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1521 research article(s) found.
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The effects of tDCS upon sustained visual attention are dependent on cognitive load.

2016 Jan

Transcranial Direct Current Stimulation (tDCS) modulates the excitability of neuronal responses and consequently can affect performance on a variety of cognitive tasks. However, the interaction between cognitive load and the effects of tDCS is currently not well-understood. We recorded the performance accuracy of participants on a bilateral multiple object tracking task while undergoing bilateral stimulation assumed to enhance (anodal) and decrease (cathodal) neuronal excitability. Stimulation was applied to the posterior parietal cortex (PPC), a region inferred to be at the centre of an attentional tracking network that shows load-dependent activation. 34 participants underwent three separate stimulation conditions across three days. Each subject received (1) left cathodal / right anodal PPC tDCS, (2) left anodal / right cathodal PPC tDCS, and (3) sham tDCS. The number of targets-to-be-tracked was also manipulated, giving a low (one target per visual field), medium (two targets per visual field) or high (three targets per visual field) tracking load condition. It was found that tracking performance at high attentional loads was significantly reduced in both stimulation conditions relative to sham, and this was apparent in both visual fields, regardless of the direction of polarity upon the brain's hemispheres. We interpret this as an interaction between cognitive load and tDCS, and suggest that tDCS may degrade attentional performance when cognitive networks become overtaxed and unable to compensate as a result. Systematically varying cognitive load may therefore be a fruitful direction to elucidate the effects of tDCS upon cognitive functions.

Neuropsychologia

Roe, JM; Nesheim, M; Mathiesen, NC; Moberget, T; Alnæs, D; Sneve, MH

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The effect of transcranial direct current stimulation on contrast sensitivity and visual evoked potential amplitude in adults with amblyopia.

2016

Amblyopia is a neurodevelopmental disorder of vision that occurs when the visual cortex receives decorrelated inputs from the two eyes during an early critical period of development. Amblyopic eyes are subject to suppression from the fellow eye, generate weaker visual evoked potentials (VEPs) than fellow eyes and have multiple visual deficits including impairments in visual acuity and contrast sensitivity. Primate models and human psychophysics indicate that stronger suppression is associated with greater deficits in amblyopic eye contrast sensitivity and visual acuity. We tested whether transcranial direct current stimulation (tDCS) of the visual cortex would modulate VEP amplitude and contrast sensitivity in adults with amblyopia. tDCS can transiently alter cortical excitability and may influence suppressive neural interactions. Twenty-one patients with amblyopia and twenty-seven controls completed separate sessions of anodal (a-), cathodal (c-) and sham (s-) visual cortex tDCS. A-tDCS transiently and significantly increased VEP amplitudes for amblyopic, fellow and control eyes and contrast sensitivity for amblyopic and control eyes. C-tDCS decreased VEP amplitude and contrast sensitivity and s-tDCS had no effect. These results suggest that tDCS can modulate visual cortex responses to information from adult amblyopic eyes and provide a foundation for future clinical studies of tDCS in adults with amblyopia.

Scientific reports

Ding, Z; Li, J; Spiegel, DP; Chen, Z; Chan, L; Luo, G; Yuan, J; Deng, D; Yu, M; Thompson, B

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Transcranial random noise stimulation mitigates increased difficulty in an arithmetic learning task.

2015 Dec

Proficiency in arithmetic learning can be achieved by using a multitude of strategies, the most salient of which are procedural learning (applying a certain set of computations) and rote learning (direct retrieval from long-term memory). Here we investigated the effect of transcranial random noise stimulation (tRNS), a non-invasive brain stimulation method previously shown to enhance cognitive training, on both types of learning in a 5-day sham-controlled training study, under two conditions of task difficulty, defined in terms of item repetition. On the basis of previous research implicating the prefrontal and posterior parietal cortex in early and late stages of arithmetic learning, respectively, sham-controlled tRNS was applied to bilateral prefrontal cortex for the first 3 days and to the posterior parietal cortex for the last 2 days of a 5-day training phase. The training involved learning to solve arithmetic problems by applying a calculation algorithm; both trained and untrained problems were used in a brief testing phase at the end of the training phase. Task difficulty was manipulated between subjects by using either a large ("easy" condition) or a small ("difficult" condition) number of repetition of problems during training. Measures of attention and working memory were acquired before and after the training phase. As compared to sham, participants in the tRNS condition displayed faster reaction times and increased learning rate during the training phase; as well as faster reaction times for both trained and untrained (new) problems, which indicated a transfer effect after the end of training. All stimulation effects reached significance only in the "difficult" condition when number of repetition was lower. There were no transfer effects of tRNS on attention or working memory. The results support the view that tRNS can produce specific facilitative effects on numerical cognition - specifically, on arithmetic learning. They also highlight the importance of task difficulty in the neuromodulation of learning, which in the current study due to the manipulation of item repetition might have being mediated by the memory system.

Neuropsychologia

Popescu, T; Krause, B; Terhune, DB; Twose, O; Page, T; Humphreys, G; Cohen Kadosh, R

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Transcranial modulation of brain oscillatory responses: A concurrent tDCS-MEG investigation.

2015 Dec

Despite the increasing use of transcranial direct current stimulation (tDCS), the physiological mechanisms underlying its effects are still largely unknown. One approach to directly investigate the effects of the neuromodulation technique on the brain is to integrate tDCS with non-invasive neuroimaging in humans. To provide new insight into the neurobiology of the method, DC stimulation (1mA, 600s) was applied concurrently with Magnetoencephalography (MEG), while participants engaged in a visuomotor task before, during and after the period of tDCS. Responses in the motor beta band (15-30Hz) and visual gamma band (30-80Hz) were localised using Synthetic Aperture Magnetometry (SAM). The resulting induced and evoked oscillatory responses were subsequently analysed. A statistically significant reduction of average power in the visual gamma band was observed for anodal compared to sham stimulation. The magnitude of motor evoked responses was also found to be significantly modulated by anodal stimulation. These results demonstrate that MEG can be used to derive inferences on the cortical mechanisms of tDCS.

NeuroImage

Hanley, CJ; Singh, KD; McGonigle, DJ

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Choice reaching with a LEGO arm robot (CoRLEGO): The motor system guides visual attention to movement-relevant information.

2015 Dec

We present an extension of a neurobiologically inspired robotics model, termed CoRLEGO (Choice reaching with a LEGO arm robot). CoRLEGO models experimental evidence from choice reaching tasks (CRT). In a CRT participants are asked to rapidly reach and touch an item presented on the screen. These experiments show that non-target items can divert the reaching movement away from the ideal trajectory to the target item. This is seen as evidence attentional selection of reaching targets can leak into the motor system. Using competitive target selection and topological representations of motor parameters (dynamic neural fields) CoRLEGO is able to mimic this leakage effect. Furthermore if the reaching target is determined by its colour oddity (i.e. a green square among red squares or vice versa), the reaching trajectories become straighter with repetitions of the target colour (colour streaks). This colour priming effect can also be modelled with CoRLEGO. The paper also presents an extension of CoRLEGO. This extension mimics findings that transcranial direct current stimulation (tDCS) over the motor cortex modulates the colour priming effect (Woodgate et al., 2015). The results with the new CoRLEGO suggest that feedback connections from the motor system to the brain's attentional system (parietal cortex) guide visual attention to extract movement-relevant information (i.e. colour) from visual stimuli. This paper adds to growing evidence that there is a close interaction between the motor system and the attention system. This evidence contradicts the traditional conceptualization of the motor system as the endpoint of a serial chain of processing stages. At the end of the paper we discuss CoRLEGO's predictions and also lessons for neurobiologically inspired robotics emerging from this work.

Neural networks : the official journal of the International Neural Network Society

Strauss, S; Woodgate, PJ; Sami, SA; Heinke, D

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Effects of adjustment of transcranial direct current stimulation on motor function of the upper extremity in stroke patients.

2015 Nov

[Purpose] The purpose of this study was to examine the effects of transcranial direct current stimulation (tDCS) applied to the cerebral cortex motor area on the upper extremity functions of hemiplegic patients. [Subjects and Methods] Twenty four Patients with hemiplegia resulting from a stroke were divided into two groups: a tDCS group that received tDCS and physical therapy and a control group that received only physical therapy. A functional evaluation of the two groups was performed, and an electrophysiological evaluation was conducted before and after the experiment. Statistical analyses were performed to verify differences before and after the experiment. All statistical significance levels were set at 0.05. [Results] The results showed that functional evaluation scores for the elbow joint and hand increased after the treatment in both the experimental group and the control group, and the increases were statistically significantly different. [Conclusion] tDCS was effective in improving the upper extremity motor function of stroke patients. Additional research is warranted on the usefulness of tDCS in the rehabilitation of stroke patients in the clinical field.

Journal of physical therapy science

Lee, DG; Lee, DY

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A technical guide to tDCS, and related non-invasive brain stimulation tools.

2015 Nov

Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain.

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

Woods, AJ; Antal, A; Bikson, M; Boggio, PS; Brunoni, AR; Celnik, P; Cohen, LG; Fregni, F; Herrmann, CS; Kappenman, ES; Knotkova, H; Liebetanz, D; Miniussi, C; Miranda, PC; Paulus, W; Priori, A; Reato, D; Stagg, C; Wenderoth, N; Nitsche, MA

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Effect of combination of transcranial direct current stimulation and feedback training on visuospatial neglect in patients with subacute stroke: a pilot randomized controlled trial.

2015 Sep

[Purpose] To investigate the effects of a combination of transcranial direct current stimulation (tDCS) and feedback training (FT) on subacute stroke patients with unilateral visuospatial neglect. [Subjects] The subjects were randomly assigned to a tDCS + FT group (n=6) and a FT group (n=6). [Methods] Patients in the tDCS + FT group received tDCS for 20 minutes and then received FT for 30 minutes a day, 5 days a week for 3 weeks. The control group received FT for 30 minutes a day, 5 days a week for 3 weeks. [Results] After the intervention, both groups showed significant improvements in the Motor-Free Visual Perception Test (MVPT), line bisection test (LBT), and modified Barthel index (MBI) over the baseline results. The comparison of the two groups after the intervention revealed that the rDCS + FT group showed more significant improvements in MVPT, LBT, and MBI. [Conclusion] The results of this study suggest that tDCS combined with FT has a positive effect on unilateral visuospatial neglect in patients with subacute stroke.

Journal of physical therapy science

Bang, DH; Bong, SY

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The Effects of Transcranial Direct-Current Stimulation on Cognition in Stroke Patients.

2015 Sep

To investigate whether transcranial direct-current stimulation (tDCS) can improve cognition in stroke patients.Forty-five stroke patients (20 males and 25 females, average age: 62.7 years) with cognitive dysfunction were included in this prospective, double-blinded, randomized case-control study. All patients were right-handed and the mean elapsed time after stroke was 39.3 days. Three different treatments groups were used: (1) anodal stimulation of the left anterior temporal lobe, (2) anodal stimulation of the right anterior temporal lobe, and (3) sham stimulation. tDCS was delivered for 30 minutes at 2 mA with 25 cm(2) electrodes, five times/week, for a total of 3 weeks, using a Phoresor II Auto Model PM 850 (IOMED(®)). The evaluation of cognitive impairment was based on a Computerized Neuropsychological Test (CNT), Korean Mini-Mental State Examination (K-MMSE). The Korean version of the Modified Barthel Index (K-MBI) was used to assess activities of daily living functionality. These evaluations were conducted in all patients before and after treatment.Each group included 15 patients. Pre-treatment evaluation showed no significant differences between the three groups for any of the parameters. There was significant improvement in the verbal learning test on the CNT in the left anodal stimulation group (P < 0.05). There were, however, no significant differences in the K-MMSE or K-MBI scores among the three groups.These results demonstrated the beneficial effects of anodal tDCS on memory function. Thus, tDCS can successfully be used as a treatment modality for patients with cognitive dysfunction after stroke.

Journal of stroke

Yun, GJ; Chun, MH; Kim, BR

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Modulating Hippocampal Plasticity with In Vivo Brain Stimulation.

2015 Sep

Investigations into the use of transcranial direct current stimulation (tDCS) in relieving symptoms of neurological disorders and enhancing cognitive or motor performance have exhibited promising results. However, the mechanisms by which tDCS effects brain function remain under scrutiny. We have demonstrated that in vivo tDCS in rats produced a lasting effect on hippocampal synaptic plasticity, as measured using extracellular recordings. Ex vivo preparations of hippocampal slices from rats that have been subjected to tDCS of 0.10 or 0.25 mA for 30 min followed by 30 min of recovery time displayed a robust twofold enhancement in long-term potentiation (LTP) induction accompanied by a 30% increase in paired-pulse facilitation (PPF). The magnitude of the LTP effect was greater with 0.25 mA compared with 0.10 mA stimulations, suggesting a dose-dependent relationship between tDCS intensity and its effect on synaptic plasticity. To test the persistence of these observed effects, animals were stimulated in vivo for 30 min at 0.25 mA and then allowed to return to their home cage for 24 h. Observation of the enhanced LTP induction, but not the enhanced PPF, continued 24 h after completion of 0.25 mA of tDCS. Addition of the NMDA blocker AP-5 abolished LTP in both control and stimulated rats but maintained the PPF enhancement in stimulated rats. The observation of enhanced LTP and PPF after tDCS demonstrates that non-invasive electrical stimulation is capable of modifying synaptic plasticity.Researchers have used brain stimulation such as transcranial direct current stimulation on human subjects to alleviate symptoms of neurological disorders and enhance their performance. Here, using rats, we have investigated the potential mechanisms of how in vivo brain stimulation can produce such effect. We recorded directly on viable brain slices from rats after brain stimulation to detect lasting changes in pattern of neuronal activity. Our results showed that 30 min of brain stimulation in rats induced a robust enhancement in synaptic plasticity, a neuronal process critical for learning and memory. Understanding such molecular effects will lead to a better understanding of the mechanisms by which brain stimulation produces its effects on cognition and performance.

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

Rohan, JG; Carhuatanta, KA; McInturf, SM; Miklasevich, MK; Jankord, R

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Transcranial Current Stimulation of the Temporoparietal Junction Improves Lie Detection.

2015 Sep

The ability to detect deception is of vital importance in human society, playing a crucial role in communication, cooperation, and trade between societies, businesses, and individuals. However, numerous studies have shown, remarkably consistently, that we are only slightly above chance when it comes to detecting deception. Here we investigate whether inconsistency between one's own opinion and the stated opinion of another impairs judgment of the veracity of that statement, in the same way that one's own mental, affective, and action states, when inconsistent, can interfere with representation of those states in another. Within the context of lie detection, individuals may be less accurate when judging the veracity of another's opinion when it is inconsistent with their own opinion. Here we present a video-mediated lie-detection task to confirm this prediction: individuals correctly identified truths or lies less often when the other's expressed opinion was inconsistent with their own (experiment 1). Transcranial direct current stimulation (tDCS) of the temporoparietal junction (TPJ) has previously been shown to improve the ability to selectively represent the self or another. We therefore predicted that TPJ stimulation would enable lie detectors to inhibit their own views, enhance those of the other, and improve their ability to determine whether another was presenting their true opinion. Experiment 2 confirmed this second prediction: anodal tDCS of the TPJ improved lie detection specifically when one's own and others' views were conflicting.

Current biology : CB

Sowden, S; Wright, GR; Banissy, MJ; Catmur, C; Bird, G

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A Feasibility Study of Bilateral Anodal Stimulation of the Prefrontal Cortex Using High-Definition Electrodes in Healthy Participants.

2015 Sep

Transcranial direct current stimulation (tDCS) studies often use one anode to increase cortical excitability in one hemisphere. However, mental processes may involve cortical regions in both hemispheres. This study's aim was to assess the safety and possible effects on affect and working memory of tDCS using two anodes for bifrontal stimulation. A group of healthy subjects participated in two bifrontal tDCS sessions on two different days, one for real and the other for sham stimulation. They performed a working memory task and reported their affect immediately before and after each tDCS session. Relative to sham, real bifrontal stimulation did not induce significant adverse effects, reduced decrement in vigor-activity during the study session, and did not improve working memory. These preliminary findings suggest that bifrontal anodal stimulation is feasible and safe and may reduce task-related fatigue in healthy participants. Its effects on neuropsychiatric patients deserve further study.

