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Transcranial direct current stimulation during treadmill training in children with cerebral palsy: A randomized controlled double-blind clinical trial.

2014 Nov

Impaired gait constitutes an important functional limitation in children with cerebral palsy (CP). Treadmill training has achieved encouraging results regarding improvements in the gait pattern of this population. Moreover, transcranial direct current stimulation (tDCS) is believed to potentiate the results achieved during the motor rehabilitation process. The aim of the present study was to determine the effect of the administration of tDCS during treadmill training on the gait pattern of children with spastic diparetic CP. A double-blind randomized controlled trial was carried out involving 24 children with CP allocated to either an experimental group (active anodal tDCS [1mA] over the primary motor cortex of the dominant hemisphere) or control group (placebo tDCS) during ten 20-min sessions of treadmill training. The experimental group exhibited improvements in temporal functional mobility, gait variables (spatiotemporal and kinematics variables). The results were maintained one month after the end of the intervention. There was a significant change in corticospinal excitability as compared to control group. In the present study, the administration of tDCS during treadmill training potentiated the effects of motor training in children with spastic diparetic CP.

Research in developmental disabilities

Grecco, LA; Duarte, Nde A; Mendonça, ME; Cimolin, V; Galli, M; Fregni, F; Oliveira, CS


Transcranial direct current stimulation over left and right DLPFC: Lateralized effects on planning performance and related eye movements.

2014 Oct

Left and right dorsolateral prefrontal cortex (dlPFC) were recently found to be differentially affected by unilateral continuous theta-burst stimulation, reflected in an oppositional alteration of initial thinking time (ITT) in the Tower of London planning task. Here, we further explored this finding using bilateral transcranial direct current stimulation (tDCS) and simultaneous tracking of eye movements. Results revealed a decrease in ITT during concurrent cathodal tDCS of left dlPFC and anodal tDCS of right dlPFC. Eye-movement analyses showed that this facilitating tDCS effect was associated with the actual planning phase, thus reflecting a planning-specific impact of stimulation. For the reverse stimulation pattern of cathodal tDCS of right dlPFC and anodal tDCS of left dlPFC, an increase in gaze shifts was observed, without a significant impact on ITT. Taken together, these findings corroborate that enhanced planning performance can be obtained by boosting right dlPFC and dismantling the inhibitory impact of left dlPFC.

Biological psychology

Heinze, K; Ruh, N; Nitschke, K; Reis, J; Fritsch, B; Unterrainer, JM; Rahm, B; Weiller, C; Kaller, CP


Prefrontal transcranial direct current stimulation improves fundamental vehicle control abilities.

2014 Oct

Noninvasive brain stimulation techniques have increasingly attracted the attention of neuroscientists because they enable the identification of the causal role of a targeted brain region. However, few studies have applied such techniques to everyday life situations. Here, we investigate the causal role of the dorsolateral prefrontal cortex (DLPFC) in fundamental vehicle control abilities. Thirteen participants underwent a simulated driving task under prefrontal transcranial direct current stimulation (tDCS) on three separate testing days. Each testing day was randomly assigned to either anodal over the right with cathodal over the left DLPFC, cathodal over the right with anodal over the left DLPFC, or sham stimulation. The driving task required the participants to maintain an inter-vehicle distance to a leading car traveling a winding road with a constant speed. Driving performance was quantified using two metrics: the root-mean-square error of inter-vehicle distance as car-following performance, and the standard deviation of lateral position as lane-keeping performance. Results showed that both car-following and lane-keeping performances were significantly greater for right anodal/left cathodal compared with right cathodal/left cathodal and sham stimulation. These results suggest not only the causal involvement of the DLPFC in driving, but also right hemisphere dominance for vehicle control. The findings of this study indicate that tDCS can be a useful tool to examine the causal role of a specific brain region in ecologically valid environments, and also might be a help to drivers with difficulties in vehicle control.

Behavioural brain research

Sakai, H; Uchiyama, Y; Tanaka, S; Sugawara, SK; Sadato, N


A pilot study of alternative transcranial direct current stimulation electrode montages for the treatment of major depression.

2014 Oct

Typically, transcranial direct current stimulation (tDCS) treatments for depression have used bifrontal montages with anodal (excitatory) stimulation targeting the left dorsolateral prefrontal cortex (DLPFC). There is limited research examining the effects of alternative electrode montages.This pilot study aimed to examine the feasibility, tolerability and safety of two alternative electrode montages and provide preliminary data on efficacy. The montages, Fronto-Occipital (F-O) and Fronto-Cerebellar (F-C), were designed respectively to target midline brain structures and the cerebellum.The anode was placed over the left supraorbital region and the cathode over the occipital and cerebellar region for the F-O and F-C montages respectively. Computational modelling was used to determine the electric fields produced in the brain regions of interest compared to a standard bifrontal montage. The two montages were evaluated in an open label study of depressed participants (N=14). Mood and neuropsychological functioning were assessed at baseline and after four weeks of tDCS.Computational modelling revealed that the novel montages resulted in greater activation in the anterior cingulate cortices and cerebellum than the bifrontal montage, while activation of the DLPFCs was higher for the bifrontal montage. After four weeks of tDCS, overall mood improvement rates of 43.8% and 15.9% were observed under the F-O and F-C conditions, respectively. No significant neuropsychological changes were found.The clinical pilot was open-label, without a control condition and computational modelling was based on one healthy participant.Results found both montages safe and feasible. The F-O montage showed promising antidepressant potential.

Journal of affective disorders

Ho, KA; Bai, S; Martin, D; Alonzo, A; Dokos, S; Puras, P; Loo, CK


Increase in PAS-induced neuroplasticity after a treatment courseof transcranial direct current stimulation for depression.

2014 Oct

Several lines of evidence suggest that neuroplasticity is impaired in depression and improves with effective treatment. However until now, this evidence has largely involved measures such as learning and memory which can be influenced by subject effort and motivation. This pilot study aimed to objectively measure neuroplasticity in the motor cortex using paired associative stimulation (PAS), which induces short term neuroplastic changes. It is hypothesized that neuroplasticity would improve after effective treatment for depression.Neuroplasticity was measured in 18 depressed subjects before and after a course of anodal transcranial direct current stimulation (tDCS), given as treatment for depression. The relationships between PAS results, mood state and brain-derived neurotrophic factor (BDNF) serum levels were examined.Neuroplasticity (PAS-induced change) was increased after a course of tDCS (t(17)=-2.651, p=0.017). Treatment with tDCS also led to significant mood improvement, but this did not correlate with improved neuroplasticity. Serum BDNF levels did not change after tDCS, or correlate with change in neuroplasticity after tDCS treatment.While this study showed evidence of improved neuroplasticity in the motor cortex after effective treatment, we are unable to present evidence that this change is generalized in the depressed brain. Also, the presence of antidepressant medications and the small sample of patients (n=18) meant the study could not definitively resolve the relationship between neuroplasticity, mood and BDNF.This novel preliminary study provides evidence that a treatment course of tDCS can improve neuroplasticity in depressed patients.

Journal of affective disorders

Player, MJ; Taylor, JL; Weickert, CS; Alonzo, A; Sachdev, PS; Martin, D; Mitchell, PB; Loo, CK


tDCS-induced alterations in GABA concentration within primary motor cortex predict motor learning and motor memory: A 7T magnetic resonance spectroscopy study.

2014 Oct

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability in a polarity specific manner and has been shown to influence learning and memory. tDCS may have both on-line and after-effects on learning and memory, and the latter are thought to be based upon tDCS-induced alterations in neurochemistry and synaptic function. We used ultra-high-field (7T) magnetic resonance spectroscopy (MRS), together with a robotic force adaptation and de-adaptation task, to investigate whether tDCS-induced alterations in GABA and Glutamate within motor cortex predict motor learning and memory. Note that adaptation to a robot-induced force field has long been considered to be a form of model-based learning that is closely associated with the computation and 'supervised' learning of internal 'forward' models within the cerebellum. Importantly, previous studies have shown that on-line tDCS to the cerebellum, but not to motor cortex, enhances model-based motor learning. Here we demonstrate that anodal tDCS delivered to the hand area of the left primary motor cortex induces a significant reduction in GABA concentration. This effect was specific to GABA, localised to the left motor cortex, and was polarity specific insofar as it was not observed following either cathodal or sham stimulation. Importantly, we show that the magnitude of tDCS-induced alterations in GABA concentration within motor cortex predicts individual differences in both motor learning and motor memory on the robotic force adaptation and de-adaptation task.

NeuroImage

Kim, S; Stephenson, MC; Morris, PG; Jackson, SR

Link to full article text


The effect of practice on random number generation task: A transcranial direct current stimulation study.

2014 Oct

Random number generation (RNG) is a procedurally-simple task related to specific executive functions, such as updating and monitoring of information and inhibition of automatic responses. The effect of practice on executive functions has been widely investigated, however little is known on the impact of practice on RNG. Transcranial direct current stimulation (tDCS) allows to modulate, non-invasively, brain activity and to enhance the effects of training on executive functions. Hence, this study aims to investigate the effect of practice on RNG and to explore the possibility to influence it by tDCS applied over dorsolateral prefrontal cortex. Twenty-six healthy volunteers have been evaluated within single session and between different sessions of RNG using several measures of randomness, which are informative of separable cognitive components servicing random behavior. We found that repetition measures significantly change within single session, seriation measures significantly change both within and between sessions, while cycling measures are not affected by practice. tDCS does not produce any additional effect, however a sub-analysis limited to the first session revealed an increasing trend in seriation measure after anodal compared to cathodal stimulation. Our findings support the hypothesis that practice selectively and consistently influences specific cognitive components related to random behavior, while tDCS transiently affects RNG performance.

Neurobiology of learning and memory

Capone, F; Capone, G; Ranieri, F; Di Pino, G; Oricchio, G; Di Lazzaro, V


Cerebellar direct current stimulation enhances motor learning in older adults.

2014 Oct

Developing novel approaches to combat age related declines in motor function is key to maintaining health and function in older adults, a subgroup of the population that is rapidly growing. Motor adaptation, a form of motor learning, has been shown to be impaired in healthy older subjects compared with their younger counterparts. Here, we tested whether excitatory anodal transcranial direct current stimulation (tDCS) over the cerebellum could enhance adaptation in older subjects. Participants performed a "center-out" reaching task, adapting to the sudden introduction of a visual cursor rotation. Older participants receiving sham tDCS (mean age 56.3 ± 6.8 years) were slower to adapt than younger participants (mean age 20.7 ± 2.1 years). In contrast, older participants who received anodal tDCS (mean age 59.6 ± 8.1 years) adapted faster, with a rate that was similar to younger subjects. We conclude that cerebellar anodal tDCS enhances motor adaptation in older individuals. Our results highlight the efficacy of the novel approach of using cerebellar tDCS to combat age related deficits in motor learning.

Neurobiology of aging

Hardwick, RM; Celnik, PA


Anodal transcranial direct current stimulation over the dorsolateral prefrontal cortex improves anorexia nervosa: A pilot Study.

2014 Sep

Background: Existing treatments for adults with anorexia nervosa (AN) have limited proven efficacy. New treatments that have been suggested involve targeted, brain-directed interventions such as transcranial direct current stimulation (tDCS). We describe findings from seven individuals with treatment-resistant AN who received 10 sessions of anodal tDCS, over the left dorsolateral prefrontal cortex (DLPFC). Material and method: In this open-label, single-arm study, seven patients received anodal tDCS (2mA) for 25 minutes over the left dorsolateral prefrontal cortex daily for ten days. Assessments pre-tDCS, post-tDCS and one month later included the Eating Attitude Test (EAT), Eating Disorder Inventory (EDI) and Beck Depression Inventory (BDI). Results: Three patients improved in all three rating scales immediately after the treatment sessions and one month later. Two patients showed improvement at the end of treatment but returned to the baseline after one month. One subject improved only on the BDI scale but not eating scales. The scores in the three rating scales were unaffected by treatment in the remaining patient. There was a significant effect of time (pre, post and 1 month later) on the three rating scores; BDI (P = 0.016), EDI (P = 0.018) and EAT (P = 0.016) and a significant correlation between the percent improvement of BDI and EAT (p = 0.01), and between BDI and EDI (P = 0.006). Conclusions: These findings suggest that tDCS has potential as an adjuvant treatment for AN and deserves further study.

Restorative neurology and neuroscience

Khedr, EM; Elfetoh, NA; Ali, AM; Noamany, M


Applications of transcranial direct current stimulation for understanding brain function.

2014 Sep

In recent years there has been an exponential rise in the number of studies employing transcranial direct current stimulation (tDCS) as a means of gaining a systems-level understanding of the cortical substrates underlying behaviour. These advances have allowed inferences to be made regarding the neural operations that shape perception, cognition, and action. Here we summarise how tDCS works, and show how research using this technique is expanding our understanding of the neural basis of cognitive and motor training. We also explain how oscillatory tDCS can elucidate the role of fluctuations in neural activity, in both frequency and phase, in perception, learning, and memory. Finally, we highlight some key methodological issues for tDCS and suggest how these can be addressed.

Trends in neurosciences

Filmer, HL; Dux, PE; Mattingley, JB


Neuromodulation in Obsessive-Compulsive Disorder.

2014 Sep

Neuromodulation techniques in obsessive-compulsive disorder (OCD) involve electroconvulsive therapy (ECT), transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS). This article reviews the available literature on the efficacy and applicability of these techniques in OCD. ECT is used for the treatment of comorbid depression or psychosis. One case report on tDCS showed no effects in OCD. Low-frequency TMS provides significant but mostly transient improvement of obsessive-compulsive symptoms. DBS shows a response rate of 60% in open and sham-controlled studies. In OCD, it can be concluded that DBS, although more invasive, is the most efficacious technique.

The Psychiatric clinics of North America

Bais, M; Figee, M; Denys, D


Additional effects of transcranial direct-current stimulation and trigger-point injection for treatment of myofascial pain syndrome: a pilot study with randomized, single-blinded trial.

2014 Sep

Abstract Background: Chronic pain caused by myofascial pain syndrome (MPS) results in generalized and debilitating conditions. Trigger-point injection (TPI) is the mainstay of MPS management to reduce acute and localized pain. Other adjunctive intervention to modulate the central pain pathway might be helpful if they are combined with TPI. Transcranial direct-current stimulation (tDCS), which is a form of neurostimulation, has been reported to be safe and effective in treating chronic pain by changing cortical excitability.To determine whether there is an additional effect of tDCS and TPI to reduce pain in patients with MPS.Twenty-one patients with newly diagnosed MPS of shoulder girdle muscles.PATIENTS were randomly assigned into 1 of 3 groups (2 active and 1 sham stimulation groups) and received TPI. Immediately after TPI, tDCS (2 mA for 20 minutes on 5 consecutive days) was administered. For the active stimulation groups, tDCS was applied over 2 different locations (primary motor cortex and dorsolateral prefrontal cortex [DLPFC]).Visual analogue scale (VAS), Pain Threshold Test, and short form of the McGill Pain Questionnaire were measured before and immediately after stimulation for 5 consecutive days.The mean VAS values were decreased in all three groups after 5 days. There was a significant change between before and after stimulation only in the DLPFC group. The significant change in the mean VAS value was shown from after the second stimulation session (p=0.031), and this remained significant until the last stimulation session (p=0.027).This study suggests that tDCS over DLPFC may have additional effects with TPI to reduce pain in patients with MPS. tDCS over DLPFC can be used to reverse central pain pathway by modulating cortical plasticity.

Journal of alternative and complementary medicine (New York, N.Y.)

Choi, YH; Jung, SJ; Lee, CH; Lee, SU


Timing-dependent priming effects of tDCS on ankle motor skill learning.

2014 Sep

Transcranial direct current stimulation (tDCS) has gained increasing interest in neurorehabilitation with its ability to modulate cortical excitability, and thereby influence neural plasticity and functional recovery. While the beneficial effects of tDCS on motor learning and function have been recognized, there is no clear consensus regarding the timing of the tDCS priming protocol in relation to the intervention especially with respect to lower limb motor learning. Depending on the time of priming in relation to the training task, the neural mechanisms of priming (gating vs. homeostatic plasticity) are different and thereby subsequently affect motor learning. Hence, the aim of this study was to examine the interaction of tDCS with subsequent vs. concurrent motor learning using an ankle visuomotor skill learning paradigm. Twelve healthy participants were tested under three stimulation conditions: (1) anodal tDCS prior to the motor task (tDCS-before), (2) anodal tDCS during the motor task (tDCS-during) and (3) sham tDCS during the motor task (tDCS-sham). Results revealed that tDCS application during practice of a skilled motor task increased motor performance compared to tDCS applied prior to motor practice. Both tDCS groups demonstrated enhanced motor learning when tested 24hours after practice. We conclude that the priming effects of tDCS are timing dependent, and maybe a critical regulatory feature in determining outcomes of priming with tDCS.

Brain research

Sriraman, A; Oishi, T; Madhavan, S


TDCS increases cortical excitability: Direct evidence from TMS-EEG.

2014 Sep

Despite transcranial direct current stimulation (tDCS) is increasingly used in experimental and clinical settings, its precise mechanisms of action remain largely unknown. At a neuronal level, tDCS modulates the resting membrane potential in a polarity-dependent fashion: anodal stimulation increases cortical excitability in the stimulated region, while cathodal decreases it. So far, the neurophysiological underpinnings of the immediate and delayed effects of tDCS, and to what extent the stimulation of a given cerebral region may affect the activity of anatomically connected regions, remain unclear. In the present study, we used a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG) in order to explore local and global cortical excitability modulation during and after active and sham tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 15 min of tDCS over the right PPC, while EEG was recorded from 60 channels. For each session, indexes of global and local cerebral excitability were obtained, computed as global and local mean field power (Global Mean Field Power, GMFP and Local Mean Field Power, LMFP) on mean TMS-evoked potentials (TEPs) for three temporal windows: 0-50, 50-100, and 100-150 msec. The global index was computed on all 60 channels. The local indexes were computed in six clusters of electrodes: left and right in frontal, parietal and temporal regions. GMFP increased, compared to baseline, both during and after active tDCS in the 0-100 msec temporal window. LMFP increased after the end of stimulation in parietal and frontal clusters bilaterally, while no difference was found in the temporal clusters. In sum, a diffuse rise of cortical excitability occurred, both during and after active tDCS. This evidence highlights the spreading of the effects of anodal tDCS over remote cortical regions of stimulated and contralateral hemispheres.

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

Romero Lauro, LJ; Rosanova, M; Mattavelli, G; Convento, S; Pisoni, A; Opitz, A; Bolognini, N; Vallar, G


Independent modulation of corticospinal and group I afferents pathways during upright standing.

2014 Sep

Balance control during upright standing is accompanied by an increased amplitude of motor-evoked potentials (MEP) induced by transcranial magnetic stimulation and a decreased amplitude of the Hoffmann (H) reflex in the soleus muscle. Nonetheless, whether these observations reflect reciprocal adjustments between corticospinal and group I afferents pathways during upright standing remains unknown. To further investigate this question, cathodal transcranial direct current stimulation (c-tDCS) applied over the motor cortex and vibration of Achilles tendons were used to modify the excitability of corticospinal and group I afferent pathways, respectively. MEPs and H reflexes were recorded in the soleus muscle during upright standing with or without bilateral Achilles tendon vibration, these recordings being performed before and after 20min of c-tDCS (1.5mA) or sham stimulation applied over the sensorimotor cortex. The results indicate that tendon vibration increased MEP amplitude (+28%) and decrease (-68%) the H-reflex amplitude (p<0.05). After c-tDCS, MEP amplitude was reduced by 13% and 26% without and with tendon vibration (p<0.05), respectively. In contrast, no significant change occurred in H-reflex amplitude after c-tDCS. Regardless of the conditions (c-tDCS and tendon vibration), no significant correlation was observed between changes in MEP and H-reflex amplitudes. The results failed to demonstrate close reciprocal changes in soleus MEP and H-reflex amplitudes during upright standing. These original findings suggest independent adjustments in corticospinal and group I afferents pathways during upright standing.

Neuroscience

Baudry, S; Duchateau, J


Contributions of the cerebellum and the motor cortex to acquisition and retention of motor memories.

2014 Sep

We investigated the contributions of the cerebellum and the motor cortex (M1) to acquisition and retention of human motor memories in a force field reaching task. We found that anodal transcranial direct current stimulation (tDCS) of the cerebellum, a technique that is thought to increase neuronal excitability, increased the ability to learn from error and form an internal model of the field, while cathodal cerebellar stimulation reduced this error-dependent learning. In addition, cathodal cerebellar stimulation disrupted the ability to respond to error within a reaching movement, reducing the gain of the sensory-motor feedback loop. By contrast, anodal M1 stimulation had no significant effects on these variables. During sham stimulation, early in training the acquired motor memory exhibited rapid decay in error-clamp trials. With further training the rate of decay decreased, suggesting that with training the motor memory was transformed from a labile to a more stable state. Surprisingly, neither cerebellar nor M1 stimulation altered these decay patterns. Participants returned 24hours later and were re-tested in error-clamp trials without stimulation. The cerebellar group that had learned the task with cathodal stimulation exhibited significantly impaired retention, and retention was not improved by M1 anodal stimulation. In summary, non-invasive cerebellar stimulation resulted in polarity-dependent up- or down-regulation of error-dependent motor learning. In addition, cathodal cerebellar stimulation during acquisition impaired the ability to retain the motor memory overnight. Thus, in the force field task we found a critical role for the cerebellum in both formation of motor memory and its retention.

NeuroImage

Herzfeld, DJ; Pastor, D; Haith, AM; Rossetti, Y; Shadmehr, R; O'Shea, J


Transcranial direct current stimulation over right posterior parietal cortex changes prestimulus alpha oscillation in visual short-term memory task.

2014 Sep

Alpha band activity changes accompanied with the level attentional state, and recent studies suggest that such oscillation is associated with activities 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 change people's prestimulus alpha power and improve subsequent performance on a visual short-term memory (VSTM) task. This modulation of alpha power and behavioral performance, however, is dependent on people's natural VSTM capability such that only the low performers benefitted from the stimulation, whereas high performers did not. This behavioral dichotomy is accounted by prestimulus alpha powers around the parieto-occipital regions: low performers showed decreased prestimulus alpha power, suggesting improvement in attention deployment in the current paradigm, whereas the high performers did not benefit from tDCS as they showed equally-low prestimulus alpha power before and after the stimulation. Together, these results suggest that prestimulus alpha power, especially in low performers, can be modulated by anodal stimulation and alter subsequent VSTM performance/capacity. Thus, measuring alpha before stimulus onset may be as important as measuring other VSTM-related electrophysiological components such as attentional allocation and memory capacity related components (i.e. N2 posterior-contralateral, N2pc, or contralateral delay activity, CDA). In addition, low VSTM performers perhaps do not suffer not only from poor VSTM capacity, but also from broad attentional mechanisms, and prestimulus alpha may be an useful tool in understanding the nature of individual differences in VSTM.

NeuroImage

Hsu, TY; Tseng, P; Liang, WK; Cheng, SK; Juan, CH


Cognitive related electrophysiological changes induced by non-invasive cortical electrical stimulation in crack-cocaine addiction.

2014 Sep

Prefrontal dysfunction is a hallmark in drug addiction, yet interventions exploring modulation of prefrontal cortex function in drug addiction have not been fully investigated with regard to physiological alterations. We tested the hypothesis that non-invasive prefrontal stimulation would change neural activity in crack-cocaine addiction, investigating the effects of transcranial Direct Current Stimulation (tDCS) of Dorsolateral Prefrontal Cortex (DLPFC) induced cortical excitability modulation on the visual P3 Event Related Potentials (ERP) component under neutral and drug cue exposition in crack-cocaine addicts. Thirteen crack-cocaine users were randomly distributed to receive five applications (once a day, every other day) of bilateral (left cathodal/right anodal) tDCS (20 min, 2 mA, 35 cm2) or sham tDCS over the DLPFC. Brain activity was measured under crack-related or neutral visual-cued ERPs. There were significant differences in P3-related parameters when comparing group of stimulation (active vs. sham tDCS) and number of sessions (single vs. repetitive tDCS). After a single session of tDCS, P3 current intensity in the left DLPFC increased during neutral cues and decreased during crack-related cues. This effect was opposite to what was observed in the sham-tDCS group. In contrast, repetitive tDCS increased current density not only in the DLPFC, but also in a wider array of prefrontal areas, including presumably the frontopolar cortex (FPC) orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC), when subjects were visualizing crack-related cues. Thus, single and repetitive application of tDCS can impact cognitive processing of neutral and especially crack-related visual cues in prefrontal areas, which may be of importance for treatment of crack-cocaine addiction.

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

Conti, CL; Moscon, JA; Fregni, F; Nitsche, MA; Nakamura-Palacios, EM


Transcranial direct current stimulation for major depression: an updated systematic review and meta-analysis.

2014 Sep

Transcranial direct cranial stimulation (tDCS) is a promising non-pharmacological intervention for treating major depressive disorder (MDD). However, results from randomized controlled trials (RCTs) and meta-analyses are mixed. Our aim was to assess the efficacy of tDCS as a treatment for MDD. We performed a systematic review in Medline and other databases from the first RCT available until January 2014. The main outcome was the Hedges' g for continuous scores; secondary outcomes were the odds ratio (ORs) to achieve response and remission. We used a random-effects model. Seven RCTs (n = 259) were included, most with small sample sizes that assessed tDCS as either a monotherapy or as an add-on therapy. Active vs. sham tDCS was significantly superior for all outcomes (g = 0.37; 95% CI 0.04-0.7; ORs for response and remission were, respectively, 1.63; 95% CI = 1.26-2.12 and 2.50; 95% CI = 1.26-2.49). Risk of publication bias was low. No predictors of response were identified, possibly owing to low statistical power. In summary, active tDCS was statistically superior to sham tDCS for the acute depression treatment, although its role as a clinical intervention is still unclear owing to the mixed findings and heterogeneity of the reviewed studies. Further RCTs with larger sample sizes and assessing tDCS efficacy beyond the acute depressive episode are warranted.

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

Shiozawa, P; Fregni, F; Benseñor, IM; Lotufo, PA; Berlim, MT; Daskalakis, JZ; Cordeiro, Q; Brunoni, AR


Within-session repeated a-tDCS: The effects of repetition rate and inter-stimulus interval on corticospinal excitability and motor performance.

2014 Sep

This study investigated the effect of rate and stimulation interval of anodal transcranial direct current stimulation (a-tDCS) on CSE and motor performance.Twelve healthy individuals participated in this study. CSE was assessed before and after five experimental conditions of one, two or three applications of 10min of a-tDCS with an interval of 5 or 25min. a-tDCS was applied with a constant current density of 0.016mA/cm(2). Purdue pegboard-test was selected for motor performance assessment.Compared to single 10min stimulation, the magnitude of the within-session repeated a-tDCS induced excitability was enhanced significantly after the second stimulation was performed with an interval of 25min, but not 5min. However, by increasing the number of a-tDCS to three repetitions the CSE was significantly increased and lasted for 2h with both 5 and 25min intervals. Furthermore, CSE enhancement remained significant for up to 24h for within session a-tDCS repetitions with 25min intervals. Likewise, significant improvement was seen in motor performance following three times repetition with 25min inter-stimulus intervals.The results suggest that within session repeated a-tDCS with longer intervals within the lasting effects of the previous stimulations are preferable for increasing induced excitability changes with longer lasting effects.It is of particular importance to increase the a-tDCS lasting effects to consolidate the neuroplastic CSE changes.

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

Bastani, A; Jaberzadeh, S


Does anodal transcranial direct current stimulation modulate sensory perception and pain? A meta-analysis study.

2014 Sep

The primary aim of this systematic review was to evaluate the effects of anodal transcranial direct current stimulation (a-tDCS) on sensory (STh) and pain thresholds (PTh) in healthy individuals and pain levels (PL) in patients with chronic pain.Electronic databases were searched for a-tDCS studies. Methodological quality was examined using the PEDro and Downs and Black (D&B) assessment tools.a-tDCS of the primary motor cortex (M1) increases both STh (P<0.005, with the effect size of 22.19%) and PTh (P<0.001, effect size of 19.28%). In addition, STh was increased by a-tDCS of the primary sensory cortex (S1) (P<0.05 with an effect size of 4.34). Likewise, PL decreased significantly in the patient group following application of a-tDCS to both the M1 and dorsolateral prefrontal cortex (DLPFC). The average decrease in visual analogue score was 14.9% and 19.3% after applying a-tDCS on the M1 and DLPFC. Moreover, meta-analysis showed that in all subgroups (except a-tDCS of S1) active a-tDCS and sham stimulation produced significant differences.This review provides evidence for the effectiveness of a-tDCS in increasing STh/PTh in healthy group and decreasing PL in patients. However, due to small sample sizes in the included studies, our results should be interpreted cautiously. Given the level of blinding did not considered in inclusion criteria, the result of current study should be interpreted with caution.Site of stimulation should have a differential effect over pain relief.

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

Vaseghi, B; Zoghi, M; Jaberzadeh, S


Effects of transcranial direct current stimulation on esophageal motility in patients with gastroesophageal reflux disease.

2014 Sep

To evaluate the effects of transcranial direct current stimulation (tDCS) on esophageal peristalsis in patients with gastroesophageal reflux disease (GERD).Patients with GERD preliminary diagnosis were included in a randomized double-blind sham-controlled study. Esophageal manometry was performed before and during transcranial direct current stimulation (tDCS) of the right precentral cortex. Half of patients were randomly assigned to anodal, half to sham stimulation. Distal waves amplitude and pathological waves percentage were measured, after swallowing water boli, for ten subsequent times. Last, a 24h pH-bilimetry was done to diagnose non-erosive reflux disease (NERD) or functional heartburn (FH). The values obtained before and during anodal or sham tDCS were compared.Sixty-eight patients were enrolled in the study. Distal waves mean amplitude increased significantly only during anodal tDCS in NERD (p=0.00002) and FH subgroups (p=0.008) while percentage of pathological waves strongly decreased only in NERDs (p=0.002).Transcranial stimulation can influence cortical control of esophageal motility and improve pathological motor pattern in NERD and FH but not in erosive reflux disease (ERD) patients.Pathophysiological processes in GERD are not only due to peripheral damage but to central neural control involvement as well. In ERD patients dysfunctions of the cortico-esophageal circuit seem to be more severe and may affect central nervous system physiology.

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

Vigneri, S; Bonventre, S; Inviati, A; Schifano, D; Cosentino, G; Puma, A; Giglia, G; Paladino, P; Brighina, F; Fierro, B


Effects of tDCS-induced Motor Cortex Modulation on Pain in HTLV-1: A Blind Randomized Clinical Trial.

2014 Sep

We aimed to evaluate the effects of transcranial direct current stimulation (tDCS) on chronic pain in human T-lymphotropic virus type I-infected patients.This is a sham-controlled randomized clinical trial. Twenty participants were randomized to receive active or sham anodal tDCS over the primary motor cortex (M1), with 2 mA, 25 cm electrodes, for 20 minutes on 5 consecutive days. Pain intensity was measured at baseline and after each day of treatment using a Visual Analog Scale. Associated factors such as pain components description, pressure pain threshold, and Timed Up and Go task were also assessed.Mild adverse events were reported by 100% of patients in the tDCS group and 90% in the sham group. Comparison of daily Visual Analog Scale pain scores from both groups demonstrated a significant effect for the factor Time (P<0.001), but not for Group (P=0.13) or Time×Group interaction (P=0.06). There were 8 (80%) responders (reduction of 50% or more in pain intensity) in the tDCS group and 3 (30%) in the sham group (P=0.03). Both groups demonstrated improvements for most associated factors evaluated. However, there was no difference in between-groups comparison analyses.The analysis of the main outcomes in this study did not demonstrate a significant advantage of anodal tDCS applied to M1 in patients with human T-lymphotropic virus type I and chronic pain in comparison with sham tDCS, although secondary analysis suggests some superiority of active tDCS over sham. The large placebo effect observed in this study may explain the small differences between sham versus active tDCS.

The Clinical journal of pain

Souto, G; Borges, IC; Goes, BT; de Mendonça, ME; Gonçalves, RG; Garcia, LB; Sá, KN; Coutinho, MR; Galvão-Castro, B; Fregni, F; Baptista, AF


Non-invasive brain stimulation (NIBS) and motor recovery after stroke.

2014 Aug

Recovery of motor function after stroke occurs largely on the basis of a sustained capacity of the adult brain for plastic changes. This brain plasticity has been validated by functional imaging and electrophysiological studies. Various concepts of how to enhance beneficial plasticity and in turn improve functional recovery are emerging based on the concept of functional interhemispheric balance between the two motor cortices. Besides conventional rehabilitation interventions and the most recent neuropharmacological approaches, non-invasive brain stimulation (NIBS) has recently been proposed as an add-on method to promote motor function recovery after stroke. Several methods can be used based either on transcranial magnetic stimulation (repetitive mode: rTMS, TBS) via a coil, or small electric current via larges electrodes placed on the scalp, (transcranial direct current stimulation tDCS). Depending on the different electrophysiological parameters of stimulation used, NIBS can induce a transient modulation of the excitability of the stimulated motor cortex (facilitation or inhibition) via a probable LTP-LTD-like mechanism. Several small studies have shown feasible and positive treatment effects for most of these strategies and their potential clinical relevance to help restoring the disruption of interhemispheric imbalance after stroke. Results of these studies are encouraging but many questions remain unsolved: what are the optimal stimulation parameters? What is the best NIBS intervention? Which cortex, injured or intact, should be stimulated? What is the best window of intervention? Is there a special subgroup of stroke patients who could strongly benefit from these interventions? Finally is it possible to boost NIBS treatment effect by motor training of the paretic hand or by additional neuropharmacological interventions? There is clearly a need for large-scale, controlled, multicenter trials to answer these questions before proposing their routine use in the management of stroke patients.

Annals of physical and rehabilitation medicine

Simonetta-Moreau, M


Effects of tDCS on Executive Function in Parkinson's Disease.

2014 Aug

Non-motor symptoms in patients with Parkinson's disease (PD) are often poorly recognized, significantly impair quality of life and cause severe disability. Currently, there is limited evidence to guide treatment of associated psychiatric and cognitive problems. Non-invasive brain stimulation techniques have emerged as non-pharmacological alternatives to target cognitive symptoms without worsening motor function. In this context, we conducted a multicenter, sham controlled, double-blinded study to assess the immediate and long-term effects of ten consecutive sessions of transcranial direct current stimulation (tDCS) over the anode on the right dorsolateral prefrontal cortex (DLPFC) (n=5), left DLPFC (n=6) or sham (n=7). We assessed cognitive functions, depressive symptoms and motor functions in 18 PD patients at baseline, at the end of the 2-week stimulation sessions and at one-month follow-up. Our results showed that active stimulation of both left and right DLPFC resulted in prolonged improvements in Trail Making Test B, an established test to measure executive function, compared to sham tDCS at the one-month follow-up. These results suggest the existence of a beneficial long-term effect on executive functions in PD patients following active tDCS over the DLPFC. Thus, our findings encourage further investigation exploring tDCS as an adjuvant therapy for cognitive and behavioral treatment in PD.

Neuroscience letters

Doruk, D; Gray, Z; Bravo, GL; Pascual-Leone, A; Fregni, F


Induction of a depression-like negativity bias by cathodal transcranial direct current stimulation.

2014 Aug

Cognitive control (CC) over emotional distraction is of particular importance for adaptive human behaviour and is associated with activity in the left dorsolateral prefrontal cortex (dlPFC). Deficient CC, e.g., presenting as negativity bias, has been suggested to underlie many of the core symptoms of major depression (MD) and is associated with impairments of dlPFC function. Correspondingly, enhancement of dlPFC activity with anodal transcranial direct current stimulation (tDCS) can ameliorate these impairments in patients with MD. Here, we tested the hypothesis that a reduction of dlPFC activity by cathodal tDCS induces CC deficits, thus triggering a depression-like negativity bias in healthy subjects. Twenty-eight individuals participated in a double-blinded, balanced randomized crossover trial of cathodal (1 mA, 20 min) and sham tDCS applied to the left dlPFC. To assess CC we conducted a delayed response working memory (DWM) task and an arithmetic inhibition task (AIT) with pictures of varying valent content (negative, neutral, positive) during and immediately after stimulation. Cathodal tDCS led to impaired CC specifically over negative material as assessed by reduced response accuracy in the DWM and prolonged response latency in the AIT. Hence, the current study supports the notion that left dlPFC is critically involved in CC over negative material. Together with previously reported beneficial anodal effects, it indicates that the hypoactivation of left dlPFC causes deficits in CC over negative material, which is a possible aetiological mechanism of depression.

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

Wolkenstein, L; Zeiller, M; Kanske, P; Plewnia, C


Cortico-spinal activity evoked and modulated by non-invasive stimulation of the intact human motor cortex.

2014 Aug

A number of methods have been developed recently that stimulate the human brain non-invasively through the intact scalp. The most common are transcranial magnetic stimulation (TMS), transcranial electric stimulation (TES) and transcranial direct current stimulation (TDCS). They are widely used to probe function and connectivity of brain areas as well as therapeutically in a variety of conditions such as depression or stroke. They are much less focal than conventional invasive methods which use small electrodes placed on or in the brain and are often thought to activate all classes of neurones in the stimulated area. However, this is not true. A large body of evidence from experiments on the motor cortex shows that non-invasive methods of brain stimulation can be surprisingly selective and can activate different classes of inhibitory and excitatory inputs to the corticospinal output cells by adjusting the intensity and direction of stimulation. Here we review data that have explored the action of TMS and TES, concentrating mainly on the most direct evidence available from spinal epidural recordings of the descending corticospinal volleys. The results show that it is potentially possible to test and condition specific neural circuits in motor cortex that could potentially be affected differentially by disease, or be used in different forms of natural behaviour. However, there is substantial interindividual variability in the specificity of these protocols. Perhaps in the future it will be possible, with the advances currently being made to model the electrical fields induced in individual brains, to develop forms of stimulation that can reliably target more specific populations of neurones, and open up the internal circuitry of the motor cortex for study in behaving humans. This article is protected by copyright. All rights reserved.

The Journal of physiology

Di Lazzaro, V; Rothwell, JC


Assessment of non-BDNF neurotrophins and GDNF levels after depression treatment with sertraline and transcranial direct current stimulation in a factorial, randomized, sham-controlled trial (SELECT-TDCS): An exploratory analysis.

2014 Aug

The neurotrophic hypothesis of depression states that the major depressive episode is associated with lower neurotrophic factors levels, which increase with amelioration of depressive symptoms. However, this hypothesis has not been extended to investigate neurotrophic factors other than the brain-derived neurotrophic factor (BDNF). We therefore explored whether plasma levels of neurotrophins 3 (NT-3) and 4 (NT-4), nerve growth factor (NGF) and glial cell line derived neurotrophic factor (GDNF) changed after antidepressant treatment and correlated with treatment response. Seventy-three patients with moderate-to-severe, antidepressant-free unipolar depression were assigned to a pharmacological (sertraline) and a non-pharmacological (transcranial direct current stimulation, tDCS) intervention in a randomized, 2×2, placebo-controlled design. The plasma levels of NT-3, NT-4, NGF and GDNF were determined by enzyme-linked immunosorbent assay before and after a 6-week treatment course and analyzed according to clinical response and allocation group. We found that tDCS and sertraline (separately and combined) produced significant improvement in depressive symptoms. Plasma levels of all neurotrophic factors were similar across groups at baseline and remained significantly unchanged regardless of the intervention and of clinical response. Also, baseline plasma levels were not associated with clinical response. To conclude, in this 6-week placebo-controlled trial, NT-3, NT-4, NGF and GDNF plasma levels did not significantly change with sertraline or tDCS. These data suggest that these neurotrophic factors are not surrogate biomarkers of treatment response or involved in the antidepressant mechanisms of tDCS.

Progress in neuro-psychopharmacology & biological psychiatry

Brunoni, AR; Machado-Vieira, R; Zarate, CA; Vieira, EL; Valiengo, L; Benseñor, IM; Lotufo, PA; Gattaz, WF; Teixeira, AL


Neurostimulation for traumatic brain injury.

2014 Aug

Traumatic brain injury (TBI) remains a significant public health problem and is a leading cause of death and disability in many countries. Durable treatments for neurological function deficits following TBI have been elusive, as there are currently no FDA-approved therapeutic modalities for mitigating the consequences of TBI. Neurostimulation strategies using various forms of electrical stimulation have recently been applied to treat functional deficits in animal models and clinical stroke trials. The results from these studies suggest that neurostimulation may augment improvements in both motor and cognitive deficits after brain injury. Several studies have taken this approach in animal models of TBI, showing both behavioral enhancement and biological evidence of recovery. There have been only a few studies using deep brain stimulation (DBS) in human TBI patients, and future studies are warranted to validate the feasibility of this technique in the clinical treatment of TBI. In this review, the authors summarize insights from studies employing neurostimulation techniques in the setting of brain injury. Moreover, they relate these findings to the future prospect of using DBS to ameliorate motor and cognitive deficits following TBI.

Journal of neurosurgery

Shin, SS; Dixon, CE; Okonkwo, DO; Richardson, RM


Anodal motor cortex stimulation paired with movement repetition increases anterograde interference but not savings.

2014 Aug

Retention of motor adaptation is evident in savings, where initial learning improves subsequent learning, and anterograde interference, where initial learning impairs subsequent learning. Previously, we proposed that use-dependent movement biases induced by movement repetition contribute to anterograde interference, but not to savings. Here, we evaluate this proposal by limiting or extending movement repetition while stimulating the motor cortex (M1) with anodal transcranial direct current stimulation (tDCS), a brain stimulation technique known to increase use-dependent plasticity when applied during movement repetition. Participants first adapted to a counterclockwise rotation of visual feedback imposed either abruptly (extended repetition) or gradually (limited repetition) in a first block (A1), during which either sham or anodal tDCS (2 mA) was applied over M1. Anterograde interference was then assessed in a second block (B) with a clockwise rotation, and savings in a third block (A2) with a counterclockwise rotation. Anodal M1 tDCS elicited more anterograde interference than sham stimulation with extended but not with limited movement repetition. Conversely, anodal M1 tDCS did not affect savings with either limited or extended repetition of the adapted movement. Crucially, the effect of anodal M1 tDCS on anterograde interference did not require large errors evoked by an abrupt perturbation schedule, as anodal M1 tDCS combined with extended movement repetition within a gradual perturbation schedule similarly increased anterograde interference but not savings. These findings demonstrate that use-dependent plasticity contributes to anterograde interference but not to savings.

The European journal of neuroscience

Leow, LA; Hammond, G; de Rugy, A


Inhibitory Transcranial Direct Current Stimulation Enhances Weak Beta Event-Related Synchronization After Foot Motor Imagery in Patients with Lower Limb Amputation.

2014 Aug

Sensorimotor rhythm (SMR) patterns in patients with lower limb amputations might be altered due to reorganization of the sensorimotor cortices. We evaluated the SMR of motor imagery (MI) in healthy subjects and patients with lower limb amputations. In addition, we investigated whether transcranial direct current stimulation (tDCS) could modulate SMR control.Six healthy subjects and six patients with lower limb amputations were assigned to receive either anodal, cathodal, or sham tDCS over the foot motor area in a randomized order. We evaluated event-related desynchronization (ERD) and event-related synchronization (ERS) of unilateral hand and bilateral foot MI before and after tDCS.Beta ERS of foot MI in patients with lower limb amputations was significantly lesser than that in healthy subjects. Compared with sham stimulation, cathodal tDCS enhanced beta ERS of foot MI in patients with lower limb amputations. In contrast, anodal tDCS decreased beta ERS of foot MI in healthy subjects.This is the first study to demonstrate that cathodal tDCS can enhance a weak beta ERS of foot MI in patients with lower limb amputations. These findings might contribute in improving the effectiveness of SMR-based brain computer interface for gait restoration after lower limb amputation.

Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society

Takeuchi, N; Mori, T; Nishijima, K; Kondo, T; Izumi, SI


Direct current brain stimulation enhances navigation efficiency in individuals with low spatial sense of direction.

2014 Aug

The aim of this study was to evaluate the influence of right versus left temporal transcranial direct current stimulation (tDCS) on navigation efficiency and spatial memory in individuals with low versus high spatial skills. A mixed design administered low (0.5 mA) versus high (2.0 mA) anodal tDCS (within-participants) over the right or the left temporal lobe (between-participants), centered at electrode site T8 (right) or T7 (left). During stimulation, participants navigated virtual environments in search of specified landmarks, and data were logged in terms of current position and heading over time. Following stimulation, participants completed pointing and map-drawing spatial memory tests. Individual differences in sense of direction reliably and inversely predicted navigation advantages in the 2.0 versus 0.5 mA right hemisphere stimulation condition (R=0.45, P<0.01); in other words, individuals with lower sense of direction showed increased navigation efficiency in the 2.0 versus 0.5 mA condition. Spatial memory tests also showed the development of relatively comprehensive spatial memories: bidimensional regression indicated lower distortion in sketch maps drawn following 2.0 versus 0.5 mA right temporal lobe stimulation (F=8.7, P<0.05). Data provide the first demonstration that right temporal anodal tDCS may hold potential for enhancing navigation efficiency in otherwise poor navigators. Data support neuroimaging studies showing the engagement of right temporal brain regions in developing and applying spatial memories during complex navigation tasks, and uniquely suggest that continuing research may find value in optimizing stimulation parameters (intensity, focality) as a function of individual differences.

Neuroreport

Brunyé, TT; Holmes, A; Cantelon, J; Eddy, MD; Gardony, AL; Mahoney, CR; Taylor, HA


Using noninvasive brain stimulation to accelerate learning and enhance human performance.

2014 Aug

The authors evaluate the effectiveness of noninvasive brain stimulation, in particular, transcranial direct current stimulation (tDCS), for accelerating learning and enhancing human performance on complex tasks.Developing expertise in complex tasks typically requires extended training and practice. Neuroergonomics research has suggested new methods that can accelerate learning and boost human performance. TDCS is one such method. It involves the application of a weak DC current to the scalp and has the potential to modulate brain networks underlying the performance of a perceptual, cognitive, or motor task.Examples of tDCS studies of declarative and procedural learning are discussed. This mini-review focuses on studies employing complex simulations representative of surveillance and security operations, intelligence analysis, and procedural learning in complex monitoring.The evidence supports the view that tDCS can accelerate learning and enhance performance in a range of complex cognitive tasks. Initial findings also suggest that such benefits can be retained over time, but additional research is needed on training schedules and transfer of training.Noninvasive brain stimulation can accelerate skill acquisition in complex tasks and may provide an alternative or addition to other training methods.

Human factors

Parasuraman, R; McKinley, RA


Electrified emotions: Modulatory effects of transcranial direct stimulation on negative emotional reactions to social exclusion.

2014 Aug

Social exclusion, ostracism, and rejection can be emotionally painful because they thwart the need to belong. Building on studies suggesting that the right ventrolateral prefrontal cortex (rVLPFC) is associated with regulation of negative emotions, the present experiment tests the hypothesis that decreasing the cortical excitability of the rVLPFC may increase negative emotional reactions to social exclusion. Specifically, we applied cathodal transcranial direct current stimulation (tDCS) over the rVLPFC and predicted an increment of negative emotional reactions to social exclusion. In Study 1, participants were either socially excluded or included, while cathodal tDCS or sham stimulation was applied over the rVLPFC. Cathodal stimulation of rVLPFC boosted the typical negative emotional reaction caused by social exclusion. No effects emerged from participants in the inclusion condition. To test the specificity of tDCS effects over rVLPFC, in Study 2, participants were socially excluded and received cathodal tDCS or sham stimulation over a control region (i.e., the right posterior parietal cortex). No effects of tDCS stimulation were found. Our results showed that the rVLPFC is specifically involved in emotion regulation and suggest that cathodal stimulation can increase negative emotional responses to social exclusion.

Social neuroscience

Riva, P; Romero Lauro, LJ; Vergallito, A; DeWall, CN; Bushman, BJ


Transcranial electrical brain stimulation modulates neuronal tuning curves in perception of numerosity and duration.

2014 Aug

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method with many putative applications and reported to effectively modulate behaviour. However, its effects have yet to be considered at a computational level. To address this we modelled the tuning curves underlying the behavioural effects of stimulation in a perceptual task. Participants judged which of the two serially presented images contained more items (numerosity judgement task) or was presented longer (duration judgement task). During presentation of the second image their posterior parietal cortices (PPCs) were stimulated bilaterally with opposite polarities for 1.6s. We also examined the impact of three stimulation conditions on behaviour: anodal right-PPC and cathodal left-PPC (rA-lC), reverse order (lA-rC) and no-stimulation condition. Behavioural results showed that participants were more accurate in numerosity and duration judgement tasks when they were stimulated with lA-rC and rA-lC stimulation conditions respectively. Simultaneously, a decrease in performance on numerosity and duration judgement tasks was observed when the stimulation condition favoured the other task. Thus, our results revealed a double-dissociation of laterality and task. Importantly, we were able to model the effects of stimulation on behaviour. Our computational modelling showed that participants' superior performance was attributable to a narrower tuning curve - smaller standard deviation of detection noise. We believe that this approach may prove useful in understanding the impact of brain stimulation on other cognitive domains.

NeuroImage

Javadi, AH; Brunec, IK; Walsh, V; Penny, WD; Spiers, HJ

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Transcranial direct current stimulation modulates ERP-indexed inhibitory control and reduces food consumption.

2014 Aug

Food craving can be defined as the "urge to eat a specific food". Previous findings suggest impairment of inhibitory control, specifically a regulatory deficit in the lateral prefrontal circuitry that is associated with a compulsion for food. As demonstrated by three previous studies, bilateral transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) (anode right/cathode left) reduces food craving and caloric intake. We designed the present study to evaluate the neural mechanisms that underlie these effects. We replicated the design of one of these previous studies but included electroencephalographic assessments to register evoked potentials in a Go/No-go task that contained pictures of food and furniture (a control visual stimulus). We collected data from nine women (mean age = 23.4 ± 2 years) in a crossover experiment. We observed that active DLPFC tDCS (anode right/cathode left), compared with sham stimulation, reduced the frontal N2 component and enhanced the P3a component of responses to No-go stimuli, regardless of the stimulus condition (food or furniture). Active tDCS was also associated with a reduction in caloric intake. We discuss our findings in the context of cortico-subcortical processing of craving and tDCS effects on inhibitory control neural circuitry.

Appetite

Lapenta, OM; Sierve, KD; de Macedo, EC; Fregni, F; Boggio, PS


The Role of the Occipital Face Area in Holistic Processing Involved in Face Detection and Discrimination: A tDCS Study.

2014 Aug

Objective: The aim of this study was to examine the role of occipital face area (OFA) in mediating observers' tendency to perceive faces as "wholes" (holistic processing) both when detecting and discriminating faces. To investigate this issue, we modulated OFA activity using transcranial direct current stimulation (tDCS). Method: In Experiment 1, participants performed a face detection task (the Mooney faces task) and a face discrimination task (the Composite faces task), which both assess holistic face processing. In Experiment 2, participants were asked to detect both Mooney faces and Mooney objects, to test face selectivity of OFA. In each experimental session, the tasks were presented once before (pre) and once after (post) administration of 20 min of excitability increasing anodal tDCS (real) and sham stimulation over the putative OFA. Results: Compared with sham stimulation, we found that real anodal tDCS interfered with both Mooney faces and objects detection, whereas it had no effect on holistic processing involved in face discrimination, as measured by the Composite faces task. Conclusions: Our results suggest that OFA is causally implicated in facial detection at least in degraded conditions (i.e., when the "face" signal needs to be extracted from a noisy background). In turn, our data do not implicate OFA in holistic processing in face discrimination. Finally, our data suggest a possible role of OFA in categorization of other nonface stimuli, a conclusion that must be taken with caution, as stimulation over OFA may affect object-selective adjacent regions. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Neuropsychology

Renzi, C; Ferrari, C; Schiavi, S; Pisoni, A; Papagno, C; Vecchi, T; Antal, A; Cattaneo, Z


Time up and go task performance improves after transcranial direct current stimulation in patient affected by Parkinson's disease.

2014 Aug

Locomotor disturbances represent one of the major distress in everyday life in people with Parkinson's disease (PD). Timed up and go test (TUG) has been advocated a useful and reliable tool for quantifying locomotor performance. The aim of this study was to assess the effect of anodal transcranial direct current stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) during timed up and go test (TUG) in a group of patients with PD. Ten participants underwent two sessions of anodal tDCS (left and right) and one session of placebo tDCS. TUG was performed before and after each tDCS session (anodal or placebo). A significant motor improvement after right DLPFC stimulation vs. placebo stimulation was observed. These results suggest that anodal tDCS can be a relevant tool to modulate walking abilities in PD.

Neuroscience letters

Manenti, R; Brambilla, M; Rosini, S; Orizio, I; Ferrari, C; Borroni, B; Cotelli, M


The role of the superior temporal lobe in auditory false perceptions: A transcranial direct current stimulation study.

2014 Aug

Neuroimaging has shown that a network of cortical areas, which includes the superior temporal gyrus, is active during auditory verbal hallucinations (AVHs). In the present study, healthy, non-hallucinating participants (N=30) completed an auditory signal detection task, in which participants were required to detect a voice in short bursts of white noise, with the variable of interest being the rate of false auditory verbal perceptions. This paradigm was coupled with transcranial direct current stimulation, a noninvasive brain stimulation technique, to test the involvement of the left posterior superior temporal gyrus in the creation of auditory false perceptions. The results showed that increasing the levels of excitability in this region led to a higher rate of 'false alarm' responses than when levels of excitability were decreased, with false alarm responses under a sham stimulation condition lying at a mid-point between anodal and cathodal stimulation conditions. There were also corresponding changes in signal detection parameters. These results are discussed in terms of prominent cognitive neuroscientific theories of AVHs, and potential future directions for research are outlined.

Neuropsychologia

Moseley, P; Fernyhough, C; Ellison, A

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Dosage-dependent effect of dopamine d2 receptor activation on motor cortex plasticity in humans.

2014 Aug

The neuromodulator dopamine plays an important role in synaptic plasticity. The effects depend on receptor subtypes, affinity, concentration level, and the kind of neuroplasticity induced. In animal experiments, dopamine D2-like receptor stimulation revealed partially antagonistic effects on plasticity, which might be explained by dosage dependency. In humans, D2 receptor block abolishes plasticity, and the D2/D3, but predominantly D3, receptor agonist ropinirol has a dosage-dependent nonlinear affect on plasticity. Here we aimed to determine the specific affect of D2 receptor activation on neuroplasticity in humans, because physiological effects of D2 and D3 receptors might differ. Therefore, we combined application of the selective D2 receptor agonist bromocriptine (2.5, 10, and 20 mg or placebo medication) with anodal and cathodal transcranial direct current stimulation (tDCS), which induces nonfocal plasticity, and with paired associative stimulation (PAS) generating a more focal kind of plasticity in the motor cortex of healthy humans. Plasticity was monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. For facilitatory tDCS, bromocriptine prevented plasticity induction independent from drug dosage. However, its application resulted in an inverted U-shaped dose-response curve on inhibitory tDCS, excitability-diminishing PAS, and to a minor degree on excitability-enhancing PAS. These data support the assumption that modulation of D2-like receptor activity exerts a nonlinear dose-dependent effect on neuroplasticity in the human motor cortex that differs from predominantly D3 receptor activation and that the kind of plasticity-induction procedure is relevant for its specific impact.

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

Fresnoza, S; Stiksrud, E; Klinker, F; Liebetanz, D; Paulus, W; Kuo, MF; Nitsche, MA


Repetitive electric brain stimulation reduces food intake in humans.

2014 Aug

The dorsolateral prefrontal cortex (DLPFC) plays an important role in appetite and food intake regulation.Because previous data revealed that transcranial direct current stimulation (tDCS) of the DLPFC reduces food cravings, we hypothesized that repetitive electric stimulation of the right DLPFC would lower food intake behavior in humans.In a single-blind, code-based, placebo-controlled, counterbalanced, randomized crossover experiment, 14 healthy young men with BMI (in kg/m(2)) from 20 to 25 were examined during 8 d of daily tDCS or a sham stimulation. After tDCS or sham stimulation on the first and the last day of both experimental conditions, participants consumed food ad libitum from a standardized test buffet.One week of daily anodal tDCS reduced overall caloric intake by 14% in comparison with sham stimulation. Moreover, repetitive tDCS diminished self-reported appetite scores.Our study implies that the application of anodal direct currents to the right DLPFC represents a promising option for reducing both caloric intake and appetite in humans. This trial was registered at the German Clinical Trials Register as DRKS00005811.

The American journal of clinical nutrition

Jauch-Chara, K; Kistenmacher, A; Herzog, N; Schwarz, M; Schweiger, U; Oltmanns, KM


Presynaptic actions of transcranial and local direct current stimulation in the red nucleus.

2014 Aug

The main aim of the present study was to examine to what extent long-lasting subcortical actions of transcranial direct current stimulation (tDCS) may be related to its presynaptic actions. This was investigated in the red nucleus, where tDCS was recently demonstrated to facilitate transmission between interpositorubral and rubrospinal neurons. Changes in the excitability of preterminal axonal branches of interpositorubral neurons close to rubrospinal neurons were investigated during and after tDCS (0.2 mA) applied over the sensorimotor cortical area in deeply anaesthetized rats and cats. As a measure of the excitability, we used the probability of antidromic activation of individual interpositorubral neurons by electrical stimuli applied in the red nucleus. Our second aim was to compare effects of weak (≤1 μA) direct current applied within the red nucleus with effects of tDCS to allow the use of local depolarization in a further analysis of mechanisms of tDCS instead of widespread and more difficult to control depolarization evoked by distant electrodes. Local cathodal polarization was found to replicate all effects of cathodal tDCS hitherto demonstrated in the rat, including long-lasting facilitation of trans-synaptically evoked descending volleys and trisynaptically evoked EMG responses in neck muscles. It also replicated all effects of anodal tDCS in the cat. In both species, it increased the excitability of preterminal axonal branches of interpositorubral neurons up to 1 h post-tDCS. Local anodal polarization evoked opposite effects. We thus show that presynaptic actions of polarizing direct current may contribute to both immediate and prolonged effects of tDCS.

The Journal of physiology

Bączyk, M; Jankowska, E


The role of language in multi-dimensional categorization: Evidence from transcranial direct current stimulation and exposure to verbal labels.

2014 Aug

Human concepts differ in their dimensionality. Some, like green-things, require representing one dimension while abstracting over many others. Others, like bird, have higher dimensionality due to numerous category-relevant properties (feathers, two-legs). Converging evidence points to the importance of verbal labels for forming low-dimensional categories. We examined the role of verbal labels in categorization by (1) using transcranial direct current stimulation over Wernicke's area (2) providing explicit verbal labels during a category learning task. We trained participants on a novel perceptual categorization task in which categories could be distinguished by either a uni- or bi-dimensional criterion. Cathodal stimulation over Wernicke's area reduced reliance on single-dimensional solutions, while presenting informationally redundant novel labels reduced reliance on the dimension that is normally incidental in the real world. These results provide further evidence that implicit and explicit verbal labels support the process of human categorization.

Brain and language

Perry, LK; Lupyan, G


Transcranial direct current stimulation of the premotor cortex: Effects on hand dexterity.

2014 Aug

Premotor cortex activity is associated with complex motor performance and motor learning and offers a potential target to improve dexterity by transcranial direct current stimulation (tDCS). We explored the effects of tDCS of premotor cortex on performance of a Strength-Dexterity test in healthy subjects.During the test a slender spring held between thumb and index finger should be compressed as much as possible without buckling. Finger forces assessed in the test provided a measure of dexterity. First, task performance was tested in 12 persons during anodal tDCS to the primary motor cortex (M1) contralateral to the performing hand, and sham stimulation. Another 12 persons participated in five sessions of anodal and cathodal tDCS over the left and the right premotor cortex and sham stimulation.tDCS over M1 as well as over the left, but not the right premotor cortex resulted in significant improvement of performance. Performance alterations correlated positively between left anodal and right cathodal tDCS and negatively between anodal tDCS of the two sides. Effective polarity for premotor stimulation to improve task performance differed between participants. Individuals who improved with anodal stimulation used lower finger force and experienced the test as more difficult compared to those who improved with cathodal stimulation.This study demonstrates that tDCS over the left premotor cortex can improve performance of a dexterity demanding task. The effective polarity of stimulation depends on the task performance strategies. The study moreover shows a functional relevance of interactions between the left and right premotor cortex.

Brain research

Pavlova, E; Kuo, MF; Nitsche, MA; Borg, J


Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists.

2014 Aug

Two neuromodulatory techniques based on applying direct current (DC) non-invasively through the skin, transcranial cerebellar direct current stimulation (tDCS) and transcutaneous spinal DCS, can induce prolonged functional changes consistent with a direct influence on the human cerebellum and spinal cord. In this article we review the major experimental works on cerebellar tDCS and on spinal tDCS, and their preliminary clinical applications. Cerebellar tDCS modulates cerebellar motor cortical inhibition, gait adaptation, motor behaviour, and cognition (learning, language, memory, attention). Spinal tDCS influences the ascending and descending spinal pathways, and spinal reflex excitability. In the anaesthetised mouse, DC stimulation applied under the skin along the entire spinal cord may affect GABAergic and glutamatergic systems. Preliminary clinical studies in patients with cerebellar disorders, and in animals and patients with spinal cord injuries, have reported beneficial effects. Overall the available data show that cerebellar tDCS and spinal tDCS are two novel approaches for inducing prolonged functional changes and neuroplasticity in the human cerebellum and spinal cord, and both are new tools for experimental and clinical neuroscientists.

The Journal of physiology

Priori, A; Ciocca, M; Parazzini, M; Vergari, M; Ferrucci, R


Multiple sclerosis fatigue relief by bilateral somatosensory cortex neuromodulation.

2014 Aug

Multiple sclerosis-related fatigue is highly common and often refractory to medical therapy. Ten fatigued multiple sclerosis patients received two blocks of 5-day anodal bilateral primary somatosensory areas transcranial direct current stimulation in a randomized, double-blind sham-controlled, cross-over study. The real neuromodulation by a personalized electrode, shaped on the MR-derived primary somatosensory cortical strip, reduced fatigue in all patients, by 26 % in average (p = 0.002), which did not change after sham (p = 0.901). Anodal tDCS over bilateral somatosensory areas was able to relief fatigue in mildly disabled MS patients, when the fatigue-related symptoms severely hamper their quality of life. These small-scale study results support the concept that interventions modifying the sensorimotor network activity balances could be a suitable non-pharmacological treatment for multiple sclerosis fatigue.

