option in both sexes, but does so more strongly in females. Whereas cathodal tDCS alters the time for utilitarian reasoning in both sexes, anodal stimulation interferes more incisively in women, modifying utilitarian reasoning and the possible consequent actions. The gender-related tDCS-induced changes suggest that the VPC differentially controls utilitarian reasoning in females and in males. The gender-specific functional organization of the brain areas involved in utilitarian behavior could be a correlate of the moral and social behavioral differences between the two sexes.

PloS one

Fumagalli, M; Vergari, M; Pasqualetti, P; Marceglia, S; Mameli, F; Ferrucci, R; Mrakic-Sposta, S; Zago, S; Sartori, G; Pravettoni, G; Barbieri, S; Cappa, S; Priori, A

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Blepharospasm and the modulation of cortical excitability in primary and secondary motor areas.

2009 Dec

Traditionally, benign essential blepharospasm (BEB) is considered a disorder caused by basal ganglia dysfunction. Electrophysiologic and brain imaging studies suggest pathologic changes in excitability in the primary motor cortex (MC), anterior cingulate (AC), and secondary motor areas, such as premotor (PMC) and supplementary motor cortices (SMA).In this pilot study of 7 patients with BEB, we experimentally reduced cortical excitability of 4 areas: MC (first dorsal interosseus area), PMC, SMA, and AC, each with 3 noninvasive techniques: low-frequency repetitive transcranial magnetic stimulation (lfrTMS), continuous theta burst stimulation (cTBS), and cathodal transcranial direct current stimulation (tDCS). Primary outcome was the clinical effects on blepharospasm (blink rate observation by an investigator blinded to the intervention and subjective rating by the patient); secondary outcome was the blink reflex recovery curve (BRR).lfrTMS resulted in a significant improvement over all 4 brain areas for physician rating, patient rating, and BRR, whereas cTBS and tDCS showed only trends for improvement in physician rating, but no improvements for patient rating and BRR. lfrTMS had a significantly higher effect over AC than MC for physician rating, but no differences were seen for other pairwise comparisons of stimulated brain areas.Electrophysiologic and clinical improvements by functional inhibition of the medial frontal areas using low-frequency repetitive transcranial magnetic stimulation suggests that hypersensitivity of the anterior cingulate is directly or indirectly involved in the pathophysiology of benign essential blepharospasm. Inhibition of these areas using low-frequency repetitive transcranial magnetic stimulation could provide a therapeutic tool and is worthy of a larger study.

Neurology

Kranz, G; Shamim, EA; Lin, PT; Kranz, GS; Voller, B; Hallett, M

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Characterizing the application of transcranial direct current stimulation in human pharyngeal motor cortex.

2009 Dec

Transcranial direct current stimulation (tDCS) is a novel intervention that can modulate brain excitability in health and disease; however, little is known about its effects on bilaterally innervated systems such as pharyngeal motor cortex. Here, we assess the effects of differing doses of tDCS on the physiology of healthy human pharyngeal motor cortex as a prelude to designing a therapeutic intervention in dysphagic patients. Healthy subjects (n = 17) underwent seven regimens of tDCS (anodal 10 min 1 mA, cathodal 10 min 1 mA, anodal 10 min 1.5 mA, cathodal 10 min 1.5 mA, anodal 20 min 1 mA, cathodal 20 min 1 mA, Sham) on separate days, in a double blind randomized order. Bihemispheric motor evoked potential (MEP) responses to single-pulse transcranial magnetic stimulation (TMS) as well as intracortical facilitation (ICF) and inhibition (ICI) were recorded using a swallowed pharyngeal catheter before and up to 60 min following the tDCS. Compared with sham, both 10 min 1.5 mA and 20 min 1 mA anodal stimulation induced increases in cortical excitability in the stimulated hemisphere (+44 +/- 17% and +59 +/- 16%, respectively; P < 0.005) whereas only 10 min 1.5 mA cathodal stimulation induced inhibition (-26 +/- 4%, P = 0.02). There were neither contralateral hemisphere changes nor any evidence for ICI or ICF in driving the ipsilateral effects. In conclusion, anodal tDCS can alter pharyngeal motor cortex excitability in an intensity-dependent manner, with little evidence for transcallosal spread. Anodal stimulation may therefore provide a useful means of stimulating pharyngeal cortex and promoting recovery in dysphagic patients.

American journal of physiology. Gastrointestinal and liver physiology

Jefferson, S; Mistry, S; Singh, S; Rothwell, J; Hamdy, S

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Impact of transcranial direct current stimulation on spinal network excitability in humans.

2009 Dec

Transcranial direct current stimulation (tDCS) when applied over the motor cortex, modulates excitability dependent on the current polarity. The impact of this cortical modulation on spinal cord network excitability has rarely been studied. In this series of experiments, performed in healthy subjects, we show that anodal tDCS increases disynaptic inhibition directed from extensor carpi radialis (ECR) to flexor carpi radialis (FCR) with no modification of presynaptic inhibition of FCR Ia terminals and FCR H-reflex recruitment curves. We also show that cathodal tDCS does not modify spinal network excitability. Our results suggest that the increase of disynaptic inhibition observed during anodal tDCS relies on an increase of disynaptic interneuron excitability and that tDCS over the motor cortex in human subjects induces effects on spinal network excitability. Our results highlight the fact that the effects of tDCS should be considered in regard to spinal motor circuits and not only to cortical circuits.

The Journal of physiology

Roche, N; Lackmy, A; Achache, V; Bussel, B; Katz, R

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Transcranial direct current stimulation priming of therapeutic repetitive transcranial magnetic stimulation: a pilot study.

2009 Dec

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be a safe treatment of depression, and research efforts are now largely focused on strategies to enhance its efficacy. Motor cortex experiments suggest that the effects of rTMS can be enhanced by first priming the same cortical area with transcranial direct current stimulation (tDCS). We explored this approach in depressed subjects.Seven depressed subjects were given sessions of combined tDCS-rTMS to the left dorsolateral prefrontal cortex, exploring a range of tDCS and rTMS stimulation parameters and interstimulation intervals. Effects of repeated stimulation sessions on mood state and neuropsychological functioning were evaluated.Most of the subjects showed little improvement with cathodal tDCS followed by 10-Hz rTMS, although 2 subjects showed marked improvement, one after a single stimulation session. Anodal tDCS followed by rTMS did not lead to any improvement. Preconditioning with tDCS seemed to greatly exacerbate the pain of subsequent rTMS. No adverse effects on neuropsychological functioning were observed.Overall, preconditioning with cathodal tDCS followed by rTMS did not re