The Yale journal of biology and medicine

Xu, J; Healy, SM; Truong, DQ; Datta, A; Bikson, M; Potenza, MN

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Friends, not foes: Magnetoencephalography as a tool to uncover brain dynamics during transcranial alternating current stimulation.

2015 Sep

Brain oscillations are supposedly crucial for normal cognitive functioning and alterations are associated with cognitive dysfunctions. To demonstrate their causal role on behavior, entrainment approaches in particular aim at driving endogenous oscillations via rhythmic stimulation. Within this context, transcranial electrical stimulation, especially transcranial alternating current stimulation (tACS), has received renewed attention. This is likely due to the possibility of defining oscillatory stimulation properties precisely. Also, measurements comparing pre-tACS with post-tACS electroencephalography (EEG) have shown impressive modulations. However, the period during tACS has remained a blackbox until now, due to the enormous stimulation artifact. By means of application of beamforming to magnetoencephalography (MEG) data, we successfully recovered modulations of the amplitude of brain oscillations during weak and strong tACS. Additionally, we demonstrate that also evoked responses to visual and auditory stimuli can be recovered during tACS. The main contribution of the present study is to provide critical evidence that during ongoing tACS, subtle modulations of oscillatory brain activity can be reconstructed even at the stimulation frequency. Future tACS experiments will be able to deliver direct physiological insights in order to further the understanding of the contribution of brain oscillations to cognition and behavior.

NeuroImage

Neuling, T; Ruhnau, P; Fuscà, M; Demarchi, G; Herrmann, CS; Weisz, N

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The neurophysiology of language: Insights from non-invasive brain stimulation in the healthy human brain.

2015 Sep

With the advent of non-invasive brain stimulation (NIBS), a new decade in the study of language has started. NIBS allows for testing the functional relevance of language-related brain activation and enables the researcher to investigate how neural activation changes in response to focal perturbations. This review focuses on the application of NIBS in the healthy brain. First, some basic mechanisms will be introduced and the prerequisites for carrying out NIBS studies of language are addressed. The next section outlines how NIBS can be used to characterize the contribution of the stimulated area to a task. In this context, novel approaches such as multifocal transcranial magnetic stimulation and the condition-and-perturb approach are discussed. The third part addresses the combination of NIBS and neuroimaging in the study of plasticity. These approaches are particularly suited to investigate short-term reorganization in the healthy brain and may inform models of language recovery in post-stroke aphasia.

Brain and language

Hartwigsen, G

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Acute seizure suppression by transcranial direct current stimulation in rats.

2015 Aug

Cathodal transcranial direct current stimulation (tDCS) is a focal neuromodulation technique that suppresses cortical excitability by low-amplitude constant electrical current, and may have an antiepileptic effect. Yet, tDCS has not been tested in status epilepticus (SE). Furthermore, a combined tDCS and pharmacotherapy antiseizure approach is unexplored. We therefore examined in the rat pentylenetetrazol (PTZ) SE model whether cathodal tDCS (1) suppresses seizures, (2) augments lorazepam (LZP) efficacy, and (3) enhances GABAergic cortical inhibition.Experiment 1 aimed to identify an effective cathodal tDCS intensity. Rats received intraperitoneal PTZ followed by tDCS (sham, cathodal 1 mA, or cathodal 0.1 mA; for 20 min), and then a second PTZ challenge. In Experiment 2, two additional animal groups received a subtherapeutic LZP dose after PTZ, and then verum or sham tDCS. Clinical and electroencephalography (EEG) epileptic activity were compared between all groups. In Experiment 3, we measured GABA-mediated paired-pulse inhibition of the motor evoked potential by paired-pulse transcranial magnetic stimulation (ppTMS) in rats that received PTZ or saline, and either verum or sham tDCS.Cathodal 1 mA tDCS (1) reduced EEG spike bursts, and suppressed clinical seizures after the second PTZ challenge, (2) in combination with LZP was more effective in seizure suppression and improved the clinical seizure outcomes compared to either tDCS or LZP alone, and (3) prevented the loss of ppTMS motor cortex inhibition that accompanied PTZ injection.These results suggest that cathodal 1 mA tDCS alone and in combination with LZP can suppress seizures by augmenting GABAergic cortical inhibition.

Annals of clinical and translational neurology

Dhamne, SC; Ekstein, D; Zhuo, Z; Gersner, R; Zurakowski, D; Loddenkemper, T; Pascual-Leone, A; Jensen, FE; Rotenberg, A

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Effects of Fronto-Temporal Transcranial Direct Current Stimulation on Auditory Verbal Hallucinations and Resting-State Functional Connectivity of the Left Temporo-Parietal Junction in Patients With Schizophrenia.

2015 Aug

Auditory verbal hallucinations (AVH) in patients with schizophrenia are associated with abnormal hyperactivity in the left temporo-parietal junction (TPJ) and abnormal connectivity between frontal and temporal areas. Recent findings suggest that fronto-temporal transcranial Direct Current stimulation (tDCS) with the cathode placed over the left TPJ and the anode over the left prefrontal cortex can alleviate treatment-resistant AVH in patients with schizophrenia. However, brain correlates of the AVH reduction are unclear. Here, we investigated the effect of tDCS on the resting-state functional connectivity (rs-FC) of the left TPJ. Twenty-three patients with schizophrenia and treatment-resistant AVH were randomly allocated to receive 10 sessions of active (2 mA, 20min) or sham tDCS (2 sessions/d for 5 d). We compared the rs-FC of the left TPJ between patients before and after they received active or sham tDCS. Relative to sham tDCS, active tDCS significantly reduced AVH as well as the negative symptoms. Active tDCS also reduced rs-FC of the left TPJ with the left anterior insula and the right inferior frontal gyrus and increased rs-FC of the left TPJ with the left angular gyrus, the left dorsolateral prefrontal cortex and the precuneus. The reduction of AVH severity was correlated with the reduction of the rs-FC between the left TPJ and the left anterior insula. These findings suggest that the reduction of AVH induced by tDCS is associated with a modulation of the rs-FC within an AVH-related brain network, including brain areas involved in inner speech production and monitoring.

Schizophrenia bulletin

Mondino, M; Jardri, R; Suaud-Chagny, MF; Saoud, M; Poulet, E; Brunelin, J

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Non-linear effects of transcranial direct current stimulation as a function of individual baseline performance: Evidence from biparietal tDCS influence on lateralized attention bias.

2015 Aug

Transcranial direct current stimulation (tDCS) is a well-established technique for non-invasive brain stimulation (NIBS). However, the technique suffers from a high variability in outcome, some of which is likely explained by the state of the brain at tDCS-delivery but for which explanatory, mechanistic models are lacking. Here, we tested the effects of bi-parietal tDCS on perceptual line bisection as a function of tDCS current strength (1 mA vs 2 mA) and individual baseline discrimination sensitivity (a measure associated with intrinsic uncertainty/signal-to-noise balance). Our main findings were threefold. We replicated a previous finding (Giglia et al., 2011) of a rightward shift in subjective midpoint after Left anode/Right cathode tDCS over parietal cortex (sham-controlled). We found this effect to be weak over our entire sample (n = 38), but to be substantial in a subset of participants when they were split according to tDCS-intensity and baseline performance. This was due to a complex, nonlinear interaction between these two factors. Our data lend further support to the notion of state-dependency in NIBS which suggests outcome to depend on the endogenous balance between task-informative 'signal' and task-uninformative 'noise' at baseline. The results highlight the strong influence of individual differences and variations in experimental parameters on tDCS outcome, and the importance of fostering knowledge on the factors influencing tDCS outcome across cognitive domains.

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

Benwell, CS; Learmonth, G; Miniussi, C; Harvey, M; Thut, G

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Treatment of Primary Progressive Aphasia.

2015 Aug

Primary progressive aphasia (PPA) is a neurodegenerative disease that primarily affects language functions and often begins in the fifth or sixth decade of life. The devastating effects on work and home life call for the investigation of treatment alternatives. In this paper, we present a review of the literature on treatment approaches for this neurodegenerative disease. We also present new data from two intervention studies we have conducted, a behavioral one and a neuromodulatory one using transcranial direct current stimulation (tDCS) combined with written production intervention. We show that speech-language intervention improves language outcomes in individuals with PPA, and especially in the short term, tDCS augments generalization and maintenance of positive language outcomes. We also outline current issues and challenges in intervention approaches in PPA.

Current treatment options in neurology

Tippett, DC; Hillis, AE; Tsapkini, K

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The implications of state-dependent tDCS effects in aging: Behavioural response is determined by baseline performance.

2015 Jul

Young adults typically display a processing advantage towards the left side of space ("pseudoneglect"), possibly as a result of right parietal dominance for spatial attention. This bias is ameliorated with age, with older adults displaying either no strongly lateralised bias, or a slight bias towards the right. This may represent an age-related reduction of right hemispheric dominance and/or increased left hemispheric involvement. Here, we applied anodal transcranial direct current stimulation (atDCS) to the right posterior parietal cortex (PPC; R-atDCS), the left PPC (L-atDCS) and a Sham protocol in young and older adults during a titrated lateralised visual detection task. We aimed to facilitate visual detection sensitivity in the contralateral visual field with both R-atDCS and L-atDCS relative to Sham. We found no differences in the effects of stimulation between young and older adults. Instead the effects of atDCS were state-dependent (i.e. related to task performance at baseline). Relative to Sham, poor task performers were impaired in both visual fields by anodal stimulation of the left posterior parietal cortex (PPC). Conversely, good performers maintained sensitivity in both visual fields in response to R-atDCS, although this effect was small. We highlight the importance of considering baseline task ability when designing tDCS experiments, particularly in older adults.

Neuropsychologia

Learmonth, G; Thut, G; Benwell, CS; Harvey, M

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Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation.

2015 Jul

The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation-participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation.

Social cognitive and affective neuroscience

Hogeveen, J; Obhi, SS; Banissy, MJ; Santiesteban, I; Press, C; Catmur, C; Bird, G

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Blunted brain energy consumption relates to insula atrophy and impaired glucose tolerance in obesity.

2015 Jun

Brain energy consumption induced by electrical stimulation increases systemic glucose tolerance in normal-weight men. In obesity, fundamental reductions in brain energy levels, gray matter density, and cortical metabolism, as well as chronically impaired glucose tolerance, suggest that disturbed neuroenergetic regulation may be involved in the development of overweight and obesity. Here, we induced neuronal excitation by anodal transcranial direct current stimulation versus sham, examined cerebral energy consumption with (31)P magnetic resonance spectroscopy, and determined systemic glucose uptake by euglycemic-hyperinsulinemic glucose clamp in 15 normal-weight and 15 obese participants. We demonstrate blunted brain energy consumption and impaired systemic glucose uptake in obese compared with normal-weight volunteers, indicating neuroenergetic dysregulation in obese humans. Broadening our understanding of reduced multifocal gray matter volumes in obesity, our findings show that reduced appetite- and taste-processing area morphometry is associated with decreased brain energy levels. Specifically, gray matter volumes of the insula relate to brain energy content in obese participants. Overall, our results imply that a diminished cerebral energy supply may underlie the decline in brain areas assigned to food intake regulation and therefore the development of obesity.

Diabetes

Jauch-Chara, K; Binkofski, F; Loebig, M; Reetz, K; Jahn, G; Melchert, UH; Schweiger, U; Oltmanns, KM

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Rethinking stimulation of the brain in stroke rehabilitation: why higher motor areas might be better alternatives for patients with greater impairments.

2015 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

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Modulating conscious movement intention by noninvasive brain stimulation and the underlying neural mechanisms.

2015 May

Conscious intention is a fundamental aspect of the human experience. Despite long-standing interest in the basis and implications of intention, its underlying neurobiological mechanisms remain poorly understood. Using high-definition transcranial DC stimulation (tDCS), we observed that enhancing spontaneous neuronal excitability in both the angular gyrus and the primary motor cortex caused the reported time of conscious movement intention to be ∼60-70 ms earlier. Slow brain waves recorded ∼2-3 s before movement onset, as well as hundreds of milliseconds after movement onset, independently correlated with the modulation of conscious intention by brain stimulation. These brain activities together accounted for 81% of interindividual variability in the modulation of movement intention by brain stimulation. A computational model using coupled leaky integrator units with biophysically plausible assumptions about the effect of tDCS captured the effects of stimulation on both neural activity and behavior. These results reveal a temporally extended brain process underlying conscious movement intention that spans seconds around movement commencement.

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

Douglas, ZH; Maniscalco, B; Hallett, M; Wassermann, EM; He, BJ

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The impact of transcranial direct current stimulation on inhibitory control in young adults.

2015 May

There is increasing evidence that the dorso-lateral prefrontal cortex (DLPFC), a brain region related to reward and motivational processes, is involved in effective response inhibition and that decreased activity in this region coincides with reduced inhibitory capacity. Using transcranial direct current stimulation (tDCS) to manipulate cortical activation, this study examined whether cross-hemispheric tDCS over the DLPFC affected performance on an inhibitory control task.Neurologically intact participants performed a modified Stroop color-word matching task before and after completing one of two tDCS conditions; (1) anodal stimulation over the left DLPFC or (2) sham tDCS.There was a statistically significant effect of tDCS condition on Stroop reaction time (RT) pre-post tDCS change scores. Participants who received anodal stimulation over the left DLPFC demonstrated statistically significant faster RT change scores on the Stroop items compared to participants in the sham condition. Although errors on Stroop incongruent items decreased before and after receiving the tDCS treatment, there were no significant differences in errors on Stroop items between the anodal stimulation over left DLPFC and sham tDCS conditions. Anodal tDCS, which is known to elevate neural excitation, may have enhanced activation levels in the left DLPFC and minimized impairment of inhibitory control, resulting in better task performance.Current findings provide preliminary evidence that increased excitation of the left DLPFC improves inhibitory control and are a step toward understanding the potential of tDCS for moderating deficits in inhibitory control.

Brain and behavior

Loftus, AM; Yalcin, O; Baughman, FD; Vanman, EJ; Hagger, MS

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Transcranial direct current stimulation to lateral prefrontal cortex could increase meta-awareness of mind wandering.

2015 May

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

Fox, KC; Christoff, K

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Effect of mirror therapy with tDCS on functional recovery of the upper extremity of stroke patients.

2015 Apr

[Purpose] This study aimed to determine the effect of mirror therapy (MT) with transcranial direct current stimulation (tDCS) on the recovery of the upper extremity function of chronic stroke patients. [Subjects] Twenty-seven patients at least 6 months after stroke onset were divided randomly into an experimental group (14 patients) and a control group (13 patients). [Methods] All subjects received tDCS for 20 min followed by a 5 min rest. Then the experimental group received MT while the control group conducted the same exercises as the experimental group using a mirror that did not show the non-paretic upper extremity. The groups performed the same exercises for 20 min. All subjects received this intervention for 45-min three times a week for 6 weeks. [Results] After the intervention, the experimental group showed significant improvements in the box and block test (BBT), grip strength, and the Fugl-Meyer assessment (FMA), and a significant decrease in the Jebsen-Taylor test. The control group showed a significant increase in grip strength after the intervention, and a significant decrease in the Jebsen-Taylor test. Comparison of the result after the intervention revealed that the experimental group showed more significant increases in the BBT and grip strength than the control group. [Conclusion] These results show that MT with tDCS has a positive effect on the functional recovery of the upper extremity of stroke patients, through activating motor regions in the brain, and thus plays an important role in recovery of neuroplasticity.

Journal of physical therapy science

Cho, HS; Cha, HG

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The role of the posterior cerebellum in saccadic adaptation: a transcranial direct current stimulation study.