Journal of neurology

Tecchio, F; Cancelli, A; Cottone, C; Zito, G; Pasqualetti, P; Ghazaryan, A; Rossini, PM; Filippi, MM


Facilitation of ipsilateral actions of corticospinal tract neurons on feline motoneurons by transcranial direct current stimulation.

2014 Aug

Ipsilateral actions of pyramidal tract (PT) neurons are weak but may, if strengthened, compensate for deficient crossed PT actions following brain damage. The purpose of the present study was to examine whether transcranial direct current stimulation (tDCS) can strengthen ipsilateral PT (iPT) actions; in particular, those relayed by reticulospinal neurons co-excited by axon collaterals of fibres descending in the iPT and contralateral PT (coPT) and of reticulospinal neurons descending in the medial longitudinal fascicle (MLF). The effects of tDCS were assessed in acute experiments on deeply anaesthetized cats by comparing postsynaptic potentials evoked in hindlimb motoneurons and discharges recorded from their axons in a ventral root, before, during and after tDCS. tDCS was consistently found to facilitate joint actions of the iPT and coPT, especially when they were stimulated together with the MLF. Both excitatory postsynaptic potentials and inhibitory postsynaptic potentials evoked in motoneurons and the ensuing ventral root discharges were facilitated, even though the facilitatory effects of tDCS were not sufficient for activation of motoneurons by iPT neurons alone. Facilitation outlasted single tDCS periods by at least a few minutes, and the effects evoked by repeated tDCS by up to 2 h. The results of this study thus indicate that tDCS may increase the contribution of iPT actions to the recovery of motor functions after injuries to coPT neurons, and thereby assist rehabilitation, provided that corticoreticular and reticulospinal connections are preserved.

The European journal of neuroscience

Bączyk, M; Pettersson, LG; Jankowska, E


Neuromodulation of parietal and motor activity affects motor planning and execution.

2014 Aug

Transcranial direct current stimulation (tDCS) is a non-invasive tool, which effectively modulates behavior, and related brain activity. When applied to the primary motor cortex (M1), tDCS affects motor function, enhancing or decreasing performance of both healthy participants and brain-damaged patients. Beyond M1, the posterior parietal cortex (PPC) is also crucially involved in controlling and guiding movement. Therefore, we explored whether the modulation of cortical excitability within PPC can also affect hand motor function in healthy right-handed participants. In Experiment 1, anodal tDCS (2 mA, 10 min) was applied to PPC and to M1 of both hemispheres. Skilled motor function of the non-dominant left hand, measured using the Jebsen-Taylor Hand Function Test (JTT), improved after anodal tDCS of the right, contralateral M1, as well as after the anodal stimulation of the left, ipsilateral PPC. Conversely, in Experiment 2, cathodal tDCS of the left PPC, or of the right M1, reduced motor performance of the left hand. Finally, Experiment 3 shows that the anodal tDCS of the left PPC selectively facilitated action planning, while the anodal tDCS of the right M1 modulated action execution only. This evidence shows that motor improvement induced by left parietal and right motor stimulations relies on substantial different mechanisms, opening up novel perspectives in the neurorehabilitation of stroke patients with motor and apraxic disorders.

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

Convento, S; Bolognini, N; Fusaro, M; Lollo, F; Vallar, G


Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and subcortical reward systems: a tDCS-fMRI study.

2014 Aug

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task-related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task-related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole-brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole-brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes.

Human brain mapping

Weber, MJ; Messing, SB; Rao, H; Detre, JA; Thompson-Schill, SL


Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task.

2014 Aug

The aim of this study was to test the hypothesis that dual-hemisphere transcranial direct current stimulation (tDCS) over the primary somatosensory cortex (S1) could improve performance in a tactile spatial discriminative task, compared with uni-hemisphere or sham tDCS.Nine healthy adults participated in this double-blind, sham-controlled, and cross-over design study. The performance in a grating orientation task (GOT) in the right index finger was evaluated before, during, immediately after and 30min after the dual-hemisphere, uni-hemisphere (1mA, 20min), or sham tDCS (1mA, 30s) over S1. In the dual-hemisphere and sham conditions, anodal tDCS was applied over the left S1, and cathodal tDCS was applied over the right S1. In the uni-hemisphere condition, anodal tDCS was applied over the left S1, and cathodal tDCS was applied over the contralateral supraorbital front.The percentage of correct responses on the GOT during dual-hemisphere tDCS was significantly higher than that in the uni-hemisphere or sham tDCS conditions when the grating width was set to 0.75mm (all p<0.05).Dual-hemisphere tDCS over S1 improved performance in a tactile spatial discrimination task in healthy volunteers.Dual-hemisphere tDCS may be a useful strategy to improve sensory function in patients with sensory dysfunctions.

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

Fujimoto, S; Yamaguchi, T; Otaka, Y; Kondo, K; Tanaka, S


Transcranial electrical stimulation modifies the neuronal response to psychosocial stress exposure.

2014 Aug

Stress is a constant characteristic of everyday life in our society, playing a role in triggering several chronic disorders. Therefore, there is an ongoing need to develop new methods in order to manage stress reactions. The regulatory function of right medial-prefrontal cortex (mPFC) is frequently reported by imaging studies during psychosocial stress situations. Here, we examined the effects of inhibitory and excitatory preconditioning stimulation via cathodal and anodal transcranial direct current stimulation (tDCS) on psychosocial stress related behavioral indicators and physiological factors, including the cortisol level in the saliva and changes in brain perfusion. Twenty minutes real or sham tDCS was applied over the right mPFC of healthy subjects before the performance of the Trier Social Stress Test (TSST). Regional cerebral blood flow (rCBF) was measured during stimulation and after TSST, using pseudo-continuous arterial spin labeling (pCASL). Comparing the effect of the different stimulation conditions, during anodal stimulation we found higher rCBF in the right mPFC, compared to the sham and in the right amygdala, superior PFC compared to the cathodal condition. Salivary cortisol levels showed a decrease in the anodal and increase in cathodal groups after completion of the TSST. The behavioral stress indicators indicated the increase of stress level, however, did not show any significant differences among groups. In this study we provide the first insights into the neuronal mechanisms mediating psychosocial stress responses by prefrontal tDCS.

Human brain mapping

Antal, A; Fischer, T; Saiote, C; Miller, R; Chaieb, L; Wang, DJ; Plessow, F; Paulus, W; Kirschbaum, C


Cathodal and anodal left prefrontal tDCS and the perception of control over pain.

2014 Aug

The prefrontal cortex may be a promising target for the use of transcranial direct current stimulation (tDCS) in the management of pain symptoms. The present study explored the effects of anodal and cathodal tDCS over the left dorsolateral prefrontal cortex on the effects of perceived pain controllability.Forty-one participants received continuous anodal or cathodal tDCS and underwent a laboratory pain task designed to manipulate the perception of pain control. Participants were told that they would be completing a reaction-time task (press keyboard button of corresponding arrow shown on computer screen with either green or red background). A thermal pain stimulus was delivered following each trial by a thermode placed on the participant's left forearm. Although pain stimuli were pseudorandomally ordered and matched for total duration between control (green) and noncontrol (red) trials, participants were told that if they responded correctly and more quickly on green trials than their average reaction times, the thermal pain stimulus duration would be decreased (ie, perceived control). Participants were told they had no control of pain stimulus duration over trials presented with the red background.There was a significant main effect for tDCS condition (anode vs. cathode) on pain unpleasantness ratings (P<0.04). Specifically, individuals receiving cathodal tDCS reported higher pain unpleasantness ratings (least squares mean=69.40, SE=3.72), whereas those receiving anodal tDCS reported lower pain unpleasantness ratings (least squares mean=58.05, SE=3.81). Exploratory analysis revealed a simple main effect for tDCS group at the level of perceived controllability (P<0.02). In addition, participants receiving cathodal tDCS subjectively reported feeling less control of the painful stimuli than those receiving anodal tDCS.Left dorsolateral prefrontal cortex tDCS may play a role in modulating the neurocircuitry involved with the perception of control over pain.

The Clinical journal of pain

Naylor, JC; Borckardt, JJ; Marx, CE; Hamer, RM; Fredrich, S; Reeves, ST; George, MS


The Effects of Anodal Stimulation of the Left Prefrontal Cortex on Sentence Production.

2014 Jul

Most studies in which Anodal Transcranial Direct Current Stimulation (A-tDCS) has been used to improve language production have focused on single words. Yet sentence production requires more than lexical retrieval. For example, successful suppression of the past and careful planning of the future are two critical requirements for producing a correct sentence. Can A-tDCS improves those, and by extension, production at the sentence level?Given that many aspects of sentence production beyond word retrieval require frontally-mediated operations, we hypothesized that A-tDCS to the left prefrontal cortex should benefit various operation involved in producing sentences, two of which, suppression of the past and planning of the future, were targeted in this study.We used a paradigm that elicited construction of sentences through event description, but was structured enough to allow for between-subject comparison, clear error identification, and implementation of experimental manipulations to probe certain aspects of production.We showed that A-tDCS to the left PFC reliably decreased the number of incomplete and errorful sentences. When the origin of this improvement was probed, we found that A-tDCS significantly decreased errors due to premature commitment to the future word (insufficient internal monitoring), and had a marginal effect on errors of perseverations (insufficient suppression of the past).We conclude that A-tDCS is a promising tool for improving production at the sentence level, and that improvement can be expected when internal monitoring and control over verbal responses is impaired, or for certain cases of perseveratory errors.

Brain stimulation

Nozari, N; Arnold, JE; Thompson-Schill, SL


tDCS modulates cortical nociceptive processing but has little to no impact on pain perception.

2014 Jul

Transcranial direct current stimulation (tDCS) effectively modulates cortical excitability. Several studies suggest clinical efficacy in chronic pain syndromes. However, little is known regarding its effects on cortical pain processing. In this double-blind, randomized, cross-over, sham controlled study, we examined the effects of anodal, cathodal, and sham stimulation of the left motor cortex in 16 healthy volunteers using functional imaging during an acute heat pain paradigm as well as pain thresholds, pain intensity ratings, and quantitative sensory testing. tDCS was applied at 1mA for 15minutes. Neither cathodal nor anodal tDCS significantly changed brain activation in response to nociceptive stimulation when compared with sham stimulation. However, contrasting the interaction of stimulation modes (anodal/cathodal) resulted in a significant decrease of activation in the hypothalamus, inferior parietal cortex, inferior parietal lobule, anterior insula, and precentral gyrus, contralateral to the stimulation site after anodal stimulation, which showed the opposite behavior after cathodal stimulation. Pain ratings and heat hyperalgesia showed only a subclinical pain reduction after anodal tDCS. Larger-scale clinical trials using higher tDCS intensities or longer durations are necessary to assess the neurophysiological effect and subsequently the therapeutic potential of tDCS.

Pain

Ihle, K; Rodriguez-Raecke, R; Luedtke, K; May, A


Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex modulates early affective processing.

2014 Jul

The dorsolateral prefrontal cortex (dlPFC) has often been suggested as a key modulator of emotional stimulus appraisal and regulation. Therefore, in clinical trials, it is one of the most frequently targeted regions for non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS). In spite of various encouraging reports that demonstrate beneficial effects of rTMS in anxiety disorders, psychophysiological studies exploring the underlying neural mechanisms are sparse. Here we investigated how inhibitory rTMS influences early affective processing when applied over the right dlPFC. Before and after rTMS or sham stimulation, subjects viewed faces with fearful or neutral expressions while whole-head magnetoencephalography (MEG) was recorded. Due to the disrupted functioning of the right dlPFC, visual processing in bilateral parietal, temporal, and occipital areas was amplified starting at around 90ms after stimulus onset. Moreover, increased fear-specific activation was found in the right TPJ area in a time-interval between 110 and 170ms. These neurophysiological effects were reflected in slowed reaction times for fearful, but not for neutral faces in a facial expression identification task while there was no such effect on a gender discrimination control task. Our study confirms the specific and important role of the dlPFC in regulation of early emotional attention and encourages future clinical research to use minimal invasive methods such as transcranial magnetic (TMS) or direct current stimulation (tDCS).

NeuroImage

Zwanzger, P; Steinberg, C; Rehbein, MA; Bröckelmann, AK; Dobel, C; Zavorotnyy, M; Domschke, K; Junghöfer, M


Comparison of Cephalic and Extracephalic Montages for Transcranial Direct Current Stimulation - A Numerical Study.

2014 Jul

While studies have shown that the application of Transcranial Direct Current Stimulation (tDCS) has been beneficial in the stimulation of cortical activity and treatment of neurological disorders in humans, open questions remain regarding the placement of electrodes for optimal targeting of currents for a given functional area. Given the difficulty of obtaining in vivo measurements of current density, modeling of conventional and alternative electrode montages via the Finite Element Method (FEM) has been utilized to provide insight into tDCS montage performance. It has been shown that extracephalic montages might create larger total current densities in deeper brain regions, specifically in white matter as compared to an equivalent cephalic montage. Extracephalic montages might also create larger average vertical current densities in the primary motor cortex and in the somatosensory cortex. At the same time, the horizontal current density either remains approximately the same or decreases. The metrics used in this paper include either the total local current density through the entire brain volume or the average vertical current density as well as the average horizontal current density for every individual lobe/cortex.

IEEE transactions on bio-medical engineering

Noetscher, G; Yanamadala, J; Makarov, S; Pascual-Leone, A


Comparison of the Effects of Transcranial Random Noise Stimulation and Transcranial Direct Current Stimulation on Motor Cortical Excitability.

2014 Jul

The objective of this study was to examine the effect of transcranial random noise stimulation (tRNS) with and without a direct current (DC) offset on motor cortical excitability and compare results to transcranial DC stimulation (tDCS).Fifteen healthy participants were tested in a within-subjects design. Motor-evoked potentials were measured before and up to 90 minutes after stimulation using transcranial magnetic stimulation. Five stimulation conditions were examined: sham, 1-mA tDCS, 2-mA tDCS, 2-mA tRNS (with no DC offset), and 2-mA tRNS + 1-mA DC offset.There were no significant differences between the stimulation conditions. An analysis of individual stimulation conditions found that there was a significant increase in motor-evoked potential amplitudes after 1-mA tDCS, 2-mA tDCS, and 2-mA tRNS + DC offset when compared with baseline. Sham and 2-mA tRNS did not result in changes in cortical excitability.Although differences between the stimulation conditions did not reach a statistical significance, the findings suggest that stimulation involving a DC (tDCS and tRNS + DC offset) but not solely tRNS is more likely to lead to increases in cortical excitability.

The journal of ECT

Ho, KA; Taylor, JL; Loo, CK


A randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence.

2014 Jul

Preliminary small studies have shown that transcranial direct current stimulation (tDCS) reduces craving in alcoholic subjects. It is unclear whether tDCS also leads to changes in clinically meaningful outcomes for alcohol dependence in a properly powered phase II randomized clinical trial. We aimed to investigate whether repetitive tDCS changes the risk of alcohol use relapse in severe alcoholics from outpatient services. Thirty-five subjects were randomized to receive active bilateral [left cathodal/right anodal over the dorsolateral prefrontal cortex (dlPFC)] repetitive (five consecutive days) tDCS (2 mA, 35 cm2, two times daily stimulation for 13 min with a 20-min interval) or sham-tDCS. There were two dropouts before treatment. From 33 alcoholic subjects, 17 (mean age 45.5 ± 8.9 s.d., 16 males) were randomized to sham and 16 (44 ± 7.8 s.d., 16 males) to real tDCS treatment. By the end of the six months of follow-up, two subjects treated with sham (11.8%) and eight treated with real tDCS (50%) were still alcohol-abstinent [p = 0.02, Long-rank (Mantel-Cox) Test, HR = 0.35 (95% CI, 0.14-0.85)]. No differences with regard to changes on scores of craving, frontal function, global mental status, depressive or anxiety symptoms were observed between groups. However, subjects from the tDCS group improved with regard to their overall perception of quality of life (p = 0.02), and increased their scores in the environment domain (p = 0.04) after treatment. Bilateral tDCS over dlPFC reduces relapse probability in severe alcoholic subjects and results in improved perception of quality of life.

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

Klauss, J; Penido Pinheiro, LC; Silva Merlo, BL; Correia Santos, GD; Fregni, F; Nitsche, MA; Miyuki Nakamura-Palacios, E


Use of transcranial direct current stimulation (tDCS) to enhance cognitive training: effect of timing of stimulation.

2014 Jul

The capacity for transcranial direct current stimulation (tDCS) to increase learning and cognition shows promise for the development of enhanced therapeutic interventions. One potential application is the combination of tDCS with cognitive training (CT), a psychological intervention which aims to improve targeted cognitive abilities. We have previously shown that tDCS enhanced performance accuracy, but not skill acquisition, on a dual n-back working memory (WM) CT task over repeated sessions. In the current study, we investigated the optimal timing for combining tDCS with the same CT task to enhance within and between session performance outcomes across two daily CT sessions. Twenty healthy participants received in a randomised order 30 min of anodal tDCS to the left dorsolateral prefrontal cortex immediately before ('offline' tDCS) and during performance ('online' tDCS) on a dual n-back WM CT task, in an intra-individual crossover design. Analyses examined within and between session consolidation effects of tDCS on CT performance outcomes. Results showed that 'online' tDCS was associated with better within session skill acquisition on the CT task, with a significant difference found between conditions the following day. These results suggest that 'online' tDCS is superior to 'offline' tDCS for enhancing skill acquisition when combining anodal tDCS with CT. This finding may assist with the development of enhanced protocols involving the combination of tDCS with CT and other rehabilitation protocols.

Experimental brain research

Martin, DM; Liu, R; Alonzo, A; Green, M; Loo, CK


High-definition transcranial direct current stimulation induces both acute and persistent changes in broadband cortical synchronization: a simultaneous tDCS-EEG study.

2014 Jul

The goal of this study was to develop methods for simultaneously acquiring electrophysiological data during high-definition transcranial direct current stimulation (tDCS) using high-resolution electroencephalography (EEG). Previous studies have pointed to the after-effects of tDCS on both motor and cognitive performance, and there appears to be potential for using tDCS in a variety of clinical applications. However, little is known about the real-time effects of tDCS on rhythmic cortical activity in humans due to the technical challenges of simultaneously obtaining electrophysiological data during ongoing stimulation. Furthermore, the mechanisms of action of tDCS in humans are not well understood. We have conducted a simultaneous tDCS-EEG study in a group of healthy human subjects. Significant acute and persistent changes in spontaneous neural activity and event-related synchronization (ERS) were observed during and after the application of high-definition tDCS over the left sensorimotor cortex. Both anodal and cathodal stimulation resulted in acute global changes in broadband cortical activity which were significantly different than the changes observed in response to sham stimulation. For the group of eight subjects studied, broadband individual changes in spontaneous activity during stimulation were apparent both locally and globally. In addition, we found that high-definition tDCS of the left sensorimotor cortex can induce significant ipsilateral and contralateral changes in event-related desynchronization and ERS during motor imagination following the end of the stimulation period. Overall, our results demonstrate the feasibility of acquiring high-resolution EEG during high-definition tDCS and provide evidence that tDCS in humans directly modulates rhythmic cortical synchronization during and after its administration.

IEEE transactions on bio-medical engineering

Roy, A; Baxter, B; He, B


Modulation of smoking and decision-making behaviors with transcranial direct current stimulation in tobacco smokers: a preliminary study.

2014 Jul

Most tobacco smokers who wish to quit fail to reach their goal. One important, insufficiently emphasized aspect of addiction relates to the decision-making system, often characterized by dysfunctional cognitive control and a powerful drive for reward. Recent proof-of-principle studies indicate that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) can transiently modulate processes involved in decision-making, and reduce substance intake and craving for various addictions. We previously proposed that this beneficial effect of stimulation for reducing addictive behaviors is in part mediated by more reflective decision-making. The goal of this study was to test whether nicotine intake and decision-making behaviors are modulated by tDCS over the DLPFC in tobacco smokers who wished to quit smoking.Subjects received two five-day tDCS regimens (active or sham). Stimulation was delivered over the right DLPFC at a 2 mA during 30 min. Nicotine cravings, cigarette consumption and decision-making were assessed before and after each session.Main findings include a significant decrease in the number of cigarettes smoked when participants received active as compared to sham stimulation. This effect lasted up to four days after the end of the stimulation regimen. In regards to decision-making, smokers rejected more often offers of cigarettes, but not offers of money, after they received active as compared to sham stimulation at the Ultimatum Game. No significant change was observed at the Risk Task with cigarettes or money as rewards.Overall, these findings suggest that tDCS over the DLPFC may be beneficial for smoking reduction and induce reward sensitive effects.

Drug and alcohol dependence

Fecteau, S; Agosta, S; Hone-Blanchet, A; Fregni, F; Boggio, P; Ciraulo, D; Pascual-Leone, A


Understanding tDCS effects in schizophrenia: a systematic review of clinical data and an integrated computation modeling analysis.

2014 Jul

Although recent clinical studies using transcranial direct current stimulation (tDCS) for schizophrenia showed encouraging results, several tDCS montages were employed and their current flow pattern has not been investigated. We performed a systematic review to identify clinical tDCS studies in schizophrenia. We then applied computer head modeling analysis for prediction of current flow. Out of 41 references, we identified 12 relevant studies. The most employed montage was anode and cathode over the left dorsolateral prefrontal and temporoparietal cortex, respectively. Computational model analysis predicted activation and under-activation under the anode and the cathode, respectively, occurring in areas respectively associated with negative and positive symptoms. We also identified tDCS-induced electrical currents in cortical areas between the electrodes (frontoparietal network) and, to a lesser extent, in deeper structures involved in schizophrenia pathophysiology. Mechanisms of tDCS effects in schizophrenia and the usefulness of computer modeling techniques for planning tDCS trials in schizophrenia are discussed.

Expert review of medical devices

Brunoni, AR; Shiozawa, P; Truong, D; Javitt, DC; Elkis, H; Fregni, F; Bikson, M


Transcranial direct current stimulation of the frontal-parietal-temporal area attenuates smoking behavior.

2014 Jul

Many brain regions are involved in smoking addiction (e.g. insula, ventral tegmental area, prefrontal cortex and hippocampus), and the manipulation of the activity of these brain regions can show a modification of smoking behavior. Low current transcranial direct current stimulation (tDCS) is a noninvasive way to manipulate cortical excitability, and thus brain function and associated behaviors. In this study, we examined the effects of inhibiting the frontal-parietal-temporal association area (FPT) on attention bias to smoking-related cues and smoking behavior in tobacco users. This inhibition is induced by cathodal tDCS stimulation. We tested three stimulation conditions: 1) bilateral cathodal over both sides of FPT; 2) cathodal over right FPT; and 3) sham-tDCS. Visual attention bias to smoking-related cues was evaluated using an eye tracking system. The measurement for smoking behavior was the number of daily cigarettes consumed before and after tDCS treatment. We found that, after bilateral cathodal stimulation of the FPT area, while the attention to smoking-related cues showed a decreased trend, the effects were not significantly different from sham stimulation. The daily cigarette consumption was reduced to a significant level. These effects were not seen under single cathodal tDCS or sham-tDCS. Our results show that low current tDCS of FPT area attenuates smoking cue-related attention and smoking behavior. This non-invasive brain stimulation technique, targeted at FPT areas, might be a promising method for treating smoking behavior.

Journal of psychiatric research

Meng, Z; Liu, C; Yu, C; Ma, Y


BDNF plasma levels after antidepressant treatment with sertraline and transcranial direct current stimulation: results from a factorial, randomized, sham-controlled trial.

2014 Jul

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention that modifies cortical excitability according to the stimulation parameters. Preclinical and clinical studies in healthy volunteers suggest that tDCS induces neuroplastic alterations of cortical excitability, which might explain its clinical effects in major depressive disorder (MDD). We therefore examined whether tDCS, as compared to the antidepressant sertraline, increases plasma brain-derived neurotrophic factor (BDNF) levels, a neurotrophin associated with neuroplasticity. Patients (n=73) with major depressive disorder were randomized to active/sham tDCS and sertraline/placebo (four groups) in this 6-week, double-blind, placebo-controlled trial. We measured BDNF plasma levels at baseline and endpoint, observing no significant changes of BDNF levels after treatment. In addition, no significant changes were observed in responders and non-responders as well as no relationships between BDNF levels and clinical and psychopathological variables related to depression. Thus, in one of the few placebo-controlled trials evaluating BDNF changes over an antidepressant treatment course, we did not observe BDNF increase regardless of clinical improvement in depressed patients. Regarding tDCS, BDNF plasma levels might not be a good candidate biomarker to evaluate depression improvement or be a predictor of response in patients treated with tDCS, as our results showed that BDNF increase was not necessary to induce clinical response. Finally, our findings do not support a relationship between BDNF and improvement of depression.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Brunoni, AR; Machado-Vieira, R; Zarate, CA; Vieira, EL; Vanderhasselt, MA; Nitsche, MA; Valiengo, L; Benseñor, IM; Lotufo, PA; Gattaz, WF; Teixeira, AL


The effects of prefrontal cortex transcranial direct current stimulation (tDCS) on food craving and temporal discounting in women with frequent food cravings.

2014 Jul

Bulimia nervosa, binge-eating disorder, and some forms of obesity are characterised by compulsive overeating that is often precipitated by food craving. Transcranial direct current stimulation (tDCS) has been used to suppress food cravings, but there is insufficient evidence to support its application in clinical practice. Furthermore, the potential moderating role of impulsivity has not been considered. This study used a randomised within-subjects crossover design to examine whether a 20-minute session of sham-controlled bilateral tDCS to the dorsolateral prefrontal cortex (anode right/cathode left) would transiently modify food cravings and temporal discounting (TD; a measure of choice impulsivity) in 17 healthy women with frequent food cravings. Whether the effects of tDCS on food craving were moderated by individual differences in TD behaviour was also explored. Participants were exposed to food and a film of people eating, and food cravings and TD were assessed before and after active and sham stimulation. Craving for sweet but not savoury foods was reduced following real tDCS. Participants that exhibited more reflective choice behaviour were more susceptible to the anti-craving effects of tDCS than those that displayed more impulsive choice behaviour. No differences were seen in TD or food consumption after real versus sham tDCS. These findings support the efficacy of tDCS in temporarily lowering food cravings and identify the moderating role of TD behaviour.

Appetite

Kekic, M; McClelland, J; Campbell, I; Nestler, S; Rubia, K; David, AS; Schmidt, U


The effects of 1 Hz rTMS preconditioned by tDCS on gait kinematics in Parkinson's disease.

2014 Jul

Hypokinetic gait is a common and very disabling symptom of Parkinson's disease (PD). Repetitive transcranial magnetic stimulation (rTMS) over the motor cortex has been used with variable effectiveness to treat hypokinesia in PD. Preconditioning rTMS by transcranial direct current stimulation (tDCS) may enhance its effectiveness to treat hypokinetic gait in PD. Three-dimensional kinematic gait analysis was performed (1) prior to, (2) immediately after and (3) 30 min after low-frequency rTMS (1 Hz, 900 pulses, 80% of resting motor threshold) over M1 contralateral to the more affected body side preconditioned by (1) cathodal, (2) anodal or (3) sham tDCS (amperage: 1 mA, duration: 10 min) in ten subjects with PD (7 females, mean age 63 ± 9 years) and ten healthy subjects (four females, mean age 50 ± 11 years). The effects of tDCS-preconditioned rTMS on gait kinematics were assessed by the following parameters: number of steps, step length, stride length, double support time, cadence, swing and stance phases. Our data suggest a bilateral improvement of hypokinetic gait in PD after 1 Hz rTMS over M1 of the more affected body side preceded by anodal tDCS. In contrast, 1 Hz rTMS alone (preceded by sham tDCS) and 1 Hz rTMS preceded by cathodal tDCS were ineffective to improve gait kinematics in PD. In healthy subjects, gait kinematics was unaffected by either intervention. Preconditioning motor cortex rTMS by tDCS is a promising approach to treat hypokinetic gait in PD.

Journal of neural transmission (Vienna, Austria : 1996)

von Papen, M; Fisse, M; Sarfeld, AS; Fink, GR; Nowak, DA


Transcranial Direct Current Stimulation in de novo Artistic Ability After Stroke.

2014 Jul

Neuromodulation : journal of the International Neuromodulation Society

Simis, M; Bravo, GL; Boggio, PS; Devido, M; Gagliardi, RJ; Fregni, F


Interaction Between Different Interneuron Networks Involved in Human Associative Plasticity.

2014 Jun

Paired associative stimulation (PAS) is a widely used method to study spike timing dependent plasticity in motor cortex. Repeated pairing of an electrical stimulus to the median nerve with transcranial magnetic stimulation (TMS) over the contralateral motor cortex at interstimulus intervals (ISIs) of 21.5-25 ms leads to a long term potentiation (LTP)-like synaptic plasticity in the corticospinal system. Previously we found that concurrent transcranial direct current stimulation (TDCS) over cerebellum blocked the effect of PAS25 but not PAS21.5, implying that two separate mechanisms were involved.We hypothesized that if PAS21.5 and PAS25 increased corticospinal excitability by two entirely separate mechanisms then their effects might summate if we intermixed them in the same session.Twenty-four healthy volunteers were studied. Eight subjects were selected who showed the expected facilitation after both standard PAS21.5 and PAS25 with 180 pairs. They participated to two sessions in which PAS consisted of 360 electrical stimuli of the right median nerve paired with a single TMS over the hotspot of right APB at randomly delivered ISIs of 25 ms and of 21.5 ms (180 pairs for each ISI) (PASvar360p). Either sham or anodal TDCS (2 mA, 30 min) was applied to the cerebellum simultaneously with PASvar360p. Subsequently, we applied a protocol with 90 pairs for each ISI (PASvar180p). We measured motor evoked potentials (MEPs) before and after each intervention.Although PAS21.5 and PAS25 each produce corticospinal facilitation when applied alone, the after-effects disappeared if we randomly intermixed PAS21.5 and PAS25 using either 180 pairs (PASvar360p) or 90 pairs (PASvar180p) for each ISI. Facilitation is restored if anodal but not sham TDCS is applied concurrently over the cerebellum to block the effect of PAS25.PAS21.5 and PAS25 not only engage two separate mechanisms but also they are mutually inhibitory.

Brain stimulation

Strigaro, G; Hamada, M; Murase, N; Cantello, R; Rothwell, JC


Transcranial Direct Current Stimulation (TDCS) Improved Cognitive Outcomes in a Cancer Survivor With Chemotherapy-induced Cognitive Difficulties.

2014 Jun

Brain stimulation

Knotkova, H; Malamud, SC; Cruciani, RA


Skin Lesions Induced by Transcranial Direct Current Stimulation (tDCS).

2014 Jun

Brain stimulation

Rodríguez, N; Opisso, E; Pascual-Leone, A; Soler, MD


The effects of transcranial direct current stimulation in patients with neuropathic pain from spinal cord injury.

2014 Jun

Transcranial direct current stimulation (tDCS) has demonstrated efficacy for reducing neuropathic pain, but the respective mechanisms remain largely unknown. The current study tested the hypothesis that pain reduction with tDCS is associated with an increase in the peak frequency spectrum density in the theta-alpha range.Twenty patients with spinal cord injury and bilateral neuropathic pain received single sessions of both sham and anodal tDCS (2mA) over the left primary motor area (M1) for 20min. Treatment order was randomly assigned. Pre- to post-procedure changes in pain intensity and peak frequency of electroencephalogram spectral analysis were compared between treatment conditions.The active treatment condition (anodal tDCS over M1) but not sham treatment resulted in significant decreases in pain intensity. In addition, consistent with the study hypothesis, peak theta-alpha frequency (PTAF) assessed from an electrode placed over the site of stimulation increased more from pre- to post-session among participants in the active tDCS condition, relative to those in the sham tDCS condition. Moreover, we found a significant association between a decrease in pain intensity and an increase in PTAF at the stimulation site.The findings are consistent with the possibility that anodal tDCS over the left M1 may be effective, at least in part, because it results in an increase in M1 cortical excitability, perhaps due to a pain inhibitory effect of motor cortex stimulation that may influence the descending pain modulation system. Future research is needed to determine if there is a causal association between increased left anterior activity and pain reduction.The results provide new findings regarding the effects of tDCS on neuropathic pain and brain oscillation changes.

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

Ngernyam, N; Jensen, MP; Arayawichanon, P; Auvichayapat, N; Tiamkao, S; Janjarasjitt, S; Punjaruk, W; Amatachaya, A; Aree-Uea, B; Auvichayapat, P


Interhemispheric modulation of dual-mode, noninvasive brain stimulation on motor function.

2014 Jun

To investigate the effects of simultaneous, bihemispheric, dual-mode stimulation using repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on motor functions and cortical excitability in healthy individuals.Twenty-five healthy, right-handed volunteers (10 men, 15 women; mean age, 25.5 years) were enrolled. All participants received four randomly arranged, dual-mode, simultaneous stimulations under the following conditions: condition 1, high-frequency rTMS over the right primary motor cortex (M1) and sham tDCS over the left M1; condition 2, high-frequency rTMS over the right M1 and anodal tDCS over the left M1; condition 3, high-frequency rTMS over the right M1 and cathodal tDCS over the left M1; and condition 4, sham rTMS and sham tDCS. The cortical excitability of the right M1 and motor functions of the left hand were assessed before and after each simulation.Motor evoked potential (MEP) amplitudes after stimulation were significantly higher than before stimulation, under the conditions 1 and 2. The MEP amplitude in condition 2 was higher than both conditions 3 and 4, while the MEP amplitude in condition 1 was higher than condition 4. The results of the Purdue Pegboard test and the box and block test showed significant improvement in conditions 1 and 2 after stimulation.Simultaneous stimulation by anodal tDCS over the left M1 with high-frequency rTMS over the right M1 could produce interhemispheric modulation and homeostatic plasticity, which resulted in modulation of cortical excitability and motor functions.

Annals of rehabilitation medicine

Park, E; Kim, YH; Chang, WH; Kwon, TG; Shin, YI

Link to full article text


The Role of Contact Media at the Skin-electrode Interface During Transcranial Direct Current Stimulation (tDCS).

2014 Jun

Brain stimulation

Palm, U; Feichtner, KB; Hasan, A; Gauglitz, G; Langguth, B; Nitsche, MA; Keeser, D; Padberg, F


Ipsilesional and contralesional regions participate in the improvement of poststroke aphasia: a transcranial direct current stimulation study.

2014 Jun

In the past few years, noninvasive cerebral stimulations have been used to modulate language task performance in healthy and aphasic patients. In this study, a dual transcranial direct current stimulation (tDCS) on anterior and posterior language areas was applied for 2 weeks to a patient with a possible crossed aphasia following a right hemisphere stroke. Inhibitory cathodal stimulation of the right Brodmann areas (BA) 44/45 and simultaneous anodal stimulation of the left BA 44/45 improved the patient's performance in picture naming. Conversely, the same bilateral montage on BA 39/40 did not produce any significant improvement; finally, electrode polarity inversion over BA 39/40 yielded a further improvement compared with the first anterior stimulation. Our findings suggest that ipsilesional and contralesional areas could be useful in poststroke functional reorganization and provide new evidences for the therapeutic value of tDCS in aphasia.

Neurocase

Costa, V; Giglia, G; Brighina, F; Indovino, S; Fierro, B


Rethinking Stimulation of the Brain in Stroke Rehabilitation: Why Higher Motor Areas Might Be Better Alternatives for Patients with Greater Impairments.

2014 Jun

Stimulating the brain to drive its adaptive plastic potential is promising to accelerate rehabilitative outcomes in stroke. The ipsilesional primary motor cortex (M1) is invariably facilitated. However, evidence supporting its efficacy is divided, indicating that we may have overgeneralized its potential. Since the M1 and its corticospinal output are frequently damaged in patients with serious lesions and impairments, ipsilesional premotor areas (PMAs) could be useful alternates instead. We base our premise on their higher probability of survival, greater descending projections, and adaptive potential, which is causal for recovery across the seriously impaired. Using a conceptual model, we describe how chronically stimulating PMAs would strongly affect key mechanisms of stroke motor recovery, such as facilitating the plasticity of alternate descending output, restoring interhemispheric balance, and establishing widespread connectivity. Although at this time it is difficult to predict whether PMAs would be "better," it is important to at least investigate whether they are reasonable substitutes for the M1. Even if the stimulation of the M1 may benefit those with maximum recovery potential, while that of PMAs may only help the more disadvantaged, it may still be reasonable to achieve some recovery across the majority rather than stimulate a single locus fated to be inconsistently effective across all.

The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry

Plow, EB; Cunningham, DA; Varnerin, N; Machado, A


Cumulative effects of transcranial direct current stimulation on EEG oscillations and attention/working memory during subacute neurorehabilitation of traumatic brain injury.

2014 Jun

To investigate in a randomized, double-blind design, cumulative effects of anodal tDCS on EEG oscillations and neuropsychological tests among patients with traumatic brain injury (TBI) undergoing subacute neurorehabilitation.Twenty-six patients were randomly assigned to active (n=13) or sham (n=13) tDCS groups. EEGs were recorded at 6 different time points, assessing both immediate and cumulative effects of tDCS on EEG oscillations. Twenty minute sessions of 1mA anodal stimulation to the left dorsolateral prefrontal cortex (F3, cathode placed at right supraorbital site, Fp2), were provided on 10 consecutive days. Neuropsychological tests were administered before and after the series of tDCS sessions.Theta was significantly reduced for active tDCS patients following the first tDCS session. Delta decreased and alpha increased, both significantly, for the active tDCS group after 10 consecutive tDCS sessions. No significant changes were seen for sham group. Decreases in delta were significantly correlated with improved performance on neuropsychological tests for the active tDCS group to far greater degree than for the sham group. Participants in the active tDCS group who had excess slow EEG activity in their initial recordings showed greater improvement on neuropsychological tests than other groups.Results suggest that 10 anodal tDCS sessions may beneficially modulate regulation of cortical excitability for patients with TBI.EEG-guided tDCS warrants further investigation as a potential intervention for TBI during subacute neurorehabilitation.

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

Ulam, F; Shelton, C; Richards, L; Davis, L; Hunter, B; Fregni, F; Higgins, K


Hemodynamic responses in rat brain during transcranial direct current stimulation: a functional near-infrared spectroscopy study.

2014 Jun

In the present study, we monitored hemodynamic responses in rat brains during transcranial direct current stimulation (tDCS) using functional near-infrared spectroscopy (fNIRS). Seven rats received transcranial anodal stimulation with 200 μA direct current (DC) on their right barrel cortex for 10 min. The concentration changes of oxygenated hemoglobin (oxy-Hb) were continuously monitored during stimulation (10 min) and after stimulation (20 min). The trend of hemodynamic response changes was modeled using linear regression, and the relationship between incremental and decremental rates of oxy-Hb was investigated by correlation analysis. Our results showed that the oxy-Hb concentration was almost linearly increased and decreased during and after stimulation, respectively. In addition, a significant negative correlation (p < 0.05) was found between the rate of increase of oxy-Hb during stimulation and the rate of decrease of oxy-Hb after stimulation, indicating that the recovery time after tDCS may not depend on the total amount of hemodynamic changes in the stimulated brain area. Our results also demonstrated considerable individual variability in the rate of change of hemodynamic responses even with the same direct current dose to identical brain regions. This suggests that individual differences in tDCS after-effects may originate from intrinsic differences in the speed of DC stimulation "uptake" rather than differences in the total capacity of DC uptake, and thus the stimulation parameters may need to be customized for each individual in order to maximize tDCS after-effects.

Biomedical optics express

Han, CH; Song, H; Kang, YG; Kim, BM; Im, CH

Link to full article text


The contribution of dorsolateral prefrontal cortex and temporoparietal areas in processing instrumental versus functional semantic violations in action representation.

2014 Jun

In the present study, we explored the contribution of different cortical areas in processing different semantic violations in action representation-that is, instrumental or functional violations. The cortical contribution in object-related action comprehension was verified by measuring changes in event-related potential (N400 effect), error rates (ERs), and response times (RTs), by applying an inhibitory transcranial direct current stimulation (tDCS) on the dorsolateral prefrontal cortex (DLPFC). Thirty-three subjects performed the detection task (action frames ending with a congruous vs. incongruous action). The tDCS effect was analyzed by comparing the N400, ERs, and RTs before and after stimulation. A significant reduction of the N400 and increased RTs were observed for incongruous stimuli in the case of inhibitory stimulation of the DLPFC. These results highlighted that DLPFC inhibition may limit the ability to analyze a semantically incongruous action, with a reduced N400 ERP effect and increased "cognitive costs" (higher RTs). Moreover, functional violation showed also the contribution of the temporoparietal areas to modulate the N400 amplitude. Therefore the existence of different cortical generators was supposed for the instrumental (more frontal) and the functional (more frontal and temporoparietal) semantic anomaly processing.

Journal of clinical and experimental neuropsychology

Balconi, M; Canavesio, Y


ANODAL TRANSCRANIAL DIRECT CURRENT STIMULATION OF THE MOTOR CORTEX INDUCES OPPOSITE MODULATION OF RECIPROCAL INHIBITION IN WRIST EXTENSOR AND FLEXOR.

2014 Jun

Transcranial direct current stimulation (tDCS) is used as a non-invasive tool to modulate brain excitability in humans. Recently, several studies have demonstrated that tDCS applied over the motor cortex also modulates spinal neural network excitability and therefore, can be used to explore the corticospinal control acting on spinal neurones. Previously, we showed that reciprocal inhibition directed to wrist flexor motoneurones is enhanced during contralateral anodal tDCS, but it is likely that corticospinal control acting on spinal networks controlling wrist flexors and extensors is not similar. The primary aim of the study was to explore the effects of anodal tDCS on reciprocal inhibition directed to wrist extensor motoneurones. To further examine the supraspinal control acting on the reciprocal inhibition between wrist flexors and extensors, we also explored the effects of the tDCS applied to the ipsilateral hand motor area. In healthy volunteers, we tested the effects induced by sham and anodal tDCS on reciprocal inhibition pathways innervating wrist muscles. Reciprocal inhibition directed from flexor to extensor muscles and the reverse situation, i.e. reciprocal inhibition, directed from extensors to flexors were studied in parallel using the H reflex technique.Our main finding was that contralateral anodal tDCS induces opposing effects on reciprocal inhibition: it decreases reciprocal inhibition directed from flexors to extensors but it increases reciprocal inhibition directed from extensors to flexors. The functional result of these opposite effects on reciprocal inhibition seems to favour wrist extension excitability suggesting an asymmetrical descending control onto the interneurones that mediate reciprocal inhibition.

Journal of neurophysiology

Lackmy-Vallée, A; Klomjai, W; Bussel, B; Katz, R; Roche, N


EEG mean frequency changes in healthy subjects during prefrontal transcranial direct current stimulation (tDCS).

2014 Jun

In this pilot study we evaluated electroencephalographic (EEG) mean frequency changes induced by prefrontal transcranial direct current stimulation (tDCS) and investigated whether they depended on tDCS electrode montage. Eight healthy volunteers underwent tDCS for 15 minutes during EEG recording. They completed six tDCS sessions, one week apart, testing left and right direct current (DC) dipole directions with six different montages: four unipolar montages (one electrode on a prefrontal area, the other on the opposite wrist) and two bipolar montages (both electrodes on prefrontal areas), and a single sham session. EEG power spectra were assessed from four one-minute EEG epochs, before, during and after tDCS. During tDCS the outcome variable, brain rate (fb), changed significantly, and the changes persisted for minutes after tDCS ended. With the DC dipole directed to the left (anode on the left prefrontal area or wrist) fb increased, with the DC dipole directed to the right (anode on the right prefrontal area or wrist) fb decreased, suggesting asymmetric prefrontal cortex functional organization in the normal human brain. Anodal and cathodal effects were opposite but equally large. Gender left these effect unchanged.

Journal of neurophysiology

Accornero, N; Capozza, M; Pieroni, L; Pro, S; Davì, L; Mecarelli, O


Transcranial Direct Current Stimulation to Primary Motor Area Improves Hand Dexterity and Selective Attention in Chronic Stroke.

2014 Jun

The aim of this study was to determine whether transcranial direct current stimulation (tDCS) applied to the primary motor hand area modulates hand dexterity and selective attention after stroke.This study was a double-blind, placebo-controlled, randomized crossover trial involving subjects with chronic stroke. Ten stroke survivors with some pinch strength in the paretic hand received three different tDCS interventions assigned in random order in separate sessions-anodal tDCS targeting the primary motor area of the lesioned hemisphere (M1lesioned), cathodal tDCS applied to the contralateral hemisphere (M1nonlesioned), and sham tDCS-each for 20 mins. The primary outcome measures were Purdue pegboard test scores for hand dexterity and response time in the color-word Stroop test for selective attention. Pinch strength of the paretic hand was the secondary outcome.Cathodal tDCS to M1nonlesioned significantly improved affected hand dexterity (by 1.1 points on the Purdue pegboard unimanual test, P = 0.014) and selective attention (0.6 secs faster response time on the level 3 Stroop interference test for response inhibition, P = 0.017), but not pinch strength. The outcomes were not improved with anodal tDCS to M1lesioned or sham tDCS.Twenty minutes of cathodal tDCS to M1nonlesioned can promote both paretic hand dexterity and selective attention in people with chronic stroke.

American journal of physical medicine & rehabilitation / Association of Academic Physiatrists

Au-Yeung, SS; Wang, J; Chen, Y; Chua, E


Effect of the Nicotinic α4β2-receptor Partial Agonist Varenicline on Non-invasive Brain Stimulation-Induced Neuroplasticity in the Human Motor Cortex.

2014 Jun

Nicotine alters cognitive functions in animals and humans most likely by modification of brain plasticity. In the human brain, it alters plasticity induced by transcranial direct current stimulation (tDCS) and paired associative stimulation (PAS), probably by interference with calcium-dependent modulation of the glutamatergic system. We aimed to test this hypothesis further by exploring the impact of the α4β2-nicotinic receptor partial agonist varenicline on focal and non-focal plasticity, induced by PAS and tDCS, respectively. We administered low (0.1 mg), medium (0.3 mg), and high (1.0 mg) single doses of varenicline or placebo medication before PAS or tDCS on the left motor cortex of 25 healthy non-smokers. Corticospinal excitability was monitored by single-pulse transcranial magnetic stimulation-induced motor evoked potential amplitudes up to 36 h after plasticity induction. Whereas low-dose varenicline had no impact on stimulation-induced neuroplasticity, medium-dose abolished tDCS-induced facilitatory after-effects, favoring focal excitatory plasticity. High-dose application preserved cathodal tDCS-induced excitability diminution and focal excitatory PAS-induced facilitatory plasticity. These results are comparable to the impact of nicotine receptor activation and might help to further explain the involvement of specific receptor subtypes in the nicotinic impact on neuroplasticity and cognitive functions in healthy subjects and patients with neuropsychiatric diseases.

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

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


Effects of anodal TDCS stimulation of left parietal cortex on visual spatial attention tasks in men and women across menstrual cycle.

2014 Jun

Sex hormonal variations have been shown to affect functional cerebral asymmetries in cognitive domains, contributing to sex-related differences in functional cerebral organization. The aim of this study was to investigate spatial attention by means of a bisection line test and computer-supported attention task during the menstrual cycle in healthy women compared to men, in basal condition and under Transcranial Direct Current Stimulation (TDCS) of the left parietal cortex. Women were studied during the menses, follicular and luteal phases, ascertained by transvaginal ultrasounds. In basal conditions, women showed a clear deviation toward the right in the bisection line test during the menstrual phase, similarly to men. The midpoint recognition in the computer-supported attention task was not influenced by the menstrual cycle for women, while men showed a significant increase in errors toward the left side. The anodal activation of the left parietal cortex did not affect the line bisection task, while in men it reduced the total amount of errors in midpoint recognition observed in the computer supported attention task. The hand-use effect demonstrated by the bisection-line test could be influenced by estrogen fluctuations, while the right hemisphere prevalence in spatial attention appears to be gender-related and scarcely influenced by the menstrual cycle. The left parietal cortex seems to exert a scarce effect on hand-use effect, while its activation is able to revert sex related right hemisphere supremacy.

Neuroscience letters

de Tommaso, M; Invitto, S; Ricci, K; Lucchese, V; Delussi, M; Quattromini, P; Bettocchi, S; Pinto, V; Lancioni, G; Livrea, P; Cicinelli, E


Cognitive control therapy and transcranial direct current stimulation for depression: a randomized, double-blinded, controlled trial.

2014 Jun

Based on findings that major depressive disorder (MDD) is associated to decreased dorsolateral prefrontal cortical (DLPFC) activity; interventions that increase DLPFC activity might theoretically present antidepressant effects. Two of them are cognitive control therapy (CCT), a neurocognitive intervention that uses computer-based working memory exercises, and transcranial direct current stimulation (tDCS), which delivers weak, electric direct currents over the scalp.We investigated whether tDCS enhanced the effects of CCT in a double-blind trial, in which participants were randomized to sham tDCS and CCT (n=17) vs. active tDCS and CCT (n=20). CCT and tDCS were applied for 10 consecutive workdays. Clinicaltrials.gov identifier: NCT01434836.Both CCT alone and combined with tDCS ameliorated depressive symptoms after the acute treatment period and at follow-up, with a response rate of approximately 25%. Older patients and those who presented better performance in the task throughout the trial (possibly indicating greater engagement and activation of the DLPFC) had greater depression improvement in the combined treatment group.Our exploratory findings should be further confirmed in prospective controlled trials.CCT and tDCS combined might be beneficial for older depressed patients, particularly for those who have cognitive resources to adequately learn and improve task performance over time. This combined therapy might be specifically relevant in this subgroup that is more prone to present cognitive decline and prefrontal cortical atrophy.

Journal of affective disorders

Brunoni, AR; Boggio, PS; De Raedt, R; Benseñor, IM; Lotufo, PA; Namur, V; Valiengo, LC; Vanderhasselt, MA


The value and cost of complexity in predictive modelling: role of tissue anisotropic conductivity and fibre tracts in neuromodulation.

2014 Jun

Computational methods are increasingly used to optimize transcranial direct current stimulation (tDCS) dose strategies and yet complexities of existing approaches limit their clinical access. Since predictive modelling indicates the relevance of subject/pathology based data and hence the need for subject specific modelling, the incremental clinical value of increasingly complex modelling methods must be balanced against the computational and clinical time and costs. For example, the incorporation of multiple tissue layers and measured diffusion tensor (DTI) based conductivity estimates increase model precision but at the cost of clinical and computational resources. Costs related to such complexities aggregate when considering individual optimization and the myriad of potential montages. Here, rather than considering if additional details change current-flow prediction, we consider when added complexities influence clinical decisions.Towards developing quantitative and qualitative metrics of value/cost associated with computational model complexity, we considered field distributions generated by two 4 × 1 high-definition montages (m1 = 4 × 1 HD montage with anode at C3 and m2 = 4 × 1 HD montage with anode at C1) and a single conventional (m3 = C3-Fp2) tDCS electrode montage. We evaluated statistical methods, including residual error (RE) and relative difference measure (RDM), to consider the clinical impact and utility of increased complexities, namely the influence of skull, muscle and brain anisotropic conductivities in a volume conductor model.Anisotropy modulated current-flow in a montage and region dependent manner. However, significant statistical changes, produced within montage by anisotropy, did not change qualitative peak and topographic comparisons across montages. Thus for the examples analysed, clinical decision on which dose to select would not be altered by the omission of anisotropic brain conductivity.Results illustrate the need to rationally balance the role of model complexity, such as anisotropy in detailed current flow analysis versus value in clinical dose design. However, when extending our analysis to include axonal polarization, the results provide presumably clinically meaningful information. Hence the importance of model complexity may be more relevant with cellular level predictions of neuromodulation.

Journal of neural engineering

Shahid, SS; Bikson, M; Salman, H; Wen, P; Ahfock, T


A dissociation between propriospinal facilitation and inhibition after bilateral transcranial direct current stimulation.

2014 Jun

Propriospinal premotoneurons (PN) are essential for accurate control of the upper limb. They receive bilateral input from premotor (PM) and primary motor (M1) cortices. In humans, excitability of PNs can be estimated from motor-evoked potentials (MEPs) by pairing a descending volley using transcranial magnetic stimulation (TMS) to summate with an ascending volley from peripheral nerve stimulation at the C3-C4 level of the spinal cord. Transcranial direct current stimulation (tDCS) alters excitability of cortical and subcortical areas. A recent study demonstrated that cathodal tDCS can suppress facilitatory (FAC) and inhibitory (INH) components of PN excitability, presumably via effects on corticoreticulospinal neurons (Bradnam LV, Stinear CM, Lewis GN, Byblow WD. J Neurophysiol 103: 2382-2389, 2010). The present study investigated the effects of bilateral tDCS with healthy subjects. The cathode was placed over left dorsal PM or M1 and the anode over right M1 in separate sessions (PM-M1, M1-M1, or Sham). TMS of right M1 elicited MEPs in left biceps brachii across a range of TMS intensities chosen to examine PN-mediated FAC and INH. Conditioning was applied using median nerve stimulation with an interstimulus interval that coincided with TMS and peripheral volleys summating at the C3-C4 level. All participants showed FAC at TMS intensities near active motor threshold and INH at slightly higher intensities. After tDCS, FAC was reduced for M1-M1 compared with Sham but not after PM-M1 stimulation. Contrary to an earlier study with cathodal tDCS, INH was unchanged across all sessions. The difference between these and earlier findings may relate to dual- vs. single-hemisphere M1 stimulation. M1-M1 tDCS may be a useful adjuvant to techniques that aim to reduce upper limb impairment after stroke.

Journal of neurophysiology

McCambridge, AB; Stinear, JW; Byblow, WD


The effect of transcranial direct current stimulation on experimentally induced heat pain.

2014 Jun

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory technique that can affect human pain perception. Placebo effects are present in most treatments and could therefore also interact with treatment effects in tDCS. The present study investigated whether short-term tDCS reduced heat pain intensity, stress, blood pressure and increased heat pain thresholds in healthy volunteers when controlling for placebo effects. Seventy-five (37 females) participants were randomized into three groups: (1) active tDCS group receiving anodal tDCS (2 mA) for 7 min to the primary motor cortex (M1), (2) placebo group receiving the tDCS electrode montage but only active tDCS stimulation for 30 s and (3) natural history group that got no tDCS montage but the same pain stimulation as the active tDCS and the placebo group. Heat pain was induced by a PC-controlled thermode attached to the left forearm. Pain intensity was significantly lower in the active tDCS group when examining change scores (pretest-posttest) for the 47 °C condition. The placebo group displayed lower pain compared with the natural history group, displaying a significant placebo effect. In the 43 and 45 °C conditions, the effect of tDCS could not be separated from placebo effects. The results revealed no effects on pain thresholds. There was a tendency that active tDCS reduced stress and systolic blood pressure, however, not significant. In sum, tDCS had an analgesic effect on high-intensity pain, but the effect of tDCS could not be separated from placebo effects for medium and low pain.

Experimental brain research

Aslaksen, PM; Vasylenko, O; Fagerlund, AJ


Does prefrontal cortex transcranial direct current stimulation influence the oxygen uptake at rest and post-exercise?

2014 Jun

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


The effect of anodal transcranial direct current stimulation over the primary motor or somatosensory cortices on somatosensory evoked magnetic fields.

2014 May

The purpose of this study was to investigate the effect of anodal transcranial direct-current stimulation (tDCS) applied over the primary motor (M1) or the primary somatosensory (S1) cortices on somatosensory evoked magnetic fields (SEFs) following median nerve stimulation.Anodal tDCS was applied for 15min on the left motor or somatosensory cortices at 1mA. SEFs were recorded following right median nerve stimulation using a magnetoencephalography (MEG) system before and after the application of tDCS. SEFs was measured and compared before and after tDCS was applied over M1 or S1.The source strengths for the P35m and P60m increased after tDCS was applied over M1 and that for the P60m increased after tDCS was applied over S1. The mean equivalent current dipole (ECD) location for the P35m was located significantly anterior to that of the N20m, but only during post 1 (10-20min after tDCS was applied over M1).Our results indicated that the anodal tDCS applied over M1 affected the P35m and P60m sources on SEF components, while that applied over S1 influenced the P60m source.We demonstrated anodal tDCS applied over M1 or S1 can modulate somatosensory processing and components of SEFs, confirming the hypothesis for locally distinct generators of the P35m and P60m sources.

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

Sugawara, K; Onishi, H; Yamashiro, K; Kojima, S; Miyaguchi, S; Kirimoto, H; Tsubaki, A; Tamaki, H; Shirozu, H; Kameyama, S


The rising tide of tDCS in the media and academic literature.

2014 May

Academic and public interest in tDCS has been fueled by strong claims of therapeutic and enhancement effects. We report a rising tide of tDCS coverage in the media, while regulatory action is lacking and ethical issues need to be addressed.

Neuron

Dubljević, V; Saigle, V; Racine, E


Combining physical training with transcranial direct current stimulation to improve gait in Parkinson's disease: a pilot randomized controlled study.

2014 May

To improve gait and balance in patients with Parkinson's disease by combining anodal transcranial direct current stimulation with physical training.In a double-blind design, one group (physical training; n = 8) underwent gait and balance training during transcranial direct current stimulation (tDCS; real/sham). Real stimulation consisted of 15 minutes of 2 mA transcranial direct current stimulation over primary motor and premotor cortex. For sham, the current was switched off after 30 seconds. Patients received the opposite stimulation (sham/real) with physical training one week later; the second group (No physical training; n = 8) received stimulation (real/sham) but no training, and also repeated a sequential transcranial direct current stimulation session one week later (sham/real).Hospital Srio Libanes, Buenos Aires, Argentina.Sixteen community-dwelling patients with Parkinson's disease.Transcranial direct current stimulation with and without concomitant physical training.Gait velocity (primary gait outcome), stride length, timed 6-minute walk test, Timed Up and Go Test (secondary outcomes), and performance on the pull test (primary balance outcome).Transcranial direct current stimulation with physical training increased gait velocity (mean = 29.5%, SD = 13; p < 0.01) and improved balance (pull test: mean = 50.9%, SD = 37; p = 0.01) compared with transcranial direct current stimulation alone. There was no isolated benefit of transcranial direct current stimulation alone. Although physical training improved gait velocity (mean = 15.5%, SD = 12.3; p = 0.03), these effects were comparatively less than with combined tDCS + physical therapy (p < 0.025). Greater stimulation-related improvements were seen in patients with more advanced disease.Anodal transcranial direct current stimulation during physical training improves gait and balance in patients with Parkinson's disease. Power calculations revealed that 14 patients per treatment arm (α = 0.05; power = 0.8) are required for a definitive trial.

Clinical rehabilitation

Kaski, D; Dominguez, R; Allum, J; Islam, A; Bronstein, A


State dependent effect of transcranial direct current stimulation (tDCS) on methamphetamine craving.

2014 May

Transcranial direct current stimulation (tDCS) has been shown to modulate subjective craving ratings in drug dependents by modification of cortical excitability in dorsolateral prefrontal cortex (DLPFC). Given the mechanism of craving in methamphetamine (meth) users, we aimed to test whether tDCS of DLPFC could also alter self-reported craving in abstinent meth users while being exposed to meth cues. In this double-blinded, crossover, sham-controlled study, thirty two right-handed abstinent male meth users were recruited. We applied 20 min 'anodal' tDCS (2 mA) or 'sham' tDCS over right DLPFC in a random sequence while subjects performed a computerized cue-induced craving task (CICT) starting after 10 min of stimulation. Immediate craving was assessed before the stimulation, after 10 min of tDCS, and after tDCS termination by visual analog scale (VAS) of 0 to 100. Anodal tDCS of rDLPFC altered craving ratings significantly. We found a significant reduction of craving at rest in real tDCS relative to the sham condition (p = 0.016) after 10 min of stimulation. On the other hand, cue-induced VAS craving was rated significantly higher in the real condition in comparison with sham stimulation (p = 0.012). Our findings showed a state dependent effect of tDCS: while active prefrontal tDCS acutely reduced craving at rest in the abstinent meth users, it increased craving during meth-related cue exposure. These findings reflect the important role of the prefrontal cortex in both cue saliency evaluation and urge to meth consumption.

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

Shahbabaie, A; Golesorkhi, M; Zamanian, B; Ebrahimpoor, M; Keshvari, F; Nejati, V; Fregni, F; Ekhtiari, H


Visualizing Simulated Electrical Fields from Electroencephalography and Transcranial Electric Brain Stimulation: A Comparative Evaluation.

2014 May

Electrical activity of neuronal populations is a crucial aspect of brain activity. This activity is not measured directly but recorded as electrical potential changes using head surface electrodes (electroencephalogram - EEG). Head surface electrodes can also be deployed to inject electrical currents in order to modulate brain activity (transcranial electric stimulation techniques) for therapeutic and neuroscientific purposes. In electroencephalography and noninvasive electric brain stimulation, electrical fields mediate between electrical signal sources and regions of interest (ROI). These fields can be very complicated in structure, and are influenced in a complex way by the conductivity profile of the human head. Visualization techniques play a central role to grasp the nature of those fields because such techniques allow for an effective conveyance of complex data and enable quick qualitative and quantitative assessments. The examination of volume conduction effects of particular head model parameterizations (e.g., skull thickness and layering), of brain anomalies (e.g., holes in the skull, tumors), location and extent of active brain areas (e.g., high concentrations of current densities) and around current injecting electrodes can be investigated using visualization. Here, we evaluate a number of widely used visualization techniques, based on either the potential distribution or on the current-flow. In particular, we focus on the extractability of quantitative and qualitative information from the obtained images, their effective integration of anatomical context information, and their interaction. We present illustrative examples from clinically and neuroscientifically relevant cases and discuss the pros and cons of the various visualization techniques.

NeuroImage

Eichelbaum, S; Dannhauer, M; Hlawitschka, M; Brooks, D; Knösche, TR; Scheuermann, G


Human memory retrieval and inhibitory control in the brain: beyond correlational evidence.

2014 May

Retrieving information from long-term memory can result in the episodic forgetting of related material. One influential account states that this retrieval-induced forgetting (RIF) phenomenon reflects inhibitory mechanisms called into play to decrease retrieval competition. Recent neuroimaging studies suggested that the prefrontal cortex, which is critically engaged in inhibitory processing, is also involved in retrieval competition situations. Here, we used transcranial direct current stimulation (tDCS) to address whether inhibitory processes could be causally linked to RIF. tDCS was administered over the right dorsolateral prefrontal cortex during the retrieval-practice phase in a standard retrieval-practice paradigm. Sixty human participants were randomly assigned to anodal, cathodal, or sham-control groups. The groups showed comparable benefits for practiced items. In contrast, unlike both the sham and anodal groups, the cathodal group exhibited no RIF. This pattern is interpreted as evidence for a causal role of inhibitory mechanisms in episodic retrieval and forgetting.