2015 Apr

The posterior vermis of the cerebellum is considered to be critically involved in saccadic adaptation. However, recent evidence suggests that the adaptive decrease (backward adaptation) and the adaptive increase (forward adaptation) of saccade amplitude rely on partially separate neural substrates. We investigated whether the posterior cerebellum could be differentially involved in backward and forward adaptation by using transcranial direct current stimulation (TDCS). To do so, participants' saccades were adapted backward or forward while they received anodal, cathodal, or sham TDCS. In two extra groups, subjects underwent a nonadaptation session while receiving anodal or cathodal TDCS to control for the direct effects of TDCS on saccadic execution. Surprisingly, cathodal stimulation tended to increase the extent of both forward and backward adaptations, while anodal TDCS strongly impaired forward adaptation and, to a smaller extent, backward adaptation. Forward adaptation was accompanied by a greater increase in velocity with cathodal stimulation, and reduced duration of change for anodal stimulation. In contrast, the expected velocity decrease in backward adaptation was noticeably weaker with anodal stimulation. Stimulation applied during nonadaptation sessions did not affect saccadic gain, velocity, or duration, demonstrating that the reported effects are not due to direct effects of the stimulation on the generation of eye movements. Our results demonstrate that cerebellar excitability is critical for saccadic adaptation. Based on our results and the growing evidence from studies of vestibulo-ocular reflex and saccadic adaptation, we conclude that the plasticity at the level of the oculomotor vermis is more fundamentally important for forward adaptation than for backward adaptation.

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

Panouillères, MT; Miall, RC; Jenkinson, N

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Emerging treatments for motor rehabilitation after stroke.

2015 Apr

Although numerous treatments are available to improve cerebral perfusion after acute stroke and prevent recurrent stroke, few rehabilitation treatments have been conclusively shown to improve neurologic recovery. The majority of stroke survivors with motor impairment do not recover to their functional baseline, and there remains a need for novel neurorehabilitation treatments to minimize long-term disability, maximize quality of life, and optimize psychosocial outcomes. In recent years, several novel therapies have emerged to restore motor function after stroke, and additional investigational treatments have also shown promise. Here, we familiarize the neurohospitalist with emerging treatments for poststroke motor rehabilitation. The rehabilitation treatments covered in this review will include selective serotonin reuptake inhibitor medications, constraint-induced movement therapy, noninvasive brain stimulation, mirror therapy, and motor imagery or mental practice.

The Neurohospitalist

Claflin, ES; Krishnan, C; Khot, SP

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Brain-computer interface training combined with transcranial direct current stimulation in patients with chronic severe hemiparesis: Proof of concept study.

2015 Apr

Brain-computer interface technology has been applied to stroke patients to improve their motor function. Event-related desynchronization during motor imagery, which is used as a brain-computer interface trigger, is sometimes difficult to detect in stroke patients. Anodal transcranial direct current stimulation (tDCS) is known to increase event-related desynchronization. This study investigated the adjunctive effect of anodal tDCS for brain-computer interface training in patients with severe hemiparesis.Eighteen patients with chronic stroke.A non-randomized controlled study.Subjects were divided between a brain-computer interface group and a tDCS- brain-computer interface group and participated in a 10-day brain-computer interface training. Event-related desynchronization was detected in the affected hemisphere during motor imagery of the affected fingers. The tDCS-brain-computer interface group received anodal tDCS before brain-computer interface training. Event-related desynchronization was evaluated before and after the intervention. The Fugl-Meyer Assessment upper extremity motor score (FM-U) was assessed before, immediately after, and 3 months after, the intervention.Event-related desynchronization was significantly increased in the tDCS- brain-computer interface group. The FM-U was significantly increased in both groups. The FM-U improvement was maintained at 3 months in the tDCS-brain-computer interface group.Anodal tDCS can be a conditioning tool for brain-computer interface training in patients with severe hemiparetic stroke.

Journal of rehabilitation medicine

Kasashima-Shindo, Y; Fujiwara, T; Ushiba, J; Matsushika, Y; Kamatani, D; Oto, M; Ono, T; Nishimoto, A; Shindo, K; Kawakami, M; Tsuji, T; Liu, M

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Effects of a single session of transcranial direct current stimulation on static balance in a patient with hemiparesis: a case study.

2015 Mar

[Purpose] Cerebrovascular accident (stroke) is characterized by an abrupt onset of focal or global neurological signs and symptoms. Asymmetry of the limbs is common following a stroke due to hemiplegia or hemiparesis. [Subject and Methods] A male patient having suffered an ischemic stroke was initially evaluated using the Timed Up-and-Go Test and the Six-Minute Walk Test. Static balance was evaluated using a force plate (Kistler model 9286BA) for the stabilometry analysis of center of pressure (COP) sway. The data were interpreted using the SWAY software program (BTS Engineering) synchronized with the SMART-D 140(®) system. Anodal transcranial direct current stimulation (tDCS; 2 mA) was applied over the primary motor cortex for 20 minutes during gait training on a treadmill. [Results] Under the condition of eyes open, reductions were found in anteroposterior sway (6.18%), trace length (3.3%) and sway velocity (3.3%) immediately following tDCS. [Conclusion] A single session of anodal tDCS combined with treadmill training had a positive effect on the static balance of a subject with chronic hemiparesis stemming from a stroke.

Journal of physical therapy science

Dumont, AJ; Araujo, MC; Lazzari, RD; Santos, CA; Carvalho, DB; Franco de Moura, RC; Ferreira, LA; Galli, M; Oliveira, CS

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Effect of a single session of transcranial direct-current stimulation combined with virtual reality training on the balance of children with cerebral palsy: a randomized, controlled, double-blind trial.

2015 Mar

[Purpose] The aim of the present study was to investigate the effects of a single session of transcranial direct current stimulation combined with virtual reality training on the balance of children with cerebral palsy. [Subjetcs and Methods] Children with cerebral palsy between four and 12 years of age were randomly allocated to two groups: an experimental group which performed a single session of mobility training with virtual reality combined with active transcranial direct current stimulation; and a control group which performed a single session of mobility training with virtual reality combined with placebo transcranial direct current stimulation. The children were evaluated before and after the training protocols. Static balance (sway area, displacement, velocity and frequency of oscillations of the center of pressure on the anteroposterior and mediolateral axes) was evaluated using a force plate under four conditions (30-second measurements for each condition): feet on the force plate with the eyes open, and with the eyes closed; feet on a foam mat with the eyes open, and with the eyes closed. [Results] An increase in sway velocity was the only significant difference found. [Conclusion] A single session of anodal transcranial direct current stimulation combined with mobility training elicited to lead to an increase in the body sway velocity of children with cerebral palsy.

Journal of physical therapy science

Lazzari, RD; Politti, F; Santos, CA; Dumont, AJ; Rezende, FL; Grecco, LA; Braun Ferreira, LA; Oliveira, CS

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Effect of application of transcranial direct current stimulation during task-related training on gait ability of patients with stroke.

2015 Mar

[Purpose] The objective of this study was to determine the effect of transcranial direct current stimulation (tDCS) during task-related training (TRT) on the gait ability of patients with chronic stroke. [Subjects and Methods] The participants were 24 patients who were diagnosed with hemiplegia due to stroke. Three groups were created: subjects who performed TRT for general exercise therapy (TRT), subjects who received sham tDCS during TRT for general exercise therapy (TST), and subjects who received tDCS during TRT for general exercise therapy (TT). [Results] The stance phase symmetry profile, the swing phase symmetry profile, and gait velocity all decreased significantly in the TT group compared with the TRT group. However, there was no significant difference in the step length symmetry profile among the groups. [Conclusion] A application of tDCS, that affects the excitatory regulation in the cortical motor area, is an effective rehabilitation method for gait improvement.

Journal of physical therapy science

Park, SD; Kim, JY; Song, HS

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Is effect of transcranial direct current stimulation on visuomotor coordination dependent on task difficulty?

2015 Mar

Transcranial direct current stimulation (tDCS), an emerging technique for non-invasive brain stimulation, is increasingly used to induce changes in cortical excitability and modulate motor behavior, especially for upper limbs. The purpose of this study was to investigate the effects of tDCS of the primary motor cortex on visuomotor coordination based on three levels of task difficulty in healthy subjects. Thirty-eight healthy participants underwent real tDCS or sham tDCS. Using a single-blind, sham-controlled crossover design, tDCS was applied to the primary motor cortex. For real tDCS conditions, tDCS intensity was 1 mA while stimulation was applied for 15 minutes. For the sham tDCS, electrodes were placed in the same position, but the stimulator was turned off after 5 seconds. Visuomotor tracking task, consisting of three levels (levels 1, 2, 3) of difficulty with higher level indicating greater difficulty, was performed before and after tDCS application. At level 2, real tDCS of the primary motor cortex improved the accurate index compared to the sham tDCS. However, at levels 1 and 3, the accurate index was not significantly increased after real tDCS compared to the sham tDCS. These findings suggest that tasks of moderate difficulty may improve visuomotor coordination in healthy subjects when tDCS is applied compared with easier or more difficult tasks.

Neural regeneration research

Kwon, YH; Kang, KW; Son, SM; Lee, NK

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Transcranial direct current stimulation in psychiatric disorders.

2015 Mar

The interest in non-invasive brain stimulation techniques is increasing in recent years. Among these techniques, transcranial direct current stimulation (tDCS) has been the subject of great interest among researchers because of its easiness to use, low cost, benign profile of side effects and encouraging results of research in the field. This interest has generated several studies and randomized clinical trials, particularly in psychiatry. In this review, we provide a summary of the development of the technique and its mechanism of action as well as a review of the methodological aspects of randomized clinical trials in psychiatry, including studies in affective disorders, schizophrenia, obsessive compulsive disorder, child psychiatry and substance use disorder. Finally, we provide an overview of tDCS use in cognitive enhancement as well as a discussion regarding its clinical use and regulatory and ethical issues. Although many promising results regarding tDCS efficacy were described, the total number of studies is still low, highlighting the need of further studies aiming to replicate these findings in larger samples as to provide a definite picture regarding tDCS efficacy in psychiatry.

World journal of psychiatry

Tortella, G; Casati, R; Aparicio, LV; Mantovani, A; Senço, N; D'Urso, G; Brunelin, J; Guarienti, F; Selingardi, PM; Muszkat, D; Junior, Bde S; Valiengo, L; Moffa, AH; Simis, M; Borrione, L; Brunoni, AR

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Stimulating minds to wander.

2015 Mar

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

Broadway, JM; Zedelius, CM; Mooneyham, BW; Mrazek, MD; Schooler, JW

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Increasing propensity to mind-wander with transcranial direct current stimulation.

2015 Mar

Humans mind-wander quite intensely. Mind wandering is markedly different from other cognitive behaviors because it is spontaneous, self-generated, and inwardly directed (inner thoughts). However, can such an internal and intimate mental function also be modulated externally by means of brain stimulation? Addressing this question could also help identify the neural correlates of mind wandering in a causal manner, in contrast to the correlational methods used previously (primarily functional MRI). In our study, participants performed a monotonous task while we periodically sampled their thoughts to assess mind wandering. Concurrently, we applied transcranial direct current stimulation (tDCS). We found that stimulation of the frontal lobes [anode electrode at the left dorsolateral prefrontal cortex (DLPFC), cathode electrode at the right supraorbital area], but not of the occipital cortex or sham stimulation, increased the propensity to mind-wander. These results demonstrate for the first time, to our knowledge, that mind wandering can be enhanced externally using brain stimulation, and that the frontal lobes play a causal role in mind-wandering behavior. These results also suggest that the executive control network associated with the DLPFC might be an integral part of mind-wandering neural machinery.

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

Axelrod, V; Rees, G; Lavidor, M; Bar, M

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The morphological and molecular changes of brain cells exposed to direct current electric field stimulation.

2015 Mar

The application of low-intensity direct current electric fields has been experimentally used in the clinic to treat a number of brain disorders, predominantly using transcranial direct current stimulation approaches. However, the cellular and molecular changes induced by such treatment remain largely unknown.Here, we tested various intensities of direct current electric fields (0, 25, 50, and 100V/m) in a well-controlled in vitro environment in order to investigate the responses of neurons, microglia, and astrocytes to this type of stimulation. This included morphological assessments of the cells, viability, as well as shape and fiber outgrowth relative to the orientation of the direct current electric field. We also undertook enzyme-linked immunosorbent assays and western immunoblotting to identify which molecular pathways were affected by direct current electric fields.In response to direct current electric field, neurons developed an elongated cell body shape with neurite outgrowth that was associated with a significant increase in growth associated protein-43. Fetal midbrain dopaminergic explants grown in a collagen gel matrix also showed a reorientation of their neurites towards the cathode. BV2 microglial cells adopted distinct morphological changes with an increase in cyclooxygenase-2 expression, but these were dependent on whether they had already been activated with lipopolysaccharide. Finally, astrocytes displayed elongated cell bodies with cellular filopodia that were oriented perpendicularly to the direct current electric field.We show that cells of the central nervous system can respond to direct current electric fields both in terms of their morphological shape and molecular expression of certain proteins, and this in turn can help us to begin understand the mechanisms underlying the clinical benefits of direct current electric field.

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

Pelletier, SJ; Lagacé, M; St-Amour, I; Arsenault, D; Cisbani, G; Chabrat, A; Fecteau, S; Lévesque, M; Cicchetti, F

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Safety and feasibility of transcranial direct current stimulation in pediatric hemiparesis: randomized controlled preliminary study.

2015 Mar

Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation that has shown improved adult stroke outcomes. Applying tDCS in children with congenital hemiparesis has not yet been explored.The primary objective of this study was to explore the safety and feasibility of single-session tDCS through an adverse events profile and symptom assessment within a double-blind, randomized placebo-controlled preliminary study in children with congenital hemiparesis. A secondary objective was to assess the stability of hand and cognitive function.A double-blind, randomized placebo-controlled pretest/posttest/follow-up study was conducted.The study was conducted in a university pediatric research laboratory.Thirteen children, ages 7 to 18 years, with congenital hemiparesis participated.Adverse events/safety assessment and hand function were measured.Participants were randomly assigned to either an intervention group or a control group, with safety and functional assessments at pretest, at posttest on the same day, and at a 1-week follow-up session. An intervention of 10 minutes of 0.7 mA tDCS was applied to bilateral primary motor cortices. The tDCS intervention was considered safe if there was no individual decline of 25% or group decline of 2 standard deviations for motor evoked potentials (MEPs) and behavioral data and no report of adverse events.No major adverse events were found, including no seizures. Two participants did not complete the study due to lack of MEP and discomfort. For the 11 participants who completed the study, group differences in MEPs and behavioral data did not exceed 2 standard deviations in those who received the tDCS (n=5) and those in the control group (n=6). The study was completed without the need for stopping per medical monitor and biostatisticial analysis.A limitation of the study was the small sample size, with data available for 11 participants.Based on the results of this study, tDCS appears to be safe, feasible, and well tolerated in most children with hemiparesis. Future investigations of serial sessions of tDCS in conjunction with rehabilitation in pediatric hemiparesis are indicated to explore the benefit of a synergistic approach to improving hand function.

Physical therapy

Gillick, BT; Feyma, T; Menk, J; Usset, M; Vaith, A; Wood, TJ; Worthington, R; Krach, LE

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Selective increase of intention-based economic decisions by noninvasive brain stimulation to the dorsolateral prefrontal cortex.

2015 Feb

The intention behind another's action and the impact of the outcome are major determinants of human economic behavior. It is poorly understood, however, whether the two systems share a core neural computation. Here, we investigated whether the two systems are causally dissociable in the brain by integrating computational modeling, functional magnetic resonance imaging, and transcranial direct current stimulation experiments in a newly developed trust game task. We show not only that right dorsolateral prefrontal cortex (DLPFC) activity is correlated with intention-based economic decisions and that ventral striatum and amygdala activity are correlated with outcome-based decisions, but also that stimulation to the DLPFC selectively enhances intention-based decisions. These findings suggest that the right DLPFC is involved in the implementation of intention-based decisions in the processing of cooperative decisions. This causal dissociation of cortical and subcortical backgrounds may indicate evolutionary and developmental differences in the two decision systems.

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

Nihonsugi, T; Ihara, A; Haruno, M

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Cerebellar direct current stimulation enhances on-line motor skill acquisition through an effect on accuracy.

2015 Feb

The cerebellum is involved in the update of motor commands during error-dependent learning. Transcranial direct current stimulation (tDCS), a form of noninvasive brain stimulation, has been shown to increase cerebellar excitability and improve learning in motor adaptation tasks. Although cerebellar involvement has been clearly demonstrated in adaptation paradigms, a type of task that heavily relies on error-dependent motor learning mechanisms, its role during motor skill learning, a behavior that likely involves error-dependent as well as reinforcement and strategic mechanisms, is not completely understood. Here, in humans, we delivered cerebellar tDCS to modulate its activity during novel motor skill training over the course of 3 d and assessed gains during training (on-line effects), between days (off-line effects), and overall improvement. We found that excitatory anodal tDCS applied over the cerebellum increased skill learning relative to sham and cathodal tDCS specifically by increasing on-line rather than off-line learning. Moreover, the larger skill improvement in the anodal group was predominantly mediated by reductions in error rate rather than changes in movement time. These results have important implications for using cerebellar tDCS as an intervention to speed up motor skill acquisition and to improve motor skill accuracy, as well as to further our understanding of cerebellar function.

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

Cantarero, G; Spampinato, D; Reis, J; Ajagbe, L; Thompson, T; Kulkarni, K; Celnik, P

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Controlling your impulses: electrical stimulation of the human supplementary motor complex prevents impulsive errors.

2015 Feb

To err is human. However, an inappropriate urge does not always result in error. Impulsive errors thus entail both a motor system capture by an urge to act and a failed inhibition of that impulse. Here we show that neuromodulatory electrical stimulation of the supplementary motor complex in healthy humans leaves action urges unchanged but prevents them from turning into overt errors. Subjects performed a choice reaction-time task known to trigger impulsive responses, leading to fast errors that can be revealed by analyzing accuracy as a function of poststimulus time. Yet, such fast errors are only the tip of the iceberg: electromyography (EMG) revealed fast subthreshold muscle activation in the incorrect response hand in an even larger proportion of overtly correct trials, revealing covert response impulses not discernible in overt behavior. Analyzing both overt and covert response tendencies enables to gauge the ability to prevent these incorrect impulses from turning into overt action errors. Hyperpolarizing the supplementary motor complex using transcranial direct current stimulation (tDCS) preserves action impulses but prevents their behavioral expression. This new combination of detailed behavioral, EMG, and tDCS techniques clarifies the neurophysiology of impulse control, and may point to avenues for improving impulse control deficits in various neurologic and psychiatric disorders.

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

Spieser, L; van den Wildenberg, W; Hasbroucq, T; Ridderinkhof, KR; Burle, B

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Dual-hemisphere transcranial direct current stimulation over primary motor cortex enhances consolidation of a ballistic thumb movement.

2015 Feb

Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates motor performance and learning. Previous studies have shown that tDCS over the primary motor cortex (M1) can facilitate consolidation of various motor skills. However, the effect of tDCS on consolidation of newly learned ballistic movements remains unknown. The present study tested the hypothesis that tDCS over M1 enhances consolidation of ballistic thumb movements in healthy adults. Twenty-eight healthy subjects participated in an experiment with a single-blind, sham-controlled, between-group design. Fourteen subjects practiced a ballistic movement with their left thumb during dual-hemisphere tDCS. Subjects received 1mA anodal tDCS over the contralateral M1 and 1mA cathodal tDCS over the ipsilateral M1 for 25min during the training session. The remaining 14 subjects underwent identical training sessions, except that dual-hemisphere tDCS was applied for only the first 15s (sham group). All subjects performed the task again at 1h and 24h later. Primary measurements examined improvement in peak acceleration of the ballistic thumb movement at 1h and 24h after stimulation. Improved peak acceleration was significantly greater in the tDCS group (144.2±15.1%) than in the sham group (98.7±9.1%) (P<0.05) at 24h, but not 1h, after stimulation. Thus, dual-hemisphere tDCS over M1 enhanced consolidation of ballistic thumb movement in healthy adults. Dual-hemisphere tDCS over M1 may be useful to improve elemental motor behaviors, such as ballistic movements, in patients with subcortical strokes.

Neuroscience letters

Koyama, S; Tanaka, S; Tanabe, S; Sadato, N

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Excitatory and inhibitory brain metabolites as targets of motor cortex transcranial direct current stimulation therapy and predictors of its efficacy in fibromyalgia.

2015 Feb

Transcranial direct current stimulation (tDCS) has been shown to improve pain symptoms in fibromyalgia (FM), a central pain syndrome whose underlying mechanisms are not well understood. This study was undertaken to explore the neurochemical action of tDCS in the brain of patients with FM, using proton magnetic resonance spectroscopy (1H-MRS).Twelve patients with FM underwent sham tDCS over the left motor cortex (anode placement) and contralateral supraorbital cortex (cathode placement) for 5 consecutive days, followed by a 7-day washout period and then active tDCS for 5 consecutive days. Clinical pain assessment and 1H-MRS testing were performed at baseline, the week following the sham tDCS trial, and the week following the active tDCS trial.Clinical pain scores decreased significantly between the baseline and active tDCS time points (P = 0.04). Levels of glutamate + glutamine (Glx) in the anterior cingulate were significantly lower at the post–active tDCS assessment compared with the post–sham tDCS assessment (P = 0.013), and the decrease in Glx levels in the thalami between these time points approached significance (P = 0.056). From baseline to the post–sham tDCS assessment, levels of N-acetylaspartate (NAA) in the posterior insula increased significantly (P = 0.015). There was a trend toward increased levels of γ-aminobutyric acid (GABA) in the anterior insula after active tDCS, compared with baseline (P = 0.064). Baseline anterior cingulate Glx levels correlated significantly with changes in pain score, both for the time period from baseline to sham tDCS (β1 = 1.31, P < 0.001) and for the time period from baseline to active tDCS (β1= 1.87, P < 0.001).The present findings suggest that GABA, Glx, and NAA play an important role in the pathophysiology of FM and its modulation by tDCS.

Arthritis & rheumatology (Hoboken, N.J.)

Foerster, BR; Nascimento, TD; DeBoer, M; Bender, MA; Rice, IC; Truong, DQ; Bikson, M; Clauw, DJ; Zubieta, JK; Harris, RE; DaSilva, AF

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Cerebellar tDCS: how to do it.

2015 Feb

Cerebellar transcranial direct current stimulation (cerebellar tDCS) is a non-invasive technique for inducing prolonged functional changes in the human cerebellum. Available data show that this simple and safe technique can modulate several motor and non-motor cerebellar functions in healthy humans. Also, preliminary data suggest that cerebellar tDCS is a possible therapeutic option in patients with cerebellar disorders. To provide a reference for those approaching this technique for the first time in healthy humans and patients, we here briefly and practically review the methodology for cerebellar tDCS, discussing electrode types, positions, DC duration and intensity. Recent modelling studies confirm that the electric field generated with the methodology reviewed here reaches the cerebellum at a strength within the range of values for modulating activity in the cerebellar neurons experimentally assessed.

Cerebellum (London, England)

Ferrucci, R; Cortese, F; Priori, A

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Results availability for analgesic device, complex regional pain syndrome, and post-stroke pain trials: comparing the RReADS, RReACT, and RReMiT databases.

2015 Jan

Evidence-based medicine rests on the assumption that treatment recommendations are robust, free from bias, and include results of all randomized clinical trials. The Repository of Registered Analgesic Clinical Trials search and analysis methodology was applied to create databases of complex regional pain syndrome (CRPS) and central post-stroke pain (CPSP) trials and adapted to create the Repository of Registered Analgesic Device Studies databases for trials of spinal cord stimulation (SCS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). We identified 34 CRPS trials, 18 CPSP trials, 72 trials of SCS, and 92 trials of rTMS/tDCS. Irrespective of time since study completion, 45% of eligible CRPS and CPSP trials and 46% of eligible SCS and rTMS/tDCS trials had available results (peer-reviewed literature, results entered on registry, or gray literature); peer-reviewed publications could be found for 38% and 39%, respectively. Examining almost 1000 trials across a spectrum of painful disorders (fibromyalgia, diabetic painful neuropathy, post-herpetic neuralgia, migraine, CRPS, CPSP) and types of treatment, no single study characteristic consistently predicts unavailability of results. Results availability is higher 12 months after study completion but remains below 60% for peer-reviewed publications. Recommendations to increase results availability include supporting organizations advocating for transparency, enforcing existing results reporting regulations, enabling all primary registries to post results, stating trial registration numbers in all publication abstracts, and reducing barriers to publishing "negative" trials. For all diseases and treatment modalities, evidence-based medicine must rigorously adjust for the sheer magnitude of missing results in formulating treatment recommendations.

Pain

Dufka, FL; Munch, T; Dworkin, RH; Rowbotham, MC

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Enhancing long-term memory with stimulation tunes visual attention in one trial.

2015 Jan

Scientists have long proposed that memory representations control the mechanisms of attention that focus processing on the task-relevant objects in our visual field. Modern theories specifically propose that we rely on working memory to store the object representations that provide top-down control over attentional selection. Here, we show that the tuning of perceptual attention can be sharply accelerated after 20 min of noninvasive brain stimulation over medial-frontal cortex. Contrary to prevailing theories of attention, these improvements did not appear to be caused by changes in the nature of the working memory representations of the search targets. Instead, improvements in attentional tuning were accompanied by changes in an electrophysiological signal hypothesized to index long-term memory. We found that this pattern of effects was reliably observed when we stimulated medial-frontal cortex, but when we stimulated posterior parietal cortex, we found that stimulation directly affected the perceptual processing of the search array elements, not the memory representations providing top-down control. Our findings appear to challenge dominant theories of attention by demonstrating that changes in the storage of target representations in long-term memory may underlie rapid changes in the efficiency with which humans can find targets in arrays of objects.

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

Reinhart, RM; Woodman, GF

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Neural substrates underlying stimulation-enhanced motor skill learning after stroke.

2015 Jan

Motor skill learning is one of the key components of motor function recovery after stroke, especially recovery driven by neurorehabilitation. Transcranial direct current stimulation can enhance neurorehabilitation and motor skill learning in stroke patients. However, the neural mechanisms underlying the retention of stimulation-enhanced motor skill learning involving a paretic upper limb have not been resolved. These neural substrates were explored by means of functional magnetic resonance imaging. Nineteen chronic hemiparetic stroke patients participated in a double-blind, cross-over randomized, sham-controlled experiment with two series. Each series consisted of two sessions: (i) an intervention session during which dual transcranial direct current stimulation or sham was applied during motor skill learning with the paretic upper limb; and (ii) an imaging session 1 week later, during which the patients performed the learned motor skill. The motor skill learning task, called the 'circuit game', involves a speed/accuracy trade-off and consists of moving a pointer controlled by a computer mouse along a complex circuit as quickly and accurately as possible. Relative to the sham series, dual transcranial direct current stimulation applied bilaterally over the primary motor cortex during motor skill learning with the paretic upper limb resulted in (i) enhanced online motor skill learning; (ii) enhanced 1-week retention; and (iii) superior transfer of performance improvement to an untrained task. The 1-week retention's enhancement driven by the intervention was associated with a trend towards normalization of the brain activation pattern during performance of the learned motor skill relative to the sham series. A similar trend towards normalization relative to sham was observed during performance of a simple, untrained task without a speed/accuracy constraint, despite a lack of behavioural difference between the dual transcranial direct current stimulation and sham series. Finally, dual transcranial direct current stimulation applied during the first session enhanced continued learning with the paretic limb 1 week later, relative to the sham series. This lasting behavioural enhancement was associated with more efficient recruitment of the motor skill learning network, that is, focused activation on the motor-premotor areas in the damaged hemisphere, especially on the dorsal premotor cortex. Dual transcranial direct current stimulation applied during motor skill learning with a paretic upper limb resulted in prolonged shaping of brain activation, which supported behavioural enhancements in stroke patients.

Brain : a journal of neurology

Lefebvre, S; Dricot, L; Laloux, P; Gradkowski, W; Desfontaines, P; Evrard, F; Peeters, A; Jamart, J; Vandermeeren, Y

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The strategy and motivational influences on the beneficial effect of neurostimulation: a tDCS and fNIRS study.

2015 Jan

Working memory (WM) capacity falls along a spectrum with some people demonstrating higher and others lower WM capacity. Efforts to improve WM include applying transcranial direct current stimulation (tDCS), in which small amounts of current modulate the activity of underlying neurons and enhance cognitive function. However, not everyone benefits equally from a given tDCS protocol. Recent findings revealed tDCS-related WM benefits for individuals with higher working memory (WM) capacity. Here, we test two hypotheses regarding those with low WM capacity to see if they too would benefit under more optimal conditions. We tested whether supplying a WM strategy (Experiment 1) or providing greater extrinsic motivation through incentives (Experiment 2) would restore tDCS benefit to the low WM capacity group. We also employed functional near infrared spectroscopy to monitor tDCS-induced changes in neural activity. Experiment 1 demonstrated that supplying a WM strategy improved the high WM capacity participants' accuracy and the amount of oxygenated blood levels following anodal tDCS, but it did not restore tDCS-linked WM benefits to the low WM capacity group. Experiment 2 demonstrated that financial motivation enhanced performance in both low and high WM capacity groups, especially after anodal tDCS. Here, only the low WM capacity participants showed a generalized increase in oxygenated blood flow across both low and high motivation conditions. These results indicate that ensuring that participants' incentives are high may expand cognitive benefits associated with tDCS. This finding is relevant for translational work using tDCS in clinical populations, in which motivation can be a concern.

NeuroImage

Jones, KT; Gözenman, F; Berryhill, ME

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Motor priming in neurorehabilitation.

2015 Jan

Priming is a type of implicit learning wherein a stimulus prompts a change in behavior. Priming has been long studied in the field of psychology. More recently, rehabilitation researchers have studied motor priming as a possible way to facilitate motor learning. For example, priming of the motor cortex is associated with changes in neuroplasticity that are associated with improvements in motor performance. Of the numerous motor priming paradigms under investigation, only a few are practical for the current clinical environment, and the optimal priming modalities for specific clinical presentations are not known. Accordingly, developing an understanding of the various types of motor priming paradigms and their underlying neural mechanisms is an important step for therapists in neurorehabilitation. Most importantly, an understanding of the methods and their underlying mechanisms is essential for optimizing rehabilitation outcomes. The future of neurorehabilitation is likely to include these priming methods, which are delivered prior to or in conjunction with primary neurorehabilitation therapies. In this Special Interest article, we discuss those priming paradigms that are supported by the greatest amount of evidence, including (i) stimulation-based priming, (ii) motor imagery and action observation, (iii) sensory priming, (iv) movement-based priming, and (v) pharmacological priming.Video Abstract available. (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A86) for more insights from the authors.

Journal of neurologic physical therapy : JNPT

Stoykov, ME; Madhavan, S

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Baseline effects of transcranial direct current stimulation on glutamatergic neurotransmission and large-scale network connectivity.