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

Penolazzi, B; Stramaccia, DF; Braga, M; Mondini, S; Galfano, G


Investigation of Central Nervous System Dysfunction in Chronic Pelvic Pain Using Magnetic Resonance Spectroscopy and Noninvasive Brain Stimulation.

2014 May

Recent studies demonstrate that chronic pelvic pain is associated with altered afferent sensory input resulting in maladaptive changes in the neural circuitry of pain. To better understand the central changes associated with chronic pelvic pain, we investigated the contributions of critical pain-related neural circuits using single-voxel proton magnetic resonance spectroscopy (MRS) and transcranial direct current stimulation (tDCS).We measured concentrations of neural metabolites in 4 regions of interest (thalamus, anterior cingulate cortex, primary motor, and occipital cortex [control]) at baseline and after 10 days of active or sham tDCS in patients with chronic pelvic pain. We then compared our results to those observed in healthy controls, matched by age and gender.We observed a significant increase in pain thresholds after active tDCS compared with sham conditions. There was a correlation between metabolite concentrations at baseline and quantitative sensory assessments. Chronic pelvic pain patients had significantly lower levels of NAA/Cr in the primary motor cortex compared with healthy patients.tDCS increases pain thresholds in patients with chronic pelvic pain. Biochemical changes in pain-related neural circuits are associated with pain levels as measured by objective pain testing. These findings support the further investigation of targeted cortical neuromodulatory interventions for chronic pelvic pain.

Pain practice : the official journal of World Institute of Pain

Simis, M; Reidler, JS; Duarte Macea, D; Moreno Duarte, I; Wang, X; Lenkinski, R; Petrozza, JC; Fregni, F


Simulating transcranial direct current stimulation with a detailed anisotropic human head model.

2014 May

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique able to induce long-lasting changes in cortical excitability that can benefit cognitive functioning and clinical treatment. In order to both better understand the mechanisms behind tDCS and possibly improve the technique, finite element models are used to simulate tDCS of the human brain. With the detailed anisotropic head model presented in this study, we provide accurate predictions of tDCS in the human brain for six of the practically most-used setups in clinical and cognitive research, targeting the primary motor cortex, dorsolateral prefrontal cortex, inferior frontal gyrus, occipital cortex, and cerebellum. We present the resulting electric field strengths in the complete brain and introduce new methods to evaluate the effectivity in the target area specifically, where we have analyzed both the strength and direction of the field. For all cerebral targets studied, the currently accepted configurations produced sub-optimal field strengths. The configuration for cerebellum stimulation produced relatively high field strengths in its target area, but it needs higher input currents than cerebral stimulation does. This study suggests that improvements in the effects of transcranial direct current stimulation are achievable.

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

Rampersad, SM; Janssen, AM; Lucka, F; Aydin, Ü; Lanfer, B; Lew, S; Wolters, CH; Stegeman, DF; Oostendorp, TF


Applying anodal tDCS during tango dancing in a patient with Parkinson's disease.

2014 May

Gait disturbance in patients with Parkinson's disease remains a therapeutic challenge, given its poor response to levodopa. Dance therapy is of recognised benefit in these patients, particularly partnered dance forms such as the tango. In parallel, non-invasive brain stimulation has begun to show promise for the rehabilitation of patients with Parkinson's disease, although effects on gait, compared to upper limbs, have been less well defined. We applied transcranial direct current stimulation (tDCS) in a 79 year old male patient with moderate Parkinson's disease during tango dancing to assess its effect on trunk motion and balance. The patient performed a total of four dances over two days, two 'tango+tDCS' and two 'tango+sham' in a randomised double-blind fashion. In a separate experimental session we also assessed the isolated effect of tDCS (and sham) on gait without tango dancing. For the dance session, trunk peak velocity during tango was significantly greater during tDCS compared to sham stimulation. In the gait experiments we observed a modest but significant reduction in the time taken to complete the 3m 'timed up and go' and 6m walk, and an increase in overall gait velocity and peak pitch trunk velocity with tDCS compared to sham. Our findings suggest that tDCS may be a useful adjunct to gait rehabilitation for patients with PD, although studies in a larger group of patients are needed to evaluate the therapeutic use of non-invasive brain stimulation during dance therapy.

Neuroscience letters

Kaski, D; Allum, JH; Bronstein, AM; Dominguez, RO


Effects of dual-mode non-invasive brain stimulation on motor function.

2014 May

The purpose of this study was to investigate the effects of dual-mode non-invasive brain stimulation (NBS) on motor function and cortical excitability using both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) over the bilateral primary motor cortices (M1s) of healthy individuals. Fifteen healthy right-handed volunteers (8 women; mean age 23.2 years) participated in this sham-controlled random-ordered crossover study. All of the participants received four randomly arranged dual-mode stimulations with a 24-h washout period: condition 1, preconditioning with cathodal tDCS over the left M1 followed by 10 Hz rTMS over the right M1; condition 2, preconditioning Lt. anodal tDCS followed by Rt. 10 Hz rTMS; condition 3, Lt. sham tDCS followed by Rt. 10 Hz rTMS; and condition 4, Lt. sham tDCS followed by Rt. sham rTMS. Corticomotor excitability and motor function were assessed in the left hand before and after stimulation. The motor evoked potential (MEP) amplitudes significantly increased after dual-mode stimulation in conditions 1 and 3, and significantly decreased in condition 2. The MEP latency became significantly shorter in condition 1. The motor function tests revealed a significant improvement in the Purdue pegboard test in condition 1, and in the box and block tests in conditions 1 and 3. The preconditioning tDCS over the contralateral M1 modulated the effects of subsequent rTMS on cortical excitability and motor function.

Neuroscience letters

Park, E; Kim, YH; Chang, WH; Kwon, TG; Shin, YI


Combination of transcranial direct current stimulation and methylphenidate in subacute stroke.

2014 May

Noninvasive transcranial direct current stimulation (tDCS) and methylphenidate (MP) are associated with motor recovery after stroke. Based on the potentially complementary mechanisms of these interventions, we examined whether there is an interactive effect between MP and tDCS. In this preliminary study, we randomized subacute stroke subjects to receive tDCS alone, MP alone or combination of tDCS and MP. A blinded rater measured safety, hand function, and cortical excitability before and after treatment. None of the treatments caused any major or severe adverse effects or induced significant differences in cortical excitability. Analysis of variance of gain score, as measured by Purdue pegboard test, showed a significant between-group difference (F(2,6)=12.167, p=0.008). Post hoc analysis showed that the combination treatment effected greater Purdue pegboard gain scores than tDCS alone (p=0.017) or MP alone (p=0.01). Our preliminary data with nine subjects shows an interesting dissociation between motor function improvement and lack of motor corticospinal plasticity changes as indexed by transcranial magnetic stimulation in subacute stroke subjects.

Neuroscience letters

Wang, QM; Cui, H; Han, SJ; Black-Schaffer, R; Volz, MS; Lee, YT; Herman, S; Latif, LA; Zafonte, R; Fregni, F


Space, time, and causality in the human brain.

2014 May

The ability to perceive causality is a central human ability constructed from elemental spatial and temporal information present in the environment. Although the nature of causality has captivated philosophers and scientists since antiquity, the neural correlates of causality remain poorly understood. In the present study, we used functional magnetic resonance imaging (fMRI) to generate hypotheses for candidate brain regions related to component processes important for perceptual causality in the human brain: elemental space perception, elemental time perception, and decision-making (Experiment 1; n=16). We then used transcranial direct current stimulation (tDCS) to test neural hypotheses generated from the fMRI experiment (Experiment 2; n=16). In both experiments, participants judged causality in billiard-ball style launching events; a blue ball approaches and contacts a red ball. Spatial and temporal contributions to causal perception were assessed by parametrically varying the spatial linearity and the temporal delays of the movement of the balls. Experiment 1 demonstrated unique patterns of activation correlated with spatial, temporal, and decision-making components of causality perception. Using tDCS, we then tested hypotheses for the specific roles of the parietal and frontal cortices found in the fMRI experiment. Parietal stimulation only decreased participants' perception of causality based on spatial violations, while frontal stimulation made participants less likely to perceive causality based on violations of space and time. Converging results from fMRI and tDCS indicate that parietal cortices contribute to causal perception because of their specific role in processing spatial relations, while the frontal cortices contribute more generally, consistent with their role in decision-making.

NeuroImage

Woods, AJ; Hamilton, RH; Kranjec, A; Minhaus, P; Bikson, M; Yu, J; Chatterjee, A


Can transcranial direct current stimulation (tDCS) alleviate symptoms and improve cognition in psychiatric disorders?

2014 May

Since the discovery of psychopharmacological treatments in the early 1950s, followed by the development of second-generation antidepressants and antipsychotics, biological psychiatry has not achieved much progress. Recent technological advances in the field of non-invasive brain stimulation open new perspectives in the treatment of psychiatric disorders. Amongst them, transcranial direct current stimulation (tDCS) modulates cortical excitability and induces long-lasting effects. Here, we aimed at evaluating whether tDCS has potential to be developed as an innovative treatment in psychiatry.We conducted a systematic review of the current state of development and application of tDCS in psychiatric disorders, exploring clinical and cognitive effects, especially in major depressive disorder (MDD), schizophrenia and substance use disorder.Systematic literature search yielded 40 publications: 22 in MDD, nine in schizophrenia, seven in substance use disorder, one in obsessive-compulsive disorder and one in mania. Our findings indicated beneficial clinical effects of tDCS for MDD and a promising literature in schizophrenia and substance use disorder.Despite methodological differences, the data published to date are promising and supports the use of tDCS as a treatment for psychiatric disorders. However, its place regarding other treatments still has to be determined before becoming a routine clinical treatment.

The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry

Mondino, M; Bennabi, D; Poulet, E; Galvao, F; Brunelin, J; Haffen, E


Late cortical plasticity in motor and auditory cortex: role of met-allele in BDNF Val66Met polymorphism.

2014 May

The brain-derived neurotropic factor (BDNF) Val66Met polymorphism has been associated with abnormalities of synaptic plasticity in animal models, and abnormalities in motor cortical plasticity have also been described in humans using transcranial direct current stimulation. No study has yet been done on plasticity in non-motor regions, and the effect of two Met alleles (i.e. 'Met dose') is not well understood. We studied the effect of the BDNF Val66Met polymorphism on the after-effects of transcranial direct current stimulation and tetanic auditory stimulation in 65 subjects (23; Val66Val, 22; Val66Met and 20; Met66Met genotypes). In the first session, motor evoked potentials (MEP) were recorded under stereotaxic guidance for 90 min after 9 min of anodal transcranial direct current stimulation (TDCS). In the second session, auditory-evoked potentials (AEP) were recorded before and after 2 min of auditory 13 Hz tetanic stimulation. There was a difference in MEP facilitation post-TDCS comparing Met carriers with non-Met carriers, with Met carriers having a modest late facilitation at 30-90 min. There was no difference in responses between Val66Met genotype and Met66Met genotype subjects. Tetanic auditory stimulation also produced late facilitation of N1-P2 AEP at 25 min, but there was no apparent effect of genetic status. This study indicates that Met66Met carriers behave like Val66Met carriers for TDCS-induced plasticity, and produce a late facilitation of MEPs. Auditory cortical plasticity was not affected by the BDNF Val66Met polymorphism. This study sheds light on the differences between auditory and motor cortical plasticity and the role of the BDNF Val66Met polymorphism.

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

Teo, JT; Bentley, G; Lawrence, P; Soltesz, F; Miller, S; Willé, D; McHugh, S; Dodds, C; Lu, B; Croft, RJ; Bullmore, ET; Nathan, PJ


Transcranial direct current stimulation of the prefrontal cortex: a means to modulate fear memories.

2014 May

Targeting memory processes by noninvasive interventions is a potential gateway to modulate fear memories as shown by animal and human studies in recent years. Modulation of fear memories by noninvasive brain stimulation techniques might be an attractive approach, which, however, has not been examined so far. We investigated the effect of transcranial direct current stimulation (tDCS) applied to the right dorsolateral prefrontal cortex and left supraorbital region on fear memories in humans. Seventy-four young, healthy individuals were assigned randomly to two groups, which underwent fear conditioning with mild electric stimuli paired with a visual stimulus. Twenty-four hours later, both groups were shown a reminder of the conditioned fearful stimulus. Shortly thereafter, they received either tDCS (right prefrontal--anodal, left supraorbital--cathodal) for 20 min at 1 mA current intensity or sham stimulation. A day later, fear responses of both groups were compared by monitoring skin conductance. On day 3, during fear response assessment, the tDCS group had a significantly (P<0.05) higher mean skin conductance in comparison with the sham group. These results suggest that tDCS (right prefrontal--anodal, left supraorbital--cathodal) enhanced fear memories, possibly by influencing the prefrontal cortex-amygdala circuit underlying the memory for fear.

Neuroreport

Mungee, A; Kazzer, P; Feeser, M; Nitsche, MA; Schiller, D; Bajbouj, M


Local and remote effects of transcranial direct current stimulation on the electrical activity of the motor cortical network.

2014 May

We systematically investigated the effects of cathodal and anodal Transcranial Direct Current Stimulation (CtDCS, AtDCS) on the electric activity of primary motor cortex during a motor task. High-density electroencephalography was used to define the spatial diffusion of tDCS after effects. Ten healthy subjects performed a finger tapping task with the right hand before and after three separate sessions of 20 minutes of Sham, AtDCS or CtDCS over left primary motor cortex (M1). During movement, we found an increment of low alpha band Event-Related Desynchronization (ERD) in bilateral central, frontal areas and in the left inferior parietal region, as well as an increment of beta ERD in fronto-central and parieto-occipital regions, after AtDCs compared to Sham and CtDCS. In the rest pre-movement period, after Sham as well as AtDCS, we documented an increment of low alpha band power over the course of pre- and post-stimulation recording sessions, localized in the sensorimotor and parieto-occipital regions. On the contrary, after CtDCS no increment of low alpha power was found. Finally beta band coherence among signals from left sensorimotor cortex and activity of bilateral parietal, occipital and right frontal regions was higher after AtDCS compared with Sham condition. Similarly, theta coherence with parietal and frontal regions was enhanced after AtDCS. We hypothesize that the local modulation of membrane polarization, as well as long-lasting synaptic modification induced by tDCS over M1, could result in changes of both local band power and functional architecture of the motor network.

Human brain mapping

Notturno, F; Marzetti, L; Pizzella, V; Uncini, A; Zappasodi, F


Reduced threshold for inhibitory homeostatic responses in migraine motor cortex? A tDCS/TMS study.

2014 Apr

Neurophysiological studies in migraine have reported conflicting findings of either cortical hyper- or hypoexcitability. In migraine with aura (MwA) patients, we recently documented an inhibitory response to suprathreshold, high-frequency repetitive transcranial magnetic stimulation (hf-rTMS) trains applied to the primary motor cortex, which is in contrast with the facilitatory response observed in the healthy subjects. The aim of the present study was to support the hypothesis that in migraine, because of a condition of basal increased cortical responsivity, inhibitory homeostatic like mechanisms of cortical excitability could be induced by high magnitude stimulation. For this purpose, the hf-rTMS trains were preconditioned by transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique able to modulate the cortical excitability state.Twenty-two MwA patients and 20 patients with migraine without aura (MwoA) underwent trains of 5-Hz repetitive transcranial magnetic stimulation at an intensity of 130% of the resting motor threshold, both at baseline and after conditioning by 15 minutes of cathodal or anodal tDCS. Motor cortical responses to the hf-rTMS trains were compared with those of 14 healthy subjects.We observed abnormal inhibitory responses to the hf-rTMS trains given at baseline in both MwA and MwoA patients as compared with the healthy subjects (P < .00001).The main result of the study was that cathodal tDCS, which reduces the cortical excitability level, but not anodal tDCS, which increases it, restored the normal facilitatory response to the hf-rTMS trains in both MwA and MwoA.The present findings strengthen the notion that, in migraine with and without aura, the threshold for inducing inhibitory mechanisms of cortical excitability might be lower in the interictal period. This could represent a protective mechanism counteracting cortical hyperresponsivity. Our results could be helpful to explain some conflicting neurophysiological findings in migraine and to get insight into the mechanisms underlying recurrence of the migraine attacks.

Headache

Cosentino, G; Brighina, F; Talamanca, S; Paladino, P; Vigneri, S; Baschi, R; Indovino, S; Maccora, S; Alfonsi, E; Fierro, B


Pitch Memory in Nonmusicians and Musicians: Revealing Functional Differences Using Transcranial Direct Current Stimulation.

2014 Apr

For music and language processing, memory for relative pitches is highly important. Functional imaging studies have shown activation of a complex neural system for pitch memory. One region that has been shown to be causally involved in the process for nonmusicians is the supramarginal gyrus (SMG). The present study aims at replicating this finding and at further examining the role of the SMG for pitch memory in musicians. Nonmusicians and musicians received cathodal transcranial direct current stimulation (tDCS) over the left SMG, right SMG, or sham stimulation, while completing a pitch recognition, pitch recall, and visual memory task. Cathodal tDCS over the left SMG led to a significant decrease in performance on both pitch memory tasks in nonmusicians. In musicians, cathodal stimulation over the left SMG had no effect, but stimulation over the right SMG impaired performance on the recognition task only. Furthermore, the results show a more pronounced deterioration effect for longer pitch sequences indicating that the SMG is involved in maintaining higher memory load. No stimulation effect was found in both groups on the visual control task. These findings provide evidence for a causal distinction of the left and right SMG function in musicians and nonmusicians.

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

Schaal, NK; Krause, V; Lange, K; Banissy, MJ; Williamson, VJ; Pollok, B


Reducing aggressive responses to social exclusion using transcranial direct current stimulation.

2014 Apr

A vast body of research showed that social exclusion can trigger aggression. However, the neural mechanisms involved in regulating aggressive responses to social exclusion are still largely unknown. Transcranial direct current stimulation (tDCS) modulates the excitability of a target region. Building on studies suggesting that activity in the right ventrolateral pre-frontal cortex (rVLPFC) might aid the regulation or inhibition of social exclusion-related distress, we hypothesized that non-invasive brain polarization through tDCS over the rVLPFC would reduce behavioral aggression following social exclusion. Participants were socially excluded or included while they received tDCS or sham stimulation to the rVLPFC. Next, they received an opportunity to aggress. Excluded participants demonstrated cognitive awareness of their inclusionary status, yet tDCS (but not sham stimulation) reduced their behavioral aggression. Excluded participants who received tDCS stimulation were no more aggressive than included participants. tDCS stimulation did not influence socially included participants' aggression. Our findings provide the first causal test for the role of rVLPFC in modulating aggressive responses to social exclusion. Our findings suggest that modulating activity in a brain area (i.e. the rVLPFC) implicated in self-control and emotion regulation can break the link between social exclusion and aggression.

Social cognitive and affective neuroscience

Riva, P; Romero Lauro, LJ; DeWall, CN; Chester, DS; Bushman, BJ


Transcranial Direct Current Stimulation Enhances Verbal Working Memory Training Performance over Time and Near-transfer Outcomes.

2014 Apr

Studies attempting to increase working memory (WM) capacity show promise in enhancing related cognitive functions but have also raised criticism in the broader scientific community given the inconsistent findings produced by these studies. Transcranial direct current stimulation (tDCS) has been shown to enhance WM performance in a single session [Fregni, F., Boggio, P., Nitsche, M., Bermpohl, F., Anatal, A., Feredoes, E., et al. Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Experimental Brain Research, 166, 23-30, 2005]; however, the extent to which tDCS might enhance learning on a WM training regime and the extent to which learning gains might transfer outside the training task remains largely unknown. To this end, participants engaged in an adaptive WM training task [previously utilized in Richmond, L., Morrison, A., Chein, J., & Olson, I. Working memory training and transfer in older adults. Psychology & Aging, 26, 813-822, 2011; Chein, J., & Morrison, A. Expanding the mind's workspace: Training and transfer effects with a complex working memory span task. Psychonomic Bulletin & Review, 17, 193-199, 2010] for 10 sessions over 2 weeks, concurrent with either active or sham stimulation of dorsolateral pFC. Before and after training, a battery of tests tapping domains known to relate to WM abilities was administered. Results show that tDCS enhanced learning on the verbal portion of the training task by 3.65 items. Furthermore, tDCS was shown to enhance near transfer to other untrained WM tasks in comparison with a no-contact control group. These results lend support to the idea that tDCS might bolster training and transfer gains in populations with compromised WM abilities.

Journal of cognitive neuroscience

Richmond, L; Wolk, D; Chein, J; Olson, IR


Impact of Two or Less Missing Treatment Sessions on tDCS Clinical Efficacy: Results From a Factorial, Randomized, Controlled Trial in Major Depression.

2014 Apr

Transcranial direct current stimulation (tDCS) is a neuromodulatory intervention with recent clinical trials showing promising results in major depression treatment. Although tDCS has some appealing characteristics (e.g., low cost, ease of use, and relatively benign profile of adverse effects), one important drawback of the technique is the need to deliver consecutive, repeated sessions for several weekdays. However, no study investigated whether absences during this acute treatment phase impact on tDCS efficacy, and, if so, whether absences should be considered dropouts, therefore increasing attrition.To examine this issue, we used data from a randomized, factorial, sham-controlled tDCS study that recruited 120 depressed patients. In this trial, the acute treatment phase consisted of ten consecutive sessions delivered once daily from Monday to Friday; two nonconsecutive missed visits were allowed, with extra tDCS sessions being performed to complete the original number of sessions.Our main finding was that the procedure of granting one to two absences during the acute treatment phase did not impact on tDCS antidepressant efficacy. Moreover, out of 103 completers, only 41 (39.8%) patients presented no missing visits and 25 (24.3%) presented two absences. These patients did not differ in clinical and demographic characteristics; thus, absences were probably circumstantial (e.g., traffic congestion, personal obligations).Absences during the acute tDCS treatment phase are common, which support the use of flexible schedules in future tDCS trials as to minimize attrition. Also, further studies should access whether higher number of absences can compromise optimal tDCS efficacy.

Neuromodulation : journal of the International Neuromodulation Society

Zanão, TA; Moffa, AH; Shiozawa, P; Lotufo, PA; Benseñor, IM; Brunoni, AR


Cerebellar-parietal connections underpin phonological storage.

2014 Apr

Previous research has accumulated convincing evidence to show that the human cerebellum contributes to the short-term storage of verbal information, but its specific role in brain networks involved in phonological storage remains uncertain. In a randomized, crossover and sham-controlled design, we here combined transcranial direct current stimulation (tDCS), applied to the right cerebellum, with fMRI to investigate systematically the contribution of the human cerebellum to encoding, maintenance, and retrieval of verbal information. After anodal, but not cathodal, tDCS, we found a reduced item recognition capacity together with an attenuated neural signal from the right cerebellar lobule VIIb, specifically during the late encoding phase. Within this phase, tDCS furthermore affected task-associated functional connections between right cerebellar lobule VIIb and the posterior parietal cortex. These findings suggest that the right cerebellar lobule VIIb interacts with the posterior parietal cortex, specifically during the late stages of verbal encoding, when verbal information enters phonological storage.

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

Macher, K; Böhringer, A; Villringer, A; Pleger, B


Device-based brain stimulation to augment fear extinction: implications for PTSD treatment and beyond.

2014 Apr

Conditioned fear acquisition and extinction paradigms have been widely used both in animals and humans to examine the neurobiology of emotional memory. Studies have also shown that patients suffering from posttraumatic stress disorder (PTSD) exhibit deficient extinction recall along with dysfunctional activation of the fear extinction network, including the ventromedial prefrontal cortex, amygdala, and hippocampus. A great deal of overlap exists between this fear extinction network and brain regions associated with symptom severity in PTSD. This suggests that the neural nodes of fear extinction could be targeted to reduce behavioral deficits that may subsequently translate into symptom improvement. In this article, we discuss potential applications of brain stimulation and neuromodulation methods, which, combined with a mechanistic understanding of the neurobiology of fear extinction, could be used to further our understanding of the pathophysiology of anxiety disorders and develop novel therapeutic tools. To this end, we discuss the following stimulation approaches: deep-brain stimulation, vagus nerve stimulation, transcranial direct current stimulation, and transcranial magnetic stimulation. We propose new translational research avenues that, from a systems neuroscience perspective, aim to expand our understanding of circuit dynamics and fear processing toward the practical development of clinical tools, to be used alone or in combination with behavioral therapies.

Depression and anxiety

Marin, MF; Camprodon, JA; Dougherty, DD; Milad, MR


Modulation of resting state functional connectivity of the motor network by transcranial pulsed current stimulation.

2014 Apr

The effects of transcranial pulsed current stimulation (tPCS) on resting state functional connectivity (rs-FC) within the motor network were investigated. Eleven healthy participants received one magnetic resonance imaging (MRI) session with three resting state functional MRI (rs-fMRI) scans, one before stimulation (PRE-STIM) to collect baseline measures, one during stimulation (STIM), and one after 13 min of stimulation (POST-STIM). Rs-FC measures during the STIM and POST-STIM conditions were compared to the PRE-STIM baseline. Regions of interest for the rs-FC analysis were extracted from the significantly activated clusters obtained during a finger tapping motor paradigm and included the right primary motor cortex (R M1), left primary motor cortex (L M1), supplemental motor area (SMA), and cerebellum (Cer). The main findings were reduced rs-FC between the left M1 and surrounding motor cortex, and increased rs-FC between the left M1 and left thalamus during stimulation, but increased rs-FC between the Cer and right insula after stimulations. Bivariate measures of connectivity demonstrate reduced strength of connectivity for the whole network average (p=0.044) and reduced diversity of connectivity for the network average during stimulation (p=0.024). During the POST-STIM condition, the trend of reduced diversity for the network average was statistically weaker (p=0.071). In conclusion, while many of the findings are comparable to previous reports using simultaneous transcranial direct current stimulation (tDCS) and fMRI acquisition, we also demonstrate additional changes in connectivity patterns that are induced by tPCS.

Brain connectivity

Sours, C; Alon, G; Roys, S; Gullapalli, RP


Norms and expectations in social decision-making.

2014 Apr

Recent research has shown that stimulating right lateral prefrontal cortex (rLPFC) via transcranial direct current stimulation (tDCS) changes social norm compliance in economic decisions, with different types of compliance affected in different ways. More broadly considering the norms involved in decision-making, and in particular expectations held by players, can help clarify the mechanisms underlying these results.

Trends in cognitive sciences

Sanfey, AG; Stallen, M; Chang, LJ


tDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study.

2014 Apr

We assessed the effects of left dorsolateral prefrontal cortex transcranial direct current stimulation (DLPF-tDCS) on Coma Recovery Scale-Revised (CRS-R) scores in severely brain-damaged patients with disorders of consciousness.In a double-blind sham-controlled crossover design, anodal and sham tDCS were delivered in randomized order over the left DLPF cortex for 20 minutes in patients in a vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in a minimally conscious state (MCS) assessed at least 1 week after acute traumatic or nontraumatic insult. Clinical assessments were performed using the CRS-R directly before and after anodal and sham tDCS stimulation. Follow-up outcome data were acquired 12 months after inclusion using the Glasgow Outcome Scale-Extended.Patients in MCS (n = 30; interval 43 ± 63 mo; 19 traumatic, 11 nontraumatic) showed a significant treatment effect (p = 0.003) as measured by CRS-R total scores. In patients with VS/UWS (n = 25; interval 24 ± 48 mo; 6 traumatic, 19 nontraumatic), no treatment effect was observed (p = 0.952). Thirteen (43%) patients in MCS and 2 (8%) patients in VS/UWS further showed postanodal tDCS-related signs of consciousness, which were observed neither during the pre-tDCS evaluation nor during the pre- or post-sham evaluation (i.e., tDCS responders). Outcome did not differ between tDCS responders and nonresponders.tDCS over left DLPF cortex may transiently improve signs of consciousness in MCS following severe brain damage as measured by changes in CRS-R total scores.This study provides Class II evidence that short-duration tDCS of the left DLPF cortex transiently improves consciousness as measured by CRS-R assessment in patients with MCS.

Neurology

Thibaut, A; Bruno, MA; Ledoux, D; Demertzi, A; Laureys, S


Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: a systematic review and meta-analysis.

2014 Apr

Recent studies have used non-invasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), to increase dorsolateral prefrontal cortex (DLPFC) activity and, consequently, working memory (WM) performance. However, such experiments have yielded mixed results, possibly due to small sample sizes and heterogeneity of outcomes. Therefore, our aim was to perform a systematic review and meta-analyses on NIBS studies assessing the n-back task, which is a reliable index for WM. From the first data available to February 2013, we looked for sham-controlled, randomized studies that used NIBS over the DLPFC using the n-back task in PubMed/MEDLINE and other databases. Twelve studies (describing 33 experiments) matched our eligibility criteria. Active vs. sham NIBS was significantly associated with faster response times (RTs), higher percentage of correct responses and lower percentage of error responses. However, meta-regressions showed that tDCS (vs. rTMS) presented only an improvement in RT, and not in accuracy. This could have occurred in part because almost all tDCS studies employed a crossover design, possibly due to the reliable tDCS blinding. Study design was also associated with no improvement in correct responses in the active vs. sham groups. To conclude, rTMS of the DLPFC significantly improved all measures of WM performance whereas tDCS significantly improved RT, but not the percentage of correct and error responses. Mechanistic insights on the role of DLPFC in WM are further discussed, as well as how NIBS techniques could be used in neuropsychiatric samples presenting WM deficits, such as major depression, dementia and schizophrenia.

Brain and cognition

Brunoni, AR; Vanderhasselt, MA


Inconsistent outcomes of transcranial direct current stimulation may originate from anatomical differences among individuals: electric field simulation using individual MRI data.

2014 Apr

Transcranial direct current stimulation (tDCS) is a neuromodulation protocol that can facilitate or inhibit cortical excitability in particular areas of the brain. Although recent studies have reported that tDCS can successfully modulate the excitability of various brain sites, outcomes of tDCS were not consistent between subjects even when identical stimulation protocols were applied. Thus far, however, no studies have clearly verified the main cause of this individual variability. In this study, the main hypothesis was that individual variability in tDCS effects might be partly explained by anatomical differences among subjects. To verify our hypothesis, we investigated the relationship between the behavioral outcomes of a verbal working memory (WM) task and current density values at the dorsolateral prefrontal cortex (DLPFC) simulated using the finite element method (FEM). A 3-back verbal working memory task experiment was conducted in 17 healthy subjects before and after tDCS with cathode and anode electrodes located at the right supraorbital and F3 locations, respectively. The results showed that participants who showed evidence of enhanced WM task performance after tDCS had a significantly larger current density at the DLPFC than other participants, suggesting that inconsistent behavioral outcomes of tDCS might be partly due to individual anatomical differences.

Neuroscience letters

Kim, JH; Kim, DW; Chang, WH; Kim, YH; Kim, K; Im, CH


Frontal tDCS modulates orbitofrontal reality filtering.

2014 Apr

Orbitofrontal reality filtering denotes a memory control mechanism necessary to keep thought and behavior in phase with reality. Its failure induces reality confusion as evident in confabulation and disorientation. In the present study, we explored the influence of orbitofrontal transcranial direct current stimulation (tDCS) on reality filtering. Twenty healthy human subjects made a reality filtering task, while receiving cathodal, anodal, or sham stimulation over the frontal pole in three sessions separated by at least 1week. Computational models predicted that this montage can produce polarity-specific current flow across the posterior medial orbitofrontal cortex (OFC). In agreement with our hypothesis, we found that cathodal tDCS over the frontal pole specifically impaired reality filtering in comparison to anodal and sham stimulation. This study shows that reality filtering, an orbitofrontal function, can be modulated with tDCS.

Neuroscience

Manuel, AL; David, AW; Bikson, M; Schnider, A


Transcranial direct current stimulation reduces the cost of performing a cognitive task on gait and postural control.

2014 Apr

This proof-of-concept, double-blind study was designed to determine the effects of transcranial direct current stimulation (tDCS) on the 'cost' of performing a secondary cognitive task on gait and postural control in healthy young adults. Twenty adults aged 22 ± 2 years completed two separate double-blind visits in which gait and postural control were assessed immediately before and after a 20 min session of either real or sham tDCS (1.5 mA) targeting the left dorsolateral prefrontal cortex. Gait speed and stride duration variability, along with standing postural sway speed and area, were recorded under normal conditions and while simultaneously performing a serial-subtraction cognitive task. The dual task cost was calculated as the percent change in each outcome from normal to dual task conditions. tDCS was well tolerated by all subjects. Stimulation did not alter gait or postural control under normal conditions. As compared with sham stimulation, real tDCS led to increased gait speed (P = 0.006), as well as decreased standing postural sway speed (P = 0.01) and area (P = 0.01), when performing the serial-subtraction task. Real tDCS also diminished (P < 0.01) the dual task cost on each of these outcomes. No effects of tDCS were observed for stride duration variability. A single session of tDCS targeting the left dorsolateral prefrontal cortex improved the ability to adapt gait and postural control to a concurrent cognitive task and reduced the cost normally associated with such dual tasking. These results highlight the involvement of cortical brain networks in gait and postural control, and implicate the modulation of prefrontal cortical excitability as a potential therapeutic intervention.

The European journal of neuroscience

Zhou, J; Hao, Y; Wang, Y; Jor'dan, A; Pascual-Leone, A; Zhang, J; Fang, J; Manor, B


Revealing the brain's adaptability and the transcranial direct current stimulation facilitating effect in inhibitory control by multiscale entropy.

2014 Apr

The abilities to inhibit impulses and withdraw certain responses are critical for human's survival in a fast-changing environment. These processes happen fast, in a complex manner, and sometimes are difficult to capture with fMRI or mean electrophysiological brain signal alone. Therefore, an alternative measure that can reveal the efficiency of the neural mechanism across multiple timescales is needed for the investigation of these brain functions. The present study employs a new approach to analyzing electroencephalography (EEG) signal: the multiscale entropy (MSE), which groups data points with different timescales to reveal any occurrence of repeated patterns, in order to theoretically quantify the complexity (indicating adaptability and efficiency) of neural systems during the process of inhibitory control. From this MSE perspective, EEG signals of successful stop trials are more complex and information rich than that of unsuccessful stop trials. We further applied transcranial direct current stimulation (tDCS), with anodal electrode over presupplementary motor area (preSMA), to test the relationship between behavioral modification with the complexity of EEG signals. We found that tDCS can further increase the EEG complexity of the frontal lobe. Furthermore, the MSE pattern was found to be different between high and low performers (divided by their stop-signal reaction time), where the high-performing group had higher complexity in smaller scales and less complexity in larger scales in comparison to the low-performing group. In addition, this between-group MSE difference was found to interact with the anodal tDCS, where the increase of MSE in low performers benefitted more from the anodal tDCS. Together, the current study demonstrates that participants who suffer from poor inhibitory control can efficiently improve their performance with 10min of electrical stimulation, and such cognitive improvement can be effectively traced back to the complexity within the EEG signals via MSE analysis, thereby offering a theoretical basis for clinical intervention via tDCS for deficits in inhibitory control.

NeuroImage

Liang, WK; Lo, MT; Yang, AC; Peng, CK; Cheng, SK; Tseng, P; Juan, CH


Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields.

2014 Apr

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS).

NeuroImage

Ruffini, G; Fox, MD; Ripolles, O; Miranda, PC; Pascual-Leone, A


Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial, randomized, controlled trial.

2014 Apr

The inflammatory hypothesis of depression states that increased levels of pro-inflammatory cytokines triggered by external and internal stressors are correlated to the acute depressive state. This hypothesis also suggests that pharmacotherapy partly acts in depression through anti-inflammatory effects. Transcranial direct current stimulation (tDCS) is a novel, promising, non-invasive somatic treatment for depression, although its antidepressant mechanisms are only partly understood.We explored the effects of tDCS and sertraline over the immune system during an antidepressant treatment trial.In a 6-week, double-blind, placebo-controlled trial, 73 antidepressant-free patients with unipolar depression were randomized to active/sham tDCS and sertraline/placebo (2 × 2 design). Plasma levels of several cytokines (IL-2, IL-4, IL-6, IL-10, IL-17a, IFN-γ, and TNF-α) were determined to investigate the effects of the interventions and of clinical response on them.All cytokines, except TNF-α, decreased over time, these effects being similar across the different intervention-groups and in responders vs. non-responders.tDCS and sertraline (separately and combined) acute antidepressant effects might not specifically involve normalization of the immune system. In addition, being one of the first placebo-controlled trials measuring cytokines over an antidepressant treatment course, our study showed that the decrease in cytokine levels during the acute depressive episode could involve a placebo effect, highlighting the need of further placebo-controlled trials and observational studies examining cytokine changes during depression treatment and also after remission of the acute depressive episode.

Psychopharmacology

Brunoni, AR; Machado-Vieira, R; Zarate, CA; Valiengo, L; Vieira, EL; Benseñor, IM; Lotufo, PA; Gattaz, WF; Teixeira, AL


Disrupting the ipsilateral motor cortex interferes with training of a complex motor task in older adults.

2014 Apr

Performance of unimanual movements is associated with bihemispheric activity in the motor cortex in old adults. However, the causal functional role of the ipsilateral MC (iMC) for motor control is still not completely known. Here, the behavioral consequences of interference of the iMC during training of a complex motor skill were tested. Healthy old (58-85 years) and young volunteers (22-35 years) were tested in a double-blind, cross-over, sham-controlled design. Participants attended 2 different study arms with either cathodal transcranial direct current stimulation (ctDCS) or sham concurrent with training. Motor performance was evaluated before, during, 90 min, and 24 h after training. During training, a reduced slope of performance with ctDCS relative to sham was observed in old compared with young (F = 5.8, P = 0.02), with a decrease of correctly rehearsed sequences, an effect that was evident even after 2 consecutive retraining periods without intervention. Furthermore, the older the subject, the more prominent was the disruptive effect of ctDCS (R(2) = 0.50, P = 0.01). These data provide direct evidence for a causal functional link between the iMC and motor skill acquisition in old subjects pointing toward the concept that the recruitment of iMC in old is an adaptive process in response to age-related declines in motor functions.

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

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


Effect of transcranial direct current stimulation of function in patients with stroke.

2014 Mar

[Purpose] The purpose of this study was to determine the effect of transcranial direct current stimulation (tDCS) on the upper limb of function of patients with post-stroke hemiplegia. [Subjects] Twenty subjects were randomly allocated to either the upper tDCS group or the functional training group, with 10 subjects in each group. [Methods] The two groups received functional training for thirty minutes a day, five days a week for four weeks. The tDCS group additionally received tDCS for 20 minutes. The outcome was assessed by the Box and Block test (BBT), grip strength, and the Fugl-Meyer assessment (FMA). [Results] There were significant improvements between pre- and post- intervention in both groups, in the BBT, grip strength, and the upper limb and lower lims sub-items of the FMA. The tDCS group showed significantly greater improvements than the control group in the BBT, and upper limb and lower limb sub-items of the FMA. [Conclusion] These findings suggest that tDCS may be more beneficial than functional training for improving the upper and lower limb functions of chronic stroke patients.

Journal of physical therapy science

Cha, HK; Ji, SG; Kim, MK; Chang, JS

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The Causal Role of the Dorsolateral Prefrontal Cortex in the Modification of Attentional Bias: Evidence from Transcranial Direct Current Stimulation.

2014 Mar

A pattern of attentional bias for threatening information is thought to be involved in the etiology of anxiety. Consistent with this idea, cognitive training techniques directly targeting such patterns of biased attention have been shown to reduce symptoms of anxiety. Research seeking to establish the neurologic underpinnings of change in the attentional bias for threat have implicated, but not confirmed, the role of lateral prefrontal regions.The current study sought to confirm experimentally the causal role of lateral prefrontal areas in the modification of attentional bias by delivering targeted cortical stimulation during attention bias modification training to assess the consequent effects on attentional bias change. While completing either an "attend threat" or "avoid threat" attention bias modification task, 77 volunteers (17-22 per group) received either active transcranial direct current stimulation of the left dorsolateral prefrontal cortex or a sham stimulation control condition.Participants receiving active stimulation showed greater evidence of attentional bias acquisition in the targeted direction (toward or away from threat) compared with participants in the sham stimulation condition.Our findings provide the first experimental evidence that increasing activity in the dorsolateral prefrontal cortex leads to greater evidence of attention bias modification. This evidence confirms the role of these areas in facilitating change in the allocation of attention to threat. We believe this study provides a critical step in the translation of neuroimaging findings to novel neuromodulatory interventions capable of enhancing the treatment of emotional pathology.

Biological psychiatry

Clarke, PJ; Browning, M; Hammond, G; Notebaert, L; Macleod, C


Transcranial direct current stimulation improves neurorehabilitation of task-specific dystonia: a pilot study.

2014 Mar

Sensory-motor returning (SMR) can help the symptoms of task-specific focal hand dystonia. However, effects vary across patients and take many sessions. Here, we present proof of principle evidence that transcranial direct current stimulation (tDCS) can enhance these effects. We compared the effects of a combined tDCS-SMR protocol (n=4 patients) with the efficacy of SMR alone (n=30 patients). All 4 patients treated with the combined protocol showed greater improvement than those undergoing SMR alone. Results encourage a larger, parallel-group clinical trial with sham tDCS control.

Medical problems of performing artists

Rosset-Llobet, J; Fàbregas-Molas, S; Pascual-Leone, A


Enhancing Hebbian Learning to Control Brain Oscillatory Activity.

2014 Mar

Sensorimotor rhythms (SMR, 8-15 Hz) are brain oscillations associated with successful motor performance, imagery, and imitation. Voluntary modulation of SMR can be used to control brain-machine interfaces (BMI) in the absence of any physical movements. The mechanisms underlying acquisition of such skill are unknown. Here, we provide evidence for a causal link between function of the primary motor cortex (M1), active during motor skill learning and retention, and successful acquisition of abstract skills such as control over SMR. Thirty healthy participants were trained on 5 consecutive days to control SMR oscillations. Each participant was randomly assigned to one of 3 groups that received either 20 min of anodal, cathodal, or sham transcranial direct current stimulation (tDCS) over M1. Learning SMR control across training days was superior in the anodal tDCS group relative to the other 2. Cathodal tDCS blocked the beneficial effects of training, as evidenced with sham tDCS. One month later, the newly acquired skill remained superior in the anodal tDCS group. Thus, application of weak electric currents of opposite polarities over M1 differentially modulates learning SMR control, pointing to this primary cortical region as a common substrate for acquisition of physical motor skills and learning to control brain oscillatory activity.

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

Soekadar, SR; Witkowski, M; Birbaumer, N; Cohen, LG


Shaping memory accuracy by left prefrontal transcranial direct current stimulation.

2014 Mar

Human memory is dynamic and flexible but is also susceptible to distortions arising from adaptive as well as pathological processes. Both accurate and false memory formation require executive control that is critically mediated by the left prefrontal cortex (PFC). Transcranial direct current stimulation (tDCS) enables noninvasive modulation of cortical activity and associated behavior. The present study reports that tDCS applied to the left dorsolateral PFC (dlPFC) shaped accuracy of episodic memory via polaritiy-specific modulation of false recognition. When applied during encoding of pictures, anodal tDCS increased whereas cathodal stimulation reduced the number of false alarms to lure pictures in subsequent recognition memory testing. These data suggest that the enhancement of excitability in the dlPFC by anodal tDCS can be associated with blurred detail memory. In contrast, activity-reducing cathodal tDCS apparently acted as a noise filter inhibiting the development of imprecise memory traces and reducing the false memory rate. Consistently, the largest effect was found in the most active condition (i.e., for stimuli cued to be remembered). This first evidence for a polarity-specific, activity-dependent effect of tDCS on false memory opens new vistas for the understanding and potential treatment of disturbed memory control.

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

Zwissler, B; Sperber, C; Aigeldinger, S; Schindler, S; Kissler, J; Plewnia, C

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Transcranial direct current stimulation over right dorsolateral prefrontal cortex enhances error awareness in older age.

2014 Mar

The ability to detect errors during cognitive performance is compromised in older age and in a range of clinical populations. This study was designed to assess the effects of transcranial direct current stimulation (tDCS) on error awareness in healthy older human adults. tDCS was applied over DLPFC while subjects performed a computerized test of error awareness. The influence of current polarity (anodal vs cathodal) and electrode location (left vs right hemisphere) was tested in a series of separate single-blind, Sham-controlled crossover trials, each including 24 healthy older adults (age 65-86 years). Anodal tDCS over right DLPFC was associated with a significant increase in the proportion of performance errors that were consciously detected, and this result was recapitulated in a separate replication experiment. No such improvements were observed when the homologous contralateral area was stimulated. The present study provides novel evidence for a causal role of right DLPFC regions in subserving error awareness and marks an important step toward developing tDCS as a tool for remediating the performance-monitoring deficits that afflict a broad range of populations.

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

Harty, S; Robertson, IH; Miniussi, C; Sheehy, OC; Devine, CA; McCreery, S; O'Connell, RG

Link to full article text


Computational modeling of transcranial direct current stimulation in the child brain: implications for the treatment of refractory childhood focal epilepsy.

2014 Mar

Transcranial direct current stimulation (tDCS) was recently proposed for the treatment of epilepsy. However, the electrode arrangement for this case is debated. This paper analyzes the influence of the position of the anodal electrode on the electric field in the brain. The simulation shows that moving the anode from scalp to shoulder does influence the electric field not only in the cortex, but also in deeper brain regions. The electric field decreases dramatically in the brain area without epileptiform activity.

International journal of neural systems

Parazzini, M; Fiocchi, S; Liorni, I; Priori, A; Ravazzani, P


Transcranial direct current stimulation (tDCS) traces the predominance of the left auditory cortex for processing of rapidly changing acoustic information.

2014 Mar

In the present study we investigated the effects of anodal transcranial direct current stimulation over the auditory cortex (AC) on the perception of rapidly changing acoustic cues. For this purpose, in 15 native German speakers the left or right AC was separately stimulated while participants performed a between-channel gap detection task. Results show that stimulation of the left but not right AC deteriorated the auditory perception of rapidly changing acoustic information. Our data indicate a left hemispheric dominance for the processing of rapid temporal cues in auditory non-speech sounds. Moreover, we demonstrate the ability of non-invasive brain stimulation to change human temporal information processing in the auditory domain.

Neuroscience

Heimrath, K; Kuehne, M; Heinze, HJ; Zaehle, T


Combination transcranial direct current stimulation and virtual reality therapy for upper extremity training in patients with subacute stroke.

2014 Mar

To investigate the effects of combination cathodal transcranial direct current stimulation (tDCS) and virtual reality (VR) therapy for upper extremity (UE) training in patients with subacute stroke.Pilot randomized controlled trial. Patients were randomly assigned to 1 of 3 groups: group A received cathodal tDCS, group B received VR, and group C received combination therapy (cathodal tDCS was simultaneously applied during VR therapy).University hospital.Patients (N=59) with impaired unilateral UE motor function after stroke.Fifteen sessions of treatment over a 3-week period.The Modified Ashworth Scale, manual muscle test (MMT), Manual Function Test (MFT), Fugl-Meyer Scale (FMS), and Box and Block Test were used to assess UE function. To evaluate activities of daily living, the Korean-Modified Barthel Index (K-MBI) was used. All outcomes were measured before and immediately after treatment.After treatment, all groups demonstrated significant improvements in MMT, MFT, FMS, and K-MBI scores. The change in MFT and FMS scores was different between the 3 groups. Post hoc analysis revealed that the improvement of MFT and FMS scores in group C was significantly higher than those of the other 2 groups.In the present pilot study, the combination of brain stimulation using tDCS and peripheral arm training using VR could facilitate a stronger beneficial effect on UE impairment than using each intervention alone. This combination therapy might be a helpful method to enhance recovery of the paretic UE in patients with stroke.

Archives of physical medicine and rehabilitation

Lee, SJ; Chun, MH


Modelling the electric field and the current density generated by cerebellar transcranial DC stimulation in humans.

2014 Mar

Transcranial Direct Current Stimulation (tDCS) over the cerebellum (or cerebellar tDCS) modulates working memory, changes cerebello-brain interaction, and affects locomotion in humans. Also, the use of tDCS has been proposed for the treatment of disorders characterized by cerebellar dysfunction. Nonetheless, the electric field (E) and current density (J) spatial distributions generated by cerebellar tDCS are unknown. This work aimed to estimate E and J distributions during cerebellar tDCS.Computational electromagnetics techniques were applied in three human realistic models of different ages and gender.The stronger E and J occurred mainly in the cerebellar cortex, with some spread (up to 4%) toward the occipital cortex. Also, changes by ±1cm in the position of the active electrode resulted in a small effect (up to 4%) in the E and J spatial distribution in the cerebellum. Finally, the E and J spreads to the brainstem and the heart were negligible, thus further supporting the safety of this technique.Despite inter-individual differences, our modeling study confirms that the cerebellum is the structure mainly involved by cerebellar tDCS.Modeling approach reveals that during cerebellar tDCS the current spread to other structures outside the cerebellum is unlike to produce functional effects.

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

Parazzini, M; Rossi, E; Ferrucci, R; Liorni, I; Priori, A; Ravazzani, P


Evidence for metaplasticity in the human visual cortex.

2014 Mar

The threshold and direction of excitability changes induced by low- and high-frequency repetitive transcranial magnetic stimulation (rTMS) in the primary motor cortex can be effectively reverted by a preceding session of transcranial direct current stimulation (tDCS), a phenomenon referred to as "metaplasticity". Here, we used a combined tDCS-rTMS protocol and visual evoked potentials (VEPs) in healthy subjects to provide direct electrophysiological evidence for metaplasticity in the human visual cortex. Specifically, we evaluated changes in VEPs at two different contrasts (90 and 20 %) before and at different time points after the application of anodal or cathodal tDCS to occipital cortex (i.e., priming), followed by an additional conditioning with low- or high-frequency rTMS. Anodal tDCS increased the amplitude of VEPs and this effect was paradoxically reverted by applying high-frequency (5 Hz), conventionally excitatory rTMS (p < 0.0001). Similarly, cathodal tDCS led to a decrease in VEPs amplitude, which was reverted by a subsequent application of conventionally inhibitory, 1 Hz rTMS (p < 0.0001). Similar changes were observed for both the N1 and P1 component of the VEP. There were no significant changes in resting motor threshold values (p > 0.5), confirming the spatial selectivity of our conditioning protocol. Our findings show that preconditioning primary visual area excitability with tDCS can modulate the direction and strength of plasticity induced by subsequent application of 1 or 5 Hz rTMS. These data indicate the presence of mechanisms of metaplasticity that keep synaptic strengths within a functional dynamic range in the human visual cortex.

Journal of neural transmission (Vienna, Austria : 1996)

Bocci, T; Caleo, M; Tognazzi, S; Francini, N; Briscese, L; Maffei, L; Rossi, S; Priori, A; Sartucci, F


Repeated transcranial direct current stimulation prevents abnormal behaviors associated with abstinence from chronic nicotine consumption.

2014 Mar

Successful available treatments to quit smoking remain scarce. Recently, the potential of transcranial direct current stimulation (tDCS) as a tool to reduce craving for nicotine has gained interest. However, there is no documented animal model to assess the neurobiological mechanisms of tDCS on addiction-related behaviors. To address this topic, we have developed a model of repeated tDCS in mice and used it to validate its effectiveness in relieving nicotine addiction. Anodal repeated tDCS was applied over the frontal cortex of Swiss female mice. The stimulation electrode (anode) was fixed directly onto the cranium, and the reference electrode was placed onto the ventral thorax. A 2 × 20 min/day stimulation paradigm for five consecutive days was used (0.2 mA). In the first study, we screened for behaviors altered by the stimulation. Second, we tested whether tDCS could alleviate abnormal behaviors associated with abstinence from nicotine consumption. In naive animals, repeated tDCS had antidepressant-like properties 3 weeks after the last stimulation, improved working memory, and decreased conditioned place preference for nicotine without affecting locomotor activity and anxiety-related behavior. Importantly, abnormal behaviors associated with chronic nicotine exposure (ie, depression-like behavior, increase in nicotine-induced place preference) were normalized by repeated tDCS. Our data show for the first time in an animal model that repeated tDCS is a promising, non-expensive clinical tool that could be used to reduce smoking craving and facilitate smoking cessation. Our animal model will be useful to investigate the mechanisms underlying the effects of tDCS on addiction and other psychiatric disorders.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Pedron, S; Monnin, J; Haffen, E; Sechter, D; Van Waes, V


Neural basis of tDCS effects on auditory verbal hallucinations in schizophrenia: a case report evidence for cortical neuroplasticity modulation.

2014 Mar

Transcranial direct current stimulation (tDCS) has been reported to ameliorate auditory hallucinations that are nonresponsive/minimally responsive to antipsychotic treatment in schizophrenia. The neurobiological basis of the tDCS effects in ameliorating auditory hallucinations is yet to be explored. In this case report, for the first time, using the novel method for noninvasive assessment of cortical plasticity, we demonstrate potential neuroplasticity effect of tDCS in improving treatment-resistant auditory hallucinations in a schizophrenic patient.

The journal of ECT

Nawani, H; Kalmady, SV; Bose, A; Shivakumar, V; Rakesh, G; Subramaniam, A; Narayanaswamy, JC; Venkatasubramanian, G


Domain-specific suppression of auditory mismatch negativity with transcranial direct current stimulation.

2014 Mar

To evaluate the influence of frontal transcranial direct current stimulation (tDCS) on auditory mismatch negativity (MMN).MMN is an event related potential calculated by subtracting the amplitude of the evoked potentials in response to a "standard" stimulus from the evoked potentials produced by a rare "oddball" stimulus. Here we assessed the influence of anodal tDCS, cathodal tDCS or sham stimulation delivered over the right inferior frontal cortex on MMN in response to duration and frequency auditory deviants in 10 healthy subjects.MMN to frequency deviants was significantly reduced after anodal tDCS compared with sham or cathodal stimulation which did not change MMN to frequency deviants. Neither anodal nor cathodal tDCS had any effect on MMN to duration deviants.Non-invasive brain stimulation with tDCS can influence MMN. The differing networks known to be activated by duration and frequency deviants could account for the differential effect of tDCS on duration and frequency MMN.Non-invasive brain stimulation could be a useful method to manipulate MMN for experimental purposes.

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

Chen, JC; Hämmerer, D; Strigaro, G; Liou, LM; Tsai, CH; Rothwell, JC; Edwards, MJ


The Effect of tDCS on Cognition and Neurologic Recovery of Rats with Alzheimer's Disease.

2014 Feb

[Purpose] This study examined the effect of the application of transcranial direct current stimulation (tDCS) on neurologic recovery and cognitive function of rats with Alzheimer-like dementia induced by scopolamine injections. [Subjects] To create a cognition dysfunction model, intraperitoneal injection of scopolamine was given to Sprague-Dawley rats that subsequently received tDCS for 4 weeks. [Methods] Changes in motor behavior were evaluated by conducting an open field test. Acetylcholine content in the cerebral cortex and hippocampus was examined for a biochemical assessment. [Results] With respect to changes in motor behavior, group II showed the most meaningful difference after scopolamine injection, followed by group III. In the biochemical assessment, the results of the examination of acetylcholine content in the tissue of the cerebral cortex and the hippocampus on the 14th and 28th days, respectively, showed the most significant increase in group II, followed by group III. [Conclusion] The above findings confirm that tDCS application after the onset of cognitive dysfunction caused by Alzheimer's disease leads to a positive effect on motor behavior and biochemical changes, and this effect is maintained over a specific period of time.

Journal of physical therapy science

Yu, SH; Park, SD; Sim, KC

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Working memory training with tDCS improves behavioral and neurophysiological symptoms in pilot group with post-traumatic stress disorder (PTSD) and with poor working memory.

2014 Feb

This pilot study investigated the feasibility of treating people suffering from both post-traumatic stress disorder (PTSD) and poor working memory by employing a combination of computerized working memory training and transcranial direct current stimulation (tDCS). After treatment, all four participants showed clinically significant improvements on a range of cognitive and emotional performance measures. Moreover, these improvements were accompanied by theoretically significant neurophysiological changes between pre- and post-treatment electroencephalographic (EEG) recordings. Specifically, the P3a component of participants' event related potentials (ERP) in response to novelty stimuli, characteristically abnormal in this clinical population, shifted significantly toward database norms. So, participants' initially slow alpha peak frequency (APF), theorized to underlie impaired cognitive processing abilities, also increased in both frequency and amplitude as a result of treatment. On the basis of these promising results, more extensive controlled studies are warranted.

Neurocase

Saunders, N; Downham, R; Turman, B; Kropotov, J; Clark, R; Yumash, R; Szatmary, A


Nonlinear dose-dependent impact of D1 receptor activation on motor cortex plasticity in humans.

2014 Feb

The neuromodulator dopamine plays an important role in synaptic plasticity. The effects are determined by receptor subtype specificity, concentration level, and the kind of neuroplasticity induced. D1-like receptors have been proposed to be involved in cognitive processes via their impact on plasticity. Cognitive studies in humans and animals revealed a dosage-dependent effect of D1-like receptor activation on task performance. In humans, D1-like receptor activation re-establishes plasticity under D2 receptor block. However, a dosage-dependent effect has not been explored so far. To determine the impact of the amount of D1-like receptor activation on neuroplasticity in humans, we combined sulpiride, a selective D2 receptor antagonist, with the dopamine precursor l-DOPA (25, 100, and 200 mg) or applied placebo medication. The impact on plasticity induced by anodal and cathodal transcranial direct current stimulation (tDCS) was compared with the impact on plasticity induced by excitatory and inhibitory paired associative stimulation (PAS) at the primary motor cortex of healthy humans. Stimulation-generated cortical excitability alterations were monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. D1-like receptor activation produced an inverted U-shaped dose-response curve on plasticity induced by both facilitatory tDCS and PAS. For excitability-diminishing tDCS and PAS, aftereffects were abolished or converted trendwise into facilitation. These data extend findings of dose-dependent inverted U-shaped effects of D1 receptor activation on neuroplasticity of the motor cortex.

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

Fresnoza, S; Paulus, W; Nitsche, MA; Kuo, MF

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Feeling better: separate pathways for targeted enhancement of spatial and temporal touch.

2014 Feb

People perceive spatial form and temporal frequency through touch. Although distinct somatosensory neurons represent spatial and temporal information, these neural populations are intermixed throughout the somatosensory system. Here, we show that spatial and temporal touch can be dissociated and separately enhanced via cortical pathways that are normally associated with vision and audition. In Experiments 1 and 2, we found that anodal transcranial direct current stimulation (tDCS) applied over visual cortex, but not auditory cortex, enhances tactile perception of spatial orientation. In Experiments 3 and 4, we found that anodal tDCS over auditory cortex, but not visual cortex, enhances tactile perception of temporal frequency. This double dissociation reveals separate cortical pathways that selectively support spatial and temporal channels. These results bolster the emerging view that sensory areas process multiple modalities and suggest that supramodal domains may be more fundamental to cortical organization.

Psychological science

Yau, JM; Celnik, P; Hsiao, SS; Desmond, JE


Bi-directional modulation of somatosensory mismatch negativity with transcranial direct current stimulation: an event related potential study.

2014 Feb

Appropriate orientation towards potentially salient novel environmental stimuli requires a system capable of detecting change in the sensorium. Mismatch negativity (MMN), an evoked potential calculated by subtracting the response to a standard repeated stimulus and a rare 'oddball' stimulus, is proposed as such a change detection mechanism. It is most widely studied in the auditory domain, but here we chose to explore the mechanism of somatosensory MMN, and specifically its dependence on the cerebellum. We recorded event-related potentials (ERPs) evoked in response to auditory and sensory stimuli from 10 healthy subjects before and after anodal, cathodal and sham transcranial direct current stimulation (tDCS) of the right cerebellar hemisphere. There was a significant increase in peak amplitude of somatosensory MMN after anodal tDCS (F(1,9) = 8.98, P < 0.02, mean difference anodal pre-post: -1.02 μV) and a significant reduction in peak amplitude of somatosensory MMN after cathodal tDCS (F(1,9) = 7.15, P < 0.03, mean difference cathodal pre-post: 0.65 μV). The amplitude of auditory MMN was unchanged by tDCS. These results reveal the capability of tDCS to cause bidirectional modulation of somatosensory MMN and the dependence of somatosensory MMN on the cerebellum.

The Journal of physiology

Chen, JC; Hämmerer, D; D'Ostilio, K; Casula, EP; Marshall, L; Tsai, CH; Rothwell, JC; Edwards, MJ


Facilitative effects of bi-hemispheric tDCS in cognitive deficits of Parkinson disease patients.

2014 Feb

Parkinson's disease (PD) is a progressive neurodegenerative disorder, primarily characterized by motor symptoms such as tremor, rigidity, bradykinesia, stiffness, slowness and impaired equilibrium. Although the motor symptoms have been the focus in PD, slight cognitive deficits are commonly found in non-demented and non-depressed PD patients, even in early stages of the disease, which have been linked to the subsequent development of pathological dementia. Thus, strongly reducing the quality of life (QoL). Both levodopa therapy and deep brain stimulation (DBS) have yield controversial results concerning the cognitive symptoms amelioration in PD patients. That does not seems to be the case with transcranial direct current stimulation (tDCS), although better stimulation parameters are needed. Therefore we hypothesize that simultaneously delivering cathodal tDCS (or ctDCS), over the right prefrontal cortex delivered with anodal tDCS (or atDCS) to left prefrontal cortex could be potentially beneficial for PD patients, either by mechanisms of homeostatic plasticity and by increases in the extracellular dopamine levels over the striatum.

Medical hypotheses

Leite, J; Gonçalves, OF; Carvalho, S


Investigation of tDCS volume conduction effects in a highly realistic head model.

2014 Feb

We investigate volume conduction effects in transcranial direct current stimulation (tDCS) and present a guideline for efficient and yet accurate volume conductor modeling in tDCS using our newly-developed finite element (FE) approach.We developed a new, accurate and fast isoparametric FE approach for high-resolution geometry-adapted hexahedral meshes and tissue anisotropy. To attain a deeper insight into tDCS, we performed computer simulations, starting with a homogenized three-compartment head model and extending this step by step to a six-compartment anisotropic model.We are able to demonstrate important tDCS effects. First, we find channeling effects of the skin, the skull spongiosa and the cerebrospinal fluid compartments. Second, current vectors tend to be oriented towards the closest higher conducting region. Third, anisotropic WM conductivity causes current flow in directions more parallel to the WM fiber tracts. Fourth, the highest cortical current magnitudes are not only found close to the stimulation sites. Fifth, the median brain current density decreases with increasing distance from the electrodes.Our results allow us to formulate a guideline for volume conductor modeling in tDCS. We recommend to accurately model the major tissues between the stimulating electrodes and the target areas, while for efficient yet accurate modeling, an exact representation of other tissues is less important. Because for the low-frequency regime in electrophysiology the quasi-static approach is justified, our results should also be valid for at least low-frequency (e.g., below 100 Hz) transcranial alternating current stimulation.

Journal of neural engineering

Wagner, S; Rampersad, SM; Aydin, Ü; Vorwerk, J; Oostendorp, TF; Neuling, T; Herrmann, CS; Stegeman, DF; Wolters, CH


Transcranial direct current stimulation reverses neurophysiological and behavioural effects of focal inhibition of human pharyngeal motor cortex on swallowing.

2014 Feb

The human cortical swallowing system exhibits bilateral but functionally asymmetric representation in health and disease as evidenced by both focal cortical inhibition (pre-conditioning with 1 Hz repetitive transcranial magnetic stimulation; rTMS) and unilateral stroke, where disruption of the stronger (dominant) pharyngeal projection alters swallowing neurophysiology and behaviour. Moreover, excitatory neurostimulation protocols capable of reversing the disruptive effects of focal cortical inhibition have demonstrated therapeutic promise in post-stroke dysphagia when applied contralaterally. In healthy participants (n = 15, 8 males, mean age (±SEM) 35 ± 9 years), optimal parameters of transcranial direct current stimulation (tDCS) (anodal, 1.5 mA, 10 min) were applied contralaterally after 1 Hz rTMS pre-conditioning to the strongest pharyngeal projection. Swallowing neurophysiology was assessed in both hemispheres by intraluminal recordings of pharyngeal motor-evoked responses (PMEPs) to single-pulse TMS as a measure of cortical excitability. Swallowing behaviour was examined using a pressure-based reaction time protocol. Measurements were made before and for up to 60 min post intervention. Subjects were randomised to active or sham tDCS after 1 Hz rTMS on separate days and data were compared using repeated measures ANOVA. Active tDCS increased PMEPs bilaterally (F1,14 = 7.4, P = 0.017) reversing the inhibitory effects of 1 Hz rTMS in the pre-conditioned hemisphere (F1,14 = 10.1, P = 0.007). Active tDCS also enhanced swallowing behaviour, increasing the number of correctly timed challenge swallows compared to sham (F1,14 = 6.3, P = 0.025). Thus, tDCS to the contralateral pharyngeal motor cortex reverses the neurophysiological and behavioural effects of focal cortical inhibition on swallowing in healthy individuals and has therapeutic potential for dysphagia rehabilitation.

The Journal of physiology

Vasant, DH; Mistry, S; Michou, E; Jefferson, S; Rothwell, JC; Hamdy, S


A computational modelling study of transcranial direct current stimulation montages used in depression.

2014 Feb

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which involves passing a mild electric current to the brain through electrodes placed on the scalp. Several clinical studies suggest that tDCS may have clinically meaningful efficacy in the treatment of depression. The objective of this study was to simulate and compare the effects of several tDCS montages either used in clinical trials or proposed, for the treatment of depression, in different high-resolution anatomically-accurate head models. Detailed segmented finite element head models of two subjects were presented, and a total of eleven tDCS electrode montages were simulated. Sensitivity analysis on the effects of changing the size of the anode, rotating both electrodes and displacing the anode was also conducted on selected montages. The F3-F8 and F3-F4 montages have been used in clinical trials reporting significant antidepressant effects and both result in relatively high electric fields in dorsolateral prefrontal cortices. Other montages using a fronto-extracephalic or fronto-occipital approach result in greater stimulation of central structures (e.g. anterior cingulate cortex) which may be advantageous in treating depression, but their efficacy has yet to be tested in randomised controlled trials. Results from sensitivity analysis suggest that electrode position and size may be adjusted slightly to accommodate other priorities, such as skin discomfort and damage.

NeuroImage

Bai, S; Dokos, S; Ho, KA; Loo, C


Dorsolateral pFC and the representation of the incorrect use of an object: the transcranial direct current stimulation effect on N400 for visual and linguistic stimuli.

2014 Feb

In this study, we explored the representation of an incongruent action (instrumentally incorrect use of an object) in comparison with sentences ending with an incongruent action word, taking into account the role of the activation of the left dorsolateral pFC (DLPFC). This activity was appositely modulated by transcranial direct current stimulation (tDCS). The effect of tDCS when participants processed congruent/incongruent object-related actions (Experiment 1) or sentences (Experiment 2) was verified by measuring changes in the ERP N400, error rates (ERs), and RTs. In Experiment 1, 30 participants performed the detection task within a dynamic context (video tapes representing a sequence of four action frames). In Experiment 2, 28 participants read sentences that represented object-related actions. The stimulation effect (a cathode applied to the DLPFC and an anode to the right supraorbital region) was analyzed by comparing the ER, RT, and ERP profiles before and after stimulation (or sham treatment). A significant reduction of the N400 was observed for incongruent stimuli in the case of cathodal (inhibitory) stimulation of the DLPFC in comparison with prestimulation conditions for Experiment 1, but not Experiment 2. Moreover, ERs were increased, and RTs were reduced in response to incongruent conditions after tDCS, but not after sham stimulation in Experiment 1. It is suggested that perturbation of the DLPFC may limit the ability to analyze a semantically anomalous action sequence as a reduced N400 ERP effect and increased random responses was observed. Finally, the contribution of the frontal area to the semantic processing of actions is discussed.

Journal of cognitive neuroscience

Balconi, M; Vitaloni, S


Transcranial direct current stimulation (tDCS) of the cortical motor areas in three cases of cerebellar ataxia.

2014 Feb

The excitability of the motor areas of the cerebral cortex is reduced in ataxia. Since transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique able to increase the cortical excitability, we assessed the effect of anodal tDCS over the motor cortex in three patients with ataxia. A clinical evaluation, a video-taped SARA rating scale and a gait analysis with cinematic parameters, were performed pre- and post-sham and anodal tDCS cycle. The full cycle was composed by five consecutive constant current sessions of stimulation. Anodal tDCS (2.0 mA, 20 min,max current density: 0.0278 mA/cm2, max total charge:0.033 C/cm2) was performed on the M1 area of the most affected side. The contralateral primary motor cortex underwent cathodal stimulation (2.0 mA, 20 min, max current density:0.0278 mA/cm2, max total charge: 0.033 C/cm2). After anodal tDCS, gait analysis revealed an improvement of the symmetry of step execution and reduction of base-width lasting 30 days associated to patients’ perception of amelioration. No relevant changes were found after sham stimulation. Our results suggest tDCS can improve gait symmetry in patients with ataxia for a short-term period. Future researches are needed in order to standardize time, amplitude, and area of stimulation in order to reach a long lasting effect on cerebellar ataxia.

Cerebellum (London, England)

Pozzi, NG; Minafra, B; Zangaglia, R; De Marzi, R; Sandrini, G; Priori, A; Pacchetti, C


Anodal transcranial pulsed current stimulation: A novel technique to enhance corticospinal excitability.

2014 Feb

We aimed to compare the effects of anodal-transcranial pulsed current stimulation (a-tPCS) with conventional anodal transcranial direct current stimulation (a-tDCS) on corticospinal excitability (CSE) in healthy individuals.CSE of the dominant primary motor cortex of the resting right extensor carpi radialis muscle was assessed before, immediately, 10, 20 and 30min after application of four experimental conditions: (1) a-tDCS, (2) a-tPCS with short inter-pulse interval (a-tPCSSIPI, 50ms), (3) a-tPCS with long inter-pulse interval (a-tPCSLIPI., 650ms) and (4) sham a-tPCS. The total charges were kept constant in all experimental conditions except sham condition. The outcome measure in this study was motor evoked potentials.Only a-tDCS and a-tPCSSIPI (P<0.05) induced significant increases in CSE, lasted for at least 30min. Post-hoc tests indicated that this increase was larger in a-tPCSSIPI (P<0.05). There were no significant changes following application of a-tPCSLIPI and sham a-tPCS. All participants tolerated the applied currents in all experimental conditions very well.Compared to a-tDCS, a-tPCSSIPI is a better technique for enhancement of CSE. There were no sham effects for application of a-tPCS. However, unlike a-tDCS which modifies neuronal excitability by tonic depolarization of the resting membrane potential, a-tPCS modifies neuronal excitability by a combination of tonic and phasic effects.a-tPCS could be considered as a promising neuromodulatory tool in basic neuroscience and as a therapeutic technique in neurorehabilitation.

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

Jaberzadeh, S; Bastani, A; Zoghi, M


Transcranial direct current stimulation effects in disorders of consciousness.

2014 Feb

To assess the efficacy of transcranial direct current stimulation (tDCS) on improving consciousness in patients with persistent unresponsive wakefulness syndrome (UWS) (previously termed persistent vegetative state [PVS]) or in a minimally conscious state (MCS).Prospective, case series trial with follow-up at 12 months.General and research hospital.Inpatients in a PVS/UWS or MCS (N=10; 7 men, 3 women; age range, 19-62y; etiology: traumatic brain injury, n=5; anoxia, n=4; postoperative infarct, n=1; duration of PVS/UWS or MCS range, 6mo-10y). No participant withdrew because of adverse effects.All patients received sham tDCS for 20 minutes per day, 5 days per week, for 1 week, and real tDCS for 20 minutes per day, 5 days per week, for 2 weeks. An anodal electrode was placed over the left primary sensorimotor cortex or the left dorsolateral prefrontal cortex, with cathodal stimulation over the right eyebrow. One patient in an MCS received a second round of 10 tDCS sessions 3 months after initial participation.JFK Coma Recovery Scale-Revised.All patients in an MCS showed clinical improvement immediately after treatment. The patient who received a second round of tDCS 3 months after initial participation showed further improvement and emergence into consciousness after stimulation, with no change between treatments. One patient who was in an MCS for <1 year before treatment (postoperative infarct) showed further improvement and emergence into consciousness at 12-month follow-up. No patient showed improvement before stimulation. No patient in a PVS/UWS showed immediate improvement after stimulation, but 1 patient who was in a PVS/UWS for 6 years before treatment showed improvement and change of status to an MCS at 12-month follow-up.tDCS seems promising for the rehabilitation of patients with severe disorders of consciousness. Severity and duration of pathology may be related to the degree of tDCS' beneficial effects.

Archives of physical medicine and rehabilitation

Angelakis, E; Liouta, E; Andreadis, N; Korfias, S; Ktonas, P; Stranjalis, G; Sakas, DE


Comparison of blinding effectiveness between sham tDCS and placebo sertraline in a 6-week major depression randomized clinical trial.

2014 Feb

To compare blinding integrity and associated factors for transcranial direct current stimulation (tDCS) vs. placebo-pill, the gold standard blinding method.Parallel trial. Depressed participants were randomized to verum/placebo sertraline and active/sham tDCS (2mA, 30-min 10-daily sessions and two additional, fortnight sessions) over 6weeks. Blinding was assessed in completers (n=102) and in a random subgroup (n=35) of raters and participants, in which we also inquired to qualitatively describe their strongest guessing reason.Participants and raters presented similar performance for predicting treatment assignment at endpoint, correctly guessing tDCS and sertraline beyond chance. Nevertheless, clinical response was associated with correct prediction and tDCS non-responders failed to predict the allocation group. For tDCS, "trouble concentrating" was inversely associated with correct prediction. "Skin redness" was more reported for active-tDCS, but did not predict the allocation group. The qualitative reasons for raters' guessing were not associated with correct prediction, whereas for participants clinical response and adverse effects were directly and inversely associated with correct prediction, respectively.Blinding integrity of tDCS and sertraline were comparable and mainly associated with efficacy rather than blinding failure.TDCS blinding can be improved by adopting parallel designs and avoiding subjects' awareness of skin redness.

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

Brunoni, AR; Schestatsky, P; Lotufo, PA; Benseñor, IM; Fregni, F


Non-invasive cerebellar stimulation--a consensus paper.

2014 Feb

The field of neurostimulation of the cerebellum either with transcranial magnetic stimulation (TMS; single pulse or repetitive (rTMS)) or transcranial direct current stimulation (tDCS; anodal or cathodal) is gaining popularity in the scientific community, in particular because these stimulation techniques are non-invasive and provide novel information on cerebellar functions. There is a consensus amongst the panel of experts that both TMS and tDCS can effectively influence cerebellar functions, not only in the motor domain, with effects on visually guided tracking tasks, motor surround inhibition, motor adaptation and learning, but also for the cognitive and affective operations handled by the cerebro-cerebellar circuits. Verbal working memory, semantic associations and predictive language processing are amongst these operations. Both TMS and tDCS modulate the connectivity between the cerebellum and the primary motor cortex, tuning cerebellar excitability. Cerebellar TMS is an effective and valuable method to evaluate the cerebello-thalamo-cortical loop functions and for the study of the pathophysiology of ataxia. In most circumstances, DCS induces a polarity-dependent site-specific modulation of cerebellar activity. Paired associative stimulation of the cerebello-dentato-thalamo-M1 pathway can induce bidirectional long-term spike-timing-dependent plasticity-like changes of corticospinal excitability. However, the panel of experts considers that several important issues still remain unresolved and require further research. In particular, the role of TMS in promoting cerebellar plasticity is not established. Moreover, the exact positioning of electrode stimulation and the duration of the after effects of tDCS remain unclear. Future studies are required to better define how DCS over particular regions of the cerebellum affects individual cerebellar symptoms, given the topographical organization of cerebellar symptoms. The long-term neural consequences of non-invasive cerebellar modulation are also unclear. Although there is an agreement that the clinical applications in cerebellar disorders are likely numerous, it is emphasized that rigorous large-scale clinical trials are missing. Further studies should be encouraged to better clarify the role of using non-invasive neurostimulation techniques over the cerebellum in motor, cognitive and psychiatric rehabilitation strategies.

Cerebellum (London, England)

Grimaldi, G; Argyropoulos, GP; Boehringer, A; Celnik, P; Edwards, MJ; Ferrucci, R; Galea, JM; Groiss, SJ; Hiraoka, K; Kassavetis, P; Lesage, E; Manto, M; Miall, RC; Priori, A; Sadnicka, A; Ugawa, Y; Ziemann, U


Enhancement of affective processing induced by bifrontal transcranial direct current stimulation in patients with major depression.

2014 Feb

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.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.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.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


Single session of dual-tDCS transiently improves precision grip and dexterity of the paretic hand after stroke.

2014 Feb

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.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.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.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.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


The effect of single session bi-cephalic transcranial direct current stimulation on gait performance in sub-acute stroke: A pilot study.

2014 Jan

Non-invasive brain stimulation with transcranial direct current stimulation (tDCS) modulates cortical excitability and improves upper limb motor performance when applied to chronic stroke patients. The objective was to evaluate whether tDCS can influence gait function in sub-acute stroke patients.We assessed the effect of single session, bi-cephalic tDCS on gait performance in 14 subacute patients with stroke involving the cerebral hemisphere (2-8 weeks post-stroke) in a double-blinded, sham-controlled study. Patients were randomly allocated to receive either active (n = 7) or sham (n = 7) tDCS. The anodal electrode was placed on the scalp over the ipsilesional lower limb primary motor cortex and the cathode was placed over the contralesional leg motor cortex. Gait performance was measured using the Timed Up and Go test and the Performance Oriented Mobility Assessment before and after active or sham tDCS.The tDCS group was significantly quicker in the Timed Up and Go test in the tDCS group, compared to the sham group (p = 0.018). The Performance Oriented Mobility Assessment was not different between groups (p = 0.897).This is the first study to examine the effects of tDCS on gait in stroke patients in the sub-acute stage. Active tDCS improved gait performance (Timed Up and Go) in stroke patients, despite no changes to limb biomechanics of the hemiparetic side (Performance Oriented Mobility Assessment), as compared to sham stimulation. These results suggest that tDCS could be used as a therapeutic adjunct for gait rehabilitation following stroke.

Restorative neurology and neuroscience

Tahtis, V; Kaski, D; Seemungal, BM


Bihemispheric transcranial direct current stimulation enhances effector-independent representations of motor synergy and sequence learning.

2014 Jan

Complex manual tasks-everything from buttoning up a shirt to playing the piano-fundamentally involve two components: (1) generating specific patterns of muscle activity (here, termed "synergies"); and (2) stringing these into purposeful sequences. Although transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) has been found to increase the learning of motor sequences, it is unknown whether it can similarly facilitate motor synergy learning. Here, we determined the effects of tDCS on the learning of motor synergies using a novel hand configuration task that required the production of difficult muscular activation patterns. Bihemispheric tDCS was applied to M1 of healthy, right-handed human participants during 4 d of repetitive left-hand configuration training in a double-blind design. tDCS augmented synergy learning, leading subsequently to faster and more synchronized execution. This effect persisted for at least 4 weeks after training. Qualitatively similar tDCS-associated improvements occurred during training of finger sequences in a separate subject cohort. We additionally determined whether tDCS only improved the acquisition of motor memories for specific synergies/sequences or whether it also facilitated more general parts of the motor representations, which could be transferred to novel movements. Critically, we observed that tDCS effects generalized to untrained hand configurations and untrained finger sequences (i.e., were nonspecific), as well as to the untrained hand (i.e., were effector-independent). Hence, bihemispheric tDCS may be a promising adjunct to neurorehabilitative training regimes, in which broad transfer to everyday tasks is highly desirable.

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

Waters-Metenier, S; Husain, M; Wiestler, T; Diedrichsen, J

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Efficacy of semantic-phonological treatment combined with tDCS for verb retrieval in a patient with aphasia.

2014 Jan

Recent studies reported enhanced performance on language tasks induced by transcranial direct current stimulation (tDCS) in patients with aphasia. One chronic patient with non-fluent aphasia received 20 sessions of a verb anomia training combined with off-line bihemispheric tDCS applied to the dorsolateral prefrontal cortex (DLPFC) - anodal tDCS over left DLPFC plus cathodal tDCS over right DLPFC. A significant improvement in verb naming was observed at all testing times (4, 12, 24, and 48 weeks from post-entry/baseline testing) for treated and untreated verbs. Our findings show beneficial effects of verb anomia training in combination with tDCS in chronic aphasic patient, suggesting a long-lasting effect of this treatment.

Neurocase

Manenti, R; Petesi, M; Brambilla, M; Rosini, S; Miozzo, A; Padovani, A; Miniussi, C; Cotelli, M


Something to talk about: enhancement of linguistic cohesion through tdCS in chronic non fluent aphasia.

2014 Jan

Several studies have shown that the modulation of cortical activity through transcranial direct current stimulation (tDCS) enhances naming performance in persons with aphasia. In this study, we investigated the potential effects of tDCS in improving spontaneous speech and the ability to use connective words to establish cohesion among adjacent utterances in a group of eight participants with chronic non fluent aphasia. They were administered five short videoclips representing everyday life contexts and two picture description tasks. Three videoclips were used to elicit spontaneous conversation during the treatment, while the remaining tasks were presented to the patients only before and after the therapy. Patients were required to talk about each videoclip, with the help of a therapist, while they were treated with tDCS (20 min, 1 mA) over the left hemisphere in three different conditions: anodic tDCS over the Broca's area, anodic tDCS over the Wernicke's area and a sham condition. Each experimental condition was performed for ten consecutive daily sessions with 14 days of intersession interval. Only after Broca's stimulation, patients showed a greater improvement in producing words that enhanced the cohesion of their speech samples (i.e., pronouns, ellipses, word repetitions, conjunctions). Beneficial effects of the stimulation were generalized also to contexts presented to the patients at the beginning and at the end of the therapy sessions. Our data further confirm the key role of the left inferior frontal gyrus in binding words into a coherent speech. We believe that positive tDCS effects may be further extended to different linguistic domains, useful to promote language recovery.

Neuropsychologia

Marangolo, P; Fiori, V; Campana, S; Calpagnano, MA; Razzano, C; Caltagirone, C; Marini, A


"If two witches would watch two watches, which witch would watch which watch?" tDCS over the left frontal region modulates tongue twister repetition in healthy subjects.

2014 Jan

Recent studies have demonstrated that transcranial direct current stimulation (tDCS) modulates cortical activity in the human brain. In the language domain, it has already been shown that during a naming task tDCS reduces vocal reaction times in healthy individuals and speeds up the recovery process in left brain-damaged aphasic subjects. In this study, we wondered whether tDCS would influence the ability to articulate tongue twisters during a repetition task. Three groups of 10 healthy individuals were asked to repeat a list of tongue twisters in three different stimulation conditions: one group performed the task during anodal tDCS (atDCS) (20 min, 2 mA) over the left frontal region; a second group during cathodal tDCS delivered over the same region; and, in a third group, sham stimulation was applied. Accuracy and vocal reaction times in repeating each tongue twister before, during and 1h after the stimulation were recorded. Participants were more accurate and faster at repeating the stimuli during atDCS than at baseline, while cathodal tDCS significantly reduced their performance in terms of accuracy and reaction times. No significant differences were observed among the three time points during the sham condition. We believe that these data clearly confirm that the left frontal region is critically involved in the process of speech repetition. They are also in line with recent evidence suggesting that frontal tDCS might be used as a therapeutic tool in patients suffering from articulatory deficits.

Neuroscience

Fiori, V; Cipollari, S; Caltagirone, C; Marangolo, P


Long-term effects of transcranial direct current stimulation combined with computer-assisted cognitive training in healthy older adults.

2014 Jan

The aim of the present study was to analyze the long-term effects of transcranial direct current stimulation (tDCS) of the bilateral prefrontal cortex combined with computer-assisted cognitive training on working memory and cognitive function in healthy older adults aged at least 65 years. Forty healthy older adults were enrolled and randomly assigned to two groups: anodal and sham tDCS. All participants completed 10 sessions of computer-assisted cognitive training, combined with tDCS of the bilateral prefrontal cortex. The accuracy of the verbal working memory task and performance of the digit span forward test were significantly improved after computer-assisted cognitive training combined with bifrontal anodal tDCS as compared with that after computer-assisted cognitive training combined with sham tDCS. Moreover, the effect lasts for 4 weeks in the verbal working memory task. We suggest that the tDCS-induced changes in the bilateral prefrontal excitability during computer-assisted cognitive training may have beneficial effects on age-related cognitive decrement in healthy older adults.

Neuroreport

Park, SH; Seo, JH; Kim, YH; Ko, MH


Invasive and non-invasive brain stimulation for treatment of neuropathic pain in patients with spinal cord injury: a review.

2014 Jan

Past evidence has shown that invasive and non-invasive brain stimulation may be effective for relieving central pain.To perform a topical review of the literature on brain neurostimulation techniques in patients with chronic neuropathic pain due to traumatic spinal cord injury (SCI) and to assess the current evidence for their therapeutic efficacy.A MEDLINE search was performed using following terms: "Spinal cord injury", "Neuropathic pain", "Brain stimulation", "Deep brain stimulation" (DBS), "Motor cortex stimulation" (MCS), "Transcranial magnetic stimulation" (TMS), "Transcranial direct current stimulation" (tDCS), "Cranial electrotherapy stimulation" (CES).Invasive neurostimulation therapies, in particular DBS and epidural MCS, have shown promise as treatments for neuropathic and phantom limb pain. However, the long-term efficacy of DBS is low, while MCS has a relatively higher potential with lesser complications that DBS. Among the non-invasive techniques, there is accumulating evidence that repetitive TMS can produce analgesic effects in healthy subjects undergoing laboratory-induced pain and in chronic pain conditions of various etiologies, at least partially and transiently. Another very safe technique of non-invasive brain stimulation - tDCS - applied over the sensory-motor cortex has been reported to decrease pain sensation and increase pain threshold in healthy subjects. CES has also proved to be effective in managing some types of pain, including neuropathic pain in subjects with SCI.A number of studies have begun to use non-invasive neuromodulatory techniques therapeutically to relieve neuropathic pain and phantom phenomena in patients with SCI. However, further studies are warranted to corroborate the early findings and confirm different targets and stimulation paradigms. The utility of these protocols in combination with pharmacological approaches should also be explored.

The journal of spinal cord medicine

Nardone, R; Höller, Y; Leis, S; Höller, P; Thon, N; Thomschewski, A; Golaszewski, S; Brigo, F; Trinka, E


Differential improvement in depressive symptoms for tDCS alone and combined with pharmacotherapy: an exploratory analysis from the Sertraline vs. Electrical Current Therapy for Treating Depression Clinical Study.

2014 Jan

Transcranial direct current stimulation (tDCS) is a promising therapy for major depression treatment, although little is known of its effects in ameliorating distinct symptoms of depression. Thus, it is important, not only to increase knowledge of its antidepressant mechanisms, but also to guide its potential use in clinical practice. Using data from a recent factorial, double-blinded, placebo-controlled trial applying tDCS-alone and combined with sertraline to treat 120 depressed outpatients over 6 wk (Brunoni et al., 2013), we investigated the pattern of improvement in symptoms of depression from the Montgomery-Asberg depression scale (MADRS). First, we performed one multivariate analysis of variance with the score improvement of the 10 MADRS items as dependent variables. Significant (p < 0.05) results were further explored with follow-up analyses of variance. TDCS (alone and combined with sertraline) improved concentration difficulties and pessimistic and suicidal thoughts. The combined treatment also improved apparent and reported sadness, lassitude and inability to feel. Indeed, tDCS/sertraline significantly ameliorated all but the 'vegetative' depression symptoms (inner tension, sleep and appetite items). We further discuss whether bifrontal tDCS over the dorsolateral prefrontal cortex could be associated with improvement in cognitive (concentration) and affective (pessimistic/suicidal thoughts) processing, while the combined treatment might have a more widespread antidepressant effect by simultaneously acting on different depression pathways. We also identified patterns of antidepressant improvement for tDCS that might aid in tailoring specific interventions for different subtypes of depressed patients, e.g. particularly those with suicidal ideation.

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

Brunoni, AR; Júnior, RF; Kemp, AH; Lotufo, PA; Benseñor, IM; Fregni, F


Neuroenhancement: enhancing brain and mind in health and in disease.

2014 Jan

Humans have long used cognitive enhancement methods to expand the proficiency and range of the various mental activities that they engage in, including writing to store and retrieve information, and computers that allow them to perform myriad activities that are now commonplace in the internet age. Neuroenhancement describes the use of neuroscience-based techniques for enhancing cognitive function by acting directly on the human brain and nervous system, altering its properties to increase performance. Cognitive neuroscience has now reached the point where it may begin to put theory derived from years of experimentation into practice. This special issue includes 16 articles that employ or examine a variety of neuroenhancement methods currently being developed to increase cognition in healthy people and in patients with neurological or psychiatric illness. This includes transcranial electromagnetic stimulation methods, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), along with deep brain stimulation, neurofeedback, behavioral training techniques, and these and other techniques in conjunction with neuroimaging. These methods can be used to improve attention, perception, memory and other forms of cognition in healthy individuals, leading to better performance in many aspects of everyday life. They may also reduce the cost, duration and overall impact of brain and mental illness in patients with neurological and psychiatric illness. Potential disadvantages of these techniques are also discussed. Given that the benefits of neuroenhancement outweigh the potential costs, these methods could potentially reduce suffering and improve quality of life for everyone, while further increasing our knowledge about the mechanisms of human cognition.

NeuroImage

Clark, VP; Parasuraman, R

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Transcranial direct current stimulation over multiple days improves learning and maintenance of a novel vocabulary.

2014 Jan

Recently, growing interest emerged in the enhancement of human potential by means of non-invasive brain stimulation. In particular, anodal transcranial direct current stimulation (atDCS) has been shown to exert beneficial effects on motor and higher cognitive functions. However, the majority of transcranial direct current stimulation (tDCS) studies have assessed effects of single stimulation sessions that are mediated by transient neural modulation. Studies assessing the impact of multiple stimulation sessions on learning that may induce long-lasting behavioural and neural changes are scarce and have not yet been accomplished in the language domain in healthy individuals.The present study probed the potential of atDCS to enhance language learning over multiple days by employing an explicit word learning paradigm. Forty healthy young participants were randomized to learning with either simultaneous atDCS or sham stimulation (N = 20/group; comparable regarding demographic variables and neurocognitive status). All participants acquired a novel vocabulary (familiar and novel object picture - non-word pairs) over five consecutive days. Two memory tasks (free recall; forced choice recognition tasks) were administered immediately after each training session. A one week follow-up tested the maintenance of learning success.Linear mixed effects model analysis revealed superior learning during atDCS compared to sham stimulation for both familiar and novel objects. atDCS yielded a steeper learning curve and significantly more pronounced learning at the end of the training during the recall task. During the recognition task, the atDCS group reached ceiling levels earlier and overall learning success was greater. For both tasks, beneficial atDCS effects were maintained during the follow-up assessment.The present study provides direct evidence that atDCS administered during multiple learning sessions facilitates language learning and that effects are maintained over time. This study contributes important novel information about the extent of stimulation effects in the healthy brain, thereby highlighting the potential of atDCS to enhance language recovery after stroke.

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

Meinzer, M; Jähnigen, S; Copland, DA; Darkow, R; Grittner, U; Avirame, K; Rodriguez, AD; Lindenberg, R; Flöel, A


Battery powered thought: enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation.

2014 Jan

This article reviews studies demonstrating enhancement with transcranial direct current stimulation (tDCS) of attention, learning, and memory processes in healthy adults. Given that these are fundamental cognitive functions, they may also mediate stimulation effects on other higher-order processes such as decision-making and problem solving. Although tDCS research is still young, there have been a variety of methods used and cognitive processes tested. While these different methods have resulted in seemingly contradictory results among studies, many consistent and noteworthy effects of tDCS on attention, learning, and memory have been reported. The literature suggests that although tDCS as typically applied may not be as useful for localization of function in the brain as some other methods of brain stimulation, tDCS may be particularly well-suited for practical applications involving the enhancement of attention, learning, and memory, in both healthy subjects and in clinical populations.

NeuroImage

Coffman, BA; Clark, VP; Parasuraman, R


Therapeutic effects of non-invasive brain stimulation with direct currents (tDCS) in neuropsychiatric diseases.

2014 Jan

Neuroplasticity, which is the dynamic structural and functional reorganization of central nervous system connectivity due to environmental and internal demands, is recognized as a major physiological basis for adaption of cognition, and behavior, and thus of utmost importance for normal brain function. Pathological alterations of plasticity are increasingly explored as pathophysiological foundation of diverse neurological and psychiatric diseases. Non-invasive brain stimulation techniques (NIBS), such as repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS), are able to induce and modulate neuroplasticity in humans. Therefore, they have potential to alter pathological plasticity on the one hand, and foster physiological plasticity on the other, in neuropsychiatric diseases to reduce symptoms, and enhance rehabilitation. tDCS is an emerging NIBS tool, which induces glutamatergic plasticity via application of relatively weak currents through the scalp in humans. In the last years its efficacy to treat neuropsychiatric diseases has been explored increasingly. In this review, we will give an overview of pathological alterations of plasticity in neuropsychiatric diseases, gather clinical studies involving tDCS to ameliorate symptoms, and discuss future directions of application, with an emphasis on optimizing stimulation effects.

NeuroImage

Kuo, MF; Paulus, W; Nitsche, MA


Targeted therapies using electrical and magnetic neural stimulation for the treatment of chronic pain in spinal cord injury.

2014 Jan

Chronic neuropathic pain is one of the most common and disabling symptoms in individuals with spinal cord injury (SCI). Over two-thirds of subjects with SCI suffer from chronic pain influencing quality of life, rehabilitation, and recovery. Given the refractoriness of chronic pain to most pharmacological treatments, the majority of individuals with SCI report worsening of this condition over time. Moreover, only 4-6% of patients in this cohort report improvement. Novel treatments targeting mechanisms associated with pain-maladaptive plasticity, such as electromagnetic neural stimulation, may be desirable to improve outcomes. To date, few, small clinical trials have assessed the effects of invasive and noninvasive nervous system stimulation on pain after SCI.We aimed to review initial efficacy, safety and potential predictors of response by assessing the effects of neural stimulation techniques to treat SCI pain.A literature search was performed using the PubMed database including studies using the following targeted stimulation strategies: transcranial Direct Current Stimulation (tDCS), High Definition tDCS (HD-tDCS), repetitive Transcranial Magnetical Stimulation (rTMS), Cranial Electrotherapy Stimulation (CES), Transcutaneous Electrical Nerve Stimulation (TENS), Spinal Cord Stimulation (SCS) and Motor Cortex Stimulation (MCS), published prior to June of 2012. We included studies from 1998 to 2012.Eight clinical trials and one naturalistic observational study (nine studies in total) met the inclusion criteria. Among the clinical trials, three studies assessed the effects of tDCS, two of CES, two of rTMS and one of TENS. The naturalistic study investigated the analgesic effects of SCS. No clinical trials for epidural motor cortex stimulation (MCS) or HD-tDCS were found. Parameters of stimulation and also clinical characteristics varied significantly across studies. Three out of eight studies showed larger effects sizes (0.73, 0.88 and 1.86 respectively) for pain reduction. Classical neuropathic pain symptoms such as dysesthesia (defined as an unpleasant burning sensation in response to touch), allodynia (pain due to a non-painful stimulus), pain in paroxysms, location of SCI in thoracic and lumbar segments and pain in the lower limbs seem to be associated with a positive response to neural stimulation. No significant adverse effects were reported in these studies.Chronic pain in SCI is disabling and resistant to common pharmacologic approaches. Electrical and magnetic neural stimulation techniques have been developed to offer a potential tool in the management of these patients. Although some of these techniques are associated with large standardized mean differences to reduce pain, we found an important variability in these results across studies. There is a clear need for the development

NeuroImage

Moreno-Duarte, I; Morse, LR; Alam, M; Bikson, M; Zafonte, R; Fregni, F


Predicting behavioural response to TDCS in chronic motor stroke.

2014 Jan

Transcranial direct current stimulation (TDCS) of primary motor cortex (M1) can transiently improve paretic hand function in chronic stroke. However, responses are variable so there is incentive to try to improve efficacy and or to predict response in individual patients. Both excitatory (Anodal) stimulation of ipsilesional M1 and inhibitory (Cathodal) stimulation of contralesional M1 can speed simple reaction time. Here we tested whether combining these two effects simultaneously, by using a bilateral M1-M1 electrode montage, would improve efficacy. We tested the physiological efficacy of Bilateral, Anodal or Cathodal TDCS in changing motor evoked potentials (MEPs) in the healthy brain and their behavioural efficacy in changing reaction times with the paretic hand in chronic stroke. In addition, we aimed to identify clinical or neurochemical predictors of patients' behavioural response to TDCS. There were three main findings: 1) unlike Anodal and Cathodal TDCS, Bilateral M1-M1 TDCS (1 mA, 20 min) had no significant effect on MEPs in the healthy brain or on reaction time with the paretic hand in chronic stroke patients; 2) GABA levels in ipsilesional M1 predicted patients' behavioural gains from Anodal TDCS; and 3) although patients were in the chronic phase, time since stroke (and its combination with Fugl-Meyer score) was a positive predictor of behavioural gain from Cathodal TDCS. These findings indicate the superiority of Anodal or Cathodal over Bilateral TDCS in changing motor cortico-spinal excitability in the healthy brain and in speeding reaction time in chronic stroke. The identified clinical and neurochemical markers of behavioural response should help to inform the optimization of TDCS delivery and to predict patient outcome variability in future TDCS intervention studies in chronic motor stroke.

NeuroImage

O'Shea, J; Boudrias, MH; Stagg, CJ; Bachtiar, V; Kischka, U; Blicher, JU; Johansen-Berg, H

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tDCS-enhanced motor and cognitive function in neurological diseases.

2014 Jan

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool that is now being widely used in neuroscientific and clinical research in humans. While initial studies focused on modulation of cortical excitability, the technique quickly progressed to studies on motor and cognitive functions in healthy humans and in patients with neurological diseases. In the present review we will first provide the reader with a brief background on the basic principles of tDCS. In the main part, we will outline recent studies with tDCS that aimed at enhancing behavioral outcome or disease-specific symptoms in patients suffering from mild cognitive impairment, Alzheimer's disease, movement disorders, and epilepsy, or persistent deficits after stroke. The review will close with a summary statement on the present use of tDCS in the treatment of neurological disorders, and an outlook to further developments in this realm. tDCS may be an ideal tool to be administered in parallel to intensive cognitive or motor training in neurological disease, but efficacy for the areas of activities and participation still needs to be established in controlled randomized trials. Its use in reducing disease-specific symptoms like dystonia or epileptic seizures is still unclear.

NeuroImage

Flöel, A


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

2014 Jan

The neurological manifestations of cerebellar diseases range from motor to 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


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

2014 Jan

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


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

2014 Jan

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

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Transcranial direct current stimulation and power spectral parameters: a tDCS/EEG co-registration study.

2014

Transcranial direct current stimulation (tDCS) delivers low electric currents to the brain through the scalp. Constant electric currents induce shifts in neuronal membrane excitability, resulting in secondary changes in cortical activity. Concomitant electroencephalography (EEG) monitoring during tDCS can provide valuable information on the tDCS mechanisms of action. This study examined the effects of anodal tDCS on spontaneous cortical activity in a resting brain to disclose possible modulation of spontaneous oscillatory brain activity. EEG activity was measured in ten healthy subjects during and after a session of anodal stimulation of the postero-parietal cortex to detect the tDCS-induced alterations. Changes in the theta, alpha, beta, and gamma power bands were investigated. Three main findings emerged: (1) an increase in theta band activity during the first minutes of stimulation; (2) an increase in alpha and beta power during and after stimulation; (3) a widespread activation in several brain regions.

Frontiers in human neuroscience

Mangia, AL; Pirini, M; Cappello, A

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Transcranial stimulation of the developing brain: a plea for extreme caution.

2014

Frontiers in human neuroscience

Davis, NJ

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Tuning and disrupting the brain-modulating the McGurk illusion with electrical stimulation.

2014

In the so-called McGurk illusion, when the synchronized presentation of the visual stimulus /ga/ is paired with the auditory stimulus /ba/, people in general hear it as /da/. Multisensory integration processing underlying this illusion seems to occur within the Superior Temporal Sulcus (STS). Herein, we present evidence demonstrating that bilateral cathodal transcranial direct current stimulation (tDCS) of this area can decrease the McGurk illusion-type responses. Additionally, we show that the manipulation of this audio-visual integrated output occurs irrespective of the number of eye-fixations on the mouth of the speaker. Bilateral anodal tDCS of the Parietal Cortex also modulates the illusion, but in the opposite manner, inducing more illusion-type responses. This is the first demonstration of using non-invasive brain stimulation to modulate multisensory speech perception in an illusory context (i.e., both increasing and decreasing illusion-type responses to a verbal audio-visual integration task). These findings provide clear evidence that both the superior temporal and parietal areas contribute to multisensory integration processing related to speech perception. Specifically, STS seems fundamental for the temporal synchronization and integration of auditory and visual inputs. For its part, posterior parietal cortex (PPC) may adjust the arrival of incoming audio and visual information to STS thereby enhancing their interaction in this latter area.

Frontiers in human neuroscience

Marques, LM; Lapenta, OM; Merabet, LB; Bolognini, N; Boggio, PS

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Facilitation of corticospinal excitability by virtual reality exercise following anodal transcranial direct current stimulation in healthy volunteers and subacute stroke subjects.

2014

There is growing evidence that the combination of non-invasive brain stimulation and motor skill training is an effective new treatment option in neurorehabilitation. We investigated the beneficial effects of the application of transcranial direct current stimulation (tDCS) combined with virtual reality (VR) motor training.In total, 15 healthy, right-handed volunteers and 15 patients with stroke in the subacute stage participated. Four different conditions (A: active wrist exercise, B: VR wrist exercise, C: VR wrist exercise following anodal tDCS (1 mV, 20 min) on the left (healthy volunteer) or affected (stroke patient) primary motor cortex, and D: anodal tDCS without exercise) were provided in random order on separate days. We compared during and post-exercise corticospinal excitability under different conditions in healthy volunteers (A, B, C, D) and stroke patients (B, C, D) by measuring the changes in amplitudes of motor evoked potentials in the extensor carpi radialis muscle, elicited with single-pulse transcranial magnetic stimulation. For statistical analyses, a linear mixed model for a repeated-measures covariance pattern model with unstructured covariance within groups (healthy or stroke groups) was used.The VR wrist exercise (B) facilitated post-exercise corticospinal excitability more than the active wrist exercise (A) or anodal tDCS without exercise (D) in healthy volunteers. Moreover, the post-exercise corticospinal facilitation after tDCS and VR exercise (C) was greater and was sustained for 20 min after exercise versus the other conditions in healthy volunteers (A, B, D) and in subacute stroke patients (B, D).The combined effect of VR motor training following tDCS was synergistic and short-term corticospinal facilitation was superior to the application of VR training, active motor training, or tDCS without exercise condition. These results support the concept of combining brain stimulation with VR motor training to promote recovery after a stroke.

Journal of neuroengineering and rehabilitation

Kim, YJ; Ku, J; Cho, S; Kim, HJ; Cho, YK; Lim, T; Kang, YJ

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Best of both worlds: promise of combining brain stimulation and brain connectome.

2014

Transcranial current brain stimulation (tCS) is becoming increasingly popular as a non-pharmacological non-invasive neuromodulatory method that alters cortical excitability by applying weak electrical currents to the scalp via a pair of electrodes. Most applications of this technique have focused on enhancing motor and learning skills, as well as a therapeutic agent in neurological and psychiatric disorders. In these applications, similarly to lesion studies, tCS was used to provide a causal link between a function or behavior and a specific brain region (e.g., primary motor cortex). Nonetheless, complex cognitive functions are known to rely on functionally connected multitude of brain regions with dynamically changing patterns of information flow rather than on isolated areas, which are most commonly targeted in typical tCS experiments. In this review article, we argue in favor of combining tCS method with other neuroimaging techniques (e.g., fMRI, EEG) and by employing state-of-the-art connectivity data analysis techniques (e.g., graph theory) to obtain a deeper understanding of the underlying spatiotemporal dynamics of functional connectivity patterns and cognitive performance. Finally, we discuss the possibilities of using these combined techniques to investigate the neural correlates of human creativity and to enhance creativity.

Frontiers in systems neuroscience

Luft, CD; Pereda, E; Banissy, MJ; Bhattacharya, J

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Hits and misses: leveraging tDCS to advance cognitive research.

2014

The popularity of non-invasive brain stimulation techniques in basic, commercial, and applied settings grew tremendously over the last decade. Here, we focus on one popular neurostimulation method: transcranial direct current stimulation (tDCS). Many assumptions regarding the outcomes of tDCS are based on the results of stimulating motor cortex. For instance, the primary motor cortex is predictably suppressed by cathodal tDCS or made more excitable by anodal tDCS. However, wide-ranging studies testing cognition provide more complex and sometimes paradoxical results that challenge this heuristic. Here, we first summarize successful efforts in applying tDCS to cognitive questions, with a focus on working memory (WM). These recent findings indicate that tDCS can result in cognitive task improvement or impairment regardless of stimulation site or direction of current flow. We then report WM and response inhibition studies that failed to replicate and/or extend previously reported effects. From these opposing outcomes, we present a series of factors to consider that are intended to facilitate future use of tDCS when applied to cognitive questions. In short, common pitfalls include testing too few participants, using insufficiently challenging tasks, using heterogeneous participant populations, and including poorly motivated participants. Furthermore, the poorly understood underlying mechanism for long-lasting tDCS effects make it likely that other important factors predict responses. In conclusion, we argue that although tDCS can be used experimentally to understand brain function its greatest potential may be in applied or translational research.

Frontiers in psychology

Berryhill, ME; Peterson, DJ; Jones, KT; Stephens, JA

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Transcranial direct current stimulation over posterior parietal cortex modulates visuospatial localization.

2014

Visual localization is based on the complex interplay of bottom-up and top-down processing. Based on previous work, the posterior parietal cortex (PPC) is assumed to play an essential role in this interplay. In this study, we investigated the causal role of the PPC in visual localization. Specifically, our goal was to determine whether modulation of the PPC via transcranial direct current stimulation (tDCS) could induce visual mislocalization similar to that induced by an exogenous attentional cue (Wright, Morris, & Krekelberg, 2011). We placed one stimulation electrode over the right PPC and the other over the left PPC (dual tDCS) and varied the polarity of the stimulation. We found that this manipulation altered visual localization; this supports the causal involvement of the PPC in visual localization. Notably, mislocalization was more rightward when the cathode was placed over the right PPC than when the anode was placed over the right PPC. This mislocalization was found within a few minutes of stimulation onset, it dissipated during stimulation, but then resurfaced after stimulation offset and lasted for another 10-15 min. On the assumption that excitability is reduced beneath the cathode and increased beneath the anode, these findings support the view that each hemisphere biases processing to the contralateral hemifield and that the balance of activation between the hemispheres contributes to position perception (Kinsbourne, 1977; Szczepanski, Konen, & Kastner, 2010).

Journal of vision

Wright, JM; Krekelberg, B

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Time Course of Corticospinal Excitability and Autonomic Function Interplay during and Following Monopolar tDCS.

2014

While polarity-specific after-effects of monopolar transcranial direct current stimulation (tDCS) on corticospinal excitability are well-documented, modulation of vital parameters due to current spread through the brainstem is still a matter of debate, raising potential concerns about its use through the general public, as well as for neurorehabilitation purposes. We monitored online and after-effects of monopolar tDCS (primary motor cortex) in 10 healthy subjects by adopting a neuronavigated transcranial magnetic stimulation (TMS)/tDCS combined protocol. Motor evoked potentials (MEPs) together with vital parameters [e.g., blood pressure, heart-rate variability (HRV), and sympathovagal balance] were recorded and monitored before, during, and after anodal, cathodal, or sham tDCS. Ten MEPs, every 2.5-min time windows, were recorded from the right first dorsal interosseous (FDI), while 5-min epochs were used to record vital parameters. The protocol included 15 min of pre-tDCS and of online tDCS (anodal, cathodal, or sham). After-effects were recorded for 30 min. We showed a polarity-independent stabilization of cortical excitability level, a polarity-specific after-effect for cathodal and anodal stimulation, and an absence of persistent excitability changes during online stimulation. No significant effects on vital parameters emerged both during and after tDCS, while a linear increase in systolic/diastolic blood pressure and HRV was observed during each tDCS condition, as a possible unspecific response to experimental demands. Taken together, current findings provide new insights on the safety of monopolar tDCS, promoting its application both in research and clinical settings.

Frontiers in psychiatry

Santarnecchi, E; Feurra, M; Barneschi, F; Acampa, M; Bianco, G; Cioncoloni, D; Rossi, A; Rossi, S

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Modeling studies for designing transcranial direct current stimulation protocol in Alzheimer's disease.

2014

Frontiers in computational neuroscience

Mahdavi, S; Yavari, F; Gharibzadeh, S; Towhidkhah, F

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Differential behavioral and physiological effects of anodal transcranial direct current stimulation in healthy adults of younger and older age.

2014

Changes in γ-aminobutyric acid (GABA) mediated synaptic transmission have been associated with age-related motor and cognitive functional decline. Since anodal transcranial direct current stimulation (atDCS) has been suggested to target cortical GABAergic inhibitory interneurons, its potential for the treatment of deficient inhibitory activity and functional decline is being increasingly discussed. Therefore, after-effects of a single session of atDCS on resting-state and event-related short-interval intracortical inhibition (SICI) as evaluated with double-pulse TMS and dexterous manual performance were examined using a sham-controlled cross-over design in a sample of older and younger participants. The atDCS effect on resting-state inhibition differed in direction, magnitude, and timing, i.e., late relative release of inhibition in the younger and early relative increase in inhibition in the older. More pronounced release of event-related inhibition after atDCS was exclusively seen in the older. Event-related modulation of inhibition prior to stimulation predicted the magnitude of atDCS-induced effects on resting-state inhibition. Specifically, older participants with high modulatory capacity showed a disinhibitory effect comparable to the younger. Beneficial effects on behavior were mainly seen in the older and in tasks requiring higher dexterity, no clear association with physiological changes was found. Differential effects of atDCS on SICI, discussed to reflect GABAergic inhibition at the level of the primary motor cortex, might be distinct in older and younger participants depending on the functional integrity of the underlying neural network. Older participants with preserved modulatory capacity, i.e., a physiologically "young" motor network, were more likely to show a disinhibitory effect of atDCS. These results favor individually tailored application of tDCS with respect to specific target groups.

Frontiers in aging neuroscience

Heise, KF; Niehoff, M; Feldheim, JF; Liuzzi, G; Gerloff, C; Hummel, FC

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Reduced discomfort during high-definition transcutaneous stimulation using 6% benzocaine.

2014

High-Definition transcranial Direct Current Stimulation (HD-tDCS) allows for non-invasive neuromodulation using an array of compact (approximately 1 cm(2) contact area) "High-Definition" (HD) electrodes, as compared to conventional tDCS (which uses two large pads that are approximately 35 cm(2)). In a previous transcutaneous study, we developed and validated designs for HD electrodes that reduce discomfort over >20 min session with 2 mA electrode current.The purpose of this study was to investigate the use of a chemical pretreatment with 6% benzocaine (topical numbing agent) to further reduce subjective discomfort during transcutaneous stimulation and to allow for better sham controlled studies.Pre-treatment with 6% benzocaine was compared with control (no pretreatment) for 22 min 2 mA of stimulation, with either CCNY-4 or Lectron II electroconductive gel, for both cathodal and anodal transcutaneous (forearm) stimulation (eight different combinations).RESULTS show that for all conditions and polarities tested, stimulation with HD electrodes is safe and well tolerated and that pretreatment further reduced subjective discomfort.Pretreatment with a mild analgesic reduces discomfort during HD-tDCS.

Frontiers in neuroengineering

Guleyupoglu, B; Febles, N; Minhas, P; Hahn, C; Bikson, M

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Transcranial extracellular impedance control (tEIC) modulates behavioral performances.

2014

Electric brain stimulations such as transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), and transcranial alternating current stimulation (tACS) electrophysiologically modulate brain activity and as a result sometimes modulate behavioral performances. These stimulations can be viewed from an engineering standpoint as involving an artificial electric source (DC, noise, or AC) attached to an impedance branch of a distributed parameter circuit. The distributed parameter circuit is an approximation of the brain and includes electric sources (neurons) and impedances (volume conductors). Such a brain model is linear, as is often the case with the electroencephalogram (EEG) forward model. Thus, the above-mentioned current stimulations change the current distribution in the brain depending on the locations of the electric sources in the brain. Now, if the attached artificial electric source were to be replaced with a resistor, or even a negative resistor, the resistor would also change the current distribution in the brain. In light of the superposition theorem, which holds for any linear electric circuit, attaching an electric source is different from attaching a resistor; the resistor affects each active electric source in the brain so as to increase (or decrease in some cases of a negative resistor) the current flowing out from each source. From an electrophysiological standpoint, the attached resistor can only control the extracellular impedance and never causes forced stimulation; we call this technique transcranial extracellular impedance control (tEIC). We conducted a behavioral experiment to evaluate tEIC and found evidence that it had real-time enhancement and depression effects on EEGs and a real-time facilitation effect on reaction times. Thus, tEIC could be another technique to modulate behavioral performance.

PloS one

Matani, A; Nakayama, M; Watanabe, M; Furuyama, Y; Hotta, A; Hoshino, S

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Building up analgesia in humans via the endogenous μ-opioid system by combining placebo and active tDCS: a preliminary report.

2014

Transcranial Direct Current Stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. However, the molecular mechanisms underlying tDCS-mediated pain control, and most important its placebo component, are not completely established. In this pilot study, we investigated in vivo the involvement of the endogenous μ-opioid system in the global tDCS-analgesia experience. Nine healthy volunteers went through positron emission tomography (PET) scans with [11C]carfentanil, a selective μ-opioid receptor (MOR) radiotracer, to measure the central MOR activity during tDCS in vivo (non-displaceable binding potential, BPND)--one of the main analgesic mechanisms in the brain. Placebo and real anodal primary motor cortex (M1/2mA) tDCS were delivered sequentially for 20 minutes each during the PET scan. The initial placebo tDCS phase induced a decrease in MOR BPND in the periaqueductal gray matter (PAG), precuneus, and thalamus, indicating activation of endogenous μ-opioid neurotransmission, even before the active tDCS. The subsequent real tDCS also induced MOR activation in the PAG and precuneus, which were positively correlated to the changes observed with placebo tDCS. Nonetheless, real tDCS had an additional MOR activation in the left prefrontal cortex. Although significant changes in the MOR BPND occurred with both placebo and real tDCS, significant analgesic effects, measured by improvements in the heat and cold pain thresholds, were only observed after real tDCS, not the placebo tDCS. This study gives preliminary evidence that the analgesic effects reported with M1-tDCS, can be in part related to the recruitment of the same endogenous MOR mechanisms induced by placebo, and that such effects can be purposely optimized by real tDCS.

PloS one

DosSantos, MF; Martikainen, IK; Nascimento, TD; Love, TM; DeBoer, MD; Schambra, HM; Bikson, M; Zubieta, JK; DaSilva, AF

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Non-invasive brain stimulation in neurorehabilitation: local and distant effects for motor recovery.

2014

Non-invasive brain stimulation (NIBS) may enhance motor recovery after neurological injury through the causal induction of plasticity processes. Neurological injury, such as stroke, often results in serious long-term physical disabilities, and despite intensive therapy, a large majority of brain injury survivors fail to regain full motor function. Emerging research suggests that NIBS techniques, such as transcranial magnetic (TMS) and direct current (tDCS) stimulation, in association with customarily used neurorehabilitative treatments, may enhance motor recovery. This paper provides a general review on TMS and tDCS paradigms, the mechanisms by which they operate and the stimulation techniques used in neurorehabilitation, specifically stroke. TMS and tDCS influence regional neural activity underlying the stimulation location and also distant interconnected network activity throughout the brain. We discuss recent studies that document NIBS effects on global brain activity measured with various neuroimaging techniques, which help to characterize better strategies for more accurate NIBS stimulation. These rapidly growing areas of inquiry may hold potential for improving the effectiveness of NIBS-based interventions for clinical rehabilitation.

Frontiers in human neuroscience

Liew, SL; Santarnecchi, E; Buch, ER; Cohen, LG

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Is neural hyperpolarization by cathodal stimulation always detrimental at the behavioral level?

2014

Cathodal transcranial direct current stimulation (c-tDCS) is usually considered an inhibitory stimulation. From a physiological perspective, c-tDCS induces hyperpolarization at the neural level. However, from a behavioral perspective, c-tDCS application does not always result in performance deterioration. In this work, we investigated the role of several important stimulation parameters (i.e., timing, presence of pauses, duration, and intensity) in shaping the behavioral effects of c-tDCS over the primary visual cortex. In Experiment 1, we applied c-tDCS at two different times (before or during an orientation discrimination task). We also studied the effects of pauses during the stimulation. In Experiments 2 and 3, we compared different durations (9 vs. 22 min) and intensities (0.75 vs. 1.5 mA) of stimulation. c-tDCS applied before task execution induced an improvement of performance, highlighting the importance of the activation state of the cortex. However, this result depended on the duration and intensity of stimulation. We suggest that the application of c-tDCS induces depression of cortical activity over a specific stimulated area; but to keep reactivity within given limits, the brain react in order to restore the equilibrium and this might result in increased sensitivity in visual performance. This is a further example of how the nervous system dynamically maintains a condition that permits adequate performance in different environments.

Frontiers in behavioral neuroscience

Pirulli, C; Fertonani, A; Miniussi, C

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The timing of cognitive plasticity in physiological aging: a tDCS study of naming.

2014

This study aimed to explore the effects of transcranial direct current stimulation (tDCS) on physiologically aging adults performing a naming task. tDCS is a method that modulates human cortical excitability. Neuroplasticity is considered to have its foundation in cortical excitability as a property that adjusts the connection strength between neurons in the brain. Language efficiency, as all functions, relies on integration of information (i.e., effectiveness of connectivity) through neurons in the brain. So the use of tDCS, to modulate cortical excitability, can help to define the state of cognitive plasticity in the aging brain. Based on Hebb's rule, an increase in synaptic efficacy does not rely only on the increase of excitability but also on the timing of activation. Therefore, a key issue in this study is the timing of tDCS application in relation to a task: When to deliver tDCS to induce modulatory effects on task execution to facilitate naming. Anodal tDCS was applied to the left dorsolateral prefrontal cortex of older and young adults before and during a naming task. In older adults, tDCS improved naming performance and decreased the verbal reaction times only if it was applied during the task execution, whereas in young subjects both stimulation conditions improved naming performance. These findings highlight that in healthy aging adults, the cerebral network dedicated to lexical retrieval processing may be facilitated only if stimulation is applied to an "active" neural network. We hypothesize that this change is due to the neuronal synaptic changes, in the aging brain, which reduce the window of when cortical excitability can facilitate synaptic efficacy and therefore plasticity.

Frontiers in aging neuroscience

Fertonani, A; Brambilla, M; Cotelli, M; Miniussi, C

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Enhanced motor skill acquisition in the non-dominant upper extremity using intermittent theta burst stimulation and transcranial direct current stimulation.

2014

Individuals suffering from motor impairments often require physical therapy (PT) to help improve their level of function. Previous investigations suggest that both intermittent theta burst stimulation (iTBS) and bihemispheric transcranial direct current stimulation (tDCS) may increase the speed and extent of motor learning/relearning. The purpose of the current study was to explore the feasibility and effectiveness of a novel, non-invasive brain stimulation approach that combined an iTBS primer, and bihemispheric stimulation coupled with motor training. We hypothesized that individuals exposed to this novel treatment would make greater functional improvements than individuals undergoing sham stimulation when tested immediately following, 24-h, and 7-days post-training. A total of 26 right-handed, healthy young adults were randomly assigned to either a treatment (n = 15) or control group (n = 12). iTBS (20 trains of 10 pulse triplets each delivered at 80% active motor threshold (AMT) / 50 Hz over 191.84 s) and bihemispheric tDCS (1.0 ma for 20 min) were used as a primer to, and in conjunction with, 20 min of motor training, respectively. Our primary outcome measure was performance on the Jebsen-Taylor Hand Function (JTHF) test. Participants tolerated the combined iTBS/bihemispheric stimulation treatment without complaint. While performance gains in the sham and stimulation group were not significant immediately after training, they were nearly significant 24-h post training (p = 0.055), and were significant at 7-days post training (p < 0.05). These results suggest that the combined iTBS/bihemispheric stimulation protocol is both feasible and effective. Future research should examine the mechanistic explanation of this approach as well as the potential of using this approach in clinical populations.

Frontiers in human neuroscience

Butts, RJ; Kolar, MB; Newman-Norlund, RD

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Toward unraveling reading-related modulations of tDCS-induced neuroplasticity in the human visual cortex.

2014

Stimulation using weak electrical direct currents has shown to be capable of inducing polarity-dependent diminutions or elevations in motor and visual cortical excitability. The aim of the present study was to test if reading during transcranial direct current stimulation (tDCS) is able to modify stimulation-induced plasticity in the visual cortex. Phosphene thresholds (PTs) in 12 healthy subjects were recorded before and after 10 min of anodal, cathodal, and sham tDCS in combination with reading. Reading alone decreased PTs significantly, compared to the sham tDCS condition without reading. Interestingly, after both anodal and cathodal stimulation there was a tendency toward smaller PTs. Our results support the observation that tDCS-induced plasticity is highly dependent on the cognitive state of the subject during stimulation, not only in the case of motor cortex but also in the case of visual cortex stimulation.

Frontiers in psychology

Antal, A; Ambrus, GG; Chaieb, L

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Delayed plastic responses to anodal tDCS in older adults.

2014

Despite the abundance of research reporting the neurophysiological and behavioral effects of transcranial direct current stimulation (tDCS) in healthy young adults and clinical populations, the extent of potential neuroplastic changes induced by tDCS in healthy older adults is not well understood. The present study compared the extent and time course of anodal tDCS-induced plastic changes in primary motor cortex (M1) in young and older adults. Furthermore, as it has been suggested that neuroplasticity and associated learning depends on the brain-derived neurotrophic factor (BDNF) gene polymorphisms, we also assessed the impact of BDNF polymorphism on these effects. Corticospinal excitability was examined using transcranial magnetic stimulation before and following (0, 10, 20, 30 min) anodal tDCS (30 min, 1 mA) or sham in young and older adults. While the overall extent of increases in corticospinal excitability induced by anodal tDCS did not vary reliably between young and older adults, older adults exhibited a delayed response; the largest increase in corticospinal excitability occurred 30 min following stimulation for older adults, but immediately post-stimulation for the young group. BDNF genotype did not result in significant differences in the observed excitability increases for either age group. The present study suggests that tDCS-induced plastic changes are delayed as a result of healthy aging, but that the overall efficacy of the plasticity mechanism remains unaffected.

Frontiers in aging neuroscience

Fujiyama, H; Hyde, J; Hinder, MR; Kim, SJ; McCormack, GH; Vickers, JC; Summers, JJ

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Modulation of cortical activity by transcranial direct current stimulation in patients with affective disorder.

2014

Transcranial direct current stimulation (tDCS) has been shown to have antidepressant efficacy in patients experiencing a major depressive episode, but little is known about the underlying neurophysiology. The purpose of our study was to investigate the acute effects of tDCS on cortical activity using electroencephalography (EEG) in patients with an affective disorder. Eighteen patients diagnosed with an affective disorder and experiencing a depressive episode participated in a sham-controlled study of tDCS, each receiving a session of active (2 mA for 20 minutes) and sham tDCS to the left dorsolateral prefrontal cortex (DLPFC). The effects of tDCS on EEG activity were assessed after each session using event-related potentials (ERP) and measurement of spectral activity during a visual working memory (VWM) task. We observed task and intervention dependent effects on both ERPs and task-related alpha and theta activity, where active compared to sham stimulation resulted in a significant reduction in the N2 amplitude and reduced theta activity over frontal areas during memory retrieval. In summary a single session of anodal tDCS stimulation to the left DLPFC during a major depressive episode resulted in modulated brain activity evident in task-related EEG. Effects on the N2 and frontal theta activity likely reflect modulated activity in the medial frontal cortex and hence indicate that the after-effects of tDCS extend beyond the direct focal effects to the left DLPFC.

PloS one

Powell, TY; Boonstra, TW; Martin, DM; Loo, CK; Breakspear, M

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The ineffective role of cathodal tDCS in enhancing the functional motor outcomes in early phase of stroke rehabilitation: an experimental trial.