2015 Jan

Transcranial direct current stimulation (tDCS) modulates glutamatergic neurotransmission and can be utilized as a novel treatment intervention for a multitude of populations. However, the exact mechanism by which tDCS modulates the brain׳s neural architecture, from the micro to macro scales, have yet to be investigated. Using a within-subjects design, resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy ((1)H MRS) were performed immediately before and after the administration of anodal tDCS over right parietal cortex. Group independent component analysis (ICA) was used to decompose fMRI scans into 75 brain networks, from which 12 resting-state networks were identified that had significant voxel-wise functional connectivity to anatomical regions of interest. (1)H MRS was used to obtain estimates of combined glutamate and glutamine (Glx) concentrations from bilateral intraparietal sulcus. Paired sample t-tests showed significantly increased Glx under the anodal electrode, but not in homologous regions of the contralateral hemisphere. Increases of within-network connectivity were observed within the superior parietal, inferior parietal, left frontal-parietal, salience and cerebellar intrinsic networks, and decreases in connectivity were observed in the anterior cingulate and the basal ganglia (p<0.05, FDR-corrected). Individual differences in Glx concentrations predicted network connectivity in most of these networks. The observed relationships between glutamatergic neurotransmission and network connectivity may be used to guide future tDCS protocols that aim to target and alter neuroplastic mechanisms in healthy individuals as well as those with psychiatric and neurologic disorders.

Brain research

Hunter, MA; Coffman, BA; Gasparovic, C; Calhoun, VD; Trumbo, MC; Clark, VP

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Illness denial in schizophrenia spectrum disorders: a function of left hemisphere dominance.

2015 Jan

Impaired illness awareness or anosognosia is a common, but poorly understood feature of schizophrenia that contributes to medication nonadherence and poor treatment outcomes. Here we present a functional imaging study to measure brain activity at the moment of illness denial. To accomplish this, participants with schizophrenia (n = 18) with varying degrees of illness awareness were confronted with their illness beliefs while undergoing functional MRI. To link structure with function, we explored the relationships among impaired illness awareness and brain activity during the illness denial task with cortical thickness. Impaired illness awareness was associated with increased brain activity in the left temporoparieto-occipital junction (TPO) and left medial prefrontal cortex (mPFC) at the moment of illness denial. Brain activity in the left mPFC appeared to be a function of participants' degree of self-reflectiveness, while the activity in the left TPO was associated with cortical thinning in this region and more specific to illness denial. Participants with impaired illness awareness had slower response times to illness related stimuli than those with good illness awareness. Increased left hemisphere brain activity in association with illness denial is consistent with the literature in other neuropsychiatric conditions attributing anosognosia or impaired illness awareness to left hemisphere dominance. The TPO and mPFC may represent putative targets for noninvasive treatment interventions, such as transcranial magnetic or direct current stimulation.

Human brain mapping

Gerretsen, P; Menon, M; Chakravarty, MM; Lerch, JP; Mamo, DC; Remington, G; Pollock, BG; Graff-Guerrero, A

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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.

2015 Jan

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

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Emotional Distraction and Bodily Reaction: Modulation of Autonomous Responses by Anodal tDCS to the Prefrontal Cortex.

2015

Prefrontal electric stimulation has been demonstrated to effectively modulate cognitive processing. Specifically, the amelioration of cognitive control (CC) over emotional distraction by transcranial direct current stimulation (tDCS) points toward targeted therapeutic applications in various psychiatric disorders. In addition to behavioral measures, autonomous nervous system (ANS) responses are fundamental bodily signatures of emotional information processing. However, interactions between the modulation of CC by tDCS and ANS responses have received limited attention. We here report on ANS data gathered in healthy subjects that performed an emotional CC task parallel to the modulation of left prefrontal cortical activity by 1 mA anodal or sham tDCS. Skin conductance responses (SCRs) to negative and neutral pictures of human scenes were reduced by anodal as compared to sham tDCS. Individual SCR amplitude variations were associated with the amount of distraction. Moreover, the stimulation-driven performance- and SCR-modulations were related in form of a quadratic, inverse-U function. Thus, our results indicate that non-invasive brain stimulation (i.e., anodal tDCS) can modulate autonomous responses synchronous to behavioral improvements, but the range of possible concurrent improvements from prefrontal stimulation is limited. Interactions between cognitive, affective, neurophysiological, and vegetative responses to emotional content can shape brain stimulation effectiveness and require theory-driven integration in potential treatment protocols.

Frontiers in cellular neuroscience

Schroeder, PA; Ehlis, AC; Wolkenstein, L; Fallgatter, AJ; Plewnia, C

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No Significant Effect of Prefrontal tDCS on Working Memory Performance in Older Adults.

2015

Transcranial direct current stimulation (tDCS) has been put forward as a non-pharmacological alternative for alleviating cognitive decline in old age. Although results have shown some promise, little is known about the optimal stimulation parameters for modulation in the cognitive domain. In this study, the effects of tDCS over the dorsolateral prefrontal cortex (dlPFC) on working memory performance were investigated in thirty older adults. An N-back task assessed working memory before, during and after anodal tDCS at a current strength of 1 mA and 2 mA, in addition to sham stimulation. The study used a single-blind, cross-over design. The results revealed no significant effect of tDCS on accuracy or response times during or after stimulation, for any of the current strengths. These results suggest that a single session of tDCS over the dlPFC is unlikely to improve working memory, as assessed by an N-back task, in old age.

Frontiers in aging neuroscience

Nilsson, J; Lebedev, AV; Lövdén, M

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Modulation of Neural Activity in the Temporoparietal Junction with Transcranial Direct Current Stimulation Changes the Role of Beliefs in Moral Judgment.

2015

Judgments about whether an action is morally right or wrong typically depend on our capacity to infer the actor's beliefs and the outcomes of the action. Prior neuroimaging studies have found that mental state (e.g., beliefs, intentions) attribution for moral judgment involves a complex neural network that includes the temporoparietal junction (TPJ). However, neuroimaging studies cannot demonstrate a direct causal relationship between the activity of this brain region and mental state attribution for moral judgment. In the current study, we used transcranial direct current stimulation (tDCS) to transiently alter neural activity in the TPJ. The participants were randomly assigned to one of three stimulation treatments (right anodal/left cathodal tDCS, left anodal/right cathodal tDCS, or sham stimulation). Each participant was required to complete two similar tasks of moral judgment before receiving tDCS and after receiving tDCS. We studied whether tDCS to the TPJ altered mental state attribution for moral judgment. The results indicated that restraining the activity of the right temporoparietal junction (RTPJ) or the left the temporoparietal junction (LTPJ) decreased the role of beliefs in moral judgments and led to an increase in the dependance of the participants' moral judgments on the action's consequences. We also found that the participants exhibited reduced reaction times both in the cases of intentional harms and attempted harms after receiving right cathodal/left anodal tDCS to the TPJ. These findings inform and extend the current neural models of moral judgment and moral development in typically developing people and in individuals with neurodevelopmental disorders such as autism.

Frontiers in human neuroscience

Ye, H; Chen, S; Huang, D; Zheng, H; Jia, Y; Luo, J

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Transcranial Direct Current Stimulation over the Medial Prefrontal Cortex and Left Primary Motor Cortex (mPFC-lPMC) Affects Subjective Beauty but Not Ugliness.

2015

Neuroaesthetics has been searching for the neural bases of the subjective experience of beauty. It has been demonstrated that neural activities in the medial prefrontal cortex (mPFC) and the left primary motor cortex (lPMC) correlate with the subjective experience of beauty. Although beauty and ugliness seem to be semantically and conceptually opposite, it is still unknown whether these two evaluations represent extreme opposites in unitary or bivariate dimensions. In this study, we applied transcranial direct current stimulation (tDCS) to examine whether non-invasive brain stimulation modulates two types of esthetic evaluation; evaluating beauty and ugliness. Participants rated the subjective beauty and ugliness of abstract paintings before and after the application of tDCS. Application of cathodal tDCS over the mPFC with anode electrode over the lPMC, which induced temporal inhibition of neural excitability of the mPFC, led to a decrease in beauty ratings but not ugliness ratings. There were no changes in ratings of both beauty and ugliness when applying anodal tDCS or sham stimulation over the mPFC. Results from our experiment indicate that the mPFC and the lPMC have a causal role in generating the subjective experience of beauty, with beauty and ugliness evaluations constituting two distinct dimensions.

Frontiers in human neuroscience

Nakamura, K; Kawabata, H

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Lasting EEG/MEG Aftereffects of Rhythmic Transcranial Brain Stimulation: Level of Control Over Oscillatory Network Activity.

2015

A number of rhythmic protocols have emerged for non-invasive brain stimulation (NIBS) in humans, including transcranial alternating current stimulation (tACS), oscillatory transcranial direct current stimulation (otDCS), and repetitive (also called rhythmic) transcranial magnetic stimulation (rTMS). With these techniques, it is possible to match the frequency of the externally applied electromagnetic fields to the intrinsic frequency of oscillatory neural population activity ("frequency-tuning"). Mounting evidence suggests that by this means tACS, otDCS, and rTMS can entrain brain oscillations and promote associated functions in a frequency-specific manner, in particular during (i.e., online to) stimulation. Here, we focus instead on the changes in oscillatory brain activity that persist after the end of stimulation. Understanding such aftereffects in healthy participants is an important step for developing these techniques into potentially useful clinical tools for the treatment of specific patient groups. Reviewing the electrophysiological evidence in healthy participants, we find aftereffects on brain oscillations to be a common outcome following tACS/otDCS and rTMS. However, we did not find a consistent, predictable pattern of aftereffects across studies, which is in contrast to the relative homogeneity of reported online effects. This indicates that aftereffects are partially dissociated from online, frequency-specific (entrainment) effects during tACS/otDCS and rTMS. We outline possible accounts and future directions for a better understanding of the link between online entrainment and offline aftereffects, which will be key for developing more targeted interventions into oscillatory brain activity.

Frontiers in cellular neuroscience

Veniero, D; Vossen, A; Gross, J; Thut, G

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Modulating Memory Performance in Healthy Subjects with Transcranial Direct Current Stimulation Over the Right Dorsolateral Prefrontal Cortex.

2015

The role of the Dorsolateral Prefrontal Cortex (DLPFC) in recognition memory has been well documented in lesion, neuroimaging and repetitive Transcranial Magnetic Stimulation (rTMS) studies. The aim of the present study was to investigate the effects of transcranial Direct Current Stimulation (tDCS) over the left and the right DLPFC during the delay interval of a non-verbal recognition memory task.36 right-handed young healthy subjects participated in the study. The experimental task was an Italian version of Recognition Memory Test for unknown faces. Study included two experiments: in a first experiment, each subject underwent one session of sham tDCS and one session of left or right cathodal tDCS; in a second experiment each subject underwent one session of sham tDCS and one session of left or right anodal tDCS.Cathodal tDCS over the right DLPFC significantly improved non verbal recognition memory performance, while cathodal tDCS over the left DLPFC had no effect. Anodal tDCS of both the left and right DLPFC did not modify non verbal recognition memory performance.Complementing the majority of previous studies, reporting long term memory facilitations following left prefrontal anodal tDCS, the present findings show that cathodal tDCS of the right DLPFC can also improve recognition memory in healthy subjects.

PloS one

Smirni, D; Turriziani, P; Mangano, GR; Cipolotti, L; Oliveri, M

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Improving Cycling Performance: Transcranial Direct Current Stimulation Increases Time to Exhaustion in Cycling.

2015

The central nervous system seems to have an important role in fatigue and exercise tolerance. Novel noninvasive techniques of neuromodulation can provide insights on the relationship between brain function and exercise performance. The purpose of this study was to determine the effects of transcranial direct current stimulation (tDCS) on physical performance and physiological and perceptual variables with regard to fatigue and exercise tolerance. Eleven physically active subjects participated in an incremental test on a cycle simulator to define peak power output. During 3 visits, the subjects experienced 3 stimulation conditions (anodal, cathodal, or sham tDCS-with an interval of at least 48 h between conditions) in a randomized, counterbalanced order to measure the effects of tDCS on time to exhaustion at 80% of peak power. Stimulation was administered before each test over 13 min at a current intensity of 2.0 mA. In each session, the Brunel Mood State questionnaire was given twice: after stimulation and after the time-to-exhaustion test. Further, during the tests, the electromyographic activity of the vastus lateralis and rectus femoris muscles, perceived exertion, and heart rate were recorded. RM-ANOVA showed that the subjects performed better during anodal primary motor cortex stimulation (491 ± 100 s) compared with cathodal stimulation (443 ± 11 s) and sham (407 ± 69 s). No significant difference was observed between the cathodal and sham conditions. The effect sizes confirmed the greater effect of anodal M1 tDCS (anodal x cathodal = 0.47; anodal x sham = 0.77; and cathodal x sham = 0.29). Magnitude-based inference suggested the anodal condition to be positive versus the cathodal and sham conditions. There were no differences among the three stimulation conditions in RPE (p = 0.07) or heart rate (p = 0.73). However, as hypothesized, RM- ANOVA revealed a main effect of time for the two variables (RPE and HR: p < 0.001). EMG activity also did not differ during the test accross the different conditions. We conclude that anodal tDCS increases exercise tolerance in a cycling-based, constant-load exercise test, performed at 80% of peak power. Performance was enhanced in the absence of changes in physiological and perceptual variables.

PloS one

Vitor-Costa, M; Okuno, NM; Bortolotti, H; Bertollo, M; Boggio, PS; Fregni, F; Altimari, LR

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Fatigue in Multiple Sclerosis: Neural Correlates and the Role of Non-Invasive Brain Stimulation.

2015

Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system (CNS) and the major cause of non-traumatic disability in young adults. Fatigue is a frequent symptom reported by the majority of MS patients during their disease course and drastically affects their quality of life. Despite its significant prevalence and impact, the underlying pathophysiological mechanisms are not well elucidated. MS fatigue is still considered the result of multifactorial and complex constellations, and is commonly classified into "primary" fatigue related to the pathological changes of the disease itself, and "secondary" fatigue attributed to mimicking symptoms, comorbid sleep and mood disorders, and medications side effects. Radiological, physiological, and endocrine data have raised hypotheses regarding the origin of this symptom, some of which have succeeded in identifying an association between MS fatigue and structural or functional abnormalities within various brain networks. Hence, the aim of this work is to reappraise the neural correlates of MS fatigue and to discuss the rationale for the emergent use of noninvasive brain stimulation (NIBS) techniques as potential treatments. This will include a presentation of the various NIBS modalities and a suggestion of their potential mechanisms of action in this context. Specific issues related to the value of transcranial direct current stimulation (tDCS) will be addressed.

Frontiers in cellular neuroscience

Chalah, MA; Riachi, N; Ahdab, R; Créange, A; Lefaucheur, JP; Ayache, SS

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The Effects of tDCS Across the Spatial Frequencies and Orientations that Comprise the Contrast Sensitivity Function.

2015

Transcranial Direct Current Stimulation (tDCS) has recently been employed in traditional psychophysical paradigms in an effort to measure direct manipulations on spatial frequency channel operations in the early visual system. However, the effects of tDCS on contrast sensitivity have only been measured at a single spatial frequency and orientation. Since contrast sensitivity is known to depend on spatial frequency and orientation, we ask how the effects of anodal and cathodal tDCS may vary according to these dimensions. We measured contrast sensitivity with sinusoidal gratings at four different spatial frequencies (0.5, 4, 8, and 12 cycles/°), two orientations (45° Oblique and Horizontal), and for two stimulus size conditions [fixed size (3°) and fixed period (1.5 cycles)]. Only contrast sensitivity measured with a 45° oblique grating with a spatial frequency of 8 cycles/° (period = 1.5 cycles) demonstrated clear polarity specific effects of tDCS, whereby cathodal tDCS increased and anodal tDCS decreased contrast sensitivity. Overall, effects of tDCS were largest for oblique stimuli presented at high spatial frequencies (i.e., 8 and 12 cycles/°), and were small or absent at lower spatial frequencies, other orientations and stimulus size. Thus, the impact of tDCS on contrast sensitivity, and therefore on spatial frequency channel operations, is opposite in direction to other behavioral effects of tDCS, and only measurable in stimuli that generally elicit lower contrast sensitivity (e.g., oblique gratings with period of 1.5 cycles at spatial frequencies above the peak of the contrast sensitivity function).

Frontiers in psychology

Richard, B; Johnson, AP; Thompson, B; Hansen, BC

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Prefrontocerebellar transcranial direct current stimulation increases amplitude and decreases latency of P3b component in patients with euthymic bipolar disorder.

2015

Neurocognitive impairments have been observed in patients with bipolar disorder (BD) even during the euthymic phase of the disease, potentially representing trait-associated rather than state-associated characteristics of the disorder. In the present study, we used transcranial direct current stimulation (tDCS) applied to cerebellar and prefrontal cortices to improve the neurophysiological performances of patients with euthymic BD.Twenty-five outpatients with BD underwent open-label prefrontocerebellar tDCS for 3 consecutive weeks. Neurophysiological performances were assessed through the examination of the P3b and P3a subcomponents of P300 event-related potential at baseline and after stimulation.Compared to baseline, P3b component after tDCS showed significantly higher amplitude and shorter latency (latency: Fz P=0.02, Cz P=0.03, and Pz P=0.04; amplitude: Fz P=0.24, Cz P=0.02, and Pz P=0.35).In our sample of patients with euthymic BD, concomitant prefrontoexcitatory and cerebellar-inhibitory modulations led to improved brain information processing stream. This improvement may at least partially result from neuroplastic modulation of prefrontocerebellar circuitry activity.

Neuropsychiatric disease and treatment

Bersani, FS; Minichino, A; Fattapposta, F; Bernabei, L; Spagnoli, F; Mannarelli, D; Francesconi, M; Pauletti, C; Corrado, A; Vergnani, L; Taddei, I; Biondi, M; Delle Chiaie, R

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Non-invasive Central and Peripheral Stimulation: New Hope for Essential Tremor?

2015

Essential tremor (ET) is among the most frequent movement disorders. It usually manifests as a postural and kinematic tremor of the arms, but may also involve the head, voice, lower limbs, and trunk. An oscillatory network has been proposed as a neural correlate of ET, and is mainly composed of the olivocerebellar system, thalamus, and motor cortex. Since pharmacological agents have limited benefits, surgical interventions like deep brain stimulation are the last-line treatment options for the most severe cases. Non-invasive brain stimulation techniques, particularly transcranial magnetic or direct current stimulation, are used to ameliorate ET. Their non-invasiveness, along with their side effects profile, makes them an appealing treatment option. In addition, peripheral stimulation has been applied in the same perspective. Hence, the aim of the present review is to shed light on the emergent use of non-invasive central and peripheral stimulation techniques in this interesting context.

Frontiers in neuroscience

Chalah, MA; Lefaucheur, JP; Ayache, SS

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Two is More Than One: How to Combine Brain Stimulation Rehabilitative Training for Functional Recovery?

2015

A number of studies have shown that non-invasive brain stimulation has an additional effect in combination with rehabilitative therapy to enhance functional recovery than either therapy alone. The combination enhances use-dependent plasticity induced by repetitive training. The neurophysiological mechanism of the effects of this combination is based on associative plasticity. However, these effects were not reported in all cases. We propose a list of possible strategies to achieve an effective association between rehabilitative training with brain stimulation for plasticity: (1) control of temporal aspect between stimulation and task execution; (2) the use of a shaped task for the combination; (3) the appropriate stimulation of neuronal circuits where use-dependent plastic changes occur; and (4) phase synchronization between rhythmically patterned brain stimulation and task-related patterned activities of neurons. To better utilize brain stimulation in neuro-rehabilitation, it is important to develop more effective techniques to combine them.

Frontiers in systems neuroscience

Koganemaru, S; Fukuyama, H; Mima, T

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Synergistic effect of combined transcranial direct current stimulation/constraint-induced movement therapy in children and young adults with hemiparesis: study protocol.

2015

Perinatal stroke occurs in more than 1 in 2,500 live births and resultant congenital hemiparesis necessitates investigation into interventions which may improve long-term function and decreased burden of care beyond current therapies ( http://www.cdc.gov/ncbddd/cp/data.html ). Constraint-Induced Movement Therapy (CIMT) is recognized as an effective hemiparesis rehabilitation intervention. Transcranial direct current stimulation as an adjunct treatment to CIMT may potentiate neuroplastic responses and improve motor function. The methodology of a clinical trial in children designed as a placebo-controlled, serial -session, non-invasive brain stimulation trial incorporating CIMT is described here. The primary hypotheses are 1) that no serious adverse events will occur in children receiving non-invasive brain stimulation and 2) that children in the stimulation intervention group will show significant improvements in hand motor function compared to children in the placebo stimulation control group.A randomized, controlled, double-blinded clinical trial. Twenty children and/or young adults (ages 8-21) with congenital hemiparesis, will be enrolled. The intervention group will receive ten 2-hour sessions of transcranial direct current stimulation combined with constraint-induced movement therapy and the control group will receive sham stimulation with CIMT. The primary outcome measure is safety assessment of transcranial direct current stimulation by physician evaluation, vital sign monitoring and symptom reports. Additionally, hand function will be evaluated using the Assisting Hand Assessment, grip strength and assessment of goals using the Canadian Occupational Performance Measure. Neuroimaging will confirm diagnoses, corticospinal tract integrity and cortical activation. Motor cortical excitability will also be examined using transcranial magnetic stimulation techniques.Combining non-invasive brain stimulation and CIMT interventions has the potential to improve motor function in children with congenital hemiparesis beyond each intervention independently. Such a combined intervention has the potential to benefit an individual throughout their lifetime.Clinicaltrials.gov, NCT02250092 Registered 18 September 2014.

BMC pediatrics

Gillick, B; Menk, J; Mueller, B; Meekins, G; Krach, LE; Feyma, T; Rudser, K

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The effect of Transcranial Direct Current Stimulation in addition to Tinnitus Retraining Therapy for treatment of chronic tinnitus patients: a study protocol for a double-blind controlled randomised trial.

2015

Currently, there still is no treatment that eliminates tinnitus in all patients. Recent studies have shown that Tinnitus Retraining Therapy (TRT) significantly improves quality of life for tinnitus patients. Also, several studies have reported that transcranial Direct Current Stimulation (tDCS) has a positive effect on attention, working memory, long-term memory and other cognitive processes. The aim of this randomised placebo-controlled double-blind study is to evaluate the added effect of tDCS to TRT in chronic tinnitus patients. To our knowledge, this is the first study to combine both methods.Patients with chronic, non-pulsatile tinnitus will be randomised in two treatment groups: TRT and real tDCS versus TRT and sham tDCS. Evaluations will take place at baseline before therapy starts, at the end of the TRT and 3 months after therapy starts. The Tinnitus Functional Index will be used as the primary outcome measurement. Secondary outcome measurements will be the Visual Analogue Scale of Loudness, Hospital Anxiety and Depression Scale (HADS), Hyperacusis Questionnaire, psychoacoustic measurements and Event-related potential (ERP).To our knowledge this is the first study to combine TRT and tDCS. The objective is to evaluate whether tDCS can provide faster and/or more relief from the annoyance experienced in chronic tinnitus patients' daily lives. The advantage of the study is that it is double-blind and placebo-controlled.The present study protocol was registered on 31 October 2014 at Clinicaltrials.gov: NCT02285803 .

Trials

Rabau, S; Van Rompaey, V; Van de Heyning, P

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Language and Memory Improvements following tDCS of Left Lateral Prefrontal Cortex.

2015

Recent research demonstrates that performance on executive-control measures can be enhanced through brain stimulation of lateral prefrontal regions. Separate psycholinguistic work emphasizes the importance of left lateral prefrontal cortex executive-control resources during sentence processing, especially when readers must override early, incorrect interpretations when faced with temporary ambiguity. Using transcranial direct current stimulation, we tested whether stimulation of left lateral prefrontal cortex had discriminate effects on language and memory conditions that rely on executive-control (versus cases with minimal executive-control demands, even in the face of task difficulty). Participants were randomly assigned to receive Anodal, Cathodal, or Sham stimulation of left lateral prefrontal cortex while they (1) processed ambiguous and unambiguous sentences in a word-by-word self-paced reading task and (2) performed an n-back memory task that, on some trials, contained interference lure items reputed to require executive-control. Across both tasks, we parametrically manipulated executive-control demands and task difficulty. Our results revealed that the Anodal group outperformed the remaining groups on (1) the sentence processing conditions requiring executive-control, and (2) only the most complex n-back conditions, regardless of executive-control demands. Together, these findings add to the mounting evidence for the selective causal role of left lateral prefrontal cortex for executive-control tasks in the language domain. Moreover, we provide the first evidence suggesting that brain stimulation is a promising method to mitigate processing demands encountered during online sentence processing.

PloS one

Hussey, EK; Ward, N; Christianson, K; Kramer, AF

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Noninvasive brain stimulation for the treatment of auditory verbal hallucinations in schizophrenia: methods, effects and challenges.

2015

This mini-review focuses on noninvasive brain stimulation techniques as an augmentation method for the treatment of persistent auditory verbal hallucinations (AVH) in patients with schizophrenia. Paradigmatically, we place emphasis on transcranial magnetic stimulation (TMS). We specifically discuss rationales of stimulation and consider methodological questions together with issues of phenotypic diversity in individuals with drug-refractory and persistent AVH. Eventually, we provide a brief outlook for future investigations and treatment directions. Taken together, current evidence suggests TMS as a promising method in the treatment of AVH. Low-frequency stimulation of the superior temporal cortex (STC) may reduce symptom severity and frequency. Yet clinical effects are of relatively short duration and effect sizes appear to decrease over time along with publication of larger trials. Apart from considering other innovative stimulation techniques, such as transcranial Direct Current Stimulation (tDCS), and optimizing stimulation protocols, treatment of AVH using noninvasive brain stimulation will essentially rely on accurate identification of potential responders and non-responders for these treatment modalities. In this regard, future studies will need to consider distinct phenotypic presentations of AVH in patients with schizophrenia, together with the putative functional neurocircuitry underlying these phenotypes.

Frontiers in systems neuroscience

Kubera, KM; Barth, A; Hirjak, D; Thomann, PA; Wolf, RC

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Investigating the cortical regions involved in MEP modulation in tDCS.

2015

Transcranial magnetic stimulation (TMS) is used in several studies to evaluate cortical excitability changes induced by transcranial direct current stimulation (tDCS) of the primary motor cortex. Interpretation of these results, however, is hindered by the very different spatial distribution of the electric field (E-field) induced by the two techniques and by the different target neurons that they might act upon. In this study we used the finite element method to calculate the E-field distribution induced by TMS and tDCS in a realistically shaped model of a human head. A model of a commercially available figure-8 coil was placed over a position above the identified hand knob (HK) region. We also modeled two configurations of bipolar tDCS montages with one of the electrodes placed over the HK and a return electrode over the contralateral orbital region. The electrodes over the HK were either rectangular in shape, with an area of 35 cm(2) or cylindrical with an area of π cm(2) (1 cm radius). To compare the E-field distribution in TMS and the two tDCS models, average values of the E-field's magnitude as well as the polar and azimuthal angle were investigated in the HK region and premotor areas. The results show that both techniques induce fields with different magnitudes and directions in the HK: the field in tDCS is predominantly perpendicular to the cortical surface, contrary to what happens in TMS where the field is mostly parallel to it. In the premotor areas, the magnitude of the E-field induced in TMS was well below the accepted threshold for MEP generation, 100 V/m. In tDCS, the magnitude of the field in these areas was comparable to that induced at the HK with a significant component perpendicular to the cortical surface. These results indicate that tDCS and TMS target preferentially different neuronal structures at the HK. Besides, they show that premotor areas may play a role in the tDCS-induced after effects on motor cortex excitability.

Frontiers in cellular neuroscience

Salvador, R; Wenger, C; Miranda, PC

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Does non-invasive brain stimulation applied over the dorsolateral prefrontal cortex non-specifically influence mood and emotional processing in healthy individuals?

2015

The dorsolateral prefrontal cortex (DLPFC) is often targeted with non-invasive brain stimulation (NIBS) to modulate in vivo human behaviors. This brain region plays a key role in mood, emotional processing, and attentional processing of emotional information. In this article, we ask the question: when we target the DLPFC with NIBS, do we modulate these processes altogether, non-specifically, or can we modulate them selectively? We thus review articles investigating the effects of NIBS applied over the DLPFC on mood, emotional processing, and attentional processing of emotional stimuli in healthy subjects. We discuss that NIBS over the DLPFC can modulate emotional processing and attentional processing of emotional stimuli, without specifically influencing mood. Indeed, there seems to be a lack of evidence that NIBS over the DLPFC influences mood in healthy individuals. Finally, there appears to be a hemispheric lateralization: when applied over the left DLPFC, NIBS improved processing of positive stimuli and reduced selective attention for stimuli expressing anger, whereas when applied over the right DLPFC, it increased selective attention for stimuli expressing anger.

Frontiers in cellular neuroscience

Mondino, M; Thiffault, F; Fecteau, S

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Neural Mechanisms Underlying Perilesional Transcranial Direct Current Stimulation in Aphasia: A Feasibility Study.

2015

Little is known about the neural mechanisms by which transcranial direct current stimulation (tDCS) impacts on language processing in post-stroke aphasia. This was addressed in a proof-of-principle study that explored the effects of tDCS application in aphasia during simultaneous functional magnetic resonance imaging (fMRI). We employed a single subject, cross-over, sham-tDCS controlled design, and the stimulation was administered to an individualized perilesional stimulation site that was identified by a baseline fMRI scan and a picture naming task. Peak activity during the baseline scan was located in the spared left inferior frontal gyrus and this area was stimulated during a subsequent cross-over phase. tDCS was successfully administered to the target region and anodal- vs. sham-tDCS resulted in selectively increased activity at the stimulation site. Our results thus demonstrate that it is feasible to precisely target an individualized stimulation site in aphasia patients during simultaneous fMRI, which allows assessing the neural mechanisms underlying tDCS application. The functional imaging results of this case report highlight one possible mechanism that may have contributed to beneficial behavioral stimulation effects in previous clinical tDCS trials in aphasia. In the future, this approach will allow identifying distinct patterns of stimulation effects on neural processing in larger cohorts of patients. This may ultimately yield information about the variability of tDCS effects on brain functions in aphasia.

Frontiers in human neuroscience

Ulm, L; McMahon, K; Copland, D; de Zubicaray, GI; Meinzer, M

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Stimulating somatosensory psychophysics: a double-blind, sham-controlled study of the neurobiological mechanisms of tDCS.

2015

The neuromodulation technique transcranial direct current stimulation (tDCS) is thought to produce its effects on behavior by altering cortical excitability. Although the mechanisms underlying the observed effects are thought to rely on the balance of excitatory and inhibitory neurotransmission, the physiological principles of the technique are not completely understood. In this study, we examine the influence of tDCS on vibrotactile adaptation, using a simple amplitude discrimination paradigm that has been shown to exhibit modifications in performance due to changes in inhibitory neurotransmission. Double-blind tDCS (Anodal/Sham) of 1 mA was delivered for 600 s to electrodes positioned in a somatosensory/contralateral orbit montage. Stimulation was applied as part of a pre/post design, between blocks of the behavioral tasks. In accordance with previous work, results obtained before the application of tDCS indicated that amplitude discrimination thresholds were significantly worsened during adaptation trials, compared to those achieved at baseline. However, tDCS failed to modify amplitude discrimination performance. Using a Bayesian approach, this finding was revealed to constitute substantial evidence for the null hypothesis. The failure of DC stimulation to alter vibrotactile adaptation thresholds is discussed in the context of several factors that may have confounded the induction of changes in cortical plasticity.

Frontiers in cellular neuroscience

Hanley, CJ; Tommerdahl, M; McGonigle, DJ

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Transcranial direct current stimulation (tDCS) in behavioral and food addiction: a systematic review of efficacy, technical, and methodological issues.