2014

Transcranial direct current stimulation (tDCS) is a noninvasive technique that could improve the rehabilitation outcomes in stroke, eliciting neuroplastic mechanisms. At the same time conflicting results have been reported in subacute phase of stroke, when neuroplasticity is crucial. The aim of this double-blind, randomized, and sham-controlled study was to determine whether a treatment with cathodal tDCS before the rehabilitative training might augment the final outcomes (upper limb function, hand dexterity and manual force, locomotion, and activities of daily living) in respect of a traditional rehabilitation for a sample of patients affected by ischemic stroke in the subacute phase. An experimental group (cathodal tDCS plus rehabilitation) and a control group (sham tDCS plus rehabilitation) were assessed at the beginning of the protocol, after 10 days of stimulation, after 30 days from ending of stimulation, and at the end of inpatient rehabilitation. Both groups showed significant improvements for all the assessed domains during the rehabilitation, except for the manual force, while no significant differences were demonstrated between groups. These results seem to indicate that the cathodal tDCS, provided in an early phase of stroke, does not lead to a functional improvement. To depict a more comprehensive scenario, further studies are needed.

BioMed research international

Fusco, A; Assenza, F; Iosa, M; Izzo, S; Altavilla, R; Paolucci, S; Vernieri, F

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Cerebral functional imaging using near-infrared spectroscopy during repeated performances of motor rehabilitation tasks tested on healthy subjects.

2014

To investigate the relationship between the frontal and sensorimotor cortices and motor learning, hemodynamic responses were recorded from the frontal and sensorimotor cortices using functional near infrared spectroscopy (NIRS) while healthy subjects performed motor learning tasks used in rehabilitation medicine. Whole-head NIRS recordings indicated that response latencies in the anterior dorsomedial prefrontal cortex (aDMPFC) were shorter than in other frontal and parietal areas. Furthermore, the increment rate of the hemodynamic responses in the aDMPFC across the eight repeated trials significantly correlated with those in the other areas, as well as with the improvement rate of task performance across the 8 repeated trials. In the second experiment, to dissociate scalp- and brain-derived hemodynamic responses, hemodynamic responses were recorded from the head over the aDMPFC using a multi-distance probe arrangement. Six probes (a single source probe and 5 detectors) were linearly placed 6 mm apart from each of the neighboring probes. Using independent component analyses of hemodynamic signals from the 5 source-detector pairs, we dissociated scalp- and brain-derived components of the hemodynamic responses. Hemodynamic responses corrected for scalp-derived responses over the aDMPFC significantly increased across the 8 trials and correlated with task performance. In the third experiment, subjects were required to perform the same task with and without transcranial direct current stimulation (tDCS) of the aDMPFC before the task. The tDCS significantly improved task performance. These results indicate that the aDMPFC is crucial for improved performance in repetitive motor learning.

Frontiers in human neuroscience

Ishikuro, K; Urakawa, S; Takamoto, K; Ishikawa, A; Ono, T; Nishijo, H

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Open questions on the mechanisms of neuromodulation with applied and endogenous electric fields.

2014

Frontiers in human neuroscience

Weiss, SA; Bikson, M

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Polarity specific suppression effects of transcranial direct current stimulation for tinnitus.

2014

Tinnitus is the perception of a sound in the absence of an external auditory stimulus and affects 10-15% of the Western population. Previous studies have demonstrated the therapeutic effect of anodal transcranial direct current stimulation (tDCS) over the left auditory cortex on tinnitus loudness, but the effect of this presumed excitatory stimulation contradicts with the underlying pathophysiological model of tinnitus. Therefore, we included 175 patients with chronic tinnitus to study polarity specific effects of a single tDCS session over the auditory cortex (39 anodal, 136 cathodal). To assess the effect of treatment, we used the numeric rating scale for tinnitus loudness and annoyance. Statistical analysis demonstrated a significant main effect for tinnitus loudness and annoyance, but for tinnitus annoyance anodal stimulation has a significantly more pronounced effect than cathodal stimulation. We hypothesize that the suppressive effect of tDCS on tinnitus loudness may be attributed to a disrupting effect of ongoing neural hyperactivity, independent of the inhibitory or excitatory effects and that the reduction of annoyance may be induced by influencing adjacent or functionally connected brain areas involved in the tinnitus related distress network. Further research is required to explain why only anodal stimulation has a suppressive effect on tinnitus annoyance.

Neural plasticity

Joos, K; De Ridder, D; Van de Heyning, P; Vanneste, S

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Transcranial direct current stimulation and simultaneous functional magnetic resonance imaging.

2014

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses weak electrical currents administered to the scalp to manipulate cortical excitability and, consequently, behavior and brain function. In the last decade, numerous studies have addressed short-term and long-term effects of tDCS on different measures of behavioral performance during motor and cognitive tasks, both in healthy individuals and in a number of different patient populations. So far, however, little is known about the neural underpinnings of tDCS-action in humans with regard to large-scale brain networks. This issue can be addressed by combining tDCS with functional brain imaging techniques like functional magnetic resonance imaging (fMRI) or electroencephalography (EEG). In particular, fMRI is the most widely used brain imaging technique to investigate the neural mechanisms underlying cognition and motor functions. Application of tDCS during fMRI allows analysis of the neural mechanisms underlying behavioral tDCS effects with high spatial resolution across the entire brain. Recent studies using this technique identified stimulation induced changes in task-related functional brain activity at the stimulation site and also in more distant brain regions, which were associated with behavioral improvement. In addition, tDCS administered during resting-state fMRI allowed identification of widespread changes in whole brain functional connectivity. Future studies using this combined protocol should yield new insights into the mechanisms of tDCS action in health and disease and new options for more targeted application of tDCS in research and clinical settings. The present manuscript describes this novel technique in a step-by-step fashion, with a focus on technical aspects of tDCS administered during fMRI.

Journal of visualized experiments : JoVE

Meinzer, M; Lindenberg, R; Darkow, R; Ulm, L; Copland, D; Flöel, A


Point-of-care-testing of standing posture with Wii balance board and Microsoft Kinect during transcranial direct current stimulation: a feasibility study.

2014

Non-invasive brain stimulation (NIBS) is a promising tool for facilitating motor function. NIBS therapy in conjunction with training using postural feedback may facilitate physical rehabilitation following posture disorders (e.g., Pusher Syndrome).The objectives of this study were, 1) to develop a low-cost point-of-care-testing (POCT) system for standing posture, 2) to investigate the effects of anodal tDCS on functional reach tasks using the POCT system.Ten community-dwelling elderly (age >50 years) subjects evaluated the POCT system for standing posture during functional reach tasks where their balance score on Berg Balance Scale was compared with that from Center-of-Mass (CoM) - Center-of-Pressure (CoP) posturography. Then, in a single-blind, sham-controlled study, five healthy right-leg dominant subjects (age: 26.4 ± 5.3 yrs) were evaluated using the POCT system under two conditions - with anodal tDCS of primary motor representations of right tibialis anterior muscle and with sham tDCS.The maximum CoP-CoM lean-angle was found to be well correlated with the BBS score in the elderly subjects The anodal tDCS strongly (p = 0.0000) affected the maximum CoP excursions but not the return reaction time in healthy.It was concluded that the CoM-CoP lean-line could be used for posture feedback and monitoring during tDCS therapy in conjunction with balance training exercises.

NeuroRehabilitation

Dutta, A; Chugh, S; Banerjee, A; Dutta, A


Restoring cognitive functions using non-invasive brain stimulation techniques in patients with cerebellar disorders.

2014

Numerous studies have highlighted the possibility of modulating the excitability of cerebro-cerebellar circuits bi-directionally using transcranial electrical brain stimulation, in a manner akin to that observed using magnetic stimulation protocols. It has been proposed that cerebellar stimulation activates Purkinje cells in the cerebellar cortex, leading to inhibition of the dentate nucleus, which exerts a tonic facilitatory drive onto motor and cognitive regions of cortex through a synaptic relay in the ventral-lateral thalamus. Some cerebellar deficits present with cognitive impairments if damage to non-motor regions of the cerebellum disrupts the coupling with cerebral cortical areas for thinking and reasoning. Indeed, white matter changes in the dentato-rubral tract correlate with cognitive assessments in patients with Friedreich ataxia, suggesting that this pathway is one component of the anatomical substrate supporting a cerebellar contribution to cognition. An understanding of the physiology of the cerebro-cerebellar pathway previously helped us to constrain our interpretation of results from two recent studies in which we showed cognitive enhancements in healthy participants during tests of arithmetic after electrical stimulation of the cerebellum, but only when task demands were high. Others studies have also shown how excitation of the prefrontal cortex can enhance performance in a variety of working memory tasks. Thus, future efforts might be guided toward neuro-enhancement in certain patient populations, using what is commonly termed "non-invasive brain stimulation" as a cognitive rehabilitation tool to modulate cerebro-cerebellar circuits, or for stimulation over the cerebral cortex to compensate for decreased cerebellar drive to this region. This article will address these possibilities with a review of the relevant literature covering ataxias and cerebellar cognitive affective disorders, which are characterized by thalamo-cortical disturbances.

Frontiers in psychiatry

Pope, PA; Miall, RC

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Effects of transcranial direct current stimulation in combination with motor practice on dexterous grasping and manipulation in healthy older adults.

2014

Abstract Transcranial anodal stimulation (tDCS) over primary motor cortex (M1) improves dexterous manipulation in healthy older adults. However, the beneficial effects of anodal tDCS in combination with motor practice on natural and clinically relevant functional manual tasks, and the associated changes in the digit contact forces are not known. To this end, we studied the effects of 20 min of tDCS applied over M1 for the dominant hand combined with motor practice (MP) in a sham-controlled crossover study. We monitored the forces applied to an object that healthy elderly individuals grasped and manipulated, and their performances on the Grooved Pegboard Test and the Key-slot task. Practice improved performance on the Pegboard test, and anodal tDCS + MP improved retention of this performance gain when tested 35 min later, whereas similar performance gains degraded in the sham group after 35 min. Interestingly, grip force variability on an isometric precision grip task performed with visual feedback of precision force increased following anodal tDCS + MP, but not sham tDCS + MP. This finding suggests that anodal tDCS over M1 might alter the descending drive to spinal motor neurons involved in the performance of isometric precision grip task under visual feedback leading to increased fluctuations in the grip force exerted on the object. Our results demonstrate that anodal stimulation in combination with motor practice helps older adults to retain their improved performance on a functionally relevant manual task in healthy older adults.

Physiological reports

Parikh, PJ; Cole, KJ

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Influence of anodal transcranial direct current stimulation (tDCS) over the right angular gyrus on brain activity during rest.

2014

Although numerous studies examined resting-state networks (RSN) in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS) modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG). We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI). Significant differences between two fMRI sessions (pre-tDCS and post-tDCS) were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site.

PloS one

Clemens, B; Jung, S; Mingoia, G; Weyer, D; Domahs, F; Willmes, K

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Non-invasive brain stimulation techniques for chronic pain.

2014

This is an updated version of the original Cochrane review published in 2010, Issue 9. 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), transcranial direct current stimulation (tDCS) and reduced impedance non-invasive cortical electrostimulation (RINCE).To evaluate the efficacy of non-invasive brain stimulation techniques in chronic pain.We searched CENTRAL (2013, Issue 6), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS and clinical trials registers. The original search for the review was run in November 2009 and searched all databases from their inception. To identify studies for inclusion in this update we searched from 2009 to July 2013.Randomised and quasi-randomised studies of rTMS, CES, tDCS or RINCE 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 used the GRADE system to summarise the quality of evidence for core comparisons.We included an additional 23 trials (involving 773 participants randomised) in this update, making a total of 56 trials in the review (involving 1710 participants randomised). This update included a total of 30 rTMS studies, 11 CES, 14 tDCS and one study of RINCE(the original review included 19 rTMS, eight CES and six tDCS studies). We judged only three studies as being at low risk of bias across all criteria.Meta-analysis of studies of rTMS (involving 528 participants) demonstrated significant heterogeneity. Pre-specified subgroup analyses suggest that low-frequency stimulation is ineffective (low-quality evidence) and that rTMS applied to the dorsolateral prefrontal cortex is ineffective (very low-quality evidence). We found a short-term effect on pain of active high-frequency stimulation of the motor cortex in single-dose studies (low-quality evidence, standardised mean difference (SMD) 0.39 (95% confidence interval (CI) -0.27 to -0.51 P < 0.01)). This equates to a 12% (95% CI 8% to 15%) reduction in pain, which does not exceed the pre-established criteria for a minimal clinically important difference (≥ 15%). Evidence for multiple-dose studies was heterogenous but did not demonstrate a significant effect (very low-quality evidence).For CES (six studies, 270 participants) no statistically significant difference was found between active stimulation and sham (low-quality evidence).Analysis of tDCS studies (11 studies, 193 people) demonstrat

The Cochrane database of systematic reviews

O'Connell, NE; Wand, BM; Marston, L; Spencer, S; Desouza, LH


Functional interaction between right parietal and bilateral frontal cortices during visual search tasks revealed using functional magnetic imaging and transcranial direct current stimulation.

2014

The existence of a network of brain regions which are activated when one undertakes a difficult visual search task is well established. Two primary nodes on this network are right posterior parietal cortex (rPPC) and right frontal eye fields. Both have been shown to be involved in the orientation of attention, but the contingency that the activity of one of these areas has on the other is less clear. We sought to investigate this question by using transcranial direct current stimulation (tDCS) to selectively decrease activity in rPPC and then asking participants to perform a visual search task whilst undergoing functional magnetic resonance imaging. Comparison with a condition in which sham tDCS was applied revealed that cathodal tDCS over rPPC causes a selective bilateral decrease in frontal activity when performing a visual search task. This result demonstrates for the first time that premotor regions within the frontal lobe and rPPC are not only necessary to carry out a visual search task, but that they work together to bring about normal function.

PloS one

Ellison, A; Ball, KL; Moseley, P; Dowsett, J; Smith, DT; Weis, S; Lane, AR

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Learned EEG-based brain self-regulation of motor-related oscillations during application of transcranial electric brain stimulation: feasibility and limitations.

2014

Transcranial direct current stimulation (tDCS) improves motor learning and can affect emotional processing and attention. However, it is unclear whether learned electroencephalography (EEG)-based brain-machine interface (BMI) control during tDCS is feasible, how application of transcranial electric currents during BMI control would interfere with feature-extraction of physiological brain signals and how it affects brain control performance. Here we tested this combination and evaluated stimulation-dependent artifacts across different EEG frequencies and stability of motor imagery-based BMI control.Ten healthy volunteers were invited to two BMI-sessions, each comprising two 60-trial blocks. During the trials, learned desynchronization of mu-rhythms (8-15 Hz) associated with motor imagery (MI) recorded over C4 was translated into online cursor movements on a computer screen. During block 2, either sham (session A) or anodal tDCS (session B) was applied at 1 mA with the stimulation electrode placed 1 cm anterior of C4.tDCS was associated with a significant signal power increase in the lower frequencies most evident in the signal spectrum of the EEG channel closest to the stimulation electrode. Stimulation-dependent signal power increase exhibited a decay of 12 dB per decade, leaving frequencies above 9 Hz unaffected. Analysis of BMI control performance did not indicate a difference between blocks and tDCS conditions.Application of tDCS during learned EEG-based self-regulation of brain oscillations above 9 Hz is feasible and safe, and might improve applicability of BMI systems.

Frontiers in behavioral neuroscience

Soekadar, SR; Witkowski, M; Cossio, EG; Birbaumer, N; Cohen, LG

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Local GABA concentration is related to network-level resting functional connectivity.

2014

Anatomically plausible networks of functionally inter-connected regions have been reliably demonstrated at rest, although the neurochemical basis of these 'resting state networks' is not well understood. In this study, we combined magnetic resonance spectroscopy (MRS) and resting state fMRI and demonstrated an inverse relationship between levels of the inhibitory neurotransmitter GABA within the primary motor cortex (M1) and the strength of functional connectivity across the resting motor network. This relationship was both neurochemically and anatomically specific. We then went on to show that anodal transcranial direct current stimulation (tDCS), an intervention previously shown to decrease GABA levels within M1, increased resting motor network connectivity. We therefore suggest that network-level functional connectivity within the motor system is related to the degree of inhibition in M1, a major node within the motor network, a finding in line with converging evidence from both simulation and empirical studies. DOI: http://dx.doi.org/10.7554/eLife.01465.001.

eLife

Stagg, CJ; Bachtiar, V; Amadi, U; Gudberg, CA; Ilie, AS; Sampaio-Baptista, C; O'Shea, J; Woolrich, M; Smith, SM; Filippini, N; Near, J; Johansen-Berg, H

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Accuracy and confidence of visual short-term memory do not go hand-in-hand: behavioral and neural dissociations.

2014

Currently influential models of working memory posit that memory content is highly accessible to conscious inspection. These models predict that metacognition of memory performance should go hand-in-hand with the accuracy of the underlying memory representation. To test this view, we investigated how visual information presented during the maintenance period affects VSTM accuracy and confidence. We used a delayed cue-target orientation discrimination task in which participants were asked to hold in memory a grating, and during the maintenance period a second memory cue could be presented. VSTM accuracy of the first memory cue was impaired when the orientation of the second memory cue was sufficiently different. However, participants' response confidence was reduced whenever the second memory cue was presented; thus VSTM accuracy and confidence were dissociated. In a second experiment, we applied transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex (DLPFC) to investigate the causal role of this region in VSTM metacognition. Relative to the sham condition, anodal tDCS induced a general reduction in confidence ratings but did not affect VSTM accuracy. Overall, these results indicate that our metacognition of memory performance is influenced by factors other than the accuracy of the underlying memory representation.

PloS one

Bona, S; Silvanto, J

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Pressure pain thresholds increase after preconditioning 1 Hz repetitive transcranial magnetic stimulation with transcranial direct current stimulation.

2014

The primary motor cortex (M1) is an effective target of non-invasive cortical stimulation (NICS) for pain threshold modulation. It has been suggested that the initial level of cortical excitability of M1 plays a key role in the plastic effects of NICS.Here we investigate whether transcranial direct current stimulation (tDCS) primed 1 Hz repetitive transcranial magnetic stimulation (rTMS) modulates experimental pressure pain thresholds and if this is related to observed alterations in cortical excitability.15 healthy, male participants received 10 min 1 mA anodal, cathodal and sham tDCS to the left M1 before 15 min 1 Hz rTMS in separate sessions over a period of 3 weeks. Motor cortical excitability was recorded at baseline, post-tDCS priming and post-rTMS through recording motor evoked potentials (MEPs) from right FDI muscle. Pressure pain thresholds were determined by quantitative sensory testing (QST) through a computerized algometer, on the palmar thenar of the right hand pre- and post-stimulation.Cathodal tDCS-primed 1 Hz-rTMS was found to reverse the expected suppressive effect of 1 Hz rTMS on cortical excitability; leading to an overall increase in activity (p<0.001) with a parallel increase in pressure pain thresholds (p<0.01). In contrast, anodal tDCS-primed 1 Hz-rTMS resulted in a corresponding decrease in cortical excitability (p<0.05), with no significant effect on pressure pain.This study demonstrates that priming the M1 before stimulation of 1 Hz-rTMS modulates experimental pressure pain thresholds in a safe and controlled manner, producing a form of analgesia.

PloS one

Moloney, TM; Witney, AG

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Does transcranial direct current stimulation to prefrontal cortex affect mood and emotional memory retrieval in healthy individuals?

2014

Studies using transcranial direct current stimulation (tDCS) of prefrontal cortex to improve symptoms of depression have had mixed results. We examined whether using tDCS to change the balance of activity between left and right dorsolateral prefrontal cortex (DLPFC) can alter mood and memory retrieval of emotional material in healthy volunteers. Participants memorised emotional images, then tDCS was applied bilaterally to DLPFC while they performed a stimulus-response compatibility task. Participants were then presented with a set of images for memory retrieval. Questionnaires to examine mood and motivational state were administered at the beginning and end of each session. Exploratory data analyses showed that the polarity of tDCS to DLPFC influenced performance on a stimulus-response compatibility task and this effect was dependent on participants' prior motivational state. However, tDCS polarity had no effect on the speed or accuracy of memory retrieval of emotional images and did not influence positive or negative affect. These findings suggest that the balance of activity between left and right DLPFC does not play a critical role in the mood state of healthy individuals. We suggest that the efficacy of prefrontal tDCS depends on the initial activation state of neurons and future work should take this into account.

PloS one

Morgan, HM; Davis, NJ; Bracewell, RM

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Combining transcranial direct current stimulation and tailor-made notched music training to decrease tinnitus-related distress--a pilot study.

2014

The central auditory system has a crucial role in tinnitus generation and maintenance. Curative treatments for tinnitus do not yet exist. However, recent attempts in the therapeutic application of both acoustic stimulation/training procedures and electric/magnetic brain stimulation techniques have yielded promising results. Here, for the first time we combined tailor-made notched music training (TMNMT) with transcranial direct current stimulation (tDCS) in an effort to modulate TMNMT efficacy in the treatment of 32 patients with tonal tinnitus and without severe hearing loss. TMNMT is characterized by regular listening to so-called notched music, which is generated by digitally removing the frequency band of one octave width centered at the individual tinnitus frequency. TMNMT was applied for 10 subsequent days (2.5 hours of daily treatment). During the initial 5 days of treatment and the initial 30 minutes of TMNMT sessions, tDCS (current strength: 2 mA; anodal (N = 10) vs. cathodal (N = 11) vs. sham (N = 11) groups) was applied simultaneously. The active electrode was placed on the head surface over left auditory cortex; the reference electrode was put over right supra-orbital cortex. To evaluate treatment outcome, tinnitus-related distress and perceived tinnitus loudness were assessed using standardized tinnitus questionnaires and a visual analogue scale. The results showed a significant treatment effect reflected in the Tinnitus Handicap Questionnaire that was largest after 5 days of treatment. This effect remained significant at the end of follow-up 31 days after treatment cessation. Crucially, tDCS did not significantly modulate treatment efficacy--it did not make a difference whether anodal, cathodal, or sham tDCS was applied. Possible explanations for the findings and functional modifications of the experimental design for future studies (e.g. the selection of control conditions) are discussed.

PloS one

Teismann, H; Wollbrink, A; Okamoto, H; Schlaug, G; Rudack, C; Pantev, C

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Increasing human leg motor cortex excitability by transcranial high frequency random noise stimulation.

2014

Transcranial random noise stimulation (tRNS) can increase the excitability of hand area of the primary motor cortex (M1). The aim of this study was to compare the efficacy of tRNS and transcranial direct current stimulation (tDCS) on the leg motor cortex.Ten healthy subjects received anodal, cathodal tDCS, tRNS and sham stimulation for 10 min using 2 mA intensity during separate experimental sessions. Single pulse transcranial magnetic stimulation (TMS) induced motor evoked potential (MEP) measurements were used to assess motor cortical excitability changes after the stimulation.Similar to the hand area, we found that both tRNS and anodal tDCS induced an increase of the amplitude of the MEPs. Anodal tDCS induced a constant gradual increase of corticospinal excitability until 60 min post-stimulation, whereas the effect of tRNS was immediate with a duration of 40 min following stimulation. The cathodal tDCS induced decrease in MEP amplitude did not reach statistical significance.Our results suggest that although the leg area has a deeper position in the cortex compared to the hand area, it can be reached by weak transcranial currents. Both anodal tDCS and tRNS had comparable effect on cortical excitability.

Restorative neurology and neuroscience

Laczó, B; Antal, A; Rothkegel, H; Paulus, W


Preliminary evidence for performance enhancement following parietal lobe stimulation in Developmental Dyscalculia.

2014

Nearly 7% of the population exhibit difficulties in dealing with numbers and performing arithmetic, a condition named Developmental Dyscalculia (DD), which significantly affects the educational and professional outcomes of these individuals, as it often persists into adulthood. Research has mainly focused on behavioral rehabilitation, while little is known about performance changes and neuroplasticity induced by the concurrent application of brain-behavioral approaches. It has been shown that numerical proficiency can be enhanced by applying a small-yet constant-current through the brain, a non-invasive technique named transcranial electrical stimulation (tES). Here we combined a numerical learning paradigm with transcranial direct current stimulation (tDCS) in two adults with DD to assess the potential benefits of this methodology to remediate their numerical difficulties. Subjects learned to associate artificial symbols to numerical quantities within the context of a trial and error paradigm, while tDCS was applied to the posterior parietal cortex (PPC). The first subject (DD1) received anodal stimulation to the right PPC and cathodal stimulation to the left PPC, which has been associated with numerical performance's improvements in healthy subjects. The second subject (DD2) received anodal stimulation to the left PPC and cathodal stimulation to the right PPC, which has been shown to impair numerical performance in healthy subjects. We examined two indices of numerical proficiency: (i) automaticity of number processing; and (ii) mapping of numbers onto space. Our results are opposite to previous findings with non-dyscalculic subjects. Only anodal stimulation to the left PPC improved both indices of numerical proficiency. These initial results represent an important step to inform the rehabilitation of developmental learning disabilities, and have relevant applications for basic and applied research in cognitive neuroscience, rehabilitation, and education.

Frontiers in human neuroscience

Iuculano, T; Cohen Kadosh, R

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Impact of transcranial direct current stimulation on fatigue in multiple sclerosis.

2014

Fatigue is a frequent and difficult to treat symptom affecting patients with multiple sclerosis (MS) with a profound negative impact on quality of life. Fatigue has been associated with functional and structural abnormalities of the frontal cortex, including frontal hypo-activation. The aim of this exploratory study was to assess whether fatigue symptoms can be reduced by excitability-enhancing anodal transcranial direct current stimulation (tDCS).In this sham-controlled, double-blind intervention study, tDCS was applied over the left prefrontal cortex of MS patients with fatigue for five consecutive days. Symptoms were tracked for 1 month via questionnaires. Lesion load at baseline was calculated for each patient and correlated with fatigue levels and responsiveness to stimulation.In the whole group analysis the scores of the fatigue scales were not altered by tDCS. However, in an exploratory analysis we found a correlation between response to the stimulation regarding subjectively perceived fatigue and lesion load in the left frontal cortex: patients responding positively to anodal tDCS had higher lesion load, compared to non-responding patients.We conclude that in patient subgroups discernible by specific morphological alterations, tDCS may be a tool for MS fatigue management.

Restorative neurology and neuroscience

Saiote, C; Goldschmidt, T; Timäus, C; Steenwijk, MD; Opitz, A; Antal, A; Paulus, W; Nitsche, MA


Marked reduction of cerebellar deficits in upper limbs following transcranial cerebello-cerebral DC stimulation: tremor reduction and re-programming of the timing of antagonist commands.

2014

Cerebellar ataxias represent a very heterogeneous group of disabling disorders for which we lack effective symptomatic therapies in most cases. There is currently an intense interest in the use of non-invasive transcranial DC stimulation (tDCS) to modulate the activity of the cerebellum in ataxic disorders. We performed a detailed laboratory assessment of the effects of transcranial cerebello-cerebral DC stimulation (tCCDCS, including a sham procedure) on upper limb tremor and dysmetria in 2 patients presenting a dominant spinocerebellar ataxia (SCA) type 2, one of the most common SCAs encountered during practice. Both patients had a very similar triplet expansion size in the ATXN2 gene (respectively, 39 and 40 triplets). tCCDCS reduced both postural tremor and action tremor, as confirmed by spectral analysis. Quadratical PSD (power spectral density) of postural tremor dropped to 38.63 and 41.42% of baseline values in patient 1 and 2, respectively. The integral of the subband 4-20 Hz dropped to 46.9 and 62.3% of baseline values, respectively. Remarkably, tCCDCS canceled hypermetria and reduced dramatically the onset latency of the antagonist EMG activity associated with fast goal-directed movements toward 3 aimed targets (0.2, 0.3, and 0.4 rad). Following tCCDCS, the latency dropped from 108-98 to 63-57 ms in patient 1, and from 74-87 to 41-46 ms in patient 2 (mean control values ± SD: 36 ± 8 to 45 ± 11 ms), corresponding to a major drop of z scores for the 2 patients from 7.12 ± 0.69 to 1.28 ± 1.27 (sham procedure: 6.79 ± 0.71). This is the first demonstration that tCCDCS improves upper limb tremor and hypermetria in SCA type 2. In particular, this is the first report of a favorable effect on the onset latency of the antagonist EMG activity, a neurophysiological marker of the defect in programming of timing of motor commands. Our results indicate that tCCDCS should be considered in the symptomatic management of upper limb motor deficits in cerebellar ataxias. Future studies addressing a tDCS-based neuromodulation to improve motor control of upper limbs are required (a) in a large group of cerebellar disorders, and (b) in different subgroups of ataxic patients. The anatomical location of the cerebellum below the skull is particularly well suited for such studies.

Frontiers in systems neuroscience

Grimaldi, G; Oulad Ben Taib, N; Manto, M; Bodranghien, F

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Facilitating myoelectric-control with transcranial direct current stimulation: a preliminary study in healthy humans.

2014

Functional Electrical Stimulation (FES) can electrically activate paretic muscles to assist movement for post-stroke neurorehabilitation. Here, sensory-motor integration may be facilitated by triggering FES with residual electromyographic (EMG) activity. However, muscle activity following stroke often suffers from delays in initiation and termination which may be alleviated with an adjuvant treatment at the central nervous system (CNS) level with transcranial direct current stimulation (tDCS) thereby facilitating re-learning and retaining of normative muscle activation patterns.This study on 12 healthy volunteers was conducted to investigate the effects of anodal tDCS of the primary motor cortex (M1) and cerebellum on latencies during isometric contraction of tibialis anterior (TA) muscle for myoelectric visual pursuit with quick initiation/termination of muscle activation i.e. 'ballistic EMG control' as well as modulation of EMG for 'proportional EMG control'.The normalized delay in initiation and termination of muscle activity during post-intervention 'ballistic EMG control' trials showed a significant main effect of the anodal tDCS target: cerebellar, M1, sham (F(2) = 2.33, p < 0.1), and interaction effect between tDCS target and step-response type: initiation/termination of muscle activation (F(2) = 62.75, p < 0.001), but no significant effect for the step-response type (F(1) = 0.03, p = 0.87). The post-intervention population marginal means during 'ballistic EMG control' showed two important findings at 95% confidence interval (critical values from Scheffe's S procedure): 1. Offline cerebellar anodal tDCS increased the delay in initiation of TA contraction while M1 anodal tDCS decreased the same when compared to sham tDCS, 2. Offline M1 anodal tDCS increased the delay in termination of TA contraction when compared to cerebellar anodal tDCS or sham tDCS. Moreover, online cerebellar anodal tDCS decreased the learning rate during 'proportional EMG control' when compared to M1 anodal and sham tDCS.The preliminary results from healthy subjects showed specific, and at least partially antagonistic effects, of M1 and cerebellar anodal tDCS on motor performance during myoelectric control. These results are encouraging, but further studies are necessary to better define how tDCS over particular regions of the cerebellum may facilitate learning of myoelectric control for brain machine interfaces.

Journal of neuroengineering and rehabilitation

Dutta, A; Paulus, W; Nitsche, MA

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Transcranial direct current stimulation: five important issues we aren't discussing (but probably should be).

2014

Transcranial Direct Current Stimulation (tDCS) is a neuromodulatory device often publicized for its ability to enhance cognitive and behavioral performance. These enhancement claims, however, are predicated upon electrophysiological evidence and descriptions which are far from conclusive. In fact, a review of the literature reveals a number of important experimental and technical issues inherent with this device that are simply not being discussed in any meaningful manner. In this paper, we will consider five of these topics. The first, inter-subject variability, explores the extensive between- and within-group differences found within the tDCS literature and highlights the need to properly examine stimulatory response at the individual level. The second, intra-subject reliability, reviews the lack of data concerning tDCS response reliability over time and emphasizes the importance of this knowledge for appropriate stimulatory application. The third, sham stimulation and blinding, draws attention to the importance (yet relative lack) of proper control and blinding practices in the tDCS literature. The fourth, motor and cognitive interference, highlights the often overlooked body of research that suggests typical behaviors and cognitions undertaken during or following tDCS can impair or abolish the effects of stimulation. Finally, the fifth, electric current influences, underscores several largely ignored variables (such as hair thickness and electrode attachments methods) influential to tDCS electric current density and flow. Through this paper, we hope to increase awareness and start an ongoing dialog of these important issues which speak to the efficacy, reliability, and mechanistic foundations of tDCS.

Frontiers in systems neuroscience

Horvath, JC; Carter, O; Forte, JD

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Effects of the addition of transcranial direct current stimulation to virtual reality therapy after stroke: a pilot randomized controlled trial.

2014

Upper limb (UL) impairment is the most common disabling deficit following a stroke. Previous studies have suggested that transcranial direct current stimulation (tDCS) enhances the effect of conventional therapies.This pilot double-blind randomized control trial aimed to determine whether or not tDCS, combined with Wii virtual reality therapy (VRT), would be superior to Wii therapy alone in improving upper limb function and quality of life in chronic stroke individuals.Twenty participants were randomly assigned either to an experimental group that received VRT and tDCS, or a control group that received VRT and sham tDCS. The therapy was delivered over 15 sessions with 13 minutes of active or sham anodal tDCS, and one hour of virtual reality therapy. The outcomes included were determined using the Fugl-Meyer scale, the Wolf motor function test, the modified Ashworth scale (MAS), grip strength, and the stroke specific quality of life scale (SSQOL). Minimal clinically important differences (MCID) were observed when assessing outcome data.Both groups demonstrated gains in all evaluated areas, except for the SSQOL-UL domain. Differences between groups were only observed in wrist spasticity levels in the experimental group, where more than 50% of the participants achieved the MCID.These findings support that tDCS, combined with VRT therapy, should be investigated and clarified further.

NeuroRehabilitation

Viana, RT; Laurentino, GE; Souza, RJ; Fonseca, JB; Silva Filho, EM; Dias, SN; Teixeira-Salmela, LF; Monte-Silva, KK


Consequences of cathodal stimulation for behavior: when does it help and when does it hurt performance?

2014

Cathodal Transcranial Direct Current Stimulation (C-tDCS) has been reported, across different studies, to facilitate or hinder performance, or simply to have no tangible effect on behavior. This discrepancy is most prominent when C-tDCS is used to alter a cognitive function, questioning the assumption that cathodal stimulation always compromises performance. In this study, we aimed to study the effect of two variables on performance in a simple cognitive task (letter Flanker), when C-tDCS was applied to the left prefrontal cortex (PFC): (1) the time of testing relative to stimulation (during or after), and (2) the nature of the cognitive activity during stimulation in case of post-tDCS testing. In three experiments, we had participants either perform the Flanker task during C-tDCS (Experiment 1), or after C-tDCS. When the Flanker task was administered after C-tDCS, we varied whether during stimulation subjects were engaged in activities that posed low (Experiment 2) or high (Experiment 3) demands on the PFC. Our findings show that the nature of the task during C-tDCS has a systematic influence on the outcome, while timing per se does not.

PloS one

Nozari, N; Woodard, K; Thompson-Schill, SL

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Transcranial slow oscillation stimulation during NREM sleep enhances acquisition of the radial maze task and modulates cortical network activity in rats.

2014

Slow wave sleep, hallmarked by the occurrence of slow oscillations (SO), plays an important role for the consolidation of hippocampus-dependent memories. Transcranial stimulation by weak electric currents oscillating at the endogenous SO frequency (SO-tDCS) during post-learning sleep was previously shown by us to boost SO activity and improve the consolidation of hippocampus-dependent memory in human subjects. Here, we aimed at replicating and extending these results to a rodent model. Rats were trained for 12 days at the beginning of their inactive phase in the reference memory version of the radial arm maze. In a between subjects design, animals received SO-tDCS over prefrontal cortex (PFC) or sham stimulation within a time frame of 1 h during subsequent non-rapid eye movement (NREM) sleep. Applied over multiple daily sessions SO-tDCS impacted cortical network activity as measured by EEG and behavior: at the EEG level, SO-tDCS enhanced post-stimulation upper delta (2-4 Hz) activity whereby the first stimulations of each day were preferentially affected. Furthermore, commencing on day 8, SO-tDCS acutely decreased theta activity indicating long-term effects on cortical networks. Behaviorally, working memory for baited maze arms was enhanced up to day 4, indicating enhanced consolidation of task-inherent rules, while reference memory errors did not differ between groups. Taken together, we could show here for the first time an effect of SO-tDCS during NREM sleep on cognitive functions and on cortical activity in a rodent model.

Frontiers in behavioral neuroscience

Binder, S; Rawohl, J; Born, J; Marshall, L

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After vs. priming effects of anodal transcranial direct current stimulation on upper extremity motor recovery in patients with subacute stroke.

2014

Transcranial direct current stimulation (tDCS) of the motor cortex seems to be effective in improving motor performance in patients with chronic stroke, while some recent findings have reported conflicting results for the subacute phase. We aimed to verify whether upper extremity motor rehabilitation could be enhanced by treatment with tDCS administered before a rehabilitative session.Hand dexterity and force in 16 individuals with subacute stroke were assessed before (T0) and after anodal stimulation (T1) and after a successive session of motor rehabilitation (T2) in a double-blind, randomized, sham-controlled, crossover trial. To confirm the value of the device as a specific effector, behavioral tests were also administered.Anodal and sham stimulation plus rehabilitation significantly improved manual dexterity (repeated-measure Anova: A-tDCS: p = 0.005; S-tDCS: p = 0.042). Post hoc analysis revealed a significant stimulation effect only for A-tDCS (p = 0.013 between T0 and T1) and not for S-tDCS, whereas the rehabilitation effect (between T1 and T2) was not significant in either group. Hand force and behavioral features were unchanged.Anodal brain stimulation improves hand dexterity but does not increase the effectiveness of the rehabilitation directly. These results suggest the presence of aftereffects, not priming effects, of A-tDCS superimposed onto motor learning phenomena.

Restorative neurology and neuroscience

Fusco, A; Iosa, M; Venturiero, V; De Angelis, D; Morone, G; Maglione, L; Bragoni, M; Coiro, P; Pratesi, L; Paolucci, S


Bihemispheric tDCS enhances language recovery but does not alter BDNF levels in chronic aphasic patients.

2014

Several studies have shown that transcranial direct current stimulation (tDCS) is a useful tool to enhance language recovery in aphasia. It has also been suggested that modulation of the neurotrophin brain-derived neurotrophic factor (BDNF) might be part of the mechanisms involved in tDCS effects on synaptic connectivity. However, all language studies have previously investigated the effects using unihemispheric stimulation. The purpose of the present study is to investigate the role of bihemispheric tDCS on language recovery and BDNF serum levels.Seven aphasic persons underwent an intensive language therapy in two different conditions: real bihemispheric stimulation over the left and right Broca's areas and a sham condition.After the stimulation, patients exibited a significant recovery in three language tasks (picture description, noun and verb naming) compared to the sham condition which persisted in the follow-up session. No significant differences were found in BDNF serum levels after tDCS stimulation and in the follow-up session. However, a significant positive correlation was present for the real stimulation condition between percent changes in BDNF levels and in the verb naming task.The data suggest that this novel approach may potentiate the recovery of language in chronic aphasia. They also emphasize the importance to further investigate the role of possible biomarkers associated with tDCS treatment response in language recovery.

Restorative neurology and neuroscience

Marangolo, P; Fiori, V; Gelfo, F; Shofany, J; Razzano, C; Caltagirone, C; Angelucci, F


Treatment of primary progressive aphasias by transcranial direct current stimulation combined with language training.

2014

Primary progressive aphasia (PPA) is an untreatable neurodegenerative disorder that disrupts language functions. Previous studies have demonstrated transcranial direct current stimulation (tDCS) may improve language symptoms in patients with post stroke aphasia or neurodegenerative diseases.The present study investigated whether the application of anodal tDCS (AtDCS) to the scalp overlying the left dorsolateral prefrontal cortex (DLPFC), which may increase cortical excitability, in combination with individualized speech therapy would improve naming accuracy in the agrammatic variant of PPA (avPPA).Sixteen avPPA patients were randomly allocated into two subgroups: AtDCS (n = 8) or placebo tDCS (PtDCS). tDCS was applied over the left DLPFC (BA 8/9) 25 minutes per day for two weeks (10 days). Each patient underwent 25 minutes of individualized speech therapy with either AtDCS or PtDCS during each treatment session. Neuropsychological assessment, experimental naming, and linguistic abilities in daily living were assessed at baseline (T0), after two weeks of intervention (T1) and at a 12-week follow-up (T2).Significant improvement in experimental naming was observed in both groups at T1 and T2, but this effect was significantly greater in AtDCS than PtDCS patients. Naming correctness, as assessed using the Aachener Aphasie Test, increased selectively in the AtDCS group from T0 to T1, and this effect remained significant at T2. The analysis of daily living language abilities improved selectively in AtDCS group.Our results support the beneficial effect of targeted language training in combination with brain stimulation in avPPA patients. tDCS should be considered a useful tool for the improvement of language functions in patients with neurodegenerative diseases in future trials.

Journal of Alzheimer's disease : JAD

Cotelli, M; Manenti, R; Petesi, M; Brambilla, M; Cosseddu, M; Zanetti, O; Miniussi, C; Padovani, A; Borroni, B


Transcranial direct current stimulation (tDCS) for fatigue in multiple sclerosis.

2014

The debilitating fatigue that patients with multiple sclerosis (MS) commonly experience during day-to-day living activities responds poorly to current therapeutic options. Direct currents (DC) delivered through the scalp (transcranial DC stimulation or tDCS) at weak intensities induce changes in motor cortical excitability that persist for almost an hour after current offset and depend on current polarity. tDCS successfully modulates cortical excitability in various clinical disorders but no information is available for MS related fatigue.In this study we aimed to assess fatigue symptom after five consecutive sessions of anodal tDCS applied over the motor cortex in patients with MS.We enrolled 25 patients with MS all of whom experienced fatigue. We delivered anodal and sham tDCS in random order in two separate experimental sessions at least 1 month apart. The stimulating current was delivered for 15 minutes once a day for 5 consecutive days. In each session the Fatigue Impact Scale (FIS) and the Back Depression Inventory (BDI) were administered before the treatment (baseline), immediately after treatment on day five (T1), one week (T2) and three weeks (T3) after the last tDCS session.All patients tolerated tDCS well without adverse events. The fatigue score significantly decreased after anodal tDCS in 65% of the patients (responders). After patients received tDCS for 5 days their FIS scores improved by about 30% and the tDCS-induced benefits persisted at T2 and T3.Our preliminary findings suggest that anodal tDCS applied over the motor cortex, could improve fatigue in most patients with MS.

NeuroRehabilitation

Ferrucci, R; Vergari, M; Cogiamanian, F; Bocci, T; Ciocca, M; Tomasini, E; De Riz, M; Scarpini, E; Priori, A


Progress and outlooks in a genetic absence epilepsy model (WAG/Rij).

2014

The WAG/Rij model is a well characterized and validated genetic animal epilepsy model in which the for absence epilepsy highly characteristic spike-wave discharges (SWDs) develop spontaneously. In this review we discuss first some older and many new studies, with an emphasis on pharmacological and neurochemical studies towards the role of GABA and glutamate and the ion channels involved in the pathological firing patterns. Next, new insights and highlights from the last 5-10 years of reaearch in WAG/Rij rats are discussed. First, early environmental factors modulate SWD characteristics and antiepileptogenesis is possible. Also new is that the classically assumed association between sleep spindles and SWDs seems no longer valid as an explanatory role for the occurrence of SWDs in the genetic rodent models. A role of cortical and thalamic glial cells has been revealed, indicating a putative role for inflammatory cytokines. Neurophysiologic and signal analytical studies in this and in another rodent model (GAERS) point towards a cortical site of origin, that SWDs do not have a sudden onset, and propose a more important role for the posterior thalamus than was previously assumed. Finally it is proposed that the reticular nucleus of the thalamus might be heterogeneous with respect to its role in propagation and maintenance of SWDs. The presence of a well-established cortical region in which SWDs are elicited allows for research towards new non-invasive treatment options, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). The first results show the feasibility of this new approach.

Current medicinal chemistry

van Luijtelaar, G; Zobeiri, M


A single session of 1 mA anodal tDCS-supported motor training does not improve motor performance in patients with multiple sclerosis.

2014

To assess the effects of atDCS on motor performance in patients with multiple sclerosis (MS). Previously, anodal transcranial direct current stimulation (atDCS) has been shown to improve motor performance in healthy subjects and neurodegenerative populations. However, the effect of atDCS on motor performance is not examined in MS.In the current study, a sham controlled double-blind crossover design was used to evaluate the effect of 20 minutes of 1 mA atDCS or sham tDCS (stDCS) on a unimanual motor sequence-training task, consisting of sequential finger presses on a computer keyboard with the most impaired hand. Patients received stimulation (atDCS or stDCS) during motor training. tDCS was applied over the primary motor cortex contralateral to the most impaired hand. Motor performance was assessed immediately before, during and 30 minutes after stimulation.Although we need to be careful with the interpretation of the data due to lack of power, our results showed no significant effect of atDCS on motor performance.Our findings indicate that atDCS-supported motor training was not able to improve motor performance more than sham-supported motor training. Possibly, the effects of atDCS are mediated by specific MS-related characteristics. Furthermore, increasing atDCS intensity and offering multiple stimulation sessions might be necessary to optimize motor performance resulting from atDCS-supported motor training.

Restorative neurology and neuroscience

Meesen, RL; Thijs, H; Leenus, DJ; Cuypers, K


Healthy aging by staying selectively connected: a mini-review.

2014

Cognitive neuroscience of the healthy aging human brain has thus far addressed age-related changes of local functional and structural properties of gray and white matter and their association with declining or preserved cognitive functions. In addition to these localized changes, recent neuroimaging research has attributed an important role to neural networks with a stronger focus on interacting rather than isolated brain regions. The analysis of functional connectivity encompasses task-dependent and -independent synchronous activity in the brain, and thus reflects the organization of the brain in distinct performance-relevant networks. Structural connectivity in white matter pathways, representing the integrity of anatomical connections, underlies the communication between the nodes of these functional networks. Both functional and structural connectivity within these networks have been demonstrated to change with aging, and to have different predictive values for cognitive abilities in older compared to young adults. Structural degeneration has been found in the entire cerebral white matter with greatest deterioration in frontal areas, affecting whole brain structural network efficiency. With regard to functional connectivity, both higher and lower functional coupling has been observed in the aging compared to the young brain. Here, high connectivity within the nodes of specific functional networks on the one hand, and low connectivity to regions outside this network on the other hand, were associated with preserved cognitive functions in aging in most cases. For example, in the language domain, connections between left-hemisphere language-related prefrontal, posterior temporal and parietal areas were described as beneficial, whereas connections between the left and right hemisphere were detrimental for language task performance. Of note, interactions between structural and functional network properties may change in the course of aging and differentially impact behavioral performance in older versus young adults. Finally, studies using noninvasive brain stimulation techniques like transcranial direct current stimulation (tDCS) to simultaneously modulate behavior and functional connectivity support the importance of 'selective connectivity' of aging brain networks for preserved cognitive functions. These studies demonstrate that enhancing task performance by tDCS is paralleled by increased connectivity within functional networks. In this review, we outline the network perspective on healthy brain aging and discuss recent developments in this field.

Gerontology

Antonenko, D; Flöel, A

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A double-blind, sham-controlled, pilot study to assess the effects of the concomitant use of transcranial direct current stimulation with the computer assisted cognitive rehabilitation to the prefrontal cortex on cognitive functions in patients with str

2013 Dec

To examine the synergistic effects of both computer-assisted cognitive rehabilitation (CACR) and transcranial direct current stimulation (tDCS) on cognitive function in patients with stroke.The current double-blind, sham-controlled study enrolled a total of 11 patients who were newly diagnosed with stroke. The patients of the tDCS group (n=6) completed sessions of the Korean computer-assisted cognitive rehabilitation program five times a week for 30 minutes a session during a mean period of 18.5 days concomitantly with the anodal tDCS over the bilateral prefrontal cortex combined with the CACR. The patients of the control group (n=5) also completed sessions of the sham stimulation during a mean period of 17.8 days. Anodal tDCS over bilateral prefrontal cortex (F3 and F4 in 10-20 EEG system) was delivered for 30 minutes at an intensity of 2 mA. Cathode electrodes were applied to the non-dominant arm. All the patients were evaluated using the Seoul Computerized Neuropsychological Test (SCNT) and the Korean Mini-Mental State Examination.Mann-Whitney U test revealed a significant difference between the two groups. The patients of the tDCS group achieved a significant improvement in the post/pre ratio of auditory continuous performance test and visual continuous performance test on the SCNT items.Our results indicate that the concomitant use of the tDCS with CACR to the prefrontal cortex may provide additional beneficial effects in improving the cognitive dysfunction for patients with stroke.

Journal of Korean Neurosurgical Society

Park, SH; Koh, EJ; Choi, HY; Ko, MH

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Randomized, sham controlled trial of transcranial direct current stimulation for painful diabetic polyneuropathy.

2013 Dec

To investigate the analgesic effect of transcranial direct current stimulation (tDCS) over the primary motor (M1), dorsolateral prefrontal cortex (DLPFC), and sham tDCS in patients with painful diabetic polyneuropathy (PDPN).Patients with PDPN (n=60) were divided randomly into the three groups (n=20 per group). Each group received anodal tDCS with the anode centered over the left M1, DLPFC, or sham stimulation for 20 minutes at intensity of 2 mA for 5 consecutive days. A blinded physician rated the patients' pain using a visual analog scale (VAS), Clinical Global Impression (CGI) score, anxiety score, sleep quality, Beck Depression Inventory (BDI), and the pain threshold (PT) to pressure.After the tDCS sessions, the M1 group showed a significantly greater reduction in VAS for pain and PT versus the sham and DLPFC groups (p<0.001). The reduction in VAS for pain was sustained after 2 and 4 weeks of follow-up in the M1 group compared with the sham group (p<0.001, p=0.007). Significant differences were observed among the three groups over time in VAS for pain (p<0.001), CGI score (p=0.01), and PT (p<0.001). No significant difference was observed among the groups in sleep quality, anxiety score, or BDI score immediately after tDCS.Five daily sessions of tDCS over the M1 can produce immediate pain relief, and relief 2- and 4-week in duration in patients with PDPN. Our findings provide the first evidence of a beneficial effect of tDCS on PDPN.

Annals of rehabilitation medicine

Kim, YJ; Ku, J; Kim, HJ; Im, DJ; Lee, HS; Han, KA; Kang, YJ

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Effect of transcranial direct current stimulation on postural stability and lower extremity strength in hemiplegic stroke patients.

2013 Dec

To evaluate the effect of anodal transcranial direct current stimulation (tDCS) over the lesioned leg motor cortex, which can enhance the strength and coordination of the contralateral lower extremity and furthermore, enhance the postural stability of the hemiplegic subject.Anodal or sham stimulation on the lesioned cortex of a lower extremity was delivered to 11 ambulatory hemiplegic patients. The stimulation intensity was 2 mA. All subjects took part in two 10-minute tDCS sessions consisting of anodal stimulation and sham stimulation. The interval period between real and sham stimulation was 48 hours. The order was counter-balanced among the subjects. Before and after each stimulation session, static postural stability was evaluated with eyes opened and closed. Also, the isometric strength of the hemiplegic side of the treated knee was measured before and after each stimulation session. Repeated measure ANOVA was used to determine the statistical significance of improvements in postural stability and strength.There was significant improvement for overall stability index with eyes opened and closed after anodal tDCS (p<0.05). Isometric strength of the lesioned quadriceps tended to increase after anodal tDCS (p<0.05). Postural stability and quadriceps strength were not changed after sham stimulation.Anodal tDCS has potential value in hemiplegic stroke patients to improve balance and strengthen the affected lower extremity.

Annals of rehabilitation medicine

Sohn, MK; Jee, SJ; Kim, YW

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Transcranial direct current stimulation in schizophrenia.

2013 Dec

Transcranial direct current stimulation (tDCS) is an upcoming treatment modality for patients with schizophrenia. A series of recent observations have demonstrated improvement in clinical status of schizophrenia patients with tDCS. This review summarizes the research work that has examined the effects of tDCS in schizophrenia patients with respect to symptom amelioration, cognitive enhancement and neuroplasticity evaluation. tDCS is emerging as a safe, rapid and effective treatment for various aspects of schizophrenia symptoms ranging from auditory hallucinations-for which the effect is most marked, to negative symptoms and cognitive symptoms as well. An interesting line of investigation involves using tDCS for altering and examining neuroplasticity in patients and healthy subjects and is likely to lead to new insights into the neurological aberrations and pathophysiology of schizophrenia. The mechanistic aspects of the technique are discussed in brief. Future work should focus on establishing the clinical efficacy of this novel technique and on evaluating this modality as an adjunct to cognitive enhancement protocols. Understanding the mechanism of action of tDCS as well as the determinants and neurobiological correlates of clinical response to tDCS remains an important goal, which will help us expand the clinical applications of tDCS for the treatment of patients with schizophrenia.

Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology

Agarwal, SM; Shivakumar, V; Bose, A; Subramaniam, A; Nawani, H; Chhabra, H; Kalmady, SV; Narayanaswamy, JC; Venkatasubramanian, G

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Acceleration of image analyst training with transcranial direct current stimulation.

2013 Dec

Humans today are routinely and increasingly presented with vast quantities of data that challenge their capacity for efficient processing. To restore the balance between man and machine, it is worthwhile to explore new methods for enhancing or accelerating this capacity. This study was designed to investigate the efficacy of transcranial DC stimulation (tDCS) to reduce training time and increase proficiency in spatial recognition using a simulated synthetic aperture radar (SAR) task. Twenty-seven Air Force active duty members volunteered to participate in the study. Each participant was assigned to 1 of 3 stimulation groups and received two, 90-min training sessions on a target search and identification task using SAR imagery followed by a test. The tDCS anode was applied to site F10 according to the 10-20 electroencephalographic electrode convention while the cathode was placed on the contralateral bicep. Group 1 received anodal tDCS at 2 mA for 30 min in the first training session and sham tDCS in the second session. Group 2 received the stimulation conditions in the opposite order. Group 3 did not receive stimulation at all. Results showed that participants receiving training plus tDCS attained visual search accuracies ~25% higher than those provided with sham stimulation or no stimulation. However, a corresponding performance improvement was not found in the first training session for the change detection portion of the task. This indicates that experience with the imagery is important in the tDCS-elicited performance improvements in change detection.

Behavioral neuroscience

McKinley, RA; McIntire, L; Bridges, N; Goodyear, C; Weisend, MP


Transcranial direct current stimulation (tDCS) of left parietal cortex facilitates gesture processing in healthy subjects.

2013 Dec

Gesture processing deficits constitute a key symptom of apraxia, a disorder of motor cognition frequently observed after left-hemispheric stroke. The clinical relevance of apraxia stands in stark contrast to the paucity of therapeutic options available. Transcranial direct current stimulation (tDCS) is a promising tool for modulating disturbed network function after stroke. Here, we investigate the effect of parietal tDCS on gesture processing in healthy human subjects. Neuropsychological and imaging studies suggest that the imitation and matching of hand gestures involve the left inferior parietal lobe (IPL). Using neuronavigation based on cytoarchitectonically defined anatomical probability maps, tDCS was applied over left IPL-areas PF, PFm, or PG in healthy participants (n = 26). Before and after tDCS, subjects performed a gesture matching task and a person discrimination task for control. Changes in error rates and reaction times were analyzed for the effects of anodal and cathodal tDCS (compared with sham tDCS). Matching of hand gestures was specifically facilitated by anodal tDCS applied over the cytoarchitectonically defined IPL-area PFm, whereas tDCS over IPL-areas PF and PG did not elucidate significant effects. Taking into account tDCS electrode size and the central position of area PFm within IPL, it can be assumed that the observed effect is rather the result of a combined stimulation of the supramarginal and angular gyrus than an isolated PFm stimulation. Our data confirm the pivotal role of the left IPL in gesture processing. Furthermore, anatomically guided tDCS of the left IPL may constitute a promising approach to neurorehabilitation of apraxic patients with gesture processing deficits.

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

Weiss, PH; Achilles, EI; Moos, K; Hesse, MD; Sparing, R; Fink, GR

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Effects of transcranial direct current stimulation on risky decision making are mediated by 'hot' and 'cold' decisions, personality, and hemisphere.

2013 Dec

Previous results point towards a lateralization of dorsolateral prefrontal cortex (DLPFC) function in risky decision making. While the right hemisphere seems involved in inhibitory cognitive control of affective impulses, the left DLPFC is crucial in the deliberative processing of information relevant for the decision. However, a lack of empirical evidence precludes definitive conclusions. The aim of our study was to determine whether anodal transcranial direct current stimulation (tDCS) over the right DLPFC with cathodal tDCS over the lDLPFC (anodal right/cathodal left) or vice versa (anodal left/cathodal right) differentially modulates risk-taking in a task [the Columbia Card Task (CCT)] specifically engaging affect-charged (Hot CCT) vs. deliberative (Cold CCT) decision making. The facilitating effect of the anodal stimulation on neuronal activity was emphasized by the use of a small anode and a big cathode. To investigate the role of individual differences in risk-taking, participants were either smokers or non-smokers. Anodal left/cathodal right stimulation decreased risk-taking in the 'cold' cognition version of the task, in both groups, probably by modulating deliberative processing. In the 'hot' version, anodal right/cathodal left stimulation led to opposite effects in smokers and non-smokers, which might be explained by the engagement of the same inhibitory control mechanism: in smokers, improved controllability of risk-seeking impulsivity led to more conservative decisions, while inhibition of risk-aversion in non-smokers resulted in riskier choices. These results provide evidence for a hemispheric asymmetry and personality-dependent tDCS effects in risky decision making, and may be important for clinical research on addiction and depression.

The European journal of neuroscience

Pripfl, J; Neumann, R; Köhler, U; Lamm, C


Multiple sessions of transcranial direct current stimulation to the intact hemisphere improves visual function after unilateral ablation of visual cortex.

2013 Dec

Damage to cerebral systems is frequently followed by the emergence of compensatory mechanisms, which serve to reduce the effects of brain damage and allow recovery of function. Intrinsic recovery, however, is rarely complete. Non-invasive brain stimulation technologies have the potential to actively shape neural circuits and enhance recovery from brain damage. In this study, a stable deficit for detecting and orienting to visual stimuli presented in the contralesional visual hemifield was generated by producing unilateral brain damage of the right posterior parietal and contiguous visual cortical areas. A long regimen of inhibitory non-invasive transcranial direct-current stimulation (cathodal tDCS, 2 mA, 20 min) was applied to the contralateral (intact) posterior parietal cortex over 14 weeks (total of 70 sessions, one per day, 5 days per week) and behavioral outcomes were periodically assessed. In three out of four stimulated cats, lasting recovery of visuospatial function was observed. Recovery started after 2-3 weeks of stimulation, and recovered targets were located first in the periphery, and moved to more central visual field locations with the accrual of stimulation sessions. Recovery for moving tasks followed a biphasic pattern before reaching plateau levels. Recovery did not occur for more difficult visual tasks. These findings highlight the ability of multiple sessions of transcranial direct-current stimulation to produce recovery of visuospatial function after unilateral brain damage.

The European journal of neuroscience

Rushmore, RJ; DeSimone, C; Valero-Cabré, A


Motor cortex-induced plasticity by noninvasive brain stimulation: a comparison between transcranial direct current stimulation and transcranial magnetic stimulation.

2013 Dec

The aim of this study was to test and compare the effects of a within-subject design of repetitive transcranial magnetic stimulation (rTMS) [coupled with sham transcranial direct current stimulation (tDCS)] and tDCS (coupled with sham rTMS) on the motor cortex excitability and also compare the results against sham tDCS/sham rTMS. We conducted a double-blinded, randomized, sham-controlled, cross-over trial. Eleven right-handed, healthy individuals (five women, mean age: 39.8 years, SD 13.4) received the three interventions (cross-over design) in a randomized order: (a) high-frequency (HF) rTMS (+sham tDCS), (b) anodal tDCS (+sham rTMS), and (c) sham stimulation (sham rTMS+sham tDCS). Cortical excitability measurements [motor threshold, motor evoked potential (MEP), intracortical facilitation and inhibition, and transcallosal inhibition] and motor behavioral assessments were used as outcome measures. Between-group analysis of variance showed that MEP amplitude after HF rTMS was significantly higher than MEP amplitude after anodal tDCS (P=0.001). Post-hoc analysis showed a significant increase in MEP amplitude after HF rTMS (25.3%, P=0.036) and a significant decrease in MEP amplitude after anodal tDCS (-32.7%, P=0.001). There was a similar increase in motor function as indexed by Jebsen-Taylor Hand Function Test in the two active groups compared with sham stimulation. In conclusion, here, we showed that although both techniques induced similar motor gains, they induce opposing results in cortical excitability. HF rTMS is associated with an increase in corticospinal excitability, whereas 20 min of tDCS induces the opposite effect. We discuss potential implications of these results to future clinical experiments using rTMS or tDCS for motor function enhancement.

Neuroreport

Simis, M; Adeyemo, BO; Medeiros, LF; Miraval, F; Gagliardi, RJ; Fregni, F


Automated MRI segmentation for individualized modeling of current flow in the human head.

2013 Dec

High-definition transcranial direct current stimulation (HD-tDCS) and high-density electroencephalography require accurate models of current flow for precise targeting and current source reconstruction. At a minimum, such modeling must capture the idiosyncratic anatomy of the brain, cerebrospinal fluid (CSF) and skull for each individual subject. Currently, the process to build such high-resolution individualized models from structural magnetic resonance images requires labor-intensive manual segmentation, even when utilizing available automated segmentation tools. Also, accurate placement of many high-density electrodes on an individual scalp is a tedious procedure. The goal was to develop fully automated techniques to reduce the manual effort in such a modeling process.A fully automated segmentation technique based on Statical Parametric Mapping 8, including an improved tissue probability map and an automated correction routine for segmentation errors, was developed, along with an automated electrode placement tool for high-density arrays. The performance of these automated routines was evaluated against results from manual segmentation on four healthy subjects and seven stroke patients. The criteria include segmentation accuracy, the difference of current flow distributions in resulting HD-tDCS models and the optimized current flow intensities on cortical targets.The segmentation tool can segment out not just the brain but also provide accurate results for CSF, skull and other soft tissues with a field of view extending to the neck. Compared to manual results, automated segmentation deviates by only 7% and 18% for normal and stroke subjects, respectively. The predicted electric fields in the brain deviate by 12% and 29% respectively, which is well within the variability observed for various modeling choices. Finally, optimized current flow intensities on cortical targets do not differ significantly.Fully automated individualized modeling may now be feasible for large-sample EEG research studies and tDCS clinical trials.