2015

Behavioral addictions (BA) are complex disorders for which pharmacological and psychotherapeutic treatments have shown their limits. Non-invasive brain stimulation, among which transcranial direct current stimulation (tDCS), has opened up new perspectives in addiction treatment. The purpose of this work is to conduct a critical and systematic review of tDCS efficacy, and of technical and methodological considerations in the field of BA.A bibliographic search has been conducted on the Medline and ScienceDirect databases until December 2014, based on the following selection criteria: clinical studies on tDCS and BA (namely eating disorders, compulsive buying, Internet addiction, pathological gambling, sexual addiction, sports addiction, video games addiction). Study selection, data analysis, and reporting were conducted according to the PRISMA guidelines.Out of 402 potential articles, seven studies were selected. So far focusing essentially on abnormal eating, these studies suggest that tDCS (right prefrontal anode/left prefrontal cathode) reduces food craving induced by visual stimuli.Despite methodological and technical differences between studies, the results are promising. So far, only few studies of tDCS in BA have been conducted. New research is recommended on the use of tDCS in BA, other than eating disorders.

Frontiers in neuroscience

Sauvaget, A; Trojak, B; Bulteau, S; Jiménez-Murcia, S; Fernández-Aranda, F; Wolz, I; Menchón, JM; Achab, S; Vanelle, JM; Grall-Bronnec, M

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Would transcranial direct current stimulation (tDCS) enhance the effects of working memory training in older adults with mild neurocognitive disorder due to Alzheimer's disease: study protocol for a randomized controlled trial.

2015

There has been longstanding interesting in cognitive training for older adults with cognitive impairment. In this study, we will investigate the effects of working memory training, and explore augmentation strategies that could possibly consolidate the effects in older adults with mild neurocognitive disorder. Transcranial direct current stimulation (tDCS) has been demonstrated to affect the neuronal excitability and reported to enhance memory performance. As tDCS may also modulate cognitive function through changes in neuroplastic response, it would be adopted as an augmentation strategy for working memory training in the present study.This is a 4-week intervention double-blind randomized controlled trial (RCT) of tDCS. Chinese older adults (aged 60 to 90 years) with mild neurocognitive disorder due to Alzheimer's disease (DSM-5 criteria) would be randomized into a 4-week intervention of either tDCS-working memory (DCS-WM), tDCS-control cognitive training (DCS-CC), and sham tDCS-working memory (WM-CD) groups. The primary outcome would be working memory test - the n-back task performance and the Chinese version of the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog). Secondary outcomes would be test performance of specific cognitive domains and mood. Intention-to-treat analysis would be carried out. Changes of efficacy indicators with time and intervention would be tested with mixed effect models.This study adopts the theory of neuroplasticity to evaluate the potential cognitive benefits of non-invasive electrical brain stimulation, working memory training and dual stimulation in older adults at risk of cognitive decline. It would also examine the tolerability, program adherence and adverse effects of this novel intervention. Information would be helpful for further research of dementia prevention studies.ChiCTR-TRC- 14005036 Date of registration: 31 July 2014.

Trials

Cheng, CP; Chan, SS; Mak, AD; Chan, WC; Cheng, ST; Shi, L; Wang, D; Lam, LC

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Editorial: The safety and efficacy of noninvasive brain stimulation in development and neurodevelopmental disorders.

2015

Frontiers in human neuroscience

Oberman, LM; Enticott, PG

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Cathodal HD-tDCS on the right V5 improves motion perception in humans.

2015

Brain lesions in the visual associative cortex are known to impair visual perception, i.e., the capacity to correctly perceive different aspects of the visual world, such as motion, color, or shapes. Visual perception can be influenced by non-invasive brain stimulation such as transcranial direct current stimulation (tDCS). In a recently developed technique called high definition (HD) tDCS, small HD-electrodes are used instead of the sponge electrodes in the conventional approach. This is believed to achieve high focality and precision over the target area. In this paper we tested the effects of cathodal and anodal HD-tDCS over the right V5 on motion and shape perception in a single blind, within-subject, sham controlled, cross-over trial. The purpose of the study was to prove the high focality of the stimulation only over the target area. Twenty one healthy volunteers received 20 min of 2 mA cathodal, anodal and sham stimulation over the right V5 and their performance on a visual test was recorded. The results showed significant improvement in motion perception in the left hemifield after cathodal HD-tDCS, but not in shape perception. Sham and anodal HD-tDCS did not affect performance. The specific effect of influencing performance of visual tasks by modulating the excitability of the neurons in the visual cortex might be explained by the complexity of perceptual information needed for the tasks. This provokes a "noisy" activation state of the encoding neuronal patterns. We speculate that in this case cathodal HD-tDCS may focus the correct perception by decreasing global excitation and thus diminishing the "noise" below threshold.

Frontiers in behavioral neuroscience

Zito, GA; Senti, T; Cazzoli, D; Müri, RM; Mosimann, UP; Nyffeler, T; Nef, T

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Potentials and limits to enhance cognitive functions in healthy and pathological aging by tDCS.

2015

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that is increasingly used in research and clinical settings to enhance the effects of cognitive training. In our present review, we will first summarize studies using tDCS alone and in combination with cognitive training in older adults and patients with Alzheimer's dementia (AD). We will also review one study (Meinzer et al., 2014c) that showed an improvement in cognitive performance during anodal tDCS over the left inferior frontal cortex in patients with mild cognitive impairment (MCI) which is regarded as a prodromal stage of AD. Although promising short-term results have been reported, evidence from randomized controlled trials (RCTs) with sufficient sample sizes is scarce. In addition, stimulation protocols (in terms of intensity, duration, and repetition of stimulation) that lead to sustained improvements in outcome measures relevant for daily life still remain to be established. Following, we will discuss modulating factors such as technical parameters as well as the question whether there are specific cognitive functions (e.g., learning, memory consolidation, executive control) which are more amenable to tDCS enhancement than others. Finally, we will highlight future directions and limitations in this field and emphasize the need to conduct RCTs to establish efficacy of interventions for activities of daily life for a given patient population.

Frontiers in cellular neuroscience

Prehn, K; Flöel, A

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Neurostimulation for cognitive rehabilitation in stroke (NeuroCog): study protocol for a randomized controlled trial.

2015

Stroke patients may present severe cognitive impairments, primarily related to executive functions. Transcranial direct current stimulation has shown promising results, with neuromodulatory and neuroplastic effects. This study is a double-blind, sham-controlled clinical trial aiming to compare the long-term effects of stimulation in two different cognitive regions after a stroke.Sixty patients who suffer from chronic strokes will be randomized into one of four groups: dorsolateral prefrontal cortex, cingulo-opercular network, motor primary cortex and sham stimulation. Each group will receive transcranial direct current stimulation at an intensity of 2 mA for 20 minutes daily for 10 consecutive days. Patients will be assessed with a Dysexecutive Questionnaire, Semantic Fluency Test, categorical verbal fluency and Go-no go tests, Wechsler Adult Intelligence Scale, Rey Auditory-Verbal Learning Test, Letter Comparison and Pattern Comparison Tasks at baseline and after their tenth stimulation session. Those who achieve clinical improvement with neurostimulation will be invited to receive treatment for 12 months as part of a follow-up study.Long-term stimulation could be analyzed in regard to possible adaptive changes on plasticity after structural brain damage and if these changes are different in terms of clinical improvement when applied to two important cognitive centers.Clinicaltrials.gov, NCT02315807 . 9 December 2014.

Trials

Andrade, SM; Fernández-Calvo, B; Boggio, PS; de Oliveira, EA; Gomes, LF; Pinheiro Júnior, JE; Rodrigues, RM; de Almeida, NL; Moreira, GM; Alves, NT

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The Neurophysiologist Perspective into MS Plasticity.

2015

Multiple sclerosis (MS) is a frequent, highly debilitating inflammatory demyelinating disease, starting to manifest in early adulthood and presenting a wide variety of symptoms, which are often resistant to pharmacological treatments. Cortical dysfunctions have been demonstrated to be key components of MS condition, and plasticity of the corticospinal motor system is highly involved in major MS symptoms, such as fatigue, spasticity, or pain. Cortical dysfunction in MS can be studied with neurophysiological tools, such as electroencephalography (EEG) and related techniques (evoked potentials) or transcranial magnetic stimulation (TMS). These techniques are now widely used to provide essential elements of MS diagnosis and can also be used to modulate plasticity. Indeed, the recent development of non-invasive brain stimulation techniques able to induce cortical plasticity, such as repetitive TMS or transcranial direct current stimulation, has brought promising results as add-on treatments. In this review, we will focus on the use of these tools (EEG and TMS) to study plasticity in MS and on the major techniques used to modulate plasticity in MS.

Frontiers in neurology

Houdayer, E; Comi, G; Leocani, L

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Impulsive delayed reward discounting as a genetically-influenced target for drug abuse prevention: a critical evaluation.

2015

This review evaluates the viability of delayed reward discounting (DRD), an index of how much an individual devalues a future reward based on its delay in time, for genetically-informed drug abuse prevention. A review of the literature suggests that impulsive DRD is robustly associated with drug addiction and meets most of the criteria for being an endophenotype, albeit with mixed findings for specific molecular genetic influences. Several modes of experimental manipulation have been demonstrated to reduce DRD acutely. These include behavioral strategies, such as mindfulness, reward bundling, and episodic future thinking; pharmacological interventions, including noradrenergic agonists, adrenergic agonists, and multiple monoamine agonists; and neuromodulatory interventions, such as transcranial magnetic stimulation and transcranial direct current stimulation. However, the generalization of these interventions to positive clinical outcomes remains unclear and no studies to date have examined interventions on DRD in the context of prevention. Collectively, these findings suggest it would be premature to target DRD for genetically-informed prevention. Indeed, given the evidence of environmental contributions to impulsive DRD, whether genetically-informed secondary prevention would ever be warranted is debatable. Progress in identifying polymorphisms associated with DRD profiles could further clarify the underlying biological systems for pharmacological and neuromodulatory interventions, and, as a qualitatively different risk factor from existing prevention programs, impulsive DRD is worthy of investigation at a more general level as a novel and promising drug abuse prevention target.

Frontiers in psychology

Gray, JC; MacKillop, J

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Promoting social plasticity in developmental disorders with non-invasive brain stimulation techniques.

2015

Being socially connected directly impacts our basic needs and survival. People with deficits in social cognition might exhibit abnormal behaviors and face many challenges in our highly social-dependent world. These challenges and limitations are associated with a substantial economical and subjective impact. As many conditions where social cognition is affected are highly prevalent, more treatments have to be developed. Based on recent research, we review studies where non-invasive neuromodulatory techniques have been used to promote Social Plasticity in developmental disorders. We focused on three populations where non-invasive brain stimulation seems to be a promising approach in inducing social plasticity: Schizophrenia, Autism Spectrum Disorder (ASD) and Williams Syndrome (WS). There are still very few studies directly evaluating the effects of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) in the social cognition of these populations. However, when considering the promising preliminary evidences presented in this review and the limited amount of clinical interventions available for treating social cognition deficits in these populations today, it is clear that the social neuroscientist arsenal may profit from non-invasive brain stimulation techniques for rehabilitation and promotion of social plasticity.

Frontiers in neuroscience

Boggio, PS; Asthana, MK; Costa, TL; Valasek, CA; Osório, AA

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Analgesic effect of cathodal transcranial current stimulation over right dorsolateral prefrontal cortex in subjects with muscular temporomandibular disorders: study protocol for a randomized controlled trial.

2015

Temporomandibular disorders are a group of orofacial pain conditions that are commonly identified in the general population. Like many other chronic pain conditions, they can be associated with anxiety/depression, which can be related to changes in the activity of the dorsolateral prefrontal cortex. Some studies have demonstrated clinical improvement in subjects with chronic pain who are given therapeutic neuromodulation. Transcranial direct current stimulation is a noninvasive brain stimulation technique that allows the modulation of neuronal membranes. This therapy can enhance or inhibit action potential generation in cortical neurons. In some instances, medications acting in the central nervous system may be helpful despite their adverse side effects. It is important to determine if cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex, an area that modulates emotion and motor cortex excitability, has an analgesic effect on chronic temporomandibular disorders pain.The investigators will run a randomized, controlled crossover double blind study with 15 chronic muscular temporomandibular disorder subjects. Each subject will undergo active (1 mA and 2 mA) and sham transcranial direct current stimulation. Inclusion criteria will be determined by the Research Diagnostic Criteria for Temporomandibular Disorders questionnaire, with subjects who have a pain visual analogic scale score of greater than 4/10 and whose pain has been present for the previous 6 months, and with a State-Trait Anxiety Inventory score of more than 42. The influence of transcranial direct current stimulation will be assessed through a visual analogic scale, quantitative sensory testing, quantitative electroencephalogram, and the State-Trait Anxiety Inventory score.Some studies have demonstrated a strong association between anxiety/depression and chronic pain, where one may be the cause of the other. This is especially true in chronic temporomandibular disorders, and breaking this cycle may have an effect over the symptoms and associated dysfunction. We believe that by inhibiting activity of the dorsolateral prefrontal cortex though cathodal transcranial direct current stimulation, there may be a change in both anxiety/depression and pain level. Transcranial direct current stimulation may emerge as a new tool to be considered for managing these patients. We envision that the information obtained from this study will provide a better understanding of the management of chronic temporomandibular disorders.This trial was registered at clinicaltrials.gov on 24 May 2014 (Identifier: NCT02152267 ).

Trials

Brandão Filho, RA; Baptista, AF; Brandão, Rde A; Meneses, FM; Okeson, J; de Sena, EP

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Modulation of GABA and resting state functional connectivity by transcranial direct current stimulation.

2015

We previously demonstrated that network level functional connectivity in the human brain could be related to levels of inhibition in a major network node at baseline (Stagg et al., 2014). In this study, we build upon this finding to directly investigate the effects of perturbing M1 GABA and resting state functional connectivity using transcranial direct current stimulation (tDCS), a neuromodulatory approach that has previously been demonstrated to modulate both metrics. FMRI data and GABA levels, as assessed by Magnetic Resonance Spectroscopy, were measured before and after 20 min of 1 mA anodal or sham tDCS. In line with previous studies, baseline GABA levels were negatively correlated with the strength of functional connectivity within the resting motor network. However, although we confirm the previously reported findings that anodal tDCS reduces GABA concentration and increases functional connectivity in the stimulated motor cortex; these changes are not correlated, suggesting they may be driven by distinct underlying mechanisms.

eLife

Bachtiar, V; Near, J; Johansen-Berg, H; Stagg, CJ

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Non-Invasive Brain Stimulation for the Treatment of Symptoms Following Traumatic Brain Injury.

2015

Traumatic brain injury (TBI) is a common cause of physical, psychological, and cognitive impairment, but many current treatments for TBI are ineffective or produce adverse side effects. Non-invasive methods of brain stimulation could help ameliorate some common trauma-induced symptoms.This review summarizes instances in which repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) have been used to treat symptoms following a TBI. A subsequent discussion attempts to determine the value of these methods in light of their potential risks.The research databases of PubMed/MEDLINE and PsycINFO were electronically searched using terms relevant to the use of rTMS and tDCS as a tool to decrease symptoms in the context of rehabilitation post-TBI.Eight case-studies and four multi-subject reports using rTMS and six multi--subject studies using tDCS were found. Two instances of seizure are discussed.There is evidence that rTMS can be an effective treatment option for some post-TBI symptoms, such as depression, tinnitus, and neglect. Although the safety of this method remains uncertain, the use of rTMS in cases of mild TBI without obvious structural damage may be justified. Evidence on the effectiveness of tDCS is mixed, highlighting the need for additional investigations.

Frontiers in psychiatry

Dhaliwal, SK; Meek, BP; Modirrousta, MM

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Non-invasive brain stimulation in early rehabilitation after stroke.

2015

The new tendency in rehabilitation involves non-invasive tools that, if applied early after stroke, promote neurorecovery. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation may correct the disruption of cortical excitability and effectively contribute to the restoration of movement and speech. The present paper analyses the results of non-invasive brain stimulation (NIBS) trials, highlighting different aspects related to the repetitive transcranial magnetic stimulation frequency, transcranial direct current stimulation polarity, the period and stimulation places in acute and subacute ischemic strokes. The risk of adverse events, the association with motor or language recovery specific training, and the cumulative positive effect evaluation are also discussed.