Journal of neural engineering

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


Testing the involvement of the prefrontal cortex in lucid dreaming: a tDCS study.

2013 Dec

Recent studies suggest that lucid dreaming (awareness of dreaming while dreaming) might be associated with increased brain activity over frontal regions during rapid eye movement (REM) sleep. By applying transcranial direct current stimulation (tDCS), we aimed to manipulate the activation of the dorsolateral prefrontal cortex (DLPFC) during REM sleep to increase dream lucidity. Nineteen participants spent three consecutive nights in a sleep laboratory. On the second and third nights they randomly received either 1 mA tDCS for 10 min or sham stimulation during each REM period starting with the second one. According to the participants' self-ratings, tDCS over the DLPFC during REM sleep increased lucidity in dreams. The effects, however, were not strong and found only in frequent lucid dreamers. While this indicates some preliminary support for the involvement of the DLPFC in lucid dreaming, further research, controlling for indirect effects of stimulation and including other brain regions, is needed.

Consciousness and cognition

Stumbrys, T; Erlacher, D; Schredl, M


Effects of non-invasive neurostimulation on craving: a meta-analysis.

2013 Dec

This meta-analysis was conducted to evaluate the available evidence regarding the effects of non-invasive neurostimulation of the dorsolateral prefrontal cortex (DLPFC), on craving in substance dependence and craving for high palatable food. Non-invasive neurostimulation techniques were restricted to repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS). A total of 17 eligible studies were identified. Random effects analysis revealed a pooled standardized effect size (Hedge's g) of 0.476 (CI: 0.316-0.636), indicating a medium effect size favouring active non-invasive neurostimulation over sham stimulation in the reduction of craving (z=5.832, p<0.001). No significant differences were found between rTMS and tDCS, between the various substances of abuse and between substances of abuse and food, or between left and right DLPFC stimulation. In conclusion, this meta-analysis provides the first clear evidence that non-invasive neurostimulation of the DLPFC decreases craving levels in substance dependence.

Neuroscience and biobehavioral reviews

Jansen, JM; Daams, JG; Koeter, MW; Veltman, DJ; van den Brink, W; Goudriaan, AE


Cathodal transcranial direct current stimulation induces regional, long-lasting reductions of cortical blood flow in rats.

2013 Dec

Transcranial direct current stimulation (tDCS) induces polarity-specific changes of cerebral blood flow (CBF). To determine whether these changes are focally limited or if they incorporate large cortical regions and thus have the potential for a therapeutic application, we investigated the effects of cathodal tDCS on CBF in an established tDCS rat model with particular attention to the spatial extension in CBF changes using laser Doppler blood perfusion imaging (LDI).Twenty-one Sprague Dawley rats received a single 15-minute session of cathodal tDCS at current intensities of 200, 400, 600, or 700 μA applied over electrode contact areas (ECA) of 3·5, 7·0, 10·5, or 14·0 mm(2). One animal died prior to the stimulation. Cerebral blood flow was measured prior and after tDCS with LDI in three defined regions of interest (ROI) over the stimulated left hemisphere (region anterior to ECA - ROI 1, ECA - ROI 2, region posterior to ECA - ROI 3).A regional decrease in CBF was measured after cathodal tDCS, the extent of the decrease depending on the current density applied. The most effective and spatially limited reduction in CBF (up to 50%, lasting as long as 90 minutes) was found after the application of 600 μA over an ECA of 10·5 mm(2). This significant reduction in CBF even lasted up to 90 minutes in distant cortical areas (ROI 1 and 3) that were not directly related to the ECA (ROI 2).Cathodal tDCS induces a regional, long-lasting, reversible decrease in CBF that is not limited to the region to which tDCS is applied.

Neurological research

Mielke, D; Wrede, A; Schulz-Schaeffer, W; Taghizadeh-Waghefi, A; Nitsche, MA; Rohde, V; Liebetanz, D


Behavioral effects of transcranial direct current stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence.

2013 Dec

Transcranial Direct Current Stimulation (tDCS) has been shown to reduce acute substance craving in drug addicts, and improve cognition in neuropsychiatric patients. Here we aimed to explore further tDCS induced behavioral and neurophysiological modulation including assessment of relapse rate over a prolonged time course in alcoholism. We examined the effects of repeated anodal tDCS (2mA, 35 cm(2), 20min) over the left dorsolateral prefrontal cortex (DLPFC) on relapse to the use of alcohol in alcoholics from outpatient services, who received additional routine clinical treatment. Furthermore, event related potentials (ERPs), cognitive and frontal executive processes, craving, depressive and anxiety symptoms were obtained before and after treatment. From thirteen alcoholic subjects, seven were randomized to sham-tDCS and six to real tDCS treatment (once a week for five consecutive weeks). Depressive symptoms and craving were reduced to a larger extent in the tDCS group compared to the sham group (p=0.005 and p=0.015, respectively). On the other hand, active tDCS was able to block the increase in neural activation triggered by alcohol related and neutral cues in prefrontal cortex (PFC) as indexed by ERP as seen in the sham-tDCS group. Finally, there was a trend for increased change in executive function in the tDCS group compared to the sham-tDCS group (p=0.082), and, similarly, a trend for more relapses in the tDCS group compared to sham tDCS (four alcoholic subjects (66.7%) vs. one (14.3%), p=0.053).These results confirm the previous findings of tDCS effects on craving in alcoholism and also extend these findings as we showed also tDCS-related mood improvement. However, potential increase in relapse is possible; thus the clinical value of an increase in craving and improvement in depression and executive function needs to be carefully assessed in further studies; including investigation of optimal parameters of stimulation.

Journal of physiology, Paris

da Silva, MC; Conti, CL; Klauss, J; Alves, LG; do Nascimento Cavalcante, HM; Fregni, F; Nitsche, MA; Nakamura-Palacios, EM


Excitability modulation of the motor system induced by transcranial direct current stimulation: a multimodal approach.

2013 Dec

Anodal and cathodal transcranial direct current stimulations (tDCS) are both established techniques to induce cortical excitability changes. Typically, in the human motor system, such cortical modulations are inferred through changes in the amplitude of the motor evoked potentials (MEPs). However, it is now possible to directly evaluate tDCS-induced changes at the cortical level by recording the transcranial magnetic stimulation evoked potentials (TEPs) using electroencephalography (EEG). The present study investigated the modulation induced by the tDCS on the motor system. The study evaluates changes in the MEPs, in the amplitude and distribution of the TEPs, in resting state oscillatory brain activity and in behavioral performance in a simple manual response task. Both the short- and long-term tDCS effects were investigated by evaluating their time course at ~0 and 30min after tDCS. Anodal tDCS over the left primary motor cortex (M1) induced an enhancement of corticospinal excitability, whereas cathodal stimulation produced a reduction. These changes in excitability were indexed by changes in MEP amplitude. More interestingly, tDCS modulated the cortical reactivity, which is the neuronal activity evoked by TMS, in a polarity-dependent and site-specific manner. Cortical reactivity increased after anodal stimulation over the left M1, whereas it decreased with cathodal stimulation. These effects were partially present also at long term evaluation. No polarity-specific effect was found either on behavioral measures or on oscillatory brain activity. The latter showed a general increase in the power density of low frequency oscillations (theta and alpha) at both stimulation polarities. Our results suggest that tDCS is able to modulate motor cortical reactivity in a polarity-specific manner, inducing a complex pattern of direct and indirect cortical activations or inhibitions of the motor system-related network, which might be related to changes in synaptic efficacy of the motor cortex.

NeuroImage

Pellicciari, MC; Brignani, D; Miniussi, C


[Interactive rTMS protocols in psychiatry].

2013 Dec

The efficiency of repetitive transcranial magnetic stimulation (rTMS) in the treatment of psychiatric disorders is robust for major depressive episode (MDE) while results are encouraging for schizophrenia. However, rTMS protocols need to be optimized. Basic researches in TMS led to the concept of "state dependency TMS". This concept suggests that the neural circuits' activation states, before and during the stimulation, influence the pulse effect. Indeed, TMS effect must be seen, not simply as a stimulus, but also as the result of an interaction between a stimulus and a level of brain activity. Those data suggest that rTMS efficiency could be increased in psychiatric disorders by triggering patients' neurocognitive activities during stimulation. Thus "interactive rTMS protocols" have been submitted.This article provides a review and a classification of different interactive protocols implemented in the treatment of MDE and schizophrenia. Protocols' interactions with cognitive activities and brain electrical activities will be discussed.Interactive rTMS protocols that manipulate cognitive activities have been developed for MDE treatments. They aim at regulating emotional states of depressed patients during the stimulation. The patients perform emotional tasks in order to activate cortical networks involving the left dorsolateral prefrontal cortex (DLPFC) into a state that may be more sensitive to the rTMS pulse effect. Simultaneous cognitive behavioral therapy ("CBT rTMS") and cognitive-emotional reactivation ("affective rTMS") have thus been tested during left DLPFC rTMS in MDE. Interactive rTMS protocols that manipulate brain electrical activities have been developed for MDE and schizophrenia treatments. Two categories of protocols should be identified. In the first set, personalized brain activity has been analyzed to determine the parameters of stimulation (i.e. frequency of stimulation) matching the patient ("personalized rTMS"). Personalized rTMS protocols can be made "online" or "offline" depending on whether the EEG activity is measured during or prior to rTMS. Online protocol is called "contingent rTMS": it consists in stimulating the brain only when a specific EEG pattern involving the intensity of alpha rhythm is recorded and recognized. Offline protocol is called "alpha rTMS", and relies on ascertaining frequency of stimulation in accordance with personalized alpha peak frequency prior to rTMS. In the second set, electrical brain activity is modulated before or during rTMS in order to stimulate the DLPFC in optimal conditions. Brain activity modulation may be obtained by transcranial direct current stimulation ("tDCS rTMS") or EEG-biofeedack ("EEG-biofeedback rTMS").Interactive rTMS studies have various limitations, notably their exploratory character on a small sample of patien

L'Encéphale

Micoulaud-Franchi, JA; Richieri, R; Lancon, C; Vion-Dury, J


Magnetoencephalographic evidence for the modulation of cortical swallowing processing by transcranial direct current stimulation.

2013 Dec

Swallowing is a complex neuromuscular task that is processed within multiple regions of the human brain. Rehabilitative treatment options for dysphagia due to neurological diseases are limited. Because the potential for adaptive cortical changes in compensation of disturbed swallowing is recognized, neuromodulation techniques like transcranial direct current stimulation (tDCS) are currently considered as a treatment option. Here we evaluate the effect of tDCS on cortical swallowing network activity and behavior. In a double-blind crossover study, anodal tDCS (20 min, 1 mA) or sham stimulation was administered over the left or right swallowing motor cortex in 21 healthy subjects in separate sessions. Cortical activation was measured using magnetoencephalography (MEG) before and after tDCS during cued "simple", "fast" and "challenged" swallow tasks with increasing levels of difficulty. Swallowing response times and accuracy were measured. Significant bilateral enhancement of cortical swallowing network activation was found in the theta frequency range after left tDCS in the fast swallow task (p=0.006) and following right tDCS in the challenged swallow task (p=0.007), but not after sham stimulation. No relevant behavioral effects were observed on swallow response time, but swallow precision improved after left tDCS (p<0.05). Anodal tDCS applied over the swallowing motor cortex of either hemisphere was able to increase bilateral swallow-related cortical network activation in a frequency specific manner. These neuroplastic effects were associated with subtle behavioral gains during complex swallow tasks in healthy individuals suggesting that tDCS deserves further evaluation as a treatment tool for dysphagia.

NeuroImage

Suntrup, S; Teismann, I; Wollbrink, A; Winkels, M; Warnecke, T; Flöel, A; Pantev, C; Dziewas, R


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

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[Stimulating the thought].

2013 Nov

Neuropsychiatric disorders are generally accompanied by a change in brain activity (hyperactivity or deficiency compared to normal activity). Therefore, intervention in brain activity may provide treatment for different disorders. In this paper we review various methods of brain stimulation: some that are familiar and have been in use for several years such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS); and others that are new and still being studied but have obtained promising preliminary results such as vagus nerve stimulation (VNS), deep brain stimulation (DBS], magnetic seizure therapy, transcranial direct current stimulation (tDCS] and near-infrared therapy. For each method we describe the procedure, proposed mechanisms, side effects and current status in research and in the practical field.

Harefuah

Israeli, D; Ben-Menahem, Y; Wertman, M; Grunhous, L


Transcranial direct current stimulation for refractory auditory hallucinations in schizophrenia.

2013 Nov

Some patients with schizophrenia may suffer from continuous or severe auditory hallucinations that are refractory to antipsychotic drugs, including clozapine. Such patients may benefit from a short trial of once- to twice-daily transcranial direct current stimulation (tDCS) with the cathode placed over the left temporoparietal cortex and the anode over the left dorsolateral prefrontal cortex; negative, cognitive, and other symptoms, if present, may also improve. At present, the case for tDCS treatment of refractory auditory hallucinations rests on 1 well-conducted randomized, sham tDCS-controlled trial and several carefully documented and instructive case reports. Benefits with up to 3 years of maintenance tDCS have also been described. In patients with refractory auditory hallucinations, tDCS has been delivered at 1- to 3-mA current intensity during 20-30 minutes in once- to twice-daily sessions for up to 3 years with no apparent adverse effects. Transcranial direct current stimulation therefore appears to be a promising noninvasive brain stimulation technique for patients with antipsychotic-refractory auditory hallucinations.

The Journal of clinical psychiatry

Andrade, C


Polarity-specific effects of motor transcranial direct current stimulation on fMRI resting state networks.

2013 Nov

Transcranial direct current stimulation (tDCS) has been used to modify motor performance in healthy and patient populations. However, our understanding of the large-scale neuroplastic changes that support such behavioural effects is limited. Here, we used both seed-based and independent component analyses (ICA) approaches to probe tDCS-induced modifications in resting state activity with the aim of establishing the effects of tDCS applied to the primary motor cortex (M1) on both motor and non-motor networks within the brain. Subjects participated in three separate sessions, during which resting fMRI scans were acquired before and after 10min of 1mA anodal, cathodal, or sham tDCS. Cathodal tDCS increased the inter-hemispheric coherence of resting fMRI signal between the left and right supplementary motor area (SMA), and between the left and right hand areas of M1. A similar trend was documented for the premotor cortex (PMC). Increased functional connectivity following cathodal tDCS was apparent within the ICA-generated motor and default mode networks. Additionally, the overall strength of the default mode network was increased. Neither anodal nor sham tDCS produced significant changes in resting state connectivity. This work indicates that cathodal tDCS to M1 affects the motor network at rest. In addition, the effects of cathodal tDCS on the default mode network support the hypothesis that diminished top-down control may contribute to the impaired motor performance induced by cathodal tDCS.

NeuroImage

Amadi, U; Ilie, A; Johansen-Berg, H; Stagg, CJ

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Individual differences in transcranial electrical stimulation current density.

2013 Nov

Transcranial electrical stimulation (TCES) is effective in treating many conditions, but it has not been possible to accurately forecast current density within the complex anatomy of a given subject's head. We sought to predict and verify TCES current densities and determine the variability of these current distributions in patient-specific models based on magnetic resonance imaging (MRI) data. Two experiments were performed. The first experiment estimated conductivity from MRIs and compared the current density results against actual measurements from the scalp surface of 3 subjects. In the second experiment, virtual electrodes were placed on the scalps of 18 subjects to model simulated current densities with 2 mA of virtually applied stimulation. This procedure was repeated for 4 electrode locations. Current densities were then calculated for 75 brain regions. Comparison of modeled and measured external current in experiment 1 yielded a correlation of r = .93. In experiment 2, modeled individual differences were greatest near the electrodes (ten-fold differences were common), but simulated current was found in all regions of the brain. Sites that were distant from the electrodes (e.g. hypothalamus) typically showed two-fold individual differences. MRI-based modeling can effectively predict current densities in individual brains. Significant variation occurs between subjects with the same applied electrode configuration. Individualized MRI-based modeling should be considered in place of the 10-20 system when accurate TCES is needed.

Journal of biomedical research

Russell, MJ; Goodman, T; Pierson, R; Shepherd, S; Wang, Q; Groshong, B; Wiley, DF

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Cathodal tDCS Over the Left Prefrontal Cortex Diminishes Choice-Induced Preference Change.

2013 Nov

In everyday life, people often find themselves facing difficult decisions between options that are equally attractive. Cognitive dissonance theory states that after making a difficult choice between 2 equally preferred options, individuals no longer find the alternatives similarly desirable. Rather, they often change their existing preferences to align more closely with the choice they have just made. Despite the relevance of cognitive dissonance in modulating behavior, little is known about the brain processes crucially involved in choice-induced preference change. In the present study, we applied cathodal transcranial Direct Current Stimulation (tDCS) with the aim of downregulating the activity of the left or the right dorsolateral prefrontal cortex (DLPFC) during a revised version of Brehm's (in 1956. Post-decision changes in the desirability of alternatives. J Abnorm Soc Psychol. 52:384-389) free-choice paradigm. We found that cathodal tDCS over the left, but not over the right, DLPFC caused a reduction of the typical behavior-induced preference change relative to sham stimulation. Our findings highlight the role of prefrontal cortex in cognitive dissonance and provide evidence that left DLPFC plays a necessary role in the implementation of choice-induced preference change.

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

Mengarelli, F; Spoglianti, S; Avenanti, A; di Pellegrino, G


Disrupting prefrontal cortex prevents performance gains from sensory-motor training.

2013 Nov

Humans show large and reliable performance impairments when required to make more than one simple decision simultaneously. Such multitasking costs are thought to largely reflect capacity limits in response selection (Welford, 1952; Pashler, 1984, 1994), the information processing stage at which sensory input is mapped to a motor response. Neuroimaging has implicated the left posterior lateral prefrontal cortex (pLPFC) as a key neural substrate of response selection (Dux et al., 2006, 2009; Ivanoff et al., 2009). For example, activity in left pLPFC tracks improvements in response selection efficiency typically observed following training (Dux et al., 2009). To date, however, there has been no causal evidence that pLPFC contributes directly to sensory-motor training effects, or the operations through which training occurs. Moreover, the left hemisphere lateralization of this operation remains controversial (Jiang and Kanwisher, 2003; Sigman and Dehaene, 2008; Verbruggen et al., 2010). We used anodal (excitatory), cathodal (inhibitory), and sham transcranial direct current stimulation (tDCS) to left and right pLPFC and measured participants' performance on high and low response selection load tasks after different amounts of training. Both anodal and cathodal stimulation of the left pLPFC disrupted training effects for the high load condition relative to sham. No disruption was found for the low load and right pLPFC stimulation conditions. The findings implicate the left pLPFC in both response selection and training effects. They also suggest that training improves response selection efficiency by fine-tuning activity in pLPFC relating to sensory-motor translations.

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

Filmer, HL; Mattingley, JB; Marois, R; Dux, PE

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[Transcranial direct current stimulation for chronic pain].

2013 Nov

Transcranial Direct Current Stimulation (tDCS) is a non-invasive method for neuromodulation. By changing the neurons' resting membrane potential, the method can alter the activity in areas of the brain. We therefore wished to review randomised controlled trials (RCTs) that investigate the treatment effect of tDCS on chronic pain.We undertook a search in PubMed with the search terms «transcranial direct current stimulation» and «pain», with «randomized controlled trial» as a filter.Five randomised, controlled trials that used quantitative outcome measures for pain were identified. The studies focused on strongly varying groups of patients suffering from pain. The results from some of the studies showed that stimulation with the aid of tDCS led to a significantly lower level of pain, but seen as a whole, the results were not conclusive.The method should be further investigated in studies that include clearly defined groups of patients suffering from pain, as well as a larger number of participants, before implementation of the method is considered as a treatment option for chronic pain.

Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række

Fagerlund, AJ; Bystad, MK; Aslaksen, PM

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Randomized Trial of Transcranial Direct Current Stimulation and Hearing Aids for Tinnitus Management.

2013 Nov

Background. The perception of sound in the absence of an external sound is tinnitus. Tinnitus can have a severe negative impact on quality of life. Objective. This trial investigated whether multisession anodal transcranial direct current stimulation (tDCS) of the left temporoparietal area would enhance sound therapy from hearing aids. Methods. Forty participants (mean age = 54 years) experiencing chronic tinnitus (minimum 2 years) completed a 7-month long double-blind randomized clinical trial. Participants were randomized into 2 groups: control receiving sham tDCS and experimental receiving tDCS. Each group underwent multisession (5 consecutive sessions with 24-hour gap) anodal tDCS (2 mA intensity and 20 minutes duration) of the left temporoparietal area, followed by hearing aid use for 6 months. The impact of tDCS and hearing aid use on tinnitus was assessed using questionnaires (primary measure: Tinnitus Functional Index) and minimum masking level measurement. Results. There was a significant reduction in the overall Tinnitus Functional Index score with time, F(2, 37) = 11.9, P = .0001, for both the groups. Similar patterns were seen for secondary measures. tDCS appeared to have a positive effect on minimum masking levels but not questionnaire responses. Conclusions. After 3 months of hearing aid use, there were significant improvements in tinnitus, which were sustained at 6 months of use. The hearing aid effects appeared independent of tDCS. Further investigations of tDCS or other neuromodulators priming the auditory system for sound therapy based tinnitus treatments are warranted.

Neurorehabilitation and neural repair

Shekhawat, GS; Searchfield, GD; Stinear, CM


Functional near-infrared spectroscopy maps cortical plasticity underlying altered motor performance induced by transcranial direct current stimulation.

2013 Nov

Transcranial direct current stimulation (tDCS) of the human sensorimotor cortex during physical rehabilitation induces plasticity in the injured brain that improves motor performance. Bi-hemispheric tDCS is a noninvasive technique that modulates cortical activation by delivering weak current through a pair of anodal-cathodal (excitation-suppression) electrodes, placed on the scalp and centered over the primary motor cortex of each hemisphere. To quantify tDCS-induced plasticity during motor performance, sensorimotor cortical activity was mapped during an event-related, wrist flexion task by functional near-infrared spectroscopy (fNIRS) before, during, and after applying both possible bi-hemispheric tDCS montages in eight healthy adults. Additionally, torque applied to a lever device during isometric wrist flexion and surface electromyography measurements of major muscle group activity in both arms were acquired concurrently with fNIRS. This multiparameter approach found that hemispheric suppression contralateral to wrist flexion changed resting-state connectivity from intra-hemispheric to inter-hemispheric and increased flexion speed (p<0.05). Conversely, exciting this hemisphere increased opposing muscle output resulting in a decrease in speed but an increase in accuracy (p<0.05 for both). The findings of this work suggest that tDCS with fNIRS and concurrent multimotor measurements can provide insights into how neuroplasticity changes muscle output, which could find future use in guiding motor rehabilitation.

Journal of biomedical optics

Khan, B; Hodics, T; Hervey, N; Kondraske, G; Stowe, AM; Alexandrakis, G


A systematic review of the effects of neuromodulation on eating and body weight: evidence from human and animal studies.

2013 Nov

Eating disorders (ED) are chronic and sometimes deadly illnesses. Existing treatments have limited proven efficacy, especially in the case of adults with anorexia nervosa (AN). Emerging neural models of ED provide a rationale for more targeted, brain-directed interventions.This systematic review has examined the effects of neuromodulation techniques on eating behaviours and body weight and assessed their potential for therapeutic use in ED.All articles in PubMed, PsychInfo and Web of Knowledge were considered and screened against a priori inclusion/exclusion criteria. The effects of repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, vagus nerve stimulation (VNS) and deep brain stimulation (DBS) were examined across studies in ED samples, other psychiatric and neurological disorders, and animal models.Sixty studies were identified. There is evidence for ED symptom reduction following rTMS and DBS in both AN and bulimia nervosa. Findings from studies of other psychiatric and neurological disorders and from animal studies demonstrate that increases in food intake and body weight can be achieved following DBS and that VNS has potential value as a means of controlling eating and inducing weight loss.Neuromodulation tools have potential for reducing ED symptomatology and related behaviours, and for altering food intake and body weight. In response to such findings, and emerging neural models of ED, treatment approaches are highly unlikely to remain 'brainless'. More research is required to evaluate the potential of neuromodulation procedures for improving long-term outcomes in ED.

European eating disorders review : the journal of the Eating Disorders Association

McClelland, J; Bozhilova, N; Campbell, I; Schmidt, U


The world can look better: enhancing beauty experience with brain stimulation.

2013 Nov

Aesthetic appreciation is part of our everyday life: it is a subjective judgment we make when looking at a painting, a landscape, or-in fact-at another person. Neuroimaging and electrophysiological evidence suggests that the left dorsolateral prefrontal cortex (DLPFC) plays a critical role in aesthetic judgments. Here, we show that the experience of beauty can be artificially enhanced with brain stimulation. Specifically, we show that aesthetic appreciation of representational paintings and photographs can be increased by applying anodal (excitatory) transcranial direct current stimulation on the left DLPFC. Our results thus show that beauty is in the brain of the beholder, and offer a novel view on the neural networks underlying aesthetic appreciation.

Social cognitive and affective neuroscience

Cattaneo, Z; Lega, C; Flexas, A; Nadal, M; Munar, E; Cela-Conde, CJ


Anodal tDCS over SMA decreases the probability of withholding an anticipated action.

2013 Nov

Previous research has shown that the supplementary motor area (SMA) is critical in movement inhibition. Recently it was shown that applying transcranial direct current stimulation (tDCS) over SMA affected participants' ability to inhibit their movement in a stop-signal reaction time task (Hsu et al. [11]). Of interest in the current study was whether modulating SMA excitability using tDCS would have similar effects in an anticipation-timing stop-signal task. Participants performed 2 sessions each consisting of a pre- and post-tDCS block of 160 trials in which they were instructed to extend their wrist concurrently with the arrival of a pointer to a target (i.e., a clock hand reaching a set position). In 20% of trials (stop trials) the pointer stopped 80, 110, 140, 170, or 200 ms prior to the target, and on these trials participants were instructed to inhibit their movement if possible. Anodal and cathodal tDCS (separated by at least 48 h) was applied for each participant between the pre- and post-tDCS blocks. No change in the proportion of successfully inhibited movements on stop trials was found following cathodal tDCS (p>.05). However, anodal tDCS resulted in a decreased proportion of successfully inhibited movements on stop trials (p=002), and an earlier movement onset on control trials (p<.01). This suggests that the SMA may be more involved in initiation than in inhibition of anticipatory movements. Furthermore these data suggest that differences in initiation and inhibitory processes exist between stop-signal reaction time and anticipation-timing stop-signal tasks.

Behavioural brain research

Hayduk-Costa, G; Drummond, NM; Carlsen, AN


Prefrontal transcranial direct current stimulation (tDCS) changes negative symptoms and functional connectivity MRI (fcMRI) in a single case of treatment-resistant schizophrenia.

2013 Nov

Schizophrenia research

Palm, U; Keeser, D; Blautzik, J; Pogarell, O; Ertl-Wagner, B; Kupka, MJ; Reiser, M; Padberg, F


More attention when speaking: does it help or does it hurt?

2013 Nov

Paying selective attention to a word in a multi-word utterance results in a decreased probability of error on that word (benefit), but an increased probability of error on the other words (cost). We ask whether excitation of the prefrontal cortex helps or hurts this cost. One hypothesis (the resource hypothesis) predicts a decrease in the cost due to the deployment of more attentional resources, while another (the focus hypothesis) predicts even greater costs due to further fine-tuning of selective attention. Our results are more consistent with the focus hypothesis: prefrontal stimulation caused a reliable increase in the benefit and a marginal increase in the cost of selective attention. To ensure that the effects are due to changes to the prefrontal cortex, we provide two checks: We show that the pattern of results is quite different if, instead, the primary motor cortex is stimulated. We also show that the stimulation-related benefits in the verbal task correlate with the stimulation-related benefits in an N-back task, which is known to tap into a prefrontal function. Our results shed light on how selective attention affects language production, and more generally, on how selective attention affects production of a sequence over time.

Neuropsychologia

Nozari, N; Thompson-Schill, SL


Nosce te ipsum--Socrates revisited? Controlling momentary ruminative self-referent thoughts by neuromodulation of emotional working memory.

2013 Nov

It becomes ever more evident that cognitive operations serve as fundamental mechanisms underlying higher order ruminative thoughts. In this sham controlled within subjects study, we performed anodal transcranial Direct Current Stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) in 32 healthy participants. We tested the causal hypothesis that the relationship between DLPFC activity and ruminative thinking is mediated by working memory operations. We used the Internal Shift Task, a paradigm in which participants have to update and shift between specific (non)emotional representations in working memory. Subsequently, during an unguided rest period approximately 20 min after the stimulation, we explored the occurrence of momentary ruminative self-referent thought. The results demonstrated that the influence of anodal tDCS of the left DLPFC (and not of sham stimulation) on momentary ruminative self-referent thinking is mediated by the enhancement of WM operations for angry faces. Moreover, the more individuals ruminate in everyday life (as measured using the Ruminative Response Style), the larger this mediation effect was. These findings suggest that enhancing cognitive self-regulation, by increasing the ability to update and shift away from negative representations in working memory, might help individuals to control unintentional streams of self-referent thoughts that are self-critical and self-evaluative, a thinking style known as rumination.

Neuropsychologia

Vanderhasselt, MA; Brunoni, AR; Loeys, T; Boggio, PS; De Raedt, R


Bihemispheric stimulation over left and right inferior frontal region enhances recovery from apraxia of speech in chronic aphasia.

2013 Nov

Several studies have already shown that transcranial direct current stimulation (tDCS) is a useful tool for enhancing recovery in aphasia. However, all tDCS studies have previously investigated the effects using unihemisperic stimulation. No reports to date have examined the role of bihemispheric tDCS on aphasia recovery. Here, eight aphasic persons with apraxia of speech underwent intensive language therapy in two different conditions: real bihemispheric anodic ipsilesional stimulation over the left Broca's area and cathodic contralesional stimulation over the right homologue of Broca's area, and a sham condition. In both conditions, patients underwent concurrent language therapy for their apraxia of speech. The language treatment lasted 10 days (Monday to Friday, then weekend off, then Monday to Friday). There was a 14-day intersession interval between the real and the sham conditions. In all patients, language measures were collected before (T0), at the end of (T10) and 1 week after the end of (F/U) treatment. Results showed that after simultaneous excitatory stimulation to the left frontal hemisphere and inhibitory stimulation to the right frontal hemisphere regions, patients exhibited a significant recovery not only in terms of better accuracy and speed in articulating the treated stimuli but also in other language tasks (picture description, noun and verb naming, word repetition, word reading) which persisted in the follow-up session. Taken together, these data suggest that bihemispheric anodic ipsilesional and cathodic contralesional stimulation in chronic aphasia patients may affect the treated function, resulting in a positive influence on different language tasks.

The European journal of neuroscience

Marangolo, P; Fiori, V; Cipollari, S; Campana, S; Razzano, C; Di Paola, M; Koch, G; Caltagirone, C


State-dependent effects of prefrontal repetitive transcranial magnetic stimulation on emotional working memory.

2013 Nov

A growing body of findings illustrates the importance of state-dependency in studies using brain stimulation.We aimed to investigate the effects of tDCS priming followed by rTMS applied over the right dorsolateral prefrontal cortex (DLPFC) on emotional working memory.In a randomized single-blind within-subjects design, participants performed an emotional 3-back task at baseline and after tDCS priming (anodal, cathodal) and subsequent low-frequency rTMS (active, sham) of the right DLPFC. Stimuli consisted of words related to the distinct emotion categories fear and anger as well as neutral words.Task accuracy increased for fear-related words and decreased for neutral words across stimulation conditions. No general state-dependent effects of prefrontal rTMS on working memory were found. We further showed a detrimental effect of negative emotional content on working memory performance.Our findings support a hemispheric lateralization of emotion processing by demonstrating that the withdrawal-related emotion fear is associated with the right DLPFC and contribute to clarifying the interaction between working memory and emotion.

Brain stimulation

Weigand, A; Richtermeier, A; Feeser, M; Guo, JS; Briesemeister, BB; Grimm, S; Bajbouj, M


Site-dependent effects of tDCS uncover dissociations in the communication network underlying the processing of visual search.

2013 Nov

The right posterior parietal cortex (rPPC) and the right frontal eye field (rFEF) form part of a network of brain areas involved in orienting spatial attention. Previous studies using transcranial magnetic stimulation (TMS) have demonstrated that both areas are critically involved in the processing of conjunction visual search tasks, since stimulation of these sites disrupts performance.This study investigated the effects of long term neuronal modulation to rPPC and rFEF using transcranial direct current stimulation (tDCS) with the aim of uncovering sharing of these resources in the processing of conjunction visual search tasks.Participants completed four blocks of conjunction search trials over the course of 45 min. Following the first block they received 15 min of either cathodal or anodal stimulation to rPPC or rFEF, or sham stimulation.A significant interaction between block and stimulation condition was found, indicating that tDCS caused different effects according to the site (rPPC or rFEF) and type of stimulation (cathodal, anodal, or sham). Practice resulted in a significant reduction in reaction time across the four blocks in all conditions except when cathodal tDCS was applied to rPPC.The effects of cathodal tDCS over rPPC are subtler than those seen with TMS, and no effect of tDCS was evident at rFEF. This suggests that rFEF has a more transient role than rPPC in the processing of conjunction visual search and is robust to longer-term methods of neuro-disruption. Our results may be explained within the framework of functional connectivity between these, and other, areas.

Brain stimulation

Ball, K; Lane, AR; Smith, DT; Ellison, A


Perception of comfort during active and sham transcranial direct current stimulation: a double blind study.

2013 Nov

A limited number of studies have assessed the tolerability and comfort experienced while undertaking transcranial direct current stimulation (tDCS).This study intended to assess tolerability and the level of comfort experienced in a large sample of participants undertaking tDCS for 30 min at 2 mA of current strength. Moreover, we assessed whether sham and active stimulation are indistinguishable.One-hundred and forty-nine participants underwent 195 tDCS sessions. The delivery of stimulation was double-blind. Participants were asked: (i) to rate comfort levels using a visual analog scale; (ii) to report any symptom experienced during the period of tDCS stimulation; (iii) to indicate, at the end of the session, whether the tDCS stimulation was active or sham.No adverse effects occurred. However, comfort levels were significantly higher in the sham than in the active stimulation condition (primarily in Study 2). A comparable number of symptoms were experienced in the active and in the sham conditions. However, in the majority of symptoms reported, a greater proportion of participants complained in the active than in the sham stimulation condition. Ancillary analyses indicated that with smaller electrodes more symptoms were experienced. However, this occurred in a comparable way in both active and sham stimulations. Finally, participants could not reliably distinguish the type of stimulation received.The present study adds and complements the growing literature suggesting that tDCS is a well-tolerated and safe neurostimulation tool. Moreover, at least under the stimulation parameters used in the present study, neurostimulation can be successfully administered using a double-blind procedure without participants being able to reliably assess whether the stimulation received is either active or sham.

Brain stimulation

Russo, R; Wallace, D; Fitzgerald, PB; Cooper, NR


No effects of slow oscillatory transcranial direct current stimulation (tDCS) on sleep-dependent memory consolidation in healthy elderly subjects.

2013 Nov

Studies in young healthy volunteers provided evidence of a beneficial impact of an anodal time-varied transcranial direct current stimulation (tDCS) during early slow wave rich sleep on declarative memory but not on procedural memory.The present study investigated whether sleep-dependent memory consolidation can also be affected by slow oscillating tDCS in a population of elderly subjects.26 subjects (69.1 years ± 7.7 years) received bi-frontal anodal stimulation (max. current density: 0.331 mA/cm(2)) during early NREM sleep in a double-blind placebo-controlled randomized crossover study. Stimulation effects on offline consolidation were tested by using a declarative and a procedural memory task. Furthermore, sleep stages were scored, EEG power was analyzed and spindle densities were assessed.Independently from stimulation condition, performance in both memory tasks significantly decreased overnight. Stimulation revealed no significant effect on sleep-dependent memory consolidation. Verum tDCS was accompanied by significantly more time awake and significantly less NREM stage 3 sleep during five 1-min stimulation free intervals.The results of the present study are in line with other studies showing that offline consolidation during sleep varies with age and is less pronounced in the elderly than in young or middle-aged subjects. Contrary to an almost identical positive study in young adults, slow oscillatory tDCS applied to the elderly failed to show a beneficial effect on memory consolidation in the present study.

Brain stimulation

Eggert, T; Dorn, H; Sauter, C; Nitsche, MA; Bajbouj, M; Danker-Hopfe, H


Anodal transcranial direct current stimulation (tDCS) decreases the amplitudes of long-latency stretch reflexes in cerebellar ataxia.

2013 Nov

Recent studies suggest that the neuromodulation of the cerebellum using transcranial direct current stimulation (tDCS) could represent a new therapeutic strategy for the management of cerebellar disorders. Anodal tDCS of the cerebellum increases the excitability of the cerebellar cortex. We tested the effects of anodal tDCS applied over the cerebellum in ataxic patients. We studied (a) stretch reflexes (SR) in upper limb (SLSR: short-latency stretch reflexes; LLSR: long-latency stretch reflexes), (b) a coordination functional task in upper limbs based on mechanical counters (MCT: mechanical counter test), and (c) computerized posturography. tDCS did not change the amplitude of SLSR, but reduced significantly the amplitudes of LLSR. tDCS did not improve the MCT scores and did not modify posture. We suggest that anodal tDCS of the cerebellum reduces the amplitudes of LLSR by increasing the inhibitory effect exerted by the cerebellar cortex upon cerebellar nuclei. The absence of effect upon upper limb coordination and posture suggests that the cerebello-cerebral networks subserving these functions are less responsive to anodal tDCS of the cerebellum. Anodal tDCS of the cerebellum represents a novel experimental tool to investigate the effects of the cerebellar cortex on the modulation of the amplitudes of LLSR.

Annals of biomedical engineering

Grimaldi, G; Manto, M


Polarity independent effects of cerebellar tDCS on short term ankle visuomotor learning.

2013 Nov

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.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.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.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.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


a-tDCS differential modulation of corticospinal excitability: the effects of electrode size.

2013 Nov

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.The current study aimed to investigate the effects of anodal tDCS (a-tDCS) with three electrode sizes on corticospinal excitability.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.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).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


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

2013 Nov

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


Transcranial direct current stimulation (tDCS) reduces postsurgical opioid consumption in total knee arthroplasty (TKA).

2013 Nov

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.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.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.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


Effects of dual transcranial direct current stimulation for aphasia in chronic stroke patients.

2013 Oct

To investigate any additional effect of dual transcranial direct current stimulation (tDCS) compared with single tDCS in chronic stroke patients with aphasia.Eleven chronic stroke patients (aged 52.6±13.4 years, nine men) with aphasia were enrolled. Single anodal tDCS was applied over the left inferior frontal gyrus (IFG) and a cathodal electrode was placed over the left buccinator muscle. Dual tDCS was applied as follows: 1) anodal tDCS over the left IFG and cathodal tDCS over the left buccinator muscle and 2) cathodal tDCS over the right IFG and anodal tDCS over the right buccinator muscle. Each tDCS was delivered for 30 minutes at a 2-mA intensity. Speech therapy was provided during the last 15 minutes of the tDCS. Before and after the stimulation, the Korean-Boston Naming Test and a verbal fluency test were performed.The dual tDCS produced a significant improvement in the response time for the Korean-Boston Naming Test compared with the baseline assessment, with a significant interaction between the time and type of interventions. Both single and dual tDCS produced a significant improvement in the number of correct responses after stimulation with no significant interaction. No significant changes in the verbal fluency test were observed after single or dual tDCS.The results conveyed that dual tDCS using anodal tDCS over the left IFG and cathodal tDCS over the right IFG may be more effective than a single anodal tDCS over the left IFG.

Annals of rehabilitation medicine

Lee, SY; Cheon, HJ; Yoon, KJ; Chang, WH; Kim, YH

Link to full article text


Transcranial direct current stimulation (tDCS): Does it have merit in stroke rehabilitation? A systematic review.

2013 Oct

Transcranial direct current stimulation has been gaining increasing interest as a potential therapeutic treatment in stroke recovery. We performed a systematic review with meta-analysis of randomized controlled trials to collate the available evidence in adults with residual motor impairments as a result of stroke. The primary outcome was change in motor function or impairment as a result of transcranial direct current stimulation, using any reported electrode montage, with or without adjunct physical therapy. The search yielded 15 relevant studies comprising 315 subjects. Compared with sham, cortical stimulation did not produce statistically significant improvements in motor performance when measured immediately after the intervention (anodal stimulation: facilitation of the affected cortex: standardized mean difference = 0·05, P = 0·71; cathodal stimulation: inhibition of the nonaffected cortex: standardized mean difference = 0·39, P = 0·08; bihemispheric stimulation: standardized mean difference = 0·24, P = 0·39). When the data were analyzed according to stroke characteristics, statistically significant improvements were evident for those with chronic stroke (standardized mean difference = 0·45, P = 0·01) and subjects with mild-to-moderate stroke impairments (standardized mean difference = 0·37, P = 0·02). Transcranial direct current stimulation is likely to be effective in enhancing motor performance in the short term when applied selectively to patients with stroke. Given the range of stimulation variables and heterogeneous nature of stroke, this modality is still experimental and further research is required to determine its clinical merit in stroke rehabilitation.

International journal of stroke : official journal of the International Stroke Society

Marquez, J; van Vliet, P; McElduff, P; Lagopoulos, J; Parsons, M


Transcranial direct current stimulation and repetitive transcranial magnetic stimulation in consultation-liaison psychiatry.

2013 Oct

Patients with clinical diseases often present psychiatric conditions whose pharmacological treatment is hampered due to hazardous interactions with the clinical treatment and/or disease. This is particularly relevant for major depressive disorder, the most common psychiatric disorder in the general hospital. In this context, nonpharmacological interventions could be useful therapies; and, among those, noninvasive brain stimulation (NIBS) might be an interesting option. The main methods of NIBS are repetitive transcranial magnetic stimulation (rTMS), which was recently approved as a nonresearch treatment for some psychiatric conditions, and transcranial direct current stimulation (tDCS), a technique that is currently limited to research scenarios but has shown promising results. Therefore, our aim was to review the main medical conditions associated with high depression rates, the main obstacles for depression treatment, and whether these therapies could be a useful intervention for such conditions. We found that depression is an important and prevalent comorbidity in a variety of diseases such as epilepsy, stroke, Parkinson's disease, myocardial infarction, cancer, and in other conditions such as pregnancy and in patients without enteral access. We found that treatment of depression is often suboptimal within the above contexts and that rTMS and tDCS therapies have been insufficiently appraised. We discuss whether rTMS and tDCS could have a significant impact in treating depression that develops within a clinical context, considering its unique characteristics such as the absence of pharmacological interactions, the use of a nonenteral route, and as an augmentation therapy for antidepressants.

Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.]

Valiengo, LC; Benseñor, IM; Lotufo, PA; Fraguas, R; Brunoni, AR

Link to full article text


Assessment of electric field distribution in anisotropic cortical and subcortical regions under the influence of tDCS.

2013 Oct

The focus of this study is to estimate the contribution of regional anisotropic conductivity on the spatial distribution of an induced electric field across gray matter (GM), white matter (WM), and subcortical regions under transcranial direct current stimulation (tDCS). The assessment was conducted using a passive high-resolution finite element head model with inhomogeneous and variable anisotropic conductivities derived from the diffusion tensor data. Electric field distribution was evaluated across different cortical as well as subcortical regions under four bicephalic electrode configurations. Results indicate that regional tissue heterogeneity and anisotropy cause the pattern of induced fields to vary in orientation and strength when compared to the isotropic scenario. Different electrode montages resulted in distinct distribution patterns with noticeable variations in field strengths. The effect of anisotropy is highly montage dependent and directional conductivity has a more profound effect in defining the strength of the induced field. The inclusion of anisotropy in the GM and subcortical regions has a significant effect on the strength and spatial distribution of the induced electric field. Under the (C3-Fp2) montage, the inclusion of GM and subcortical anisotropy increased the average percentage difference in the electric field strength of brain from 5% to 34% (WM anisotropy only). In terms of patterns distribution, the topographic errors increased from 9.9% to 40% (WM anisotropy only) across the brain. Bioelectromagnetics 9999:1-17. © 2013 Wiley Periodicals, Inc.

Bioelectromagnetics

Shahid, S; Wen, P; Ahfock, T


Facilitation of inferior frontal cortex by transcranial direct current stimulation induces perceptual learning of severely degraded speech.

2013 Oct

Perceptual learning requires the generalization of categorical perceptual sensitivity from trained to untrained items. For degraded speech, perceptual learning modulates activation in a left-lateralized network, including inferior frontal gyrus (IFG) and inferior parietal cortex (IPC). Here we demonstrate that facilitatory anodal transcranial direct current stimulation (tDCS(anodal)) can induce perceptual learning in healthy humans. In a sham-controlled, parallel design study, 36 volunteers were allocated to the three following intervention groups: tDCS(anodal) over left IFG, IPC, or sham. Participants decided on the match between an acoustically degraded and an undegraded written word by forced same-different choice. Acoustic degradation varied in four noise-vocoding levels (2, 3, 4, and 6 bands). Participants were trained to discriminate between minimal (/Tisch/-FISCH) and identical word pairs (/Tisch/-TISCH) over a period of 3 d, and tDCS(anodal) was applied during the first 20 min of training. Perceptual sensitivity (d') for trained word pairs, and an equal number of untrained word pairs, was tested before and after training. Increases in d' indicate perceptual learning for untrained word pairs, and a combination of item-specific and perceptual learning for trained word pairs. Most notably for the lowest intelligibility level, perceptual learning occurred only when tDCS(anodal) was applied over left IFG. For trained pairs, improved d' was seen on all intelligibility levels regardless of tDCS intervention. Over left IPC, tDCS(anodal) did not modulate learning but instead introduced a response bias during training. Volunteers were more likely to respond "same," potentially indicating enhanced perceptual fusion of degraded auditory with undegraded written input. Our results supply first evidence that neural facilitation of higher-order language areas can induce perceptual learning of severely degraded speech.

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

Sehm, B; Schnitzler, T; Obleser, J; Groba, A; Ragert, P; Villringer, A; Obrig, H

Link to full article text


Anodal tDCS increases corticospinal output and projection strength in multiple sclerosis.

2013 Oct

The application of anodal transcranial direct current stimulation (atDCS) to the human brain has been shown to elicit corticospinal (CS) excitability changes. This study evaluated the effect of a single session of atDCS on CS excitability in patients with multiple sclerosis (MS). atDCS and sham tDCS (stDCS) were applied to the primary motor cortex (M1) contralateral to the more severely impaired hand for 20min in a double-blinded crossover design. Changes in CS excitability were assessed using transcranial magnetic stimulation (TMS). The area under the recruitment curves increased significantly after application of atDCS (+56.58%, p=0.023) but not after stDCS. A sigmoidal curve-analysis revealed a higher plateau of the curve after atDCS (+22.2%, p<0.001). Our results showed that atDCS over M1 has the ability to increase CS output and projection strength in MS-patients, suggesting that atDCS can be considered during neural rehabilitation to facilitate motor recovery in MS.

Neuroscience letters

Cuypers, K; Leenus, DJ; Van Wijmeersch, B; Thijs, H; Levin, O; Swinnen, SP; Meesen, RL


Effects of dual transcranial direct current stimulation on post-stroke unilateral visuospatial neglect.

2013 Oct

Based on the interhemispheric inhibition model of unilateral visuospatial neglect (USN) after stroke, the effects of dual-mode transcranial direct current stimulation (tDCS) over the parietal cortices were assessed in a double-blind random-order cross-over experiment. Ten chronic right hemispheric stroke patients (4 men; mean age: 62.6 years) with USN were recruited. All participants underwent three randomly arranged tDCS sessions: (1) dual-mode, anodal tDCS over the right posterior parietal cortex (PPC) and cathodal tDCS over the left PPC; (2) single-mode, anodal tDCS over the right PPC; and (3) sham mode. Each session lasted 20min. Before and immediately after the stimulation, a line bisection test and star cancelation test were carried out. In the line bisection test, significant improvements were observed after both the dual- and the single-mode tDCS (p<0.05), but not after sham stimulation. Statistical analysis showed a significant interaction between time and tDCS mode, where the dual tDCS had a stronger effect than the single or sham stimulation modes (p<0.05). The star cancelation test did not show any significant change. These results suggest that dual tDCS over the bilateral PPC is an effective method for the treatment of USN in stroke patients.

Neuroscience letters

Sunwoo, H; Kim, YH; Chang, WH; Noh, S; Kim, EJ; Ko, MH


The effect of transcranial direct current stimulation on perception of effort in an isolated isometric elbow flexion task.

2013 Oct

The purported ergogenic actions of transcranial direct current stimulation (tDCS) applied to motor cortex (M1) on force production and perception of effort were investigated using a 10-item numerical rating scale (0-10 NRS) in nonfatiguing bouts of a force-matching task utilizing isometric elbow flexion. Using a crossover design, 12 healthy volunteers received sham, anodal, and cathodal tDCS randomly for 10 min (1.5 mA, 62 μA/cm2) to the left M1 in a double-blind manner. Corticospinal excitability changes were also monitored using transcranial magnetic stimulation (TMS) with surface electromyography (sEMG) to monitor both motor evoked potentials (MEPs) and force-EMG from right m. biceps brachii and m. brachioradialis brachii. No significant differences between the verum and sham stimulation were obtained for elbow flexion maximum voluntary force, perception of effort, or sEMG. There were also no significant differences in MEP changes for the types of tDCS, which is consistent with reports that tDCS excitability effects are diminished during ongoing cognitive and motor activities.

Motor control

Lampropoulou, SI; Nowicky, AV


Classification of methods in transcranial electrical stimulation (tES) and evolving strategy from historical approaches to contemporary innovations.

2013 Oct

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.

Journal of neuroscience methods

Guleyupoglu, B; Schestatsky, P; Edwards, D; Fregni, F; Bikson, M


Transcranial direct-current stimulation reduced the excitability of diaphragmatic corticospinal pathways whatever the polarity used.

2013 Oct

We investigated effects of transcranial direct-current stimulation (tDCS) on the diaphragmatic corticospinal pathways in healthy human. Anodal, cathodal, and sham tDCS were randomly applied upon the left diaphragmatic motor cortex in twelve healthy right-handed men. Corticospinal pathways excitability was assessed by means of transcranial magnetic stimulation (TMS) elicited motor-evoked-potential (MEP). For each tDCS condition, MEPs were recorded before (Pre) tDCS then after 10 min (Post1, at tDCS discontinuation in the anodal and cathodal sessions) and 20 min (Post2). As result, both anodal and cathodal tDCS significantly decreased MEP amplitude of the right hemidiaphragm at both Post1 and Post2, versus Pre. MEP amplitude was unchanged versus Pre during the sham condition. The effects of cathodal and anodal tDCS applied to the diaphragm motor cortex differ from those observed during tDCS of the limb motor cortex. These differences may be related to specific characteristics of the diaphragmatic corticospinal pathways as well as to the diaphragm's functional peculiarities compared with the limb muscles.

Respiratory physiology & neurobiology

Azabou, E; Roche, N; Sharshar, T; Bussel, B; Lofaso, F; Petitjean, M


Effect of transcranial direct current stimulation on vestibular-ocular and vestibulo-perceptual thresholds.

2013 Oct

Transcranial direct current stimulation (tDCS) was used in 17 normal individuals to modulate vestibulo-ocular reflex (VOR) and self-motion perception rotational thresholds. The electrodes were applied over the temporoparietal junction bilaterally. Both vestibular nystagmic and perceptual thresholds were increased during as well as after tDCS stimulation. Body rotation was labeled as ipsilateral or contralateral to the anode side, but no difference was observed depending on the direction of rotation or hemisphere polarity. Threshold increase during tDCS was greater for VOR than for motion perception. 'Sham' stimulation had no effect on thresholds. We conclude that tDCS produces an immediate and sustained depression of cortical regions controlling VOR and movement perception. Temporoparietal areas appear to be involved in vestibular threshold modulation but the differential effects observed between VOR and perception suggest a partial dissociation between cortical processing of reflexive and perceptual responses.

Neuroreport

Kyriakareli, A; Cousins, S; Pettorossi, VE; Bronstein, AM


Longstanding neuropathic pain after spinal cord injury is refractory to transcranial direct current stimulation: a randomized controlled trial.

2013 Oct

Neuropathic pain remains one of the most difficult consequences of spinal cord injury (SCI) to manage. It is a major cause of suffering and adds to the physical, emotional, and societal impact of the injury. Despite the use of the best available treatments, two thirds of people experiencing neuropathic pain after SCI do not achieve satisfactory pain relief. This study was undertaken in response to a recent clinical trial reporting short-term, clinically significant reductions in neuropathic SCI pain with primary motor cortex transcranial direct current stimulation (tDCS). In this investigation, we aimed to build on this previous clinical trial by extending the assessment period to determine the short-, medium-, and long-term efficacy of tDCS for the treatment of neuropathic pain after SCI. We found that, contrary to previous reports, after 5 tDCS treatment periods, mean pain intensity and unpleasantness rating were not significantly different from initial assessment. That is, in this trial tDCS did not provide any pain relief in subjects with neuropathic SCI pain (n=10). A similar lack of effect was also seen after sham treatment. Because the injury duration in this study was significantly greater than that of previous investigations, it is possible that tDCS is an effective analgesic only in individuals with relatively recent injuries and pain. Future investigations comparing a range of injury durations are required if we are to determine whether this is indeed the case.

Pain

Wrigley, PJ; Gustin, SM; McIndoe, LN; Chakiath, RJ; Henderson, LA; Siddall, PJ


Anodal transcranial direct current stimulation transiently improves contrast sensitivity and normalizes visual cortex activation in individuals with amblyopia.

2013 Oct

Amblyopia is a neurodevelopmental disorder of vision that is associated with abnormal patterns of neural inhibition within the visual cortex. This disorder is often considered to be untreatable in adulthood because of insufficient visual cortex plasticity. There is increasing evidence that interventions that target inhibitory interactions within the visual cortex, including certain types of noninvasive brain stimulation, can improve visual function in adults with amblyopia.We tested the hypothesis that anodal transcranial direct current stimulation (a-tDCS) would improve visual function in adults with amblyopia by enhancing the neural response to inputs from the amblyopic eye.Thirteen adults with amblyopia participated and contrast sensitivity in the amblyopic and fellow fixing eye was assessed before, during and after a-tDCS or cathodal tDCS (c-tDCS). Five participants also completed a functional magnetic resonance imaging (fMRI) study designed to investigate the effect of a-tDCS on the blood oxygen level-dependent response within the visual cortex to inputs from the amblyopic versus the fellow fixing eye.A subgroup of 8/13 participants showed a transient improvement in amblyopic eye contrast sensitivity for at least 30 minutes after a-tDCS. fMRI measurements indicated that the characteristic cortical response asymmetry in amblyopes, which favors the fellow eye, was reduced by a-tDCS.These preliminary results suggest that a-tDCS deserves further investigation as a potential tool to enhance amblyopia treatment outcomes in adults.

Neurorehabilitation and neural repair

Spiegel, DP; Byblow, WD; Hess, RF; Thompson, B


Heart rate variability is a trait marker of major depressive disorder: evidence from the sertraline vs. electric current therapy to treat depression clinical study.

2013 Oct

Decreased heart rate variability (HRV) is a cardiovascular predictor of mortality. Recent debate has focused on whether reductions in HRV in major depressive disorder (MDD) are a consequence of the disorder or a consequence of pharmacotherapy. Here we report on the impact of transcranial direct current stimulation (tDCS), a non-pharmacological intervention, vs. sertraline to further investigate this issue. The employed design was a double-blind, randomized, factorial, placebo-controlled trial. One hundred and eighteen moderate-to-severe, medication-free, low-cardiovascular risk depressed patients were recruited for this study and allocated to either active/sham tDCS (10 consecutive sessions plus two extra sessions every other week) or placebo/sertraline (50 mg/d) for 6 wk. Patients were age and gender-matched to healthy controls from a concurrent cohort study [the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)]. The impact of disorder, treatment and clinical response on HRV (root mean square of successive differences and high frequency) was examined. Our findings confirmed that patients displayed decreased HRV relative to controls. Furthermore, HRV scores did not change following treatment with either a non-pharmacological (tDCS) or pharmacological (sertraline) intervention, nor did HRV increase with clinical response to treatment. Based on these findings, we discuss whether reduced HRV is a trait-marker for MDD, which may predispose patients to a host of conditions and disease even after response to treatment. Our findings have important implications for our understanding of depression pathophysiology and the relationship between MDD, cardiovascular disorders and mortality.

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

Brunoni, AR; Kemp, AH; Dantas, EM; Goulart, AC; Nunes, MA; Boggio, PS; Mill, JG; Lotufo, PA; Fregni, F; Benseñor, IM


Can transcranial direct current stimulation enhance outcomes from cognitive training? A randomized controlled trial in healthy participants.

2013 Oct

Computer-administered cognitive training (CT) tasks are a common component of cognitive remediation treatments. There is growing evidence that transcranial direct current stimulation (tDCS), when given during cognitive tasks, improves performance. This randomized, controlled trial explored the potential synergistic effects of CT combined with tDCS in healthy participants. Altogether, 60 healthy participants were randomized to receive either active or sham tDCS administered during training on an adaptive CT task (dual n-back task), or tDCS alone, over 10 daily sessions. Cognitive testing (working memory, processing speed, executive function, reaction time) was conducted at baseline, end of the 10 sessions, and at 4-wk follow-up to examine potential transfer effects to non-trained tasks. Altogether, 54 participants completed the study. Over the 10 'online' sessions, participants in the active tDCS+CT condition performed more accurately on the CT task than participants who received sham tDCS+CT. The performance enhancing effect, however, was present only during tDCS and did not result in greater learning (i.e. improvement over sessions) on the CT task. These results confirm prior reports of enhancement of cognitive function during tDCS stimulation. At follow-up, the active tDCS+CT group, but not the sham tDCS+CT group, showed greater gains on a non-trained test of attention and working memory than the tDCS-only group (p < 0.01). Although this gain can mainly be attributable to training, this result suggests that active tDCS may have a role in further enhancing outcomes.

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

Martin, DM; Liu, R; Alonzo, A; Green, M; Player, MJ; Sachdev, P; Loo, CK


Effects of non-pharmacological pain treatments on brain states.

2013 Oct

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.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).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.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.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


Effect of serotonin on paired associative stimulation-induced plasticity in the human motor cortex.

2013 Oct

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 enhance long-term potentiation-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. As 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 with 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-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 with 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 : official publication of the American College of Neuropsychopharmacology

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


Cathodal transcranial direct current stimulation in children with dystonia: a pilot open-label trial.

2013 Oct

Studies suggest that dystonia is associated with increased motor cortex excitability. Cathodal transcranial direct current stimulation can temporarily reduce motor cortex excitability. To test whether stimulation of the motor cortex can reduce dystonic symptoms in children, we measured tracking performance and muscle overflow using an electromyogram tracking task before and after stimulation. Of 10 participants, 3 showed a significant reduction in overflow, and a fourth showed a significant reduction in tracking error. Overflow decreased more when the hand contralateral to the cathode performed the task than when the hand ipsilateral to the cathode performed the task. Averaged over all participants, the results did not reach statistical significance. These results suggest that cathodal stimulation may allow a subset of children to control muscles or reduce involuntary overflow activity. Further testing is needed to confirm these results in a blinded trial and identify the subset of children who are likely to respond.

Journal of child neurology

Young, SJ; Bertucco, M; Sheehan-Stross, R; Sanger, TD


Response Inhibition Induced in the Stop-signal Task by Transcranial Direct Current Stimulation of the Pre-supplementary Motor Area and Primary Sensoriomotor Cortex.

2013 Sep

[Purpose] This study examined whether transcranial direct current stimulation (tDCS) of both the pre-supplementary motor area (pre-SMA) and primary sensoriomotor cortex (M1) alters the response time in response inhibition using the stop-signal task (SST). [Methods] Forty healthy subjects were enrolled in this study. The subjects were randomly tested under the three: the pre-SMA tDCS, M1 tDCS, and Sham tDCS conditions. All subjects performed a SST in two consecutive phases: without or after the delivery of anodal tDCS over one of the target sites (pre-SMA or the M1) and under the Sham tDCS condition. [Results] Our findings demonstrated significant reductions in the stop processing times after the anodal tDCS over pre-SMA, and change response times were significantly greater under the pre-SMA tDCS condition compared to both the M1 tDCS condition and the Sham tDCS condition. There was no significant major effect after delivery of the tDCS for the go processing times observed among the three conditions. [Conclusion] Anodal tDCS of the pre-SMA or M1 during performance of the SST resulted in enhancement of the volitional stop movement in inhibitory control. Our results suggest that when concurrently applied with the SST, tDCS might be a useful adjuvant therapeutic modality for modulation of the response inhibition and its related dynamic behavioral changes between motor execution and suppression.

Journal of physical therapy science

Kwon, YH; Kwon, JW

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Feasibility of Transcranial Direct Current Stimulation Use in Children Aged 5 to 12 Years.

2013 Sep

Transcranial direct current stimulation is a noninvasive brain stimulation technique that has been studied for the treatment of neuropsychiatric disorders in adults, with minimal side effects. The objective of this study is to report the feasibility, tolerability, and the short-term adverse effects of transcranial direct current stimulation in children from 5 to 12 years of age. It is a naturalistic study of 14 children who underwent 10 sessions of transcranial direct current stimulation as an alternative, off-label, and open-label treatment for various languages disorders. Frequency, intensity, adverse effects, and perception of improvement reported by parents were collected. The main side effects detected were tingling (28.6%) and itching (28.6%), acute mood changes (42.9%), and irritability (35.7%). Transcranial direct current stimulation is a feasible and tolerable technique in children, although studies regarding plastic and cognitive changes in children are needed to confirm its safety. In conclusion, this is a naturalistic report in which we considered transcranial direct current stimulation as feasible in children.

Journal of child neurology

Andrade, AC; Magnavita, GM; Allegro, JV; Neto, CE; Lucena, RD; Fregni, F


Effect of transcranial direct current stimulation (tDCS) during complex whole body motor skill learning.

2013 Sep

The aim of the study was to investigate tDCS effects on motor skill learning in a complex whole body dynamic balance task (DBT). We hypothesized that tDCS over the supplementary motor area (SMA), a region that is known to be involved in the control of multi-joint whole body movements, will result in polarity specific changes in DBT learning. In a randomized sham-controlled, double-blinded parallel design, we applied 20 min of tDCS over the supplementary motor area (SMA) and prefrontal cortex (PFC) while subjects performed a DBT. Anodal tDCS over SMA with the cathode placed over contralateral PFC impaired motor skill learning of the DBT compared to sham. This effect was still present on the second day of training. Reversing the polarity (cathode over SMA, anode over PFC) did not affect motor skill learning neither on the first nor on the second day of training. To better disentangle whether the impaired motor skill learning was due to a modulation of SMA or PFC, we performed an additional control experiment. Here, we applied anodal tDCS over SMA together with a larger and presumably more ineffective electrode (cathode) over PFC. Interestingly this alternative tDCS electrode setup did not affect the outcome of DBT learning. Our results provide novel evidence that a modulation of the (right) PFC seems to impair complex multi-joint motor skill learning. Hence, future studies should take the positioning of both tDCS electrodes into account when investigating complex motor skill learning.

Neuroscience letters

Kaminski, E; Hoff, M; Sehm, B; Taubert, M; Conde, V; Steele, CJ; Villringer, A; Ragert, P


Corticomotor excitability induced by anodal transcranial direct current stimulation with and without non-exhaustive movement.

2013 Sep

We investigated whether anodal transcranial direct current stimulation (tDCS) applied to the motor cortex during non-exhaustive active or passive movements enhances corticomotor excitability after tDCS or whether it reduces post-exercise depression (PED) after non-exhaustive active or passive movements if PED was observed without tDCS. Nine healthy subjects participated in this study. Anodal tDCS with a current of 2 mA was applied to the left scalp over the primary motor area. All subjects underwent the following five interventions: tDCS delivered for 10 min during relaxation (tDCS condition) and repetitive voluntary and passive finger abduction-adduction movements, each performed without and with tDCS for 10 min (active condition, tDCS+active condition, passive condition, tDCS+passive condition). The active movements were performed at 10% maximum voluntary contraction. Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseus muscle before the intervention (pre-intervention) and 2 and 10 min after the intervention (post-2 min and post-10 min, respectively). Under the tDCS condition, the MEP amplitudes at post-2 and -10 min were significantly increased compared with those before the intervention. Under the active, passive, and tDCS+active conditions, the MEP amplitudes at post-2 min were significantly decreased compared with those before the interventions. Under the tDCS+passive condition, the MEP amplitude remained unchanged. These results demonstrated that anodal tDCS did not reduce PED after active movements but after passive movements and that the anodal tDCS effects were highly dependent on the state of the subject during stimulation.

Brain research

Miyaguchi, S; Onishi, H; Kojima, S; Sugawara, K; Tsubaki, A; Kirimoto, H; Tamaki, H; Yamamoto, N


Non-invasive brain stimulation (rTMS and tDCS) in patients with aphasia: mode of action at the cellular level.

2013 Sep

A high proportion of patients who have suffered a stroke also suffer from aphasia. Approximately half of those affected will remain in this state despite intensive language therapy. Non-invasive brain stimulation allows us to directly and focally stimulate areas of the brain. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), methods used in the treatment of aphasia, are based on an imbalance of mutual interhemispheric inhibition. In open and sham-controlled studies, a low-frequency, 1Hz stimulation of the non-lesioned hemisphere (the homologue of Broca's area) for a week or more significantly improved spontaneous speech and anomia in patients with non-fluent aphasia. These positive outcomes from rTMS stimulation developed slowly, often over months following treatment, and persisted. Effects of intermittent theta burst stimulation (iTBS) developed faster than the low-frequency stimulation, and high-activity enhancement was detected in the left hemisphere after the stimulation of Broca's region. Both types of tDCS stimulation resulted in improved comprehension and reduced anomia, their primary modes of action are distinct, however, both share a common site of action with regard to the balance that occurs between inhibitory and excitatory neurotransmitters (synaptic and non-synaptic). Both types of non-invasive stimulation prepare the lesioned brain for better outcome.

Brain research bulletin

Málly, J


Beyond the silence: bilateral somatosensory stimulation enhances skilled movement quality and neural density in intact behaving rats.

2013 Sep

It is thought that a close dialogue between the primary motor (M1) and somatosensory (S1) cortices is necessary for skilled motor learning. The extent of the relative S1 contribution in producing skilled reaching movements, however, is still unclear. Here we used anodal transcranial direct current stimulation (tDCS), which is able to alter polarity-specific excitability in the S1, to facilitate skilled movement in intact behaving rats. We hypothesized that the critical role of S1 in reaching performance can be enhanced by bilateral tDCS. Pretrained rats were assigned to control or stimulation conditions: (1) UnAno: the unilateral application of an anodal current to the side contralateral to the paw preferred for reaching; (2) BiAno1: bilateral anodal current; (3) BiAno2: a bilateral anodal current with additional 30ms of 65μA pulses every 5s. Rats received tDCS (65μA; 10min/rat) to the S1 during skilled reach training for 20 days (online-effect phase). After-effect assessment occurred for the next ten days in the absence of electrical stimulation. Quantitative and qualitative analyses of online-effects of tDCS showed that UnAno and BiAno1 somatosensory stimulation significantly improve skilled reaching performance. Bilateral BiAno1 stimulation was associated with greater qualitative functional improvement than unilateral UnAno stimulation. tDCS-induced improvements were not observed in the after-effects phase. Quantitative cytoarchitectonic analysis revealed that somatosensory tDCS bilaterally increases cortical neural density. The findings emphasize the central role of bilateral somatosensory feedback in skill acquisition through modulation of cortico-motor excitability.

Behavioural brain research

Faraji, J; Gomez-Palacio-Schjetnan, A; Luczak, A; Metz, GA


Modelling non-invasive brain stimulation in cognitive neuroscience.

2013 Sep

Non-invasive brain stimulation (NIBS) is a method for the study of cognitive function that is quickly gaining popularity. It bypasses the correlative approaches of other imaging techniques, making it possible to establish a causal relationship between cognitive processes and the functioning of specific brain areas. Like lesion studies, NIBS can provide information about where a particular process occurs. However, NIBS offers the opportunity to study brain mechanisms beyond process localisation, providing information about when activity in a given brain region is involved in a cognitive process, and even how it is involved. When using NIBS to explore cognitive processes, it is important to understand not only how NIBS functions but also the functioning of the neural structures themselves. We know that NIBS techniques have the potential to transiently influence behaviour by altering neuronal activity, which may have facilitatory or inhibitory behavioural effects, and these alterations can be used to understand how the brain works. Given that NIBS necessarily involves the relatively indiscriminate activation of large numbers of neurons, its impact on a neural system can be easily understood as modulation of neural activity that changes the relation between noise and signal. In this review, we describe the mutual interactions between NIBS and brain activity and provide an updated and precise perspective on the theoretical frameworks of NIBS and their impact on cognitive neuroscience. By transitioning our discussion from one aspect (NIBS) to the other (cognition), we aim to provide insights to guide future research.

Neuroscience and biobehavioral reviews

Miniussi, C; Harris, JA; Ruzzoli, M

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Augmenting transcranial direct current stimulation with (D)-cycloserine for depression: a pilot study.

2013 Sep

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that causes changes in cortical excitability. Recent double-blind placebo-controlled clinical trials suggest that tDCS may be efficacious in the treatment of depression. Pharmacological agents that prolong the effects of tDCS could lead to greater cumulative changes in cortical excitability, producing greater and more prolonged efficacy. One agent shown to prolong the excitability-enhancing effects of tDCS in healthy subjects is D-Cycloserine, a partial agonist at the glycine-binding site of N-methyl-D-aspartate receptors. We investigated whether combining prefrontal tDCS with D-Cycloserine could enhance and/or prolong the antidepressant effect of tDCS.Five depressed subjects who had relapsed or failed to achieve remission after receiving a previous course of prefrontal tDCS were recruited. In this open-label pilot study, subjects ingested 100-mg D-Cycloserine 2 hours before tDCS sessions. Subjects received 20 minutes of tDCS at 2 mA on consecutive weekdays for a total of 20 sessions. The anode was placed at pF3 and the cathode at F8 (10/20 system). Clinical response was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS).The change in Montgomery-Åsberg Depression Rating Scale scores was not greater with the combination of D-Cycloserine and tDCS than had previously been produced by tDCS alone. No significant additional adverse effects were reported.This pilot open-label study found that pretreatment with 100-mg D-Cycloserine 2 hours before tDCS was well tolerated but did not enhance the antidepressant efficacy of anodal prefrontal tDCS.

The journal of ECT

Chan, HN; Alonzo, A; Martin, DM; Mitchell, PB; Sachdev, P; Loo, CK


Anodal transcranial direct current stimulation over auditory cortex degrades frequency discrimination by affecting temporal, but not place, coding.

2013 Sep

We report three studies of the effects of anodal transcranial direct current stimulation (tDCS) over auditory cortex on audition in humans. Experiment 1 examined whether tDCS enhances rapid frequency discrimination learning. Human subjects were trained on a frequency discrimination task for 2 days with anodal tDCS applied during the first day with the second day used to assess effects of stimulation on retention. This revealed that tDCS did not affect learning but did degrade frequency discrimination during both days. Follow-up testing 2-3 months after stimulation showed no long-term effects. Following the unexpected results, two additional experiments examined the effects of tDCS on the underlying mechanisms of frequency discrimination, place and temporal coding. Place coding underlies frequency selectivity and was measured using psychophysical tuning curves with broader curves indicating poorer frequency selectivity. Temporal coding is determined by measuring the ability to discriminate sounds with different fine temporal structure. We found that tDCS does not broaden frequency selectivity but instead degraded the ability to discriminate tones with different fine temporal structure. The overall results suggest anodal tDCS applied over auditory cortex degrades frequency discrimination by affecting temporal, but not place, coding mechanisms.

The European journal of neuroscience

Tang, MF; Hammond, GR


Non-invasive brain stimulation and the autonomic nervous system.

2013 Sep

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


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

2013 Sep

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.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 2 mA for 20 min, anode over the left dorsolateral prefrontal cortex, cathode right supraorbital cortex).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.The small sample size, its heterogeneity, the short observation period and a cross-over design without an interval between both conditions.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


Effect of anodal versus cathodal transcranial direct current stimulation on stroke rehabilitation: a pilot randomized controlled trial.

2013 Sep

We compared the long-term effect of anodal versus cathodal transcranial direct current stimulation (tDCS) on motor recovery in patients after subacute stroke.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.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.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


Transcranial direct current stimulation (tDCS) for the treatment of persistent visual and auditory hallucinations in schizophrenia: a case study.

2013 Sep

Brain stimulation

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


Impaired motor cortex responses in non-psychotic first-degree relatives of schizophrenia patients: a cathodal tDCS pilot study.

2013 Sep

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.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.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.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.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


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

2013 Sep

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 Sep

The objective of this study was to assess the effect of anodal transcranial direct current stimulation (a-tDCS) on voluntary dynamic strength and cortical plasticity when applied during a 3-wk strength training program for the wrist extensors.Thirty right-handed participants were randomly allocated to the tDCS, sham, or control group. The tDCS and sham group underwent 3 wk 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.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 amplitude at 15%, 20%, and 25% above active motor threshold, which was accompanied by a decrease in SICI during 50% maximal voluntary isometric contraction and 20% maximal voluntary isometric contraction (all P < 0.05). Silent period decreased for both the tDCS and sham groups (P < 0.001).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


Once- to twice-daily, 3-year domiciliary maintenance transcranial direct current stimulation for severe, disabling, clozapine-refractory continuous auditory hallucinations in schizophrenia.

2013 Sep

Some patients with schizophrenia suffer from continuous auditory hallucinations that are refractory to antipsychotic medications.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.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.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


Generalised and regional soft tissue pain syndromes. The role of physical and rehabilitation medicine physicians. The European perspective based on the best evidence. A paper by the UEMS-PRM Section Professional Practice Committee.

2013 Aug

One of the objectives of the Professional Practice Committee (PPC) of the Physical and Rehabilitation Medicine (PRM) Section of the Union of European Medical Specialists (UEMS) is the development of the field of competence of PRM physicians in Europe. To achieve this objective, UEMS PRM Section PPC has adopted a systematic action plan of preparing a series of papers describing the role of PRM physicians in a number of disabling health conditions, based on the evidence of effectiveness of PRM interventions. Generalised and regional soft tissue pain syndromes constitute a major problem leading to loss of function and disability, resulting in enormous societal burden. The aim of this paper is to describe the unique role of PRM physicians in the management of these disabling conditions that require not only pharmacological interventions but also a holistic approach including the consideration of body functions, activities and participation as well as contextual factors as described in the ICF. Evidence-based effective PRM interventions include exercise and multicomponent treatment including a psychotherapeutic intervention such as cognitive behavioural therapy (CBT) in addition to exercise, the latter based on strong evidence for reducing pain and improving quality of life in fibromyalgia syndrome (FMS). Balneotherapy, meditative movement therapies, and acupuncture have also been shown as efficacious in improving symptoms in FMS. Emerging evidence suggests the use of transcranial magnetic or direct current stimulation (rTMS or tDCS) in FMS patients with intractable pain not alleviated by other interventions. Graded exercise therapy and CBT are evidence-based options for chronic fatigue syndrome. The use of some physical modalities and manipulation for myofascial pain syndrome is also supported by evidence. As for complex regional pain syndrome (CRPS), strong evidence exists for rTMS and graded motor imagery as well as moderate evidence for mirror therapy. Interventional techniques such as blocks and spinal cord stimulation may also be considered for CRPS based on varying levels of evidence. PRM physicians' functioning oriented approaches on the assessment and management, adopting the ICF as a reference, may well meet the needs of patients with soft tissue pain syndromes, the common problems for whom are loss of function and impaired quality of life. Available evidence for the effectiveness of PRM interventions serves as the basis for the explicit role of PRM specialists in the management of these health conditions.

European journal of physical and rehabilitation medicine

Oral, A; Ilieva, EM; Küçükdeveci, AA; Varela, E; Valero, R; Berteanu, M; Christodoulou, N

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Augmentative transcranial direct current stimulation (tDCS) in poor responder depressed patients: a follow-up study.

2013 Aug

Transcranial direct current stimulation (tDCS) is a non-invasive neurostimulation technique that has received increasing interest in the area of mood disorders over the last several years. While acute, double-blind, sham-controlled studies have already reported positive findings in terms of efficacy and safety for tDCS, follow-up data are lacking. This need prompted the present follow-up study, which assesses post-acute effects of tDCS (no maintenance stimulation was performed), in the mid-term, in a sample of major depressives. Methods After completing an acute, open trial of tDCS, 23 outpatients with either major depressive disorder or bipolar disorder entered a naturalistic follow-up (T1) with clinical evaluations at one week (T2), 1 month (T3), and 3 months (T4). A quantitative analysis of Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS) total scores, through repeated measures analysis of variance (ANOVA) (T1-T4) and paired t-test for comparing specific time points (T1-T2, T2-T3, and T3-T4), was performed. In addition, a qualitative analysis on the basis of treatment response and remission (HAM-D) was performed.Even though a progressive reduction of follow-up completers was observed from T2 to T4 (95.6% at T2, 65.2% at T3, and 47.8% at T4), the antidepressant effects of acute tDCS persisted over 3 months in almost half of the sample. Of note, no post-acute side effects emerged during the follow-up observation. The most frequent causes of drop-out from this study included major modifications in therapeutic regimen (30%) and poor adherence to follow-up visits (17%).In this mid-term, open, follow-up study, tDCS showed mixed results. Further controlled studies are urgently needed to assess its effects beyond the acute phase.

CNS spectrums

Dell'osso, B; Dobrea, C; Arici, C; Benatti, B; Ferrucci, R; Vergari, M; Priori, A; Altamura, AC


Time- but Not Sleep-Dependent Consolidation of tDCS-Enhanced Visuomotor Skills.

2013 Aug

Consolidation of motor skills after training can occur in a time- or sleep-dependent fashion. Recent studies revealed time-dependent consolidation as a common feature of visuomotor tasks. We have previously shown that anodal transcranial direct current stimulation (tDCS) in combination with repeated motor training benefits consolidation by the induction of offline skill gains in a complex visuomotor task, preventing the regular occurrence of skill loss between days. Here, we asked 2 questions: What is the time course of consolidation between days for this task and do exogenously induced offline gains develop as a function of time or overnight sleep? We found that both the development of offline skill loss in sham-stimulated subjects and offline skill gains induced by anodal tDCS critically depend on the passage of time after training, but not on overnight sleep. These findings support the view that tDCS interacts directly with the physiological consolidation process. However, in a control experiment, anodal tDCS applied after the training did not induce skill gains, implying that coapplication of tDCS and training is required to induce offline skill gains, pointing to the initiation of consolidation already during training.

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

Reis, J; Fischer, JT; Prichard, G; Weiller, C; Cohen, LG; Fritsch, B


An image-guided transcranial direct current stimulation system: a pilot phantom study.

2013 Aug

In this study, an image-guided transcranial direct current stimulation (IG-tDCS) system that can deliver an increased stimulation current to a target brain area without the need to adjust the location of an active electrode was implemented. This IG-tDCS system was based on the array-type tDCS concept, which was validated through computer simulations in a previous study. Unlike a previous study, the present IG-tDCS system adopts a single reference electrode and an active electrode array consisting of 16 (4 × 4) sub-electrodes. The proposed IG-tDCS system is capable of shaping current flow inside the human head by controlling the input currents of the arrayed electrodes. Once a target brain area has been selected, the optimal injection current of each arrayed sub-electrode is evaluated automatically using a genetic algorithm in order to deliver the maximum available current to the target area. The operation of our pilot system was confirmed through a simple phantom experiment.

Physiological measurement

Jung, YJ; Kim, JH; Kim, D; Im, CH


Effects of transcranial direct current stimulation on language improvement and cortical activation in nonfluent variant primary progressive aphasia.

2013 Aug

We investigate the effects of transcranial direct current stimulation (tDCS) on language improvement and cortical activation in nonfluent variant primary progressive aphasia (nfvPPA). A 67-year-old woman diagnosed as nfvPPA received sham-tDCS for 5 days over the left posterior perisylvian region (PPR) in the morning and over left Broca's area in the afternoon in Phases A1 and A2, and tDCS for 5 days with an anodal electrode over the left PPR in the morning and over left Broca's area in the afternoon in Phases B1 and B2. Auditory word comprehension, picture naming, oral word reading and word repetition subtests of the Psycholinguistic Assessment in Chinese Aphasia (PACA) were administered before and after each phase. The EEG nonlinear index of approximate entropy (ApEn) was calculated before Phase A1, and after Phases B1 and B2. Our findings revealed that the patient improved greatly in the four subtests after A-tDCS and ApEn indices increased in stimulated areas and non-stimulated areas. We demonstrated that anodal tDCS over the left PPR and Broca's area can improve language performance of nfvPPA. tDCS may be used as an alternative therapeutic tool for PPA.

Neuroscience letters

Wang, J; Wu, D; Chen, Y; Yuan, Y; Zhang, M


Subcortical effects of transcranial direct current stimulation in the rat.

2013 Aug

Transcranial direct current stimulation (tDCS) affects neurons at both cortical and subcortical levels. The subcortical effects involve several descending motor systems but appeared to be relatively weak, as only small increases in the amplitude of subcortically initiated descending volleys and a minute shortening of latencies of these volleys were found. The aim of the present study was therefore to evaluate the consequences of facilitation of these volleys on the ensuing muscle activation. The experiments were carried out on deeply anaesthetized rats without neuromuscular blockade. Effects of tDCS were tested on EMG potentials recorded from neck muscles evoked by weak (20-60 μA) single, double or triple stimuli applied in the medial longitudinal fascicle (MLF) or in the red nucleus (RN). Short latencies of these potentials were compatible with monosynaptic or disynaptic actions of reticulospinal and disynaptic or trisynaptic actions of rubrospinal neurons on neck motoneurons. Despite only weak effects on indirect descending volleys, the EMG responses from both the MLF and the RN were potently facilitated by cathodal tDCS and depressed by anodal tDCS. Both the facilitation and the depression developed relatively rapidly (within the first minute) but both outlasted tDCS and were present for up to 1 h after tDCS. The study thus demonstrates long-lasting effects of tDCS on subcortical neurons in the rat, albeit evoked by an opposite polarity of tDCS to that found to be effective on subcortical neurons in the cat investigated in the preceding study, or for cortical neurons in the humans.

The Journal of physiology

Bolzoni, F; Bączyk, M; Jankowska, E

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Transcranial direct current stimulation changes human endowment effect.

2013 Aug

To test whether the right inferior frontal gyrus (IFG) plays role in the endowment effect, we investigated the effects of transcranial direct current stimulation (tDCS) of the right IFG on the willingness to accept/willingness to pay (WTA/WTP) discrepancy. Twelve healthy subjects underwent anodal, cathodal and sham tDCS on separate days. Stimulation was applied over the right IFG for 20min at 2mA. Subjects participated in the pricing task where they evaluated the presented items under WTA and WTP framings during tDCS intervention. The results showed that the WTA/WTP ratio after anodal tDCS was significantly higher than that after cathodal one. In addition, we found that the reaction time during the cathodal tDCS condition was significantly longer compared to those during anodal or sham tDCS conditions. Our findings suggest the functional relevance of the right IFG for producing endowment effect.

Neuroscience research

Votinov, M; Aso, T; Koganemaru, S; Fukuyama, H; Mima, T


Testing the limits: Investigating the effect of tDCS dose on working memory enhancement in healthy controls.

2013 Aug

Transcranial Direct Current Stimulation (tDCS) is a non-invasive form of brain stimulation which has been shown to induce changes in brain activity and subsequent functioning. In particular, there is a rapidly growing evidence base showing that anodal tDCS applied to the left prefrontal cortex (PFC) is able to enhance aspects of cognitive functioning, in particular working memory (WM). This has led to both excitement and concerns regarding the possibility of 'electrodoping' in order to greatly improve one's cognitive performance. We investigated the behavioural and neurophysiological effects of increasing the current (or 'dose') of tDCS on the degree of WM improvement in healthy controls. Single sessions of 1 mA, 2 mA and sham anodal tDCS to the left PFC were undertaken over a period of three weeks. Participants underwent a WM task at three time points post-stimulation (0, 20 and 40 min) with concurrent electrophysiological (EEG) recordings. Our results showed that while active tDCS can enhance behavioural performance, with neurophysiological findings indicating improve efficiency of cognitive processing; we showed that 1 mA produced the most significant effects. These findings are somewhat unexpected as tDCS dose effects in cognitive enhancement have been shown previously in patient populations. Our results provide valuable information regarding the potential limits of tDCS induced cognitive enhancement in healthy controls, as well as providing additional insights into the possible mechanisms of action of tDCS.

Neuropsychologia

Hoy, KE; Emonson, MR; Arnold, SL; Thomson, RH; Daskalakis, ZJ; Fitzgerald, PB


Facilitation of corticospinal tract excitability by transcranial direct current stimulation combined with voluntary grip exercise.

2013 Aug

Previous studies have established that transcranial direct current stimulation (tDCS) is a powerful technique for the deliberate manipulation of the activity of human cerebral cortex. Moreover, it has also been shown that the non-exhausted voluntary motor exercise increases the excitability of corticospinal tract. We conducted this study to define the facilitation effect following anodal tDCS combined with the voluntary grip exercise as compared with single use of tDCS or voluntary grip exercise. Our result showed that the combination of anodal tDCS with voluntary grip exercise produced a 2-fold increase in the amplitude of MEP as compared with single use of anodal tDCS or voluntary grip exercise. In conclusion, our result could indicate that the treatment outcomes of brain and neurorehabilitation using tDCS would be better when tDCS is combined with the appropriate method of voluntary exercise as compared with single use of tDCS.

Neuroscience letters

Kim, GW; Ko, MH


Postoperative analgesic effect of transcranial direct current stimulation in lumbar spine surgery: a randomized control trial.

2013 Aug

Ultimately, the experience of pain derives from changes in brain excitability. Therefore, modulating the excitability of cortical areas involved in pain processing may become an attractive option in the context of multimodal analgesia during the postoperative period. Repetitive transcranial magnetic stimulation (rTMS) can reduce morphine consumption during the postoperative period after gastric bypass surgery. We tested the potential of another method of noninvasive brain stimulation, transcranial direct current stimulation (tDCS), to reduce morphine consumption or pain perception during the postoperative period.Fifty-nine ASA I to II patients undergoing lumbar spine surgery were randomized to receive anodal (n=20), cathodal (n=20), or sham (n=19) tDCS in the recovery room in a double-blind manner. Morphine consumption administrated through patient-controlled analgesia (PCA) was the primary outcome; pain perception as measured by visual analog scale was the secondary outcome.There were no statistically significant differences between the 3 groups of patients, either for PCA morphine consumption or for pain scores.Several factors may explain the observed lack of impact of tDCS on PCA morphine consumption and pain perception: the method of brain stimulation (tDCS/rTMS), potential interactions with anesthetic drugs, differences in patients population (gastric bypass surgery/lumbar spine surgery), and the previous experience of pain and chronic consumption of analgesic drugs. Further studies with tDCS should be performed before concluding that tDCS is inefficient for postoperative pain control, because noninvasive brain stimulation methods, such as rTMS and tDCS, may become attractive in the setting of multimodal analgesia.

The Clinical journal of pain

Dubois, PE; Ossemann, M; de Fays, K; De Bue, P; Gourdin, M; Jamart, J; Vandermeeren, Y


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

2013 Aug

Limb amputation may lead to chronic painful sensations referred to 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 (2 mA, 15 min) 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


Modulation of chest wall intermuscular coherence: effects of lung volume excursion and transcranial direct current stimulation.

2013 Aug

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 yr; 2 men, 8 women) 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 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 with phonation and vital capacity (all P < 0.05) and between tidal breathing compared with speech breathing (P < 0.05). Anodal tDCS increased chest wall area of intermuscular coherence from 0.04 ± 0.09 prestimulation to 0.18 ± 0.19 poststimulation 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 with 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

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

2013 Aug

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


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

2013 Aug

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.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.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.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.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


Modulating human procedural learning by cerebellar transcranial direct current stimulation.

2013 Aug

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


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

2013 Aug

Transcranial direct current stimulation (tDCS) is a non-invasive, neuromodulatory technique with an emerging role for treating major depression.To investigate the interactions between tDCS and drug therapy in unipolar and bipolar depressed patients who were refractory for at least one pharmacological treatment.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.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.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


Transcranial direct current stimulation (tDCS) and language.

2013 Aug

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

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

2013 Aug

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


Effect of transcranial direct current stimulation on elbow flexor maximal voluntary isometric strength and endurance.

2013 Jul

The effects of transcranial direct current stimulation (tDCS) on maximal voluntary isometric contraction (MVC) strength and the time to failure (TTF) in an isometric (30% MVC) muscle endurance test of the elbow flexors were investigated. Fifteen men (mean age, 27.7 ± 8.4 years) were tested for MVC strength and TTF 2 times, separated by a 60-min rest. During the last 10 min of the rest period, 1 of 2 tDCS treatments or 1 sham intervention session was administered, in a randomized order, with 1 week between sessions. In the tDCS intervention, a 2 mA direct current was delivered for 10 min through an anode placed on the scalp, overlying the right motor cortical representation of the left arm; a cathode was secured over the right shoulder. In the sham intervention, the current was delivered for the first 30 s only. No significant differences between the first and second tDCS sessions were evident for MVC strength or TTF. For MVC strength (baseline, 66.0 ± 11.4 Nm), postintervention measures decreased by 5.9% ± 4.2% (p < 0.05), but no significant difference in the changes was evident between tDCS and sham sessions. TTF did not change significantly from preintervention (309.2 ± 91.6 s) to postintervention (327.2 ± 128.5 s), and there was no significant difference between interventions. It was concluded that the tDCS intervention did not affect muscle function, perhaps because of ceiling effects, in which the intervention does not enhance muscle function further when muscle function is already maximal.

Applied physiology, nutrition, and metabolism = Physiologie appliquée, nutrition et métabolisme

Kan, B; Dundas, JE; Nosaka, K


Widespread modulation of cerebral perfusion induced during and after transcranial direct current stimulation applied to the left dorsolateral prefrontal cortex.

2013 Jul

Noninvasive neuromodulatory techniques such as transcranial direct current stimulation (tDCS) are attracting increasing interest as potential therapies for a wide range of neurological and psychiatric conditions. When targeted to the dorsolateral prefrontal cortex (DLPFC), anodal, facilitatory tDCS has been shown to improve symptoms in a range of domains including working memory, mood, and pain perception (Boggio et al., 2008a; Dockery et al., 2009; Kalu et al., 2012). However, the mechanisms underlying these promising behavioral effects are not well understood. Here, we investigated brain perfusion changes, as assessed using whole-brain arterial spin labeling (ASL), during tDCS applied to the left DLPFC in healthy humans. We demonstrated increased perfusion in regions closely anatomically connected to the DLPFC during anodal tDCS in conjunction with a decreased functional coupling between the left DLPFC and the thalami bilaterally. Despite highly similar effects on cortical excitability during and after stimulation (Nitsche and Paulus, 2000, 2001), cortical perfusion changes were markedly different during these two time periods, with widespread decreases in cortical perfusion being demonstrated after both anodal and cathodal tDCS compared to the period during stimulation. These findings may at least partially explain the different effects on behavior in these time periods described previously in the motor system (Stagg et al., 2011). In addition, the data presented here provide mechanistic explanations for the behavioral effects of anodal tDCS applied to the left DLPFC in terms of modulating functional connectivity between the DLPFC and thalami, as has been hypothesized previously (Lorenz et al., 2003).

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

Stagg, CJ; Lin, RL; Mezue, M; Segerdahl, A; Kong, Y; Xie, J; Tracey, I

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Transcranial alternating current stimulation modulates large-scale cortical network activity by network resonance.

2013 Jul

Transcranial direct current stimulation (tDCS) has emerged as a potentially safe and effective brain stimulation modality that alters cortical excitability by passing a small, constant electric current through the scalp. tDCS creates an electric field that weakly modulates the membrane voltage of a large number of cortical neurons. Recent human studies have suggested that sine-wave stimulation waveforms [transcranial alternating current stimulation (tACS)] represent a more targeted stimulation paradigm for the enhancement of cortical oscillations. Yet, the underlying mechanisms of how periodic, weak global perturbations alter the spatiotemporal dynamics of large-scale cortical network dynamics remain a matter of debate. Here, we simulated large-scale networks of spiking neuron models to address this question in endogenously rhythmic networks. We identified distinct roles of the depolarizing and hyperpolarizing phases of tACS in entrainment, which entailed moving network activity toward and away from a strong nonlinearity provided by the local excitatory coupling of pyramidal cells. Together, these mechanisms gave rise to resonance dynamics characterized by an Arnold tongue centered on the resonance frequency of the network. We then performed multichannel extracellular recordings of multiunit firing activity during tACS in anesthetized ferrets (Mustela putoris furo), a model species with a gyrencephalic brain, to verify that weak global perturbations can selectively enhance oscillations at the applied stimulation frequency. Together, these results provide a detailed mechanistic understanding of tACS at the level of large-scale network dynamics and support the future design of activity-dependent feedback tACS paradigms that dynamically tailor stimulation frequency to the spectral peak of ongoing brain activity.

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

Ali, MM; Sellers, KK; Fröhlich, F

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

2013 Jul

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

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

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The sertraline versus electrical current therapy for treating depression clinical study (select-TDCS): results of the crossover and follow-up phases.

2013 Jul

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).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.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.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


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

2013 Jul

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, 2 mA current was delivered for 20 min. Participants performed the semantic fluency task before the stimulation, immediately after it, and 15 min 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


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

2013 Jul

This study evaluated the effects of weak transcranial direct current stimulation (tDCS), a new non-invasive brain 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 the last cathodal tDCS session, comparing with those of pre-treatment controls. Furthermore, the effects of cathodal tDCS on cognitive function were also studied by a water maze test (WMT) two days after the last tDCS session. Cathodal tDCS treatment significantly improved the seizure stage and decreased ADD together with elevated ADT one day after the last tDCS session. The treatment also showed significant improvement in the performance of WMT. The findings suggest that cathodal tDCS has anticonvulsive after-effects last at least for one day on the amygdala-kindled rats and positively affects cognitive performance.

Neurological research

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


Evidence for long-lasting subcortical facilitation by transcranial direct current stimulation in the cat.

2013 Jul

The main aim of the study was to examine the effects of transcranial polarization on neurons in two descending motor systems, rubro- and reticulospinal. 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 transcranial direct current stimulation (tDCS) and outlasted the polarization by at least 1-2 h, replicating tDCS effects on indirect activation of cortical neurons. The results indicate that the beneficial effects of tDCS on motor performance in humans may be due to more efficient activation of not only 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. 249/250.

The Journal of physiology

Bolzoni, F; Pettersson, LG; Jankowska, E

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Targeted transcranial direct current stimulation for rehabilitation after stroke.

2013 Jul

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 (25 cm(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

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

2013 Jul

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.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.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.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.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 Jul

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.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.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.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


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


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

2013 Jul

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.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).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.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.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


Transcranial direct current stimulation (tDCS) relieved itching in a patient with chronic neuropathic pain.

2013 Jul

Itching is often called the second modality of nociception besides pain, and affects many chronic pain patients.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.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.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.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


Differential frontal involvement in shifts of internal and perceptual attention.

2013 Jul

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).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.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.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.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

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

2013 Jul

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.We aim to compare the physiological effects of both tDCS electrode arrangements on motor cortex excitability.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.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.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


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

2013 Jul

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.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).Sixteen participants received cross-hemispheric tDCS over the PFC in two task-switching paradigms.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.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) enhances reconsolidation of long-term memory.

2013 Jul

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.

2013 Jul

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.In the present study, we investigated whether tDCS may be effective in ameliorating tactile sensory deficit in MS patients.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.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.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.

2013 Jul

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.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.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.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.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


Interaction between simultaneously applied neuromodulatory interventions in humans.

2013 Jul

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).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.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.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.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.

2013 Jul

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.To further elucidate the underlying physiological mechanisms of tDCS.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.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.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


Noninvasive transcranial direct current stimulation over the left prefrontal cortex facilitates cognitive flexibility in tool use.

2013 Jun

Recent neuroscience evidence suggests that some higher-order tasks might benefit from a reduction in sensory filtering associated with low levels of cognitive control. Guided by neuroimaging findings, we hypothesized that cathodal (inhibitory) transcranial direct current stimulation (tDCS) will facilitate performance in a flexible use generation task. Participants saw pictures of artifacts and generated aloud either the object’s common use or an uncommon use for it, while receiving cathodal tDCS (1.5 mA) either over left or right PFC, or sham stimulation. A forward digit span task served as a negative control for potential general effects of stimulation. Analysis of voice-onset reaction times and number of responses generated showed significant facilitative effects of left PFC stimulation for the uncommon, but not the common use generation task and no effects of stimulation on the control task. The results support the hypothesis that certain tasks may benefit from a state of diminished cognitive control.

Cognitive neuroscience

Chrysikou, EG; Hamilton, RH; Coslett, HB; Datta, A; Bikson, M; Thompson-Schill, SL

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The challenge of crafting policy for do-it-yourself brain stimulation.

2013 Jun

Transcranial direct current stimulation (tDCS), a simple means of brain stimulation, possesses a trifecta of appealing features: it is relatively safe, relatively inexpensive and relatively effective. It is also relatively easy to obtain a device and the do-it-yourself (DIY) community has become galvanised by reports that tDCS can be used as an all-purpose cognitive enhancer. We provide practical recommendations designed to guide balanced discourse, propagate norms of safe use and stimulate dialogue between the DIY community and regulatory authorities. We call on all stakeholders-regulators, scientists and the DIY community-to share in crafting policy proposals that ensure public safety while supporting DIY innovation.

Journal of medical ethics

Fitz, NS; Reiner, PB

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

2013 Jun

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-, 30 min post-, and 60 min 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


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

2013 Jun

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


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

2013 Jun

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 (250-500 ms 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


Anodal tDCS to V1 blocks visual perceptual learning consolidation.

2013 Jun

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


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 (2 mA intensity for 20 min 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

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

2013 Jun

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


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

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

2013 May

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

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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


Transcranial current brain stimulation (tCS): models and technologies.

2013 May

In this paper, we provide a broad overview of models and technologies pertaining to transcranial current brain stimulation (tCS), a family of related noninvasive 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 noninvasive, 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; Mekonnen, A; Salvador, R; Soria-Frisch, A; Grau, C; Dunne, S; Miranda, PC


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


Transcranial direct current stimulation accelerates allocentric target detection.

2013 May

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.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.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.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.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

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

2013 May

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.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.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.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.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


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

2013 May

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.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.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).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.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


Perceptual pseudoneglect in schizophrenia: candidate endophenotype and the role of the right parietal cortex.

2013 May

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

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[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


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

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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

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

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

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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

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


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

2013 Apr

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


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

Link to full article text


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

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


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

2013 Mar

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


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

2013 Mar

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.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.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)).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).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


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


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

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

Link to full article text


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

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


Efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation for treating fibromyalgia syndrome: a systematic review.

2013 Feb

 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). 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". 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. Studies involving excitatory rTMS/tDCS at M1 showed analogous pain reductions as well as considerably fewer side effects compared to FDA apaproved 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 apapropriately 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


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

2013 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


TMS and tDCS in post-stroke aphasia: Integrating novel treatment approaches with mechanisms of plasticity.

2013 Jan

Aphasia is a common result of stroke, affecting over one million Americans. Currently, intensive speech therapy is the mainstay of treatment, although its efficacy has been variable at best. Recent years have seen the emergence of non-invasive brain stimulation, specifically Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), as potential treatments for post-stroke aphasia. A growing body of investigations has shown the efficacy of both modalities in facilitating recovery from chronic aphasia, while data regarding subacute aphasia are much more limited and evidence in the acute post-stroke phase are still lacking. Much remains unknown about how these techniques cause clinical improvement or about their long-term efficacy, side-effects, and safety. In this article, we examine the data demonstrating the safety and efficacy of TMS and tDCS, discuss the major differences between them, and consider how those differences may inform the use of each modality. We also consider the different models of neuroplasticity in the setting of post-stroke aphasia and how these models may influence when and in which patients each modality would impart the most benefit.

Restorative neurology and neuroscience

Torres, J; Drebing, D; Hamilton, R


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


Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders?

2013 Jan

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, AM; Pascual-Leone, A

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Non-invasive brain stimulation in neurological diseases.

2013 Jan

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


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

2013 Jan

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


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.

2013 Jan

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.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.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.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


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

2013 Jan

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.  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, 50 acute stroke patients received either five-daily sessions of anodal (n=25) at 2mA for 20min 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 5days after stroke and after 3months.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.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


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

2013 Jan

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.

2013 Jan

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.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.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).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.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


Does excitatory fronto-extracerebral tDCS lead to improved working memory performance?

2013

Evidence suggests that excitatory transcranial direct current stimulation (tDCS) may improve performance on a wide variety of cognitive tasks. Due to the non-invasive and inexpensive nature of the method, harnessing its potential could be particularly useful for the treatment of neuropsychiatric illnesses involving cognitive dysfunction. However, questions remain regarding the efficacious stimulation parameters. Here, using a double-blind between-subjects design, we explored whether 1 mA excitatory (anodal) left dorsolateral prefrontal cortex stimulation with a contralateral extracerebral reference electrode, leads to enhanced working memory performance across two days, relative to sham stimulation. Participants performed the 3-back, a test of working memory, at baseline, and during and immediately following stimulation on two days, separated by 24-48 hours. Active stimulation did not significantly enhance performance versus sham over the course of the experiment. However, exploratory comparisons did reveal a significant effect of stimulation group on performance during the first stimulation phase only, with active stimulation recipients performing better than sham. While these results do not support the hypothesis that dorsolateral prefrontal cortex tDCS boosts working memory, they raise the possibility that its effects may be greatest during early learning stages.

F1000Research

Lally, N; Nord, CL; Walsh, V; Roiser, JP

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Induction of neuroplasticity and recovery in post-stroke aphasia by non-invasive brain stimulation.

2013

Stroke victims tend to prioritize speaking, writing, and walking as the three most important rehabilitation goals. Of note is that two of these goals involve communication. This underscores the significance of developing successful approaches to aphasia treatment for the several hundred thousand new aphasia patients each year and over 1 million stroke survivors with chronic aphasia in the U.S. alone. After several years of growth as a research tool, non-invasive brain stimulation (NBS) is gradually entering the arena of clinical aphasiology. In this review, we first examine the current state of knowledge of post-stroke language recovery including the contributions from the dominant and non-dominant hemispheres. Next, we briefly discuss the methods and the physiologic basis of the use of inhibitory and excitatory repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) as research tools in patients who experience post-stroke aphasia. Finally, we provide a critical review of the most influential evidence behind the potential use of these two brain stimulation methods as clinical rehabilitative tools.

Frontiers in human neuroscience

Shah, PP; Szaflarski, JP; Allendorfer, J; Hamilton, RH

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Head-to-Head Comparison of Transcranial Random Noise Stimulation, Transcranial AC Stimulation, and Transcranial DC Stimulation for Tinnitus.

2013

Tinnitus is the perception of a sound in the absence of an external sound stimulus. This phantom sound has been related to plastic changes and hyperactivity in the auditory cortex. Different neuromodulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation (tDCS) have been used in an attempt to modify local and distant neuroplasticity as to reduce tinnitus symptoms. Recently, two techniques of pulsed electrical stimulation using weak electrical currents - transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS) - have also shown significant neuromodulatory effects. In the present study we conducted the first head-to-head comparison of three different transcranial electrical stimulation (tES) techniques, namely tDCS, tACS, and tRNS in 111 tinnitus patients by placing the electrodes overlying the auditory cortex bilaterally. The results demonstrated that tRNS induced the larger transient suppressive effect on the tinnitus loudness and the tinnitus related distress as compared to tDCS and tACS. Both tDCS and tACS induced small and non-significant effects on tinnitus symptoms, supporting the superior effects of tRNS as a method for tinnitus suppression.

Frontiers in psychiatry

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

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Is it ethical and safe to use non-invasive brain stimulation as a cognitive and motor enhancer device for military services? A reply to Sehm and Ragert ().

2013

Frontiers in human neuroscience

Brunelin, J; Levasseur-Moreau, J; Fecteau, S

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Enhanced motor learning following task-concurrent dual transcranial direct current stimulation.

2013

Transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) has beneficial effects on motor performance and motor learning in healthy subjects and is emerging as a promising tool for motor neurorehabilitation. Applying tDCS concurrently with a motor task has recently been found to be more effective than applying stimulation before the motor task. This study extends this finding to examine whether such task-concurrent stimulation further enhances motor learning on a dual M1 montage.Twenty healthy, right-handed subjects received anodal tDCS to the right M1, dual tDCS (anodal current over right M1 and cathodal over left M1) and sham tDCS in a repeated-measures design. Stimulation was applied for 10 mins at 1.5 mA during an explicit motor learning task. Response times (RT) and accuracy were measured at baseline, during, directly after and 15 mins after stimulation. Motor cortical excitability was recorded from both hemispheres before and after stimulation using single-pulse transcranial magnetic stimulation.Task-concurrent stimulation with a dual M1 montage significantly reduced RTs by 23% as early as with the onset of stimulation (p<0.01) with this effect increasing to 30% at the final measurement. Polarity-specific changes in cortical excitability were observed with MEPs significantly reduced by 12% in the left M1 and increased by 69% in the right M1.Performance improvement occurred earliest in the dual M1 condition with a stable and lasting effect. Unilateral anodal stimulation resulted only in trendwise improvement when compared to sham. Therefore, task-concurrent dual M1 stimulation is most suited for obtaining the desired neuromodulatory effects of tDCS in explicit motor learning.

PloS one

Karok, S; Witney, AG

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Studying the effects of transcranial direct-current stimulation in stroke recovery using magnetic resonance imaging.

2013

Transcranial direct-current stimulation (tDCS) is showing increasing promise as an adjunct therapy in stroke rehabilitation. However questions still remain concerning its mechanisms of action, which currently limit its potential. Magnetic resonance (MR) techniques are increasingly being applied to understand the neural effects of tDCS. Here, we review the MR evidence supporting the use of tDCS to aid recovery after stroke and discuss the important open questions that remain.

Frontiers in human neuroscience

Stagg, CJ; Johansen-Berg, H

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Formation of cortical plasticity in older adults following tDCS and motor training.

2013

Neurodegeneration accompanies the process of natural aging, reducing the ability to perform functional daily activities. Transcranial direct current stimulation (tDCS) alters neuronal excitability and motor performance; however its beneficial effect on the induction of primary motor cortex (M1) plasticity in older adults is unclear. Moreover, little is known as to whether the tDCS electrode arrangement differentially affects M1 plasticity and motor performance in this population. In a double-blinded, cross-over trial, we compared unilateral, bilateral and sham tDCS combined with visuomotor tracking, on M1 plasticity and motor performance of the non-dominant upper limb, immediately post and 30 min following stimulation. We found (a) unilateral and bilateral tDCS decreased tracking error by 12-22% at both time points; with sham decreasing tracking error by 10% at 30 min only, (b) at both time points, motor evoked potentials (MEPs) were facilitated (38-54%) and short-interval intracortical inhibition was released (21-36%) for unilateral and bilateral conditions relative to sham, (c) there were no differences between unilateral and bilateral conditions for any measure. These findings suggest that tDCS modulated elements of M1 plasticity, which improved motor performance irrespective of the electrode arrangement. The results provide preliminary evidence indicating that tDCS is a safe non-invasive tool to preserve or improve neurological function and motor control in older adults.

Frontiers in aging neuroscience

Goodwill, AM; Reynolds, J; Daly, RM; Kidgell, DJ

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Preliminary evidence that anodal transcranial direct current stimulation enhances time to task failure of a sustained submaximal contraction.

2013

The purpose of this study was to determine whether anodal transcranial direct current stimulation (tDCS) delivered while performing a sustained submaximal contraction would increase time to task failure (TTF) compared to sham stimulation. Healthy volunteers (n = 18) performed two fatiguing contractions at 20% of maximum strength with the elbow flexors on separate occasions. During fatigue task performance, either anodal or sham stimulation was delivered to the motor cortex for up to 20 minutes. Transcranial magnetic stimulation (TMS) was used to assess changes in cortical excitability during stimulation. There was no systematic effect of the anodal tDCS stimulation on TTF for the entire subject set (n = 18; p = 0.64). Accordingly, a posteriori subjects were divided into two tDCS-time groups: Full-Time (n = 8), where TTF occurred prior to the termination of tDCS, and Part-Time (n = 10), where TTF extended after tDCS terminated. The TTF for the Full-Time group was 31% longer with anodal tDCS compared to sham (p = 0.04), whereas TTF for the Part-Time group did not differ (p = 0.81). Therefore, the remainder of our analysis addressed the Full-Time group. With anodal tDCS, the amount of muscle fatigue was 6% greater at task failure (p = 0.05) and the amount of time the Full-Time group performed the task at an RPE between 8-10 ("very hard") increased by 38% (p = 0.04) compared to sham. There was no difference in measures of cortical excitability between stimulation conditions (p = 0.90). That the targeted delivery of anodal tDCS during task performance both increased TTF and the amount of muscle fatigue in a subset of subjects suggests that augmenting cortical excitability with tDCS enhanced descending drive to the spinal motorpool to recruit more motor units. The results also suggest that the application of tDCS during performance of fatiguing activity has the potential to bolster the capacity to exercise under conditions required to derive benefits due to overload.

PloS one

Williams, PS; Hoffman, RL; Clark, BC

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Transcranial direct current stimulation of the dorsolateral prefrontal cortex modulates repetition suppression to unfamiliar faces: an ERP study.

2013

Repeated visual processing of an unfamiliar face suppresses neural activity in face-specific areas of the occipito-temporal cortex. This "repetition suppression" (RS) is a primitive mechanism involved in learning of unfamiliar faces, which can be detected through amplitude reduction of the N170 event-related potential (ERP). The dorsolateral prefrontal cortex (DLPFC) exerts top-down influence on early visual processing. However, its contribution to N170 RS and learning of unfamiliar faces remains unclear. Transcranial direct current stimulation (tDCS) transiently increases or decreases cortical excitability, as a function of polarity. We hypothesized that DLPFC excitability modulation by tDCS would cause polarity-dependent modulations of N170 RS during encoding of unfamiliar faces. tDCS-induced N170 RS enhancement would improve long-term recognition reaction time (RT) and/or accuracy rates, whereas N170 RS impairment would compromise recognition ability. Participants underwent three tDCS conditions in random order at ∼72 hour intervals: right anodal/left cathodal, right cathodal/left anodal and sham. Immediately following tDCS conditions, an EEG was recorded during encoding of unfamiliar faces for assessment of P100 and N170 visual ERPs. The P3a component was analyzed to detect prefrontal function modulation. Recognition tasks were administered ∼72 hours following encoding. Results indicate the right anodal/left cathodal condition facilitated N170 RS and induced larger P3a amplitudes, leading to faster recognition RT. Conversely, the right cathodal/left anodal condition caused N170 amplitude and RTs to increase, and a delay in P3a latency. These data demonstrate that DLPFC excitability modulation can influence early visual encoding of unfamiliar faces, highlighting the importance of DLPFC in basic learning mechanisms.

PloS one

Lafontaine, MP; Théoret, H; Gosselin, F; Lippé, S

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Novel insights in the rehabilitation of neglect.

2013

Visuospatial neglect due to right hemisphere damage, usually a stroke, is a major cause of disability, impairing the ability to perform a whole range of everyday life activities. Conventional and long-established methods for the rehabilitation of neglect like visual scanning training, optokinetic stimulation, or limb activation training have produced positive results, with varying degrees of generalization to (un)trained tasks, lasting from several minutes up to various months after training. Nevertheless, some promising novel approaches to the remediation of left visuospatial neglect have emerged in the last decade. These new therapy methods can be broadly classified into four categories. First, non-invasive brain stimulation techniques by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS), after a period of mainly diagnostic utilization, are increasingly applied as neurorehabilitative tools. Second, two classes of drugs, dopaminergic and noradrenergic, have been investigated for their potential effectiveness in rehabilitating neglect. Third, prism adaptation treatment has been shown to improve several neglect symptoms consistently, sometimes during longer periods of time. Finally, virtual reality technologies hold new opportunities for the development of effective training techniques for neglect. They provide realistic, rich, and highly controllable training environments. In this paper the degree of effectiveness and the evidence gathered to support the therapeutic claims of these new approaches is reviewed and discussed. The conclusion is that for all these approaches there still is insufficient unbiased evidence to support their effectiveness. Further neglect rehabilitation research should focus on the maintenance of therapy results over time, on a more functional evaluation of treatment effects, on the design and execution of true replication studies and on the exploration of optimal combinations of treatments.

Frontiers in human neuroscience

Fasotti, L; van Kessel, M

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[Neuromodulation as an intervention for addiction: overview and future prospects].

2013

In recent years several neuromodulation techniques have been introduced as interventions for addiction.To review and discuss studies that have investigated the effects of treating addiction by means of electroencephalography (EEG) neurofeedback, real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback, transcranial magnetic stimulation/transcranial direct current stimulation (TMS/tDCS) and deep brain stimulation (DBS).We reviewed the literature, focusing on Dutch studies in particular.Studies using EEG neurofeedback were shown to have positive effects on drug use, treatment compliance, and cue reactivity in patients with cocaine and alcohol dependence. A pilot study investigating the effects of rt-fMRI neurofeedback on nicotine dependent patients showed that modulation of the anterior cingulate cortex can decrease smokers' craving for nicotine. In several studies decreased craving was found in alcohol dependent patients after TMS or tDCS stimulation of the anterior cingulate cortex or the dorsolateral prefrontal cortex. The first DBS pilot studies suggest that the nucleus accumbens is a promising target region for the treatment of alcohol and heroin dependence.Neuromodulation provides us with a unique opportunity to directly apply neuroscientific knowledge to the treatment of addiction. However, more research is needed to ensure the efficacy, safety and feasibility of the various neuromodulation techniques that are now available.

Tijdschrift voor psychiatrie

Luigjes, J; Breteler, R; Vanneste, S; de Ridder, D

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Transcranial direct current stimulation (tDCS) for improving function and activities of daily living in patients after stroke.

2013

Stroke is one of the leading causes of disability worldwide. Functional impairment resulting in poor performance in activities of daily living (ADLs) among stroke survivors is common. Current rehabilitation approaches have limited effectiveness in improving ADL performance and function after stroke, but a possible adjunct to stroke rehabilitation might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability and hence to improve ADL performance and function.To assess the effects of tDCS on generic activities of daily living (ADLs) and motor function in people with stroke.We searched the Cochrane Stroke Group Trials Register (March 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, May 2013), MEDLINE (1948 to May 2013), EMBASE (1980 to May 2013), CINAHL (1982 to May 2013), AMED (1985 to May 2013), Science Citation Index (1899 to May 2013) and four additional databases. In an effort to identify further published, unpublished and ongoing trials, we searched trials registers and reference lists, handsearched conference proceedings and contacted authors and equipment manufacturers.We included only randomised controlled trials (RCTs) and randomised controlled cross-over trials (from which we analysed only the first period as a parallel-group design) that compared tDCS versus control in adults with stroke for improving ADL performance and function.Two review authors independently assessed trial quality (JM and MP) and extracted data (BE and JM). If necessary, we contacted study authors to ask for additional information. We collected information on dropouts and adverse events from the trial reports.We included 15 studies involving a total of 455 participants. Analysis of six studies involving 326 participants regarding our primary outcome, ADL, showed no evidence of an effect in favour of tDCS at the end of the intervention phase (mean difference (MD) 5.31 Barthel Index (BI) points; 95% confidence interval (CI) -0.52 to 11.14; inverse variance method with random-effects model), whereas at follow-up (MD 11.13 BI points; 95% CI 2.89 to 19.37; inverse variance method with random-effects model), we found evidence of an effect. However, the confidence intervals were wide and the effect was not sustained when only studies with low risk of bias were included. For our secondary outcome, upper limb function, we analysed eight trials with 358 participants, which showed evidence of an effect in favour of tDCS at the end of the intervention phase (MD 3.45 Upper Extremity Fugl-Meyer Score points (UE-FM points); 95% CI 1.24 to 5.67; inverse variance method with random-effects model) but not at the end of follow-up three months after the intervention (MD 9.23 UE-FM points; 95% CI -13.47 to 31.94; inverse variance

The Cochrane database of systematic reviews

Elsner, B; Kugler, J; Pohl, M; Mehrholz, J


Do studies on cortical plasticity provide a rationale for using non-invasive brain stimulation as a treatment for Parkinson's disease patients?

2013

Animal models of Parkinson's disease (PD) have shown that key mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD) can be impaired by the PD pathology. In humans protocols of non-invasive brain stimulation, such as paired associative stimulation (PAS) and theta-burst stimulation (TBS), can be used to investigate cortical plasticity of the primary motor cortex. Through the amplitude of the motor evoked potential these transcranial magnetic stimulation methods allow to measure both LTP-like and LTD-like mechanisms of cortical plasticity. So far these protocols have reported some controversial findings when tested in PD patients. While various studies described evidence for reduced LTP- and LTD-like plasticity, others showed different results, demonstrating increased LTP-like and normal LTD-like plasticity. Recent evidence provided support to the hypothesis that these different patterns of cortical plasticity likely depend on the stage of the disease and on the concomitant administration of l-DOPA. However, it is still unclear how and if these altered mechanisms of cortical plasticity can be taken as a reliable model to build appropriate protocols aimed at treating PD symptoms by applying repetitive sessions of repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS). The current article will provide an up-to-date overview of these issues together with some reflections on future studies in the field.

Frontiers in neurology

Koch, G

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Effects of weak transcranial alternating current stimulation on brain activity-a review of known mechanisms from animal studies.

2013

Rhythmic neuronal activity is ubiquitous in the human brain. These rhythms originate from a variety of different network mechanisms, which give rise to a wide-ranging spectrum of oscillation frequencies. In the last few years an increasing number of clinical research studies have explored transcranial alternating current stimulation (tACS) with weak current as a tool for affecting brain function. The premise of these interventions is that tACS will interact with ongoing brain oscillations. However, the exact mechanisms by which weak currents could affect neuronal oscillations at different frequency bands are not well known and this, in turn, limits the rational optimization of human experiments. Here we review the available in vitro and in vivo animal studies that attempt to provide mechanistic explanations. The findings can be summarized into a few generic principles, such as periodic modulation of excitability, shifts in spike timing, modulation of firing rate, and shifts in the balance of excitation and inhibition. These effects result from weak but simultaneous polarization of a large number of neurons. Whether this can lead to an entrainment or a modulation of brain oscillations, or whether AC currents have no effect at all, depends entirely on the specific dynamic that gives rise to the different brain rhythms, as discussed here for slow wave oscillations (∼1 Hz) and gamma oscillations (∼30 Hz). We conclude with suggestions for further experiments to investigate the role of AC stimulation for other physiologically relevant brain rhythms.

Frontiers in human neuroscience

Reato, D; Rahman, A; Bikson, M; Parra, LC

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Computational modeling of transcranial direct current stimulation (tDCS) in obesity: Impact of head fat and dose guidelines.

2013

Recent studies show that acute neuromodulation of the prefrontal cortex with transcranial direct current stimulation (tDCS) can decrease food craving, attentional bias to food, and actual food intake. These data suggest potential clinical applications for tDCS in the field of obesity. However, optimal stimulation parameters in obese individuals are uncertain. One fundamental concern is whether a thick, low-conductivity layer of subcutaneous fat around the head can affect current density distribution and require dose adjustments during tDCS administration. The aim of this study was to investigate the role of head fat on the distribution of current during tDCS and evaluate whether dosing standards for tDCS developed for adult individuals in general are adequate for the obese population. We used MRI-derived high-resolution computational models that delineated fat layers in five human heads from subjects with body mass index (BMI) ranging from "normal-lean" to "super-obese" (20.9 to 53.5 kg/m(2)). Data derived from these simulations suggest that head fat influences tDCS current density across the brain, but its relative contribution is small when other components of head anatomy are added. Current density variability between subjects does not appear to have a direct and/or simple link to BMI. These results indicate that guidelines for the use of tDCS can be extrapolated to obese subjects without sacrificing efficacy and/or treatment safety; the recommended standard parameters can lead to the delivery of adequate current flow to induce neuromodulation of brain activity in the obese population.

NeuroImage. Clinical

Truong, DQ; Magerowski, G; Blackburn, GL; Bikson, M; Alonso-Alonso, M

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Origins of specificity during tDCS: anatomical, activity-selective, and input-bias mechanisms.

2013

Transcranial Direct Current Stimulation (tDCS) is investigated for a broad range of neuropsychiatric indications, various rehabilitation applications, and to modulate cognitive performance in diverse tasks. Specificity of tDCS refers broadly to the ability of tDCS to produce precise, as opposed to diffuse, changes in brain function. Practically, specificity of tDCS implies application-specific customization of protocols to maximize desired outcomes and minimize undesired effects. Especially given the simplicity of tDCS and the complexity of brain function, understanding the mechanisms leading to specificity is fundamental to the rational advancement of tDCS. We define the origins of specificity based on anatomical and functional factors. Anatomical specificity derives from guiding current to targeted brain structures. Functional specificity may derive from either activity-selectivity, where active neuronal networks are preferentially modulated by tDCS, or input-selectivity, where bias is applied to different synaptic inputs. Rational advancement of tDCS may require leveraging all forms of specificity.

Frontiers in human neuroscience

Bikson, M; Name, A; Rahman, A

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Putative physiological mechanisms underlying tDCS analgesic effects.

2013

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that induces changes in excitability, and activation of brain neurons and neuronal circuits. It has been observed that beyond regional effects under the electrodes, tDCS also alters activity of remote interconnected cortical and subcortical areas. This makes the tDCS stimulation technique potentially promising for modulation of pain syndromes. Indeed, utilizing specific montages, tDCS resulted in analgesic effects in experimental settings, as well as in post-operative acute pain and chronic pain syndromes. The promising evidence of tDCS-induced analgesic effects raises the challenging and complex question of potential physiologic mechanisms that underlie/mediate the accomplished pain relief. Here we present hypotheses on how the specific montages and targets for stimulation may affect the pain processing network.

Frontiers in human neuroscience

Knotkova, H; Nitsche, MA; Cruciani, RA

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Contribution of transcranial oscillatory stimulation to research on neural networks: an emphasis on hippocampo-neocortical rhythms.

2013

EEG rhythms reflect the synchronized activity of underlying biological neuronal network oscillations, and certain predominant frequencies are typically linked to certain behavioral states. For instance, slow wave activity characterized by sleep slow oscillation (SO) emerges normally during slow-wave sleep (SWS). In this mini-review we will first give a background leading up to the present day association between specific oscillations and their functional relevance for learning and memory consolidation. Following, some principles on oscillatory activity are summarized and finally results of studies employing slowly oscillating transcranial electric stimulation are given. We underscore that oscillatory transcranial electric stimulation presents a tool to study principles of cortical network function.

Frontiers in human neuroscience

Marshall, L; Binder, S

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Effectiveness and neural mechanisms associated with tDCS delivered to premotor cortex in stroke rehabilitation: study protocol for a randomized controlled trial.

2013

More than 60% of stroke survivors experience residual deficits of the paretic upper limb/hand. Standard rehabilitation generates modest gains. Stimulation delivered to the surviving Primary Motor Cortex in the stroke-affected hemisphere has been considered a promising adjunct. However, recent trials challenge its advantage. We discuss our pilot clinical trial that aims to address factors implicated in divergent success of the approach. We assess safety, feasibility and efficacy of targeting an alternate locus during rehabilitation- the premotor cortex. In anticipating variance across patients, we measure neural markers differentiating response from non-response.In a randomized, sham-controlled, double-blinded pilot clinical study, patients with chronic stroke (n = 20) are assigned to receive transcranial direct current stimulation delivered to the premotor cortex or sham during rehabilitation of the paretic arm/hand. Patients receive the designated intervention for 30 min, twice a day for 3 days a week for 5 weeks. We assess hand function and patients' reports of use of paretic hand. A general linear mixed methods model will analyze changes from pre- to post-intervention. Responders and non-responders will be compared upon baseline level of function, and neural substrates, including function and integrity of output tracts, bi-hemispheric balance, and lesion profile. Incidence of adverse events will be compared using Fisher's Exact test, while rigor of blinding will be assessed with Chi-square analysis to ascertain feasibility.Variable success of cortical stimulation in rehabilitation can be related to gaps in theoretical basis and clinical investigation. Given that most patients with severe deficits have damage to the primary motor cortex or its output pathways, it would be futile to target stimulation to this site. We suggest targeting premotor cortex because it contributes substantially to descending output, a role that is amplified with greater damage to the motor cortex. With regards to clinical investigation, paired cortical stimulation in rehabilitation has been compared to rehabilitation alone in unblinded trials or to unconvincing sham conditions. Transcranial direct current stimulation, a noninvasive technique of brain stimulation, which offers a more effective placebo and has a favorable safety-feasibility profile, may improve scientific rigor. Neural markers of response would help inform patient selection for future clinical trials so we can address limitations of recent negative studies.NCT01539096.

Trials

Plow, EB; Cunningham, DA; Beall, E; Jones, S; Wyant, A; Bonnett, C; Yue, GH; Lowe, M; Wang, XF; Sakaie, K; Machado, A

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Transcranial stimulation and cognition.

2013

Noninvasive brain stimulation (NIBS) is a unique method for studying cognitive function. For the study of cognition, NIBS has gained popularity as a complementary method to functional neuroimaging. By bypassing the correlative approaches of standard imaging techniques, it is possible to establish a putative relationship between brain cognition. In fact, functional neuroimaging data cannot demonstrate the actual role of a particular cortical activation in a specific function because an activated area may simply be correlated with task performance, rather than being responsible for it. NIBS can induce a temporary modification of performance only if the stimulated area is causally engaged in the task. In analogy with lesion studies, NIBS can provide information about where and when a particular process occurs. Based on this assumption, NIBS has been used in many different cognitive domains. However, one of the most interesting questions in neuroscience may not be where and when, but how cognitive activity occurs. Beyond localization approaches, NIBS can be employed to study brain mechanisms. NIBS techniques have the potential to influence behavior transiently by altering neuronal activity, which may have facilitatory or inhibitory behavioral effects. NIBS techniques include transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES). TMS has been shown transiently to modulate neural excitability in a manner that is dependent mainly on the timing and frequency of stimulation (high versus low). The mechanism underlying tES is a change in neuronal membrane potentials that appears to be dependent mainly on the direction of current flow (anodal versus cathodal). Nevertheless, the final effects induced by TMS or tES depend on many technical parameters used during stimulation, such as the intensity of stimulation, coil orientation, site of the reference electrode, and time of application. Moreover, an important factor is the possible interactions between these factors and the physiological and cognitive state of the subject. To use NIBS in cognition, it is important to understand not only how NIBS functions but also the brain mechanisms being studied and the features of the area of interest. To describe better the advanced knowledge provided by NIBS in cognition, we will treat each NIBS technique separately and underline the related hypotheses beyond applications.

Handbook of clinical neurology

Miniussi, C; Ruzzoli, M


Learning and memory.

2013

Learning and memory functions are crucial in the interaction of an individual with the environment and involve the interplay of large, distributed brain networks. Recent advances in technologies to explore neurobiological correlates of neuropsychological paradigms have increased our knowledge about human learning and memory. In this chapter we first review and define memory and learning processes from a neuropsychological perspective. Then we provide some illustrations of how noninvasive brain stimulation can play a major role in the investigation of memory functions, as it can be used to identify cause-effect relationships and chronometric properties of neural processes underlying cognitive steps. In clinical medicine, transcranial magnetic stimulation may be used as a diagnostic tool to understand memory and learning deficits in various patient populations. Furthermore, noninvasive brain stimulation is also being applied to enhance cognitive functions, offering exciting translational therapeutic opportunities in neurology and psychiatry.

Handbook of clinical neurology

Brem, AK; Ran, K; Pascual-Leone, A


Dementia.

2013

Transcranial magnetic stimulation (TMS) has been used extensively to characterize motor system pathophysiology in Alzheimer's disease (AD) and other forms of dementia, as well to monitor the effects of certain pharmacological agents. Among the studies focusing on motor cortical excitability measures, the most consistent finding is a significant reduction of short-latency afferent inhibition (SAI) in AD and other forms of dementia in which the cholinergic system is affected, such as dementia with Lewy bodies. SAI evaluation may thus provide a reliable biomarker of cortical cholinergic dysfunction in dementias. Moreover, most TMS studies have demonstrated cortical hyperexcitability and asymptomatic motor cortex functional reorganization in the early stages of the disease. Integrated approaches utilizing TMS together with high-density EEG have indicated impaired cortical plasticity and functional connectivity across different neural networks in AD. Paired associative stimulation-induced plasticity has also been found to be abnormal in patients with AD. The development of novel noninvasive methods of brain stimulation, in particular repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS), has increased the interest in neuromodulatory techniques as potential therapeutic tools for cognitive rehabilitation in AD. Preliminary studies have revealed that rTMS and tDCS can induce beneficial effects on specific cognitive functions in AD. Future studies are warranted to replicate and extend the initial findings.

Handbook of clinical neurology

Nardone, R; Golaszewski, S; Trinka, E


Brain stimulation in migraine.

2013

Migraine is a very prevalent disease with great individual disability and socioeconomic burden. Despite intensive research effort in recent years, the etiopathogenesis of the disease remains to be elucidated. Recently, much importance has been given to mechanisms underlying the cortical excitability that has been suggested to be dysfunctional in migraine. In recent years, noninvasive brain stimulation techniques based on magnetic fields (transcranial magnetic stimulation, TMS) and on direct electrical currents (transcranial direct current stimulation, tDCS) have been shown to be safe and effective tools to explore the issue of cortical excitability, activation, and plasticity in migraine. Moreover, TMS, repetitive TMS (rTMS), and tDCS, thanks to their ability to interfere with and/or modulate cortical activity inducing plastic, persistent effects, have been also explored as potential therapeutic approaches, opening an interesting perspective for noninvasive neurostimulation for both symptomatic and preventive treatment of migraine and other types of headache. In this chapter we critically review evidence regarding the role of noninvasive brain stimulation in the pathophysiology and treatment of migraine, delineating the advantages and limits of these techniques together with potential development and future application.

Handbook of clinical neurology

Brighina, F; Cosentino, G; Fierro, B


Noninvasive brain stimulation in neurorehabilitation.

2013

Stroke is the major cause of long-term disability worldwide, with impaired manual dexterity being a common feature. In the past few years, noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have been investigated as adjuvant strategies to neurorehabilitative interventions. These NIBS techniques can be used to modulate cortical excitability during and for several minutes after the end of the stimulation period. Depending on the stimulation parameters, cortical excitability can be reduced (inhibition) or enhanced (facilitation). Differential modulation of cortical excitability in the affected and unaffected hemisphere of patients with stroke may induce plastic changes within neural networks active during functional recovery. The aims of this chapter are to describe results from these proof-of-principle trials and discuss possible putative mechanisms underlying such effects. Neurophysiological and neuroimaging changes induced by application of NIBS are reviewed briefly.

Handbook of clinical neurology

Sandrini, M; Cohen, LG


Epilepsy.

2013

Noninvasive brain stimulation, particularly transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), are emerging as realistic tools for seizure control. Numerous open-label trials and a few recent randomized controlled trials suggest the capacity of both techniques to suppress seizures. Additionally, specialized TMS protocols aimed to map cortical function and to measure cortical excitability may have realistic roles as diagnostic tools in epilepsy. As the prevalence of drug-resistant epilepsy has not changed in recent years, TMS and tDCS offer noninvasive and nonpharmacological options to improve control of intractable seizures.

Handbook of clinical neurology

Rotenberg, A


Parkinson's disease.

2013

In advanced Parkinson's disease (PD), the emergence of symptoms refractory to conventional therapy poses therapeutic challenges. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in noninvasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, although whether a causal interaction exists remains largely undetermined. Most trials of noninvasive brain stimulation in PD have applied repetitive transcranial magnetic stimulation (rTMS), targeting the motor cortex. Current studies suggest a possible therapeutic potential for rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible with regard to functional independence and quality of life. Approaches to potentiate the efficacy of rTMS include increasing stimulation intensity and novel stimulation parameters that derive their rationale from studies on brain physiology. These novel parameters are intended to simulate normal firing patterns or to act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia with regard to motor control and its contribution to the pathogenesis of motor disorders. Noninvasive brain stimulation studies will enhance our understanding of PD pathophysiology and might provide further evidence for potential therapeutic applications.

Handbook of clinical neurology

Benninger, DH


Tinnitus: therapeutic use of superficial brain stimulation.

2013

Tinnitus is a common disorder and traditional treatment approaches such as medication, active or passive sound enhancement, and cognitive behavioral therapy have limited efficacy. Thus, there is an urgent need for more effective treatment approaches. Functional imaging studies in patients with tinnitus have revealed alterations in neuronal activity of central auditory pathways, probably resulting as a consequence of sensory deafferentation. However, nonauditory brain areas are also involved. These nonauditory brain areas might represent both an "awareness" network involved in the conscious perception of the tinnitus signal as well as areas related to a nontinnitus-specific distress network consisting of the anterior cingulate cortex, anterior insula, and amygdala. Moreover, memory mechanisms involving the hippocampus and the parahippocampal region may play a role in the persistence of the awareness of the phantom percept, as well as in the reinforcement of the associated distress. All of these networks represent potential targets for treatment via pharmacological treatment or noninvasive and invasive brain stimulation. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method of applying electromagnetic fields to the brain that can induce alterations of neuronal activity that outlast the stimulation period. Single sessions of rTMS over the temporal or temporoparietal cortex have been successful in transiently reducing tinnitus perception. Repeated sessions of rTMS have resulted in tinnitus relief in a subgroup of patients, lasting from several days to several months. However, effect sizes of rTMS in the treatment of tinnitus are only moderate, and interindividual variability is high. Larger and longer lasting effects have been observed with direct electrical stimulation of the auditory cortex via implanted epidural electrodes. Transcranial direct current stimulation (tDCS) has also shown potential for the treatment of tinnitus. Both auditory and frontal tDCS have shown tinnitus reduction in a subgroup of patients. In spite of the promising results of the different brain stimulation approaches, further research is needed before these techniques can be recommended for routine clinical use.

Handbook of clinical neurology

Langguth, B; De Ridder, D


Pain.

2013

Invasive stimulation of the motor (precentral) cortex using surgically implanted epidural electrodes is indicated for the treatment of neuropathic pain that is refractory to medical treatment. Controlled trials have demonstrated the efficacy of epidural motor cortex stimulation (MCS), but MCS outcome remains variable and validated criteria for selecting good candidates for implantation are lacking. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive approach that could be used as a preoperative tool to predict MCS outcome and also could serve as a therapeutic procedure in itself to treat pain disorders. This requires repeated rTMS sessions and a maintenance protocol. Other studies have also demonstrated the efficacy of transcranial direct current stimulation (tDCS) in relieving chronic pain syndromes. The most studied target is the precentral cortex, but other targets, such as the prefrontal and parietal cortices, could be of interest. The analgesic effects of cortical stimulation relate to the activation of various circuits modulating neural activities in remote structures, such as the thalamus, limbic cortex, insula, or descending inhibitory controls. In addition to the treatment of refractory neuropathic pain by epidural MCS, new developments of this type of strategy are ongoing, for other types of pain syndrome and stimulation techniques.

Handbook of clinical neurology

Lefaucheur, JP


Physics of effects of transcranial brain stimulation.

2013

The effects of transcranial stimulation are determined to a large extent by the spatial distribution and temporal variation of the electric field produced in the brain. In this chapter, we first describe some of the factors that affect the electric field in the brain generally, such as the effect of tissue heterogeneity and anisotropy, or focality. These are common to transcranial magnetic stimulation (TMS) and to several forms of transcranial current stimulation (tCS), such as transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS). Then the main features of the electric field in the human brain during TMS and tCS are presented. This knowledge is important to predict the location and extent of the stimulated region as well as the stimulation intensity in the brain.

Handbook of clinical neurology

Miranda, PC


Transcranial electric and magnetic stimulation: technique and paradigms.

2013

Transcranial electrical and magnetic stimulation techniques encompass a broad physical variety of stimuli, ranging from static magnetic fields or direct current stimulation to pulsed magnetic or alternating current stimulation with an almost infinite number of possible stimulus parameters. These techniques are continuously refined by new device developments, including coil or electrode design and flexible control of the stimulus waveforms. They allow us to influence brain function acutely and/or by inducing transient plastic after-effects in a range from minutes to days. Manipulation of stimulus parameters such as pulse shape, intensity, duration, and frequency, and location, size, and orientation of the electrodes or coils enables control of the immediate effects and after-effects. Physiological aspects such as stimulation at rest or during attention or activation may alter effects dramatically, as does neuropharmacological drug co-application. Non-linear relationships between stimulus parameters and physiological effects have to be taken into account.

Handbook of clinical neurology

Paulus, W; Peterchev, AV; Ridding, M


Inconsistent outcomes of transcranial direct current stimulation (tDCS) may be originated from the anatomical differences among individuals: a simulation study using individual MRI data.

2013

Transcranial direct current stimulation (tDCS) is a kind of neuromodulation protocol, which transmits small amount of DC currents through scalp electrodes to facilitate or inhibit particular areas of the brain. Although many studies have demonstrated that tDCS can effectively modulate excitability of various brain sites, the outcomes of the tDCS treatment are not consistent among subjects to whom identical electrode montages were applied. So far, no studies have clearly elucidated the main cause of this individual variability. The hypothesis of our study was that the individual variability in the tDCS effect might be originated due to the anatomical differences among subjects. To verify our hypothesis, we investigated the relationship between the current density value at dorsolateral prefrontal cortex (DLPFC) simulated using finite element method (FEM) and the behavioral outcomes of a simple working memory (WM) task. A 3-back WM task experiment was conducted with twenty-five healthy subjects before and after the DC stimulation, when the cathode and anode electrodes were attached to right supraorbital area and F3 location, respectively, for all subjects. The results showed that participants who showed enhanced WM task performance after tDCS had a significantly larger current density on DLPFC, suggesting that the inconsistent behavioral outcomes of tDCS might be partially due to the anatomical differences among subjects.

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

Kim, JH; Kim, DW; Chang, WH; Kim, YH; Im, CH


Computational model of cerebellar transcranial direct current stimulation.

2013

This work aimed to estimate the distribution of the electric field and current density generated by cerebellar tDCS using electromagnetics computational techniques applied to a realistic human models of different ages and gender. Results show that the stronger electric field and current density occur mainly in the cerebellar cortex, with a spread toward the occipital region of the cortex, while the current spread to other structures is negligible. Moreover, changes of about 1 cm in the position of the scalp electrode delivering tDCS did not influence the E and J distribution in the cerebellum.

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

Parazzini, M; Rossi, E; Ferrucci, R; Fiocchi, S; Liorni, I; Priori, A; Ravazzani, P


Impairments of motor-cortex responses to unilateral and bilateral direct current stimulation in schizophrenia.

2013

Transcranial direct current stimulation (tDCS) is a non-invasive stimulation technique that can be applied to modulate cortical activity through induction of cortical plasticity. Since various neuropsychiatric disorders are characterized by fluctuations in cortical activity levels (e.g., schizophrenia), tDCS is increasingly investigated as a treatment tool. Several studies have shown that the induction of cortical plasticity following classical, unilateral tDCS is reduced or impaired in the stimulated and non-stimulated primary motor cortices (M1) of patients with schizophrenia. Moreover, an alternative, bilateral tDCS setup has recently been shown to modulate cortical plasticity in both hemispheres in healthy subjects, highlighting another potential treatment approach. Here we present the first study comparing the efficacy of unilateral tDCS (cathode left M1, anode right supraorbital) with simultaneous bilateral tDCS (cathode left M1, anode right M1) in patients with schizophrenia. tDCS-induced cortical plasticity was monitored by investigating motor-evoked potentials induced by single-pulse transcranial magnetic stimulation applied to both hemispheres. Healthy subjects showed a reduction of left M1 excitability following unilateral tDCS on the stimulated left hemisphere and an increase in right M1 excitability following bilateral tDCS. In schizophrenia, no plasticity was induced following both stimulation paradigms. The pattern of these results indicates a complex interplay between plasticity and connectivity that is impaired in patients with schizophrenia. Further studies are needed to clarify the biological underpinnings and clinical impact of these findings.

Frontiers in psychiatry

Hasan, A; Bergener, T; Nitsche, MA; Strube, W; Bunse, T; Falkai, P; Wobrock, T

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Predicting the behavioral impact of transcranial direct current stimulation: issues and limitations.

2013

The transcranial application of weak currents to the human brain has enjoyed a decade of widespread use, providing a simple and powerful tool for non-invasively altering human brain function. However, our understanding of current delivery and its impact upon neural circuitry leaves much to be desired. We argue that the credibility of conclusions drawn with transcranial direct current stimulation (tDCS) is contingent upon realistic explanations of how tDCS works, and that our present understanding of tDCS limits the technique's use to localize function in the human brain. We outline two central issues where progress is required: the localization of currents, and predicting their functional consequence. We encourage experimenters to eschew simplistic explanations of mechanisms of transcranial current stimulation. We suggest the use of individualized current modeling, together with computational neurostimulation to inform mechanistic frameworks in which to interpret the physiological impact of tDCS. We hope that through mechanistically richer descriptions of current flow and action, insight into the biological processes by which transcranial currents influence behavior can be gained, leading to more effective stimulation protocols and empowering conclusions drawn with tDCS.

Frontiers in human neuroscience

de Berker, AO; Bikson, M; Bestmann, S

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Dosage considerations for transcranial direct current stimulation in children: a computational modeling study.

2013

Transcranial direct current stimulation (tDCS) is being widely investigated in adults as a therapeutic modality for brain disorders involving abnormal cortical excitability or disordered network activity. Interest is also growing in studying tDCS in children. Limited empirical studies in children suggest that tDCS is well tolerated and may have a similar safety profile as in adults. However, in electrotherapy as in pharmacotherapy, dose selection in children requires special attention, and simple extrapolation from adult studies may be inadequate. Critical aspects of dose adjustment include 1) differences in neurophysiology and disease, and 2) variation in brain electric fields for a specified dose due to gross anatomical differences between children and adults. In this study, we used high-resolution MRI derived finite element modeling simulations of two healthy children, ages 8 years and 12 years, and three healthy adults with varying head size to compare differences in electric field intensity and distribution. Multiple conventional and high-definition tDCS montages were tested. Our results suggest that on average, children will be exposed to higher peak electrical fields for a given applied current intensity than adults, but there is likely to be overlap between adults with smaller head size and children. In addition, exposure is montage specific. Variations in peak electrical fields were seen between the two pediatric models, despite comparable head size, suggesting that the relationship between neuroanatomic factors and bioavailable current dose is not trivial. In conclusion, caution is advised in using higher tDCS doses in children until 1) further modeling studies in a larger group shed light on the range of exposure possible by applied dose and age and 2) further studies correlate bioavailable dose estimates from modeling studies with empirically tested physiologic effects, such as modulation of motor evoked potentials after stimulation.

PloS one

Kessler, SK; Minhas, P; Woods, AJ; Rosen, A; Gorman, C; Bikson, M

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Effects of transcranial direct current stimulation on consolidation of fear memory.

2013

It has been shown that applying transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) influences declarative memory processes. This study investigates the efficacy of tDCS on emotional memory consolidation, especially experimental fear conditioning. We applied an auditory fear-conditioning paradigm, in which two differently colored squares (blue and yellow) were presented as conditioned stimuli (CS) and an auditory stimulus as unconditioned stimulus (UCS). Sixty-nine participants were randomly assigned into three groups: anodal, cathodal, and sham stimulation. The participants of the two active groups (i.e., anodal and cathodal) received tDCS over the left DLPFC for 12 min after fear conditioning. The effect of fear conditioning and consolidation (24 h later) was measured by assessing the skin conductance response (SCR) to the CS. The results provide evidence that cathodal stimulation of the left DLPFC leads to an inhibitory effect on fear memory consolidation compared to anodal and sham stimulation, as indicated by decreased SCRs to CS+ presentation during extinction training at day 2. In conclusion, current work suggests that cathodal stimulation interferes with processes of fear memory consolidation.

Frontiers in psychiatry

Asthana, M; Nueckel, K; Mühlberger, A; Neueder, D; Polak, T; Domschke, K; Deckert, J; Herrmann, MJ

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The effect of transcranial direct current stimulation: a role for cortical excitation/inhibition balance?

2013

Transcranial direct current stimulation (tDCS) is a promising tool for cognitive enhancement and neurorehabilitation in clinical disorders in both cognitive and clinical domains (e.g., chronic pain, tinnitus). Here we suggest the potential role of tDCS in modulating cortical excitation/inhibition (E/I) balance and thereby inducing improvements. We suggest that part of the mechanism of action of tDCS can be explained by non-invasive modulations of the E/I balance.

Frontiers in human neuroscience

Krause, B; Márquez-Ruiz, J; Cohen Kadosh, R

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Transcranial direct current stimulation reduces negative affect but not cigarette craving in overnight abstinent smokers.

2013

Transcranial direct current stimulation (tDCS) can enhance cognitive control functions including attention and top-down regulation over negative affect and substance craving in both healthy and clinical populations, including early abstinent (∼1.5 h) smokers. The aim of this study was to assess whether tDCS modulates negative affect, cigarette craving, and attention of overnight abstinent tobacco dependent smokers. In this study, 24 smokers received a real and a sham session of tDCS after overnight abstinence from smoking on two different days. We applied anode to the left dorsolateral prefrontal cortex and cathode to the right supra-orbital area for 20 min with a current of 2.0 mA. We used self-report questionnaires Profile of Mood States (POMS) to assess negative affect and Urge to Smoke (UTS) Scale to assess craving for cigarette smoking, and a computerized visual target identification task to assess attention immediately before and after each tDCS. Smokers reported significantly greater reductions in POMS scores of total mood disturbance and scores of tension-anxiety, depression-dejection, and confusion-bewilderment subscales after real relative to sham tDCS. Furthermore, this reduction in negative affect positively correlated with the level of nicotine dependence as assessed by Fagerström scale. However, reductions in cigarette craving after real vs. sham tDCS did not differ, nor were there differences in reaction time or hit rate change on the visual task. Smokers did not report significant side effects of tDCS. This study demonstrates the safety of tDCS and its promising effect in ameliorating negative affect in overnight abstinent smokers. Its efficacy in treating tobacco dependence deserves further investigation.

Frontiers in psychiatry

Xu, J; Fregni, F; Brody, AL; Rahman, AS

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Enhancing verbal episodic memory in older and young subjects after non-invasive brain stimulation.

2013

Memory is the capacity to store, maintain, and retrieve events or information from the mind. Difficulties in verbal episodic memory commonly occur in healthy aging. In this paper, we assess the hypothesis that anodal transcranial direct current stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) or over the parietal cortex (PARC) could facilitate verbal episodic memory in a group of 32 healthy older adults and in a group of 32 young subjects relative to a sham stimulation using a single-blind randomized controlled design. Each participant underwent two sessions of anodal tDCS (left and right) and one session of sham stimulation. Overall, our results demonstrated that, in young and in older subjects, anodal tDCS applied during the retrieval phase facilitates verbal episodic memory. In particular, we found that tDCS applied over the left and right regions (DLPFC and PARC) induced better performance in young participants; only tDCS applied over the left regions (DLPFC and PARC) increased retrieval in older subjects. These results suggest that anodal tDCS can be a relevant tool to modulate the long-term episodic memory capacities of young and older subjects.

Frontiers in aging neuroscience

Manenti, R; Brambilla, M; Petesi, M; Ferrari, C; Cotelli, M

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Modulation of cortical-subcortical networks in Parkinson's disease by applied field effects.

2013

Studies suggest that endogenous field effects may play a role in neuronal oscillations and communication. Non-invasive transcranial electrical stimulation with low-intensity currents can also have direct effects on the underlying cortex as well as distant network effects. While Parkinson's disease (PD) is amenable to invasive neuromodulation in the basal ganglia by deep brain stimulation (DBS), techniques of non-invasive neuromodulation like transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are being investigated as possible therapies. tDCS and tACS have the potential to influence the abnormal cortical-subcortical network activity that occurs in PD through sub-threshold changes in cortical excitability or through entrainment or disruption of ongoing rhythmic cortical activity. This may allow for the targeting of specific features of the disease involving abnormal oscillatory activity, as well as the enhancement of potential cortical compensation for basal ganglia dysfunction and modulation of cortical plasticity in neurorehabilitation. However, little is currently known about how cortical stimulation will affect subcortical structures, the size of any effect, and the factors of stimulation that will influence these effects.

Frontiers in human neuroscience

Hess, CW

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What the online manipulation of linguistic activity can tell us about language and thought.

2013

Frontiers in behavioral neuroscience

Perry, LK; Lupyan, G

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Anodal transcranial direct current stimulation in early rehabilitation of patients with post-stroke non-fluent aphasia: a randomized, double-blind, sham-controlled pilot study.

2013

Recent research in patients with chronic aphasia shows an association between excitatory anodal transcranial direct current stimulation (A-tDCS) of the stroke-affected left hemisphere coupled with speech and language therapy (SLT) and better language performance. The present study aimed to investigate this association during the early post-stroke rehabilitation period, when adaptive changes are most possible on neurophysiological and behavioral levels.We randomized 24 patients with non-fluent aphasia to receive 15 consecutive sessions (5 days/week for 3 weeks) of A-tDCS (1 mA, 10 min; n = 14) or sham tDCS (S-tDCS: 1 mA, 25 sec; n = 10) over Broca's area followed by 45-min SLT. Naming ability was assessed before the rehabilitation, after its completion, and three months later.Both groups significantly improved after the therapy. There were no statistically significant between-group differences in the short-term or long-term tDCS effects on naming accuracy and naming time. The A-tDCS group obtained higher effect sizes in naming time, both post-treatment and at the 3-month follow-up, suggesting potential benefits of the stimulation.The findings provide only weak evidence for A-tDCS-related language gains during early neurorehabilitation of post-stroke aphasia. Further research is needed to explore the effectiveness of this kind of neuromodulation.

Restorative neurology and neuroscience

Polanowska, KE; Leśniak, MM; Seniów, JB; Czepiel, W; Członkowska, A


tDCS over the left inferior frontal cortex improves speech production in aphasia.

2013

In this study, we investigated the combined effect of transcranial direct current stimulation (tDCS) and an intensive Conversational therapy treatment on discourse skills in 12 persons with chronic aphasia. Six short video clips depicting everyday life contexts were prepared. Three videoclips were used to elicit spontaneous conversation during treatment. The remaining three were presented only before and after the therapy. Participants were prompted to talk about the contents of each videoclip while stimulated with tDCS (20 min 1 mA) over the left hemisphere in three conditions: anodic tDCS over the Broca's area, anodic tDCS over the Wernicke's area, and a sham condition. Each experimental condition was performed for 10 consecutive daily sessions with 14 days of intersession interval. After stimulation over Broca's area, the participants produced more Content Units, verbs and sentences than in the remaining two conditions. Importantly, this improvement was still detectable 1 month after the end of treatment and its effects were generalized also to the three videoclips that had been administered at the beginning and at the end of the therapy sessions. In conclusion, anodic tDCS applied over the left Broca's area together with an intensive "Conversational Therapy" treatment improves informative speech in persons with chronic aphasia. We believe that positive tDCS effects may be further extended to other language domains, such as the recovery of speech production.

Frontiers in human neuroscience

Marangolo, P; Fiori, V; Calpagnano, MA; Campana, S; Razzano, C; Caltagirone, C; Marini, A

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Modulation of spontaneous alpha brain rhythms using low-intensity transcranial direct-current stimulation.

2013

Transcranial direct-current stimulation (tDCS) is a form of neurostimulation in which a constant, low current is delivered directly to the brain area of interest by small electrodes. The overall aim of this study was to examine and monitor the modulation of brain activity by electroencephalogram (EEG) in the frequency domain during tDCS in the resting state. To this end, we considered the modulation of spontaneous EEG to be a marker of the perturbation that was induced through the direct current (1.5 mA for 15 min). In all conditions (anodal, cathodal, and sham), an active electrode was placed over the right posterior parietal cortex, and a reference electrode was placed on the ipsilateral deltoid muscle. The EEG was recorded using a 64-channel system. The effect of tDCS was limited to the alpha rhythm, and the anodal stimulation significantly affected the alpha rhythm, whereas the cathodal stimulation did not elicit any modifications. Further, we observed modulation of alpha activity in areas that were stimulated directly through tDCS and in anterior noncontiguous areas. Finally, the anodal effect peaked 7.5 min after stimulation and decreased gradually over time. Our study demonstrates that in the resting brain, monocephalic anodal tDCS over posterior parietal areas alters ongoing brain activity, specifically in the alpha band rhythm. Our data can be used to fine-tune tDCS protocols in neurorehabilitation settings.

Frontiers in human neuroscience

Spitoni, GF; Cimmino, RL; Bozzacchi, C; Pizzamiglio, L; Di Russo, F

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Differential modulation of corticospinal excitability by different current densities of anodal transcranial direct current stimulation.

2013

Novel non-invasive 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 intensity and stimulation duration. Despite clinical success with existing tDCS parameters, optimal protocols are still not entirely set.The current study aimed to investigate the effects of four different anodal tDCS (a-tDCS) current densities on corticospinal excitability.Four current intensities of 0.3, 0.7, 1.4 and 2 mA resulting in current densities (CDs) of 0.013, 0.029, 0.058 and 0.083 mA/cm(2) were applied on twelve right-handed (mean age 34.5±10.32 yrs) healthy individuals in different sessions at least 48 hours apart. a-tDCS was applied continuously for 10 minute, with constant active and reference electrode sizes of 24 and 35 cm(2) respectively. The corticospinal excitability of the extensor carpi radialis muscle (ECR) was measured before and immediately after the intervention and at 10, 20 and 30 minutes thereafter.Post hoc comparisons showed significant differences in corticospinal excitability changes for CDs of 0.013 mA/cm(2) and 0.029 mA/cm(2) (P = 0.003). There were no significant differences between excitability changes for the 0.013 mA/cm(2) and 0.058 mA/cm(2) (P = 0.080) or 0.013 mA/cm(2) and 0.083 mA/cm(2) (P = 0.484) conditions.This study found that a-tDCS with a current density of 0.013 mA/cm(2) induces significantly larger corticospinal excitability changes than CDs of 0.029 mA/cm(2). The implication is that might help to avoid applying unwanted amount of current to the cortical areas.

PloS one

Bastani, A; Jaberzadeh, S

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Translating tDCS into the field of obesity: mechanism-driven approaches.

2013

Transcranial direct current stimulation (tDCS) is emerging as a promising technique for neuromodulation in a variety of clinical conditions. Recent neuroimaging studies suggest that modifying the activity of brain circuits involved in eating behavior could provide therapeutic benefits in obesity. One session of tDCS over the dorsolateral prefrontal cortex can induce an acute decrease in food craving, according to three small clinical trials, but the extension of these findings into the field of obesity remains unexplored. Importantly, there has been little/no interaction of our current understanding of tDCS and its mechanisms with obesity-related research. How can we start closing this gap and rationally guide the translation of tDCS into the field of obesity? In this mini-review I summarize some of the challenges and questions ahead, related to basic science and technical aspects, and suggest future directions.

Frontiers in human neuroscience

Alonso-Alonso, M

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Tracking the neuroplastic changes associated with transcranial direct current stimulation: a push for multimodal imaging.

2013

Frontiers in human neuroscience

Hunter, MA; Coffman, BA; Trumbo, MC; Clark, VP

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Non-invasive brain stimulation can induce paradoxical facilitation. Are these neuroenhancements transferable and meaningful to security services?

2013

For ages, we have been looking for ways to enhance our physical and cognitive capacities in order to augment our security. One potential way to enhance our capacities may be to externally stimulate the brain. Methods of non-invasive brain stimulation (NIBS), such as repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), have been recently developed to modulate brain activity. Both techniques are relatively safe and can transiently modify motor and cognitive functions outlasting the stimulation period. The purpose of this paper is to review data suggesting that NIBS can enhance motor and cognitive performance in healthy volunteers. We frame these findings in the context of whether they may serve security purposes. Specifically, we review studies reporting that NIBS induces paradoxical facilitation in motor (precision, speed, strength, acceleration endurance, and execution of daily motor task) and cognitive functions (attention, impulsive behavior, risk-taking, working memory, planning, and deceptive capacities). Although transferability and meaningfulness of these NIBS-induced paradoxical facilitations into real-life situations are not clear yet, NIBS may contribute at improving training of motor and cognitive functions relevant for military, civil, and forensic security services. This is an enthusiastic perspective that also calls for fair and open debates on the ethics of using NIBS in healthy individuals to enhance normal functions.

Frontiers in human neuroscience

Levasseur-Moreau, J; Brunelin, J; Fecteau, S

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Bilateral bi-cephalic tDCS with two active electrodes of the same polarity modulates bilateral cognitive processes differentially [corrected].

2013

Transcranial direct current stimulation (tDCS) is an innovative method to explore the causal structure-function relationship of brain areas. We investigated the specificity of bilateral bi-cephalic tDCS with two active electrodes of the same polarity (e.g., cathodal on both hemispheres) applied to intraparietal cortices bilaterally using a combined between- and within-task approach. Regarding between-task specificity, we observed that bilateral bi-cephalic tDCS affected a numerical (mental addition) but not a control task (colour word Stroop), indicating a specific influence of tDCS on numerical but not on domain general cognitive processes associated with the bilateral IPS. In particular, the numerical effect of distractor distance was more pronounced under cathodal than under anodal stimulation. Moreover, with respect to within-task specificity we only found the numerical distractor distance effect in mental addition to be modulated by direct current stimulation, whereas the effect of target identity was not affected. This implies a differential influence of bilateral bi-cephalic tDCS on the recruitment of different processing components within the same task (number magnitude processing vs. recognition of familiarity). In sum, this first successful application of bilateral bi-cephalic tDCS with two active electrodes of the same polarity in numerical cognition research corroborates the specific proposition of the Triple Code Model that number magnitude information is represented bilaterally in the intraparietal cortices.

PloS one

Klein, E; Mann, A; Huber, S; Bloechle, J; Willmes, K; Karim, AA; Nuerk, HC; Moeller, K

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Brain stimulation paired with novel locomotor training with robotic gait orthosis in chronic stroke: a feasibility study.

2013

1) To investigate the feasibility of combining transcranial direct current stimulation (tDCS) to the lower extremity (LE) motor cortex with novel locomotor training to facilitate gait in subjects with chronic stroke and low ambulatory status, and 2) to obtain insight from study subjects and their caregivers to inform future trial design.Double-blind, randomized controlled study with additional qualitative exploratory descriptive design. One-month follow-up.10 subjects with stroke were recruited and randomized to active tDCS or sham tDCS for 12 sessions. Both groups participated in identical locomotor training with a robotic gait orthosis (RGO) following each tDCS session. RGO training protocol was designed to harness cortical neuroplasticity. Data analysis included assessment of functional and participation outcome measures and qualitative thematic analysis.Eight subjects completed the study. Both groups demonstrated trends toward improvement, but the active tDCS group showed greater improvement than the sham group. Qualitative analyses indicated beneficial effects of this combined intervention.It is feasible to combine tDCS targeting the LE motor cortex with our novel locomotor training. It appears that tDCS has the potential to enhance the effectiveness of gait training in chronic stroke. Insights from participants provide additional guidance in designing future trials.

NeuroRehabilitation

Danzl, MM; Chelette, KC; Lee, K; Lykins, D; Sawaki, L


Transcranial direct current stimulation (tDCS) and robotic practice in chronic stroke: the dimension of timing.

2013

Combining tDCS with robotic therapy is a new and promising form of neurorehabilitation after stroke, however the effectiveness of this approach is likely to be influenced by the relative timing of the brain stimulation and the therapy.To measure the kinematic and neurophysiological effects of delivering tDCS before, during and after a single session of robotic motor practice (wrist extension).We used a within-subjects repeated-measurement design in 12 chronic (>6 months) stroke survivors. Twenty minutes of anodal tDCS was delivered to the affected hemisphere before, during, or after a 20-minute session of robotic practice. Sham tDCS was also applied during motor practice. Robotic motor performance and corticomotor excitability, assessed through transcranial magnetic stimulation (TMS), were evaluated pre- and post-intervention.Movement speed was increased after motor training (sham tDCS) by ∼20%. Movement smoothness was improved when tDCS was delivered before motor practice (∼15%). TDCS delivered during practice did not offer any benefit, whereas it reduced speed when delivered after practice (∼10%). MEPs were present in ∼50% of patients at baseline; in these subjects motor practice increased corticomotor excitability to the trained muscle.In a cohort of stroke survivors, motor performance kinematics improved when tDCS was delivered prior to robotic training, but not when delivered during or after training. The temporal relationship between non-invasive brain stimulation and neurorehabilitation is important in determining the efficacy and outcome of this combined therapy.

NeuroRehabilitation

Giacobbe, V; Krebs, HI; Volpe, BT; Pascual-Leone, A; Rykman, A; Zeiarati, G; Fregni, F; Dipietro, L; Thickbroom, GW; Edwards, DJ


Combining functional magnetic resonance imaging with transcranial electrical stimulation.

2013

Transcranial electrical stimulation (tES) is a neuromodulatory method with promising potential for basic research and as a therapeutic tool. The most explored type of tES is transcranial direct current stimulation (tDCS), but also transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS) have been shown to affect cortical excitability, behavioral performance and brain activity. Although providing indirect measure of brain activity, functional magnetic resonance imaging (fMRI) can tell us more about the global effects of stimulation in the whole brain and what is more, on how it modulates functional interactions between brain regions, complementing what is known from electrophysiological methods such as measurement of motor evoked potentials. With this review, we aim to present the studies that have combined these techniques, the current approaches and discuss the results obtained so far.

Frontiers in human neuroscience

Saiote, C; Turi, Z; Paulus, W; Antal, A

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Technique and considerations in the use of 4x1 ring high-definition transcranial direct current stimulation (HD-tDCS).

2013

High-definition transcranial direct current stimulation (HD-tDCS) has recently been developed as a noninvasive brain stimulation approach that increases the accuracy of current delivery to the brain by using arrays of smaller "high-definition" electrodes, instead of the larger pad-electrodes of conventional tDCS. Targeting is achieved by energizing electrodes placed in predetermined configurations. One of these is the 4x1-ring configuration. In this approach, a center ring electrode (anode or cathode) overlying the target cortical region is surrounded by four return electrodes, which help circumscribe the area of stimulation. Delivery of 4x1-ring HD-tDCS is capable of inducing significant neurophysiological and clinical effects in both healthy subjects and patients. Furthermore, its tolerability is supported by studies using intensities as high as 2.0 milliamperes for up to twenty minutes. Even though 4x1 HD-tDCS is simple to perform, correct electrode positioning is important in order to accurately stimulate target cortical regions and exert its neuromodulatory effects. The use of electrodes and hardware that have specifically been tested for HD-tDCS is critical for safety and tolerability. Given that most published studies on 4x1 HD-tDCS have targeted the primary motor cortex (M1), particularly for pain-related outcomes, the purpose of this article is to systematically describe its use for M1 stimulation, as well as the considerations to be taken for safe and effective stimulation. However, the methods outlined here can be adapted for other HD-tDCS configurations and cortical targets.

Journal of visualized experiments : JoVE

Villamar, MF; Volz, MS; Bikson, M; Datta, A; Dasilva, AF; Fregni, F

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Transcranial direct current stimulation (tDCS) for sleep disturbances and fatigue in patients with post-polio syndrome.

2013

Post-polio syndrome develops about 20-40 years after acute paralytic poliomyelitis, and manifests with progressively deteriorating muscle strength and endurance. Here, we assessed whether transcranial direct current stimulation (tDCS) improves sleep and fatigue symptoms in patients with post-polio syndrome.We enrolled 32 patients with a diagnosis of post-polio syndrome. tDCS (1.5 mA, 15 min) was delivered by a direct current stimulator connected to three electrodes: two anodal electrodes on the scalp over the right and left pre-motor cortex and the other above the left shoulder (cathode). 16 patients received anodal tDCS and the remainder sham tDCS. We evaluated changes induced by tDCS (daily for five days a week, for three weeks) on clinical scales (Short Form Health Survey [SF-36], Piper Fatigue Scale [PFS], Fatigue Severity Scale [FSS], 101-Point Numerical Rating [PNR-101], Hamilton Rating Scale for Depression [HRSD], Pittsburgh Sleep Quality Index [PSQI]) at baseline (T0) and three weeks later (T1).At T1 SF-36 sub-items physical functioning, role physical, vitality, social functioning and role emotional improved significantly more in patients who received tDCS (p < 0.01) than in sham-treated patients. Also, PSQI scores improved more in treated patients (p < 0.05, two-way ANOVA with "stimulation" and "time" as factors: p < 0.01). tDCS-induced benefits were more pronounced in patients who were younger at primary infection (p < 0.05).Anodal tDCS over the pre-motor areas for fifteen days improved sleep and fatigue symptoms in patients with post-polio syndrome. tDCS could be a non-invasive and valuable new tool for managing post-polio patients.

Restorative neurology and neuroscience

Acler, M; Bocci, T; Valenti, D; Turri, M; Priori, A; Bertolasi, L


Novel methods to study aphasia recovery after stroke.

2013

The neural mechanisms that support aphasia recovery are not yet fully understood. It has been argued that the functional reorganization of language networks after left-hemisphere stroke may engage perilesional left brain areas as well as homologous right-hemisphere regions. In this chapter, we summarize how noninvasive brain stimulation can be used to elucidate mechanisms of plasticity in language networks and enhance language recovery after stroke. We first outline some basic principles of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). We then present evidence from studies in healthy volunteers for a causal role of the right hemisphere in different language functions. Finally, we review recent studies that used TMS or tDCS to promote language recovery after stroke. Most of these studies applied noninvasive brain stimulation over contralateral right-hemisphere areas to suppress maladaptive plasticity. However, some studies also suggest that right-hemisphere regions may beneficially contribute to recovery in some patients. More recently, some investigators have targeted perilesional brain regions to promote neurorehabilitation. In sum, these studies indicate that language recovery after stroke may integrate left- as well as right-hemisphere brain regions to a different degree over the time course of recovery. Although the results of these preliminary studies provide some evidence that noninvasive brain stimulation may promote aphasia recovery, the reported effect sizes are not striking. Future studies on larger patient collectives are needed to explore whether noninvasive brain stimulation can enhance language functions at a level that is clinically relevant.

Frontiers of neurology and neuroscience

Hartwigsen, G; Siebner, HR


Effects of transcranial direct current stimulation of the motor cortex on prefrontal cortex activation during a neuromuscular fatigue task: an fNIRS study.

2013

This study investigated whether manipulation of motor cortex excitability by transcranial direct current stimulation (tDCS) modulates neuromuscular fatigue and functional near-infrared spectroscopy (fNIRS)-derived prefrontal cortex (PFC) activation. Fifteen healthy men (27.7 ± 8.4 years) underwent anodal (2 mA, 10 min) and sham (2 mA, first 30 s only) tDCS delivered to the scalp over the right motor cortex. Subjects initially performed a baseline sustained submaximal (30 % maximal voluntary isometric contraction, MVC) isometric contraction task (SSIT) of the left elbow flexors until task failure, which was followed 50 min later by either an anodal or sham treatment condition, then a subsequent posttreatment SSIT. Endurance time (ET), torque integral (TI), and fNIRS-derived contralateral PFC oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentration changes were determined at task failure. Results indicated that during the baseline and posttreatment SSIT, there were no significant differences in TI and ET, and increases in fNIRS-derived PFC activation at task failure were observed similarly regardless of the tDCS conditions. This suggests that the PFC neuronal activation to maintain muscle force production was not modulated by anodal tDCS.

Advances in experimental medicine and biology

Muthalib, M; Kan, B; Nosaka, K; Perrey, S


Simultaneous EEG monitoring during transcranial direct current stimulation.

2013

Transcranial direct current stimulation (tDCS) is a technique that delivers weak electric currents through the scalp. This constant electric current induces shifts in neuronal membrane excitability, resulting in secondary changes in cortical activity. Although tDCS has most of its neuromodulatory effects on the underlying cortex, tDCS effects can also be observed in distant neural networks. Therefore, concomitant EEG monitoring of the effects of tDCS can provide valuable information on the mechanisms of tDCS. In addition, EEG findings can be an important surrogate marker for the effects of tDCS and thus can be used to optimize its parameters. This combined EEG-tDCS system can also be used for preventive treatment of neurological conditions characterized by abnormal peaks of cortical excitability, such as seizures. Such a system would be the basis of a non-invasive closed-loop device. In this article, we present a novel device that is capable of utilizing tDCS and EEG simultaneously. For that, we describe in a step-by-step fashion the main procedures of the application of this device using schematic figures, tables and video demonstrations. Additionally, we provide a literature review on clinical uses of tDCS and its cortical effects measured by EEG techniques.

Journal of visualized experiments : JoVE

Schestatsky, P; Morales-Quezada, L; Fregni, F

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Task-specific effect of transcranial direct current stimulation on motor learning.

2013

Transcranial direct current stimulation (tDCS) is a relatively new non-invasive brain stimulation technique that modulates neural processes. When applied to the human primary motor cortex (M1), tDCS has beneficial effects on motor skill learning and consolidation in healthy controls and in patients. However, it remains unclear whether tDCS improves motor learning in a general manner or whether these effects depend on which motor task is acquired. Here we compare whether the effect of tDCS differs when the same individual acquires (1) a Sequential Finger Tapping Task (SEQTAP) and (2) a Visual Isometric Pinch Force Task (FORCE). Both tasks have been shown to be sensitive to tDCS applied over M1, however, the underlying processes mediating learning and memory formation might benefit differently from anodal transcranial direct current stimulation (anodal-tDCS). Thirty healthy subjects were randomly assigned to an anodal-tDCS group or sham-group. Using a double-blind, sham-controlled cross-over design, tDCS was applied over M1 while subjects acquired each of the motor tasks over three consecutive days, with the order being randomized across subjects. We found that anodal-tDCS affected each task differently: the SEQTAP task benefited from anodal-tDCS during learning, whereas the FORCE task showed improvements only at retention. These findings suggest that anodal-tDCS applied over M1 appears to have a task-dependent effect on learning and memory formation.

Frontiers in human neuroscience

Saucedo Marquez, CM; Zhang, X; Swinnen, SP; Meesen, R; Wenderoth, N

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[Transcranial direct current stimulation; potential new treatment for unilateral neglect].

2013

One of the most devastating cognitive deficits following a stroke is when the patient neglects one half of the body and surroundings (unilateral neglect). Unilateral neglect following a stroke has a high prevalence and is one of the most important predictors of poor functional outcome. Various treatment methods have been studied over the past decades but their effects appear too short-term or task-specific and therefore, difficult to extrapolate to other untrained situations. A possible new intervention is transcranial direct current stimulation (tDCS), which is capable of modulating brain activity by polarizing neurons with the aid of a constant low current. Recent research suggests that inhibiting the intact hemisphere or increasing the neuronal activity in the damaged hemisphere might reduce unilateral neglect. For treating unilateral neglect, tDCS appears to be a promising technique; however, more research is necessary to reveal its therapeutic potential.

Nederlands tijdschrift voor geneeskunde

Smit, M; Schutter, DJ; Nijboer, TC; Dijkerman, HC; Kappelle, LJ


Neuropathic pain: transcranial electric motor cortex stimulation using high frequency random noise. Case report of a novel treatment.

2013

Electric motor cortex stimulation has been reported to be effective for many cases of neuropathic pain, in the form of epidural stimulation or transcranial direct current stimulation (tDCS). A novel technique is transcranial random noise stimulation (tRNS), which increases the cortical excitability irrespective of the orientation of the current. The aim of this study was to investigate the effect of tRNS on neuropathic pain in a small number of subjects, and in a case study explore the effects of different stimulation parameters and the long-term stability of treatment effects.THE STUDY WAS DIVIDED INTO THREE PHASES: (1) a double-blind crossover study, with four subjects; (2) a double-blind extended case study with one responder; and (3) open continued treatment. The motor cortex stimulation consisted of alternating current random noise (100-600 Hz), varying from 0.5 to 10 minutes and from 50 to 1500 μA, at intervals ranging from daily to fortnightly.One out of four participants showed a strong positive effect (also compared with direct-current-sham, P = 0.006). Unexpectedly, this effect was shown to occur also for very weak (100 μA, P = 0.048) and brief (0.5 minutes, P = 0.028) stimulation. The effect was largest during the first month, but remained at a highly motivating level for the patient after 6 months.The study suggests that tRNS may be an effective treatment for some cases of neuropathic pain. An important result was the indication that even low levels of stimulation may have substantial effects.

Journal of pain research

Alm, PA; Dreimanis, K

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Is motor learning mediated by tDCS intensity?

2013

Although tDCS has been shown to improve motor learning, previous studies reported rather small effects. Since physiological effects of tDCS depend on intensity, the present study evaluated this parameter in order to enhance the effect of tDCS on skill acquisition. The effect of different stimulation intensities of anodal tDCS (atDCS) was investigated in a double blind, sham controlled crossover design. In each condition, thirteen healthy subjects were instructed to perform a unimanual motor (sequence) learning task. Our results showed (1) a significant increase in the slope of the learning curve and (2) a significant improvement in motor performance at retention for 1.5 mA atDCS as compared to sham tDCS. No significant differences were reported between 1 mA atDCS and sham tDCS; and between 1.5 mA atDCS and 1 mA atDCS.

PloS one

Cuypers, K; Leenus, DJ; van den Berg, FE; Nitsche, MA; Thijs, H; Wenderoth, N; Meesen, RL

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Induction of cortical plasticity and improved motor performance following unilateral and bilateral transcranial direct current stimulation of the primary motor cortex.

2013

Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates the excitability of neurons within the primary motor cortex (M1). Research shows that anodal-tDCS applied over the non-dominant M1 (i.e. unilateral stimulation) improves motor function of the non-dominant hand. Similarly, previous studies also show that applying cathodal tDCS over the dominant M1 improves motor function of the non-dominant hand, presumably by reducing interhemispheric inhibition. In the present study, one condition involved anodal-tDCS over the non-dominant M1 (unilateral stimulation) whilst a second condition involved applying cathodal-tDCS over the dominant M1 and anodal-tDCS over non-dominant M1 (bilateral stimulation) to determine if unilateral or bilateral stimulation differentially modulates motor function of the non-dominant hand. Using a randomized, cross-over design, 11 right-handed participants underwent three stimulation conditions: 1) unilateral stimulation, that involved anodal-tDCS applied over the non-dominant M1, 2) bilateral stimulation, whereby anodal-tDCS was applied over the non-dominant M1, and cathodal-tDCS over the dominant M1, and 3) sham stimulation. Transcranial magnetic stimulation (TMS) was performed before, immediately after, 30 and 60 minutes after stimulation to elucidate the neural mechanisms underlying any potential after-effects on motor performance. Motor function was evaluated by the Purdue pegboard test.There were significant improvements in motor function following unilateral and bilateral stimulation when compared to sham stimulation at all-time points (all P < 0.05); however there was no difference across time points between unilateral and bilateral stimulation. There was also a similar significant increase in corticomotor excitability with both unilateral and bilateral stimulation immediately post, 30 minutes and 60 minutes compared to sham stimulation (all P < 0.05). Unilateral and bilateral stimulation reduced short-interval intracortical inhibition (SICI) immediately post and at 30 minutes (all P < 0.05), but returned to baseline in both conditions at 60 minutes. There was no difference between unilateral and bilateral stimulation for SICI (P > 0.05). Furthermore, changes in corticomotor plasticity were not related to changes in motor performance.These results indicate that tDCS induced behavioural changes in the non-dominant hand as a consequence of mechanisms associated with use-dependant cortical plasticity that is independent of the electrode arrangement.

BMC neuroscience

Kidgell, DJ; Goodwill, AM; Frazer, AK; Daly, RM

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Long-Term Effects of Serial Anodal tDCS on Motion Perception in Subjects with Occipital Stroke Measured in the Unaffected Visual Hemifield.

2013

Transcranial direct current stimulation (tDCS) is a novel neuromodulatory tool that has seen early transition to clinical trials, although the high variability of these findings necessitates further studies in clinically relevant populations. The majority of evidence into effects of repeated tDCS is based on research in the human motor system, but it is unclear whether the long-term effects of serial tDCS are motor-specific or transferable to other brain areas. This study aimed to examine whether serial anodal tDCS over the visual cortex can exogenously induce long-term neuroplastic changes in the visual cortex. However, when the visual cortex is affected by a cortical lesion, up-regulated endogenous neuroplastic adaptation processes may alter the susceptibility to tDCS. To this end, motion perception was investigated in the unaffected hemifield of subjects with unilateral visual cortex lesions. Twelve subjects with occipital ischemic lesions participated in a within-subject, sham-controlled, double-blind study. MRI-registered sham or anodal tDCS (1.5 mA, 20 min) was applied on five consecutive days over the visual cortex. Motion perception was tested before and after stimulation sessions and at 14- and 28-day follow-up. After a 16-day interval an identical study block with the other stimulation condition (anodal or sham tDCS) followed. Serial anodal tDCS over the visual cortex resulted in an improvement in motion perception, a function attributed to MT/V5. This effect was still measurable at 14- and 28-day follow-up measurements. Thus, this may represent evidence for long-term tDCS-induced plasticity and has implications for the design of studies examining the time course of tDCS effects in both the visual and motor systems.

Frontiers in human neuroscience

Olma, MC; Dargie, RA; Behrens, JR; Kraft, A; Irlbacher, K; Fahle, M; Brandt, SA

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Transcranial direct current stimulation (tDCS) for improving aphasia in patients after stroke.

2013

Stroke is one of the leading causes of disability worldwide. Aphasia among stroke survivors is common. Current speech and language therapy (SLT) strategies have only limited effectiveness in improving aphasia. A possible adjunct to SLT for improving SLT outcomes might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability and hence to improve aphasia.To assess the effects of tDCS for improving aphasia in patients after stroke.We searched the Cochrane Stroke Group Trials Register (April 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, March 2012), MEDLINE (1948 to March 2012), EMBASE (1980 to March 2012), CINAHL (1982 to March 2012), AMED (1985 to April 2012), Science Citation Index (1899 to April 2012) and seven additional databases. We also searched trials registers and reference lists, handsearched conference proceedings and contacted authors and equipment manufacturers.We included only randomised controlled trials (RCTs) and randomised controlled cross-over trials (from which we only analysed the first period as a parallel group design) comparing tDCS versus control in adults with aphasia due to stroke.Two review authors independently assessed trial quality and extracted the data. If necessary, we contacted study authors for additional information. We collected information on dropouts and adverse events from the trials.We included five trials involving 54 participants. None of the included studies used any formal outcome measure for measuring functional communication, that is measuring aphasia in a real-life communicative setting. All five trials measured correct picture naming as a surrogate for aphasia. There was no evidence that tDCS enhanced SLT outcomes. No adverse events were reported and the proportion of dropouts was comparable between groups.Currently there is no evidence of the effectiveness of tDCS (anodal tDCS, cathodal tDCS) versus control (sham tDCS). However, it appears that cathodal tDCS over the non-lesioned hemisphere might be the most promising approach.

The Cochrane database of systematic reviews

Elsner, B; Kugler, J; Pohl, M; Mehrholz, J


Bihemispheric anodal corticomotor stimulation using transcranial direct current stimulation improves bimanual typing task performance.

2013

Transcranial direct current stimulation (tDCS) is associated with improved unimanual skilled hand use. The authors assessed effects of bihemispheric anodal corticomotor tDCS (BAC-tDCS) on bimanual skilled hand use. Twenty-eight nondisabled subjects were randomized to either BAC-tDCS or sham-tDCS, 20 min daily for 5 consecutive days. Performance on a bimanual typing (BT) task and a short-term memory (STM) task was assessed daily and at 1-week follow-up. Mean change between Day 1 and Day 5 in BT score with BAC-tDCS (19.4 points; 95% CI [12.82, 25.99]) was significantly greater (p =.04) than change with sham-tDCS (12.5 points; 95% CI [7.6, 17.3]). Neither group retained improvements in BT score at follow-up. BAC-tDCS had no effect on STM. These results may have implications for interventions to improve hand function in persons with bilateral hand dysfunction.

Journal of motor behavior

Gomes-Osman, J; Field-Fote, EC


tDCS stimulation segregates words in the brain: evidence from aphasia.

2013

A number of studies have already shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) improves noun or verb naming in aphasic patients. However, it is not yet clear whether these effects are equally obtained through stimulation over the frontal or the temporal regions. In the present study, the same group of aphasic subjects participated in two randomized double-blind experiments involving two intensive language treatments for their noun and verb retrieval difficulties. During each training, each subject was treated with tDCS (20 min, 1 mA) over the left hemisphere in three different conditions: anodic tDCS over the temporal areas, anodic tDCS over the frontal areas, and sham stimulation, while they performed a noun and an action naming tasks. Each experimental condition was run in five consecutive daily sessions over three weeks with 6 days of intersession interval. The order of administration of the two language trainings was randomly assigned to all patients. Overall, with respect to the other two conditions, results showed a significant greater improvement in noun naming after stimulation over the temporal region, while verb naming recovered significantly better after stimulation of the frontal region. These improvements persisted at one month after the end of each treatment suggesting a long-term effect on recovery of the patients' noun and verb difficulties. These data clearly suggest that the mechanisms of recovery for naming can be segregated coupling tDCS with an intensive language training.

Frontiers in human neuroscience

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

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Sensing, assessing, and augmenting threat detection: behavioral, neuroimaging, and brain stimulation evidence for the critical role of attention.

2013

Rapidly identifying the potentially threatening movements of other people and objects-biological motion perception and action understanding-is critical to maintaining security in many civilian and military settings. A key approach to improving threat detection in these environments is to sense when less than ideal conditions exist for the human observer, assess that condition relative to an expected standard, and if necessary use tools to augment human performance. Action perception is typically viewed as a relatively "primitive," automatic function immune to top-down effects. However, recent research shows that attention is a top-down factor that has a critical influence on the identification of threat-related targets. In this paper we show that detection of motion-based threats is attention sensitive when surveillance images are obscured by other movements, when they are visually degraded, when other stimuli or tasks compete for attention, or when low-probability threats must be watched for over long periods of time-all features typical of operational security settings. Neuroimaging studies reveal that action understanding recruits a distributed network of brain regions, including the superior temporal cortex, intraparietal cortex, and inferior frontal cortex. Within this network, attention modulates activation of the superior temporal sulcus (STS) and middle temporal gyrus. The dorsal frontoparietal network may provide the source of attention-modulation signals to action representation areas. Stimulation of this attention network should therefore enhance threat detection. We show that transcranial Direct Current Stimulation (tDCS) at 2 mA accelerates perceptual learning of participants performing a challenging threat-detection task. Together, cognitive, neuroimaging, and brain stimulation studies provide converging evidence for the critical role of attention in the detection and understanding of threat-related intentional actions.

Frontiers in human neuroscience

Parasuraman, R; Galster, S

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Non-invasive brain stimulation in neglect rehabilitation: an update.

2013

Here, we review the effects of non-invasive brain stimulation such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) in the rehabilitation of neglect. We found 12 studies including 172 patients (10 TMS studies and 2 tDCS studies) fulfilling our search criteria. Activity of daily living measures such as the Barthel Index or, more specifically for neglect, the Catherine Bergego Scale were the outcome measure in three studies. Five studies were randomized controlled trials with a follow-up time after intervention of up to 6 weeks. One TMS study fulfilled criteria for Class I and one for Class III evidence. The studies are heterogeneous concerning their methodology, outcome measures, and stimulation parameters making firm comparisons and conclusions difficult. Overall, there are however promising results for theta-burst stimulation, suggesting that TMS is a powerful add-on therapy in the rehabilitation of neglect patients.

Frontiers in human neuroscience

Müri, RM; Cazzoli, D; Nef, T; Mosimann, UP; Hopfner, S; Nyffeler, T

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Je pense donc je fais: transcranial direct current stimulation modulates brain oscillations associated with motor imagery and movement observation.

2013

Motor system neural networks are activated during movement imagery, observation and execution, with a neural signature characterized by suppression of the Mu rhythm. In order to investigate the origin of this neurophysiological marker, we tested whether transcranial direct current stimulation (tDCS) modifies Mu rhythm oscillations during tasks involving observation and imagery of biological and non-biological movements. We applied tDCS (anodal, cathodal, and sham) in 21 male participants (mean age 23.8 ± 3.06), over the left M1 with a current of 2 mA for 20 min. Following this, we recorded the EEG at C3, C4, and Cz and surrounding C3 and C4 electrodes. Analyses of C3 and C4 showed significant effects for biological vs. non-biological movement (p = 0.005), and differential hemisphere effects according to the type of stimulation (p = 0.04) and type of movement (p = 0.02). Analyses of surrounding electrodes revealed significant interaction effects considering type of stimulation and imagery or observation of biological or non-biological movement (p = 0.03). The main findings of this study were (1) Mu desynchronization during biological movement of the hand region in the contralateral hemisphere after sham tDCS; (2) polarity-dependent modulation effects of tDCS on the Mu rhythm, i.e., anodal tDCS led to Mu synchronization while cathodal tDCS led to Mu desynchronization during movement observation and imagery (3) specific focal and opposite inter-hemispheric effects, i.e., contrary effects for the surrounding electrodes during imagery condition and also for inter-hemispheric electrodes (C3 vs. C4). These findings provide insights into the cortical oscillations during movement observation and imagery. Furthermore, it shows that tDCS can be highly focal when guided by a behavioral task.

Frontiers in human neuroscience

Lapenta, OM; Minati, L; Fregni, F; Boggio, PS

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Enhancing performance in numerical magnitude processing and mental arithmetic using transcranial Direct Current Stimulation (tDCS).

2013

The ability to accurately process numerical magnitudes and solve mental arithmetic is of highest importance for schooling and professional career. Although impairments in these domains in disorders such as developmental dyscalculia (DD) are highly detrimental, remediation is still sparse. In recent years, transcranial brain stimulation methods such as transcranial Direct Current Stimulation (tDCS) have been suggested as a treatment for various neurologic and neuropsychiatric disorders. The posterior parietal cortex (PPC) is known to be crucially involved in numerical magnitude processing and mental arithmetic. In this study, we evaluated whether tDCS has a beneficial effect on numerical magnitude processing and mental arithmetic. Due to the unclear lateralization, we stimulated the left, right as well as both hemispheres simultaneously in two experiments. We found that left anodal tDCS significantly enhanced performance in a number comparison and a subtraction task, while bilateral and right anodal tDCS did not induce any improvements compared to sham. Our findings demonstrate that the left PPC is causally involved in numerical magnitude processing and mental arithmetic. Furthermore, we show that these cognitive functions can be enhanced by means of tDCS. These findings encourage to further investigate the beneficial effect of tDCS in the domain of mathematics in healthy and impaired humans.

Frontiers in human neuroscience

Hauser, TU; Rotzer, S; Grabner, RH; Mérillat, S; Jäncke, L

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Noninvasive remote activation of the ventral midbrain by tra