Journal of medicine and life

Blesneag, AV; Popa, L; Stan, AD

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Prefronto-cerebellar transcranial direct current stimulation improves visuospatial memory, executive functions, and neurological soft signs in patients with euthymic bipolar disorder.

2015

The aim of the study was to improve neuropsychological functioning of euthymic patients with bipolar disorder (BD) using transcranial direct current stimulation (tDCS) applied to cerebellar and prefrontal cortices.Twenty-five BD outpatients underwent prefrontal (anodal) and cerebellar (cathodal) tDCS for 3 consecutive weeks. All participants were assessed through the Rey Complex Figure Test delay and copy and the Neurological Examination Scale at baseline and after therapy with tDCS.After tDCS treatment, patients showed significant improvements in visuospatial memory tasks. Patients with worse baseline cognitive performances also showed a significant improvement in executive functioning tasks. Neurological Examination Scale total score and motor coordination subscale significantly improved.Prefrontal-excitatory and cerebellar-inhibitory stimulations in euthymic BD patients may lead to better neurocognitive performances. This improvement could result from the modulation of prefronto-thalamic-cerebellar circuit activity pattern, which can be disrupted in BD.

Neuropsychiatric disease and treatment

Minichino, A; Bersani, FS; Bernabei, L; Spagnoli, F; Vergnani, L; Corrado, A; Taddei, I; Biondi, M; Delle Chiaie, R

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Translational treatment of aphasia combining neuromodulation and behavioral intervention for lexical retrieval: implications from a single case study.

2015

Transcranial direct current stimulation (tDCS), a non-invasive method of brain stimulation, is an adjunctive research-therapy for aphasia. The concept supporting translational application of tDCS is that brain plasticity, facilitated by language intervention, can be enhanced by non-invasive brain stimulation. This study combined tDCS with an ecologically focused behavioral approach that involved training nouns and verbs in sentences.A 43-year-old, right-handed male with fluent-anomic aphasia who sustained a single-left-hemisphere-temporal-parietal stroke was recruited.Instrumentation included the Soterix Medical 1 × 1 Device. Anodal tDCS was applied over Broca's area. Behavioral materials included: sentence production, naming in the sentence context, and implementation of a social-conversational-discourse treatment.The independent variable of this crossover case-study was tDCS, and the dependent variables were language and quality-of-life measures. In each session the subject received language treatment with the first 20 minutes additionally including tDCS.Performance in naming nouns and verbs in single words and sentences were obtained. Verb production in the sentence context increased after active anodal tDCS and speech-language treatment.Aphasia treatment that involves naming in the sentence context in conjunction with translational application of tDCS may be a promising approach for language-recovery post stroke.

Frontiers in human neuroscience

Galletta, EE; Vogel-Eyny, A

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Bidirectional interactions between neuronal and hemodynamic responses to transcranial direct current stimulation (tDCS): challenges for brain-state dependent tDCS.

2015

Transcranial direct current stimulation (tDCS) has been shown to modulate cortical neural activity. During neural activity, the electric currents from excitable membranes of brain tissue superimpose in the extracellular medium and generate a potential at scalp, which is referred as the electroencephalogram (EEG). Respective neural activity (energy demand) has been shown to be closely related, spatially and temporally, to cerebral blood flow (CBF) that supplies glucose (energy supply) via neurovascular coupling. The hemodynamic response can be captured by near-infrared spectroscopy (NIRS), which enables continuous monitoring of cerebral oxygenation and blood volume. This neurovascular coupling phenomenon led to the concept of neurovascular unit (NVU) that consists of the endothelium, glia, neurons, pericytes, and the basal lamina. Here, recent works suggest NVU as an integrated system working in concert using feedback mechanisms to enable proper brain homeostasis and function where the challenge remains in capturing these mostly nonlinear spatiotemporal interactions within NVU for brain-state dependent tDCS. In principal accordance, we propose EEG-NIRS-based whole-head monitoring of tDCS-induced neuronal and hemodynamic alterations during tDCS.

Frontiers in systems neuroscience

Dutta, A

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Slow oscillating transcranial direct current stimulation during non-rapid eye movement sleep improves behavioral inhibition in attention-deficit/hyperactivity disorder.

2015

Behavioral inhibition, which is a later-developing executive function (EF) and anatomically located in prefrontal areas, is impaired in attention-deficit and hyperactivity disorder (ADHD). While optimal EFs have been shown to depend on efficient sleep in healthy subjects, the impact of sleep problems, frequently reported in ADHD, remains elusive. Findings of macroscopic sleep changes in ADHD are inconsistent, but there is emerging evidence for distinct microscopic changes with a focus on prefrontal cortical regions and non-rapid eye movement (non-REM) slow-wave sleep. Recently, slow oscillations (SO) during non-REM sleep were found to be less functional and, as such, may be involved in sleep-dependent memory impairments in ADHD.By augmenting slow-wave power through bilateral, slow oscillating transcranial direct current stimulation (so-tDCS, frequency = 0.75 Hz) during non-REM sleep, we aimed to improve daytime behavioral inhibition in children with ADHD.Fourteen boys (10-14 years) diagnosed with ADHD were included. In a randomized, double-blind, cross-over design, patients received so-tDCS either in the first or in the second experimental sleep night. Inhibition control was assessed with a visuomotor go/no-go task. Intrinsic alertness was assessed with a simple stimulus response task. To control for visuomotor performance, motor memory was assessed with a finger sequence tapping task.SO-power was enhanced during early non-REM sleep, accompanied by slowed reaction times and decreased standard deviations of reaction times, in the go/no-go task after so-tDCS. In contrast, intrinsic alertness, and motor memory performance were not improved by so-tDCS.Since behavioral inhibition but not intrinsic alertness or motor memory was improved by so-tDCS, our results suggest that lateral prefrontal slow oscillations during sleep might play a specific role for executive functioning in ADHD.

Frontiers in cellular neuroscience

Munz, MT; Prehn-Kristensen, A; Thielking, F; Mölle, M; Göder, R; Baving, L

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Spreading Effect of tDCS in Individuals with Attention-Deficit/Hyperactivity Disorder as Shown by Functional Cortical Networks: A Randomized, Double-Blind, Sham-Controlled Trial.

2015

Transcranial direct current stimulation (tDCS) is known to modulate spontaneous neural network excitability. The cognitive improvement observed in previous trials raises the potential of this technique as a possible therapeutic tool for use in attention-deficit/hyperactivity disorder (ADHD) population. However, to explore the potential of this technique as a treatment approach, the functional parameters of brain connectivity and the extent of its effects need to be more fully investigated.The aim of this study was to investigate a functional cortical network (FCN) model based on electroencephalographic activity for studying the dynamic patterns of brain connectivity modulated by tDCS and the distribution of its effects in individuals with ADHD.Sixty ADHD patients participated in a parallel, randomized, double-blind, sham-controlled trial. Individuals underwent a single session of sham or anodal tDCS at 1 mA of current intensity over the left dorsolateral prefrontal cortex for 20 min. The acute effects of stimulation on brain connectivity were assessed using the FCN model based on electroencephalography activity.Comparing the weighted node degree within groups prior to and following the intervention, a statistically significant difference was found in the electrodes located on the target and correlated areas in the active group (p < 0.05), while no statistically significant results were found in the sham group (p ≥ 0.05; paired-sample Wilcoxon signed-rank test).Anodal tDCS increased functional brain connectivity in individuals with ADHD compared to data recorded in the baseline resting state. In addition, although some studies have suggested that the effects of tDCS are selective, the present findings show that its modulatory activity spreads. Further studies need to be performed to investigate the dynamic patterns and physiological mechanisms underlying the modulatory effects of tDCS.ClinicalTrials.gov NCT01968512.

Frontiers in psychiatry

Cosmo, C; Ferreira, C; Miranda, JG; do Rosário, RS; Baptista, AF; Montoya, P; de Sena, EP

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Combined exercise and transcranial direct current stimulation intervention for knee osteoarthritis: protocol for a pilot randomised controlled trial.

2015

Osteoarthritis (OA) is a major health problem and a leading cause of disability. The knee joint is commonly affected, resulting in pain and physical dysfunction. Exercise is considered the cornerstone of conservative management, yet meta-analyses indicate, at best, moderate effect sizes. Treatments that bolster the effects of exercise, such as transcranial direct current stimulation (tDCS), may improve outcomes in knee OA. The aims of this pilot study are to (1) determine the feasibility, safety and perceived patient response to a combined tDCS and exercise intervention in knee OA, and (2) provide data to support a sample size calculation for a fully-powered trial should trends of effectiveness be present.A pilot randomised, assessor-blind and participant-blind, sham-controlled trial. 20 individuals with knee OA who report a pain score of 40 or more on a 100 mm visual analogue scale on walking, and meet a priori selection criteria will be randomly allocated to receive either: (1) active tDCS plus exercise, or (2) sham tDCS plus exercise. All participants will receive 20 min of either active or sham tDCS immediately prior to 30 min of supervised muscle strengthening exercise twice a week for 8 weeks. Participants in both groups will also complete unsupervised home exercises twice per week. Outcome measures of feasibility, safety, pain, disability and pain system function will be assessed immediately before and after the 8-week intervention. Analyses of feasibility and safety will be performed using descriptive statistics. Statistical analyses will be used to determine trends of effectiveness and will be based on intention-to-treat as well as per protocol.This study was approved by the institutional ethics committee (H10184). Written informed consent will be obtained from all participants. The results of this study will be submitted for peer-reviewed publication.ANZCTR365331.

BMJ open

Chang, WJ; Bennell, KL; Hodges, PW; Hinman, RS; Liston, MB; Schabrun, SM

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Effects of Transcranial Direct Current Stimulation on the Recognition of Bodily Emotions from Point-Light Displays.

2015

Perceiving human motion, recognizing actions, and interpreting emotional body language are tasks we perform daily and which are supported by a network of brain areas including the human posterior superior temporal sulcus (pSTS). Here, we applied transcranial direct current stimulation (tDCS) with anodal (excitatory) or cathodal (inhibitory) electrodes mounted over right pSTS (target) and orbito-frontal cortex (reference) while healthy participants performed a bodily emotion recognition task using biological motion point-light displays (PLDs). Performance (accuracy and reaction times) was also assessed on a control task which was matched to the emotion recognition task in terms of cognitive and motor demands. Each subject participated in two experimental sessions, receiving either anodal or cathodal stimulation, which were separated by one week to avoid residual effects of previous stimulations. Overall, tDCS brain stimulation did not affect the recognition of emotional states from PLDs. However, when emotions with a negative or positive-neutral emotional valence were analyzed separately, effects of stimulation were shown for recognizing emotions with a negative emotional valence (sadness and anger), indicating increased recognition performance when receiving anodal (excitatory) stimulation compared to cathodal (inhibitory) stimulation over pSTS. No stimulation effects were shown for the recognition of emotions with positive-neutral emotional valences. These findings extend previous studies showing structure-function relationships between STS and biological motion processing from PLDs and provide indications that stimulation effects may be modulated by the emotional valence of the stimuli.

Frontiers in human neuroscience

Vonck, S; Swinnen, SP; Wenderoth, N; Alaerts, K

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A Randomized, Double-Blind, Sham-Controlled Trial of Transcranial Direct Current Stimulation in Attention-Deficit/Hyperactivity Disorder.

2015

Current standardized treatments for cognitive impairment in attention-deficit/hyperactivity disorder remain limited and their efficacy restricted. Transcranial direct current stimulation (tDCS) is a promising tool for enhancing cognitive performance in several neuropsychiatric disorders. Nevertheless, the effects of tDCS in reducing cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD) have not yet been investigated.A parallel, randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on the modulation of inhibitory control in adults with ADHD. Thirty patients were randomly allocated to each group and performed a go/no-go task before and after a single session of either anodal stimulation (1 mA) over the left dorsolateral prefrontal cortex or sham stimulation.A nonparametric two-sample Wilcoxon rank-sum (Mann-Whitney) test revealed no significant differences between the two groups of individuals with ADHD (tDCS vs. sham) in regard to behavioral performance in the go/no go tasks. Furthermore, the effect sizes of group differences after treatment for the primary outcome measures-correct responses, impulsivity and omission errors--were small. No adverse events resulting from stimulation were reported.According to these findings, there is no evidence in support of the use of anodal stimulation over the left dorsolateral prefrontal cortex as an approach for improving inhibitory control in ADHD patients. To the best of our knowledge, this is the first clinical study to assess the cognitive effects of tDCS in individuals with ADHD. Further research is needed to assess the clinical efficacy of tDCS in this population.ClinicalTrials.gov NCT01968512.

PloS one

Cosmo, C; Baptista, AF; de Araújo, AN; do Rosário, RS; Miranda, JG; Montoya, P; de Sena, EP

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Effect of the Interindividual Variability on Computational Modeling of Transcranial Direct Current Stimulation.

2015

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. This paper investigates how normal variations in anatomy may affect the current flow through the brain. This was done by applying electromagnetic computational methods to human models of different age and gender and by comparing the electric field and current density amplitude distributions within the tissues. Results of this study showed that the general trend of the spatial distributions of the field amplitude shares some gross characteristics among the different human models for the same electrode montages. However, the physical dimension of the subject and his/her morphological and anatomical characteristics somehow influence the detailed field distributions such as the field values.

Computational intelligence and neuroscience

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

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The combined effects of neurostimulation and priming on creative thinking. A preliminary tDCS study on dorsolateral prefrontal cortex.

2015

The role of prefrontal cortex (PFC) in influencing creative thinking has been investigated by many researchers who, while succeeding in proving an effective involvement of PFC, reported suggestive but sometimes conflicting results. In order to better understand the relationships between creative thinking and brain activation in a more specific area of the PFC, we explored the role of dorsolateral PFC (DLPFC). We devised an experimental protocol using transcranial direct-current stimulation (tDCS). The study was based on a 3 (kind of stimulation: anodal vs. cathodal vs. sham) × 2 (priming: divergent vs. convergent) design. Forty-five healthy adults were randomly assigned to one stimulation condition. Participants' creativity skills were assessed using the Product Improvement subtest from the Torrance Tests of Creative Thinking (TTCT). After 20 min of tDCS stimulation, participants were presented with visual images of common objects. Half of the participants were instructed to visualize themselves using the object in an unusual way (divergent priming), whereas the other half were asked to visualize themselves while using the object in a common way (convergent priming). Priming was aimed at inducing participants to adopt different attitudes toward the creative task. Afterwards, participants were asked to describe all of the possible uses of the objects that were presented. Participants' physiological activation was recorded using a biofeedback equipment. Results showed a significant effect of anodal stimulation that enhanced creative performance, but only after divergent priming. Participants showed lower skin temperature values after cathodal stimulation, a finding which is coherent with studies reporting that, when a task is not creative or creative thinking is not prompted, people show lower levels of arousal. Differences in individual levels of creativity as assessed by the Product Improvement test were not influential. The involvement of DLPFC in creativity has been supported, presumably in association to shift of attention modulated by priming.

Frontiers in human neuroscience

Colombo, B; Bartesaghi, N; Simonelli, L; Antonietti, A

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State-of-art neuroanatomical target analysis of high-definition and conventional tDCS montages used for migraine and pain control.

2015

Although transcranial direct current stimulation (tDCS) studies promise to modulate cortical regions associated with pain, the electric current produced usually spreads beyond the area of the electrodes' placement. Using a forward-model analysis, this study compared the neuroanatomic location and strength of the predicted electric current peaks, at cortical and subcortical levels, induced by conventional and High-Definition-tDCS (HD-tDCS) montages developed for migraine and other chronic pain disorders. The electrodes were positioned in accordance with the 10-20 or 10-10 electroencephalogram (EEG) landmarks: motor cortex-supraorbital (M1-SO, anode and cathode over C3 and Fp2, respectively), dorsolateral prefrontal cortex (PFC) bilateral (DLPFC, anode over F3, cathode over F4), vertex-occipital cortex (anode over Cz and cathode over Oz), HD-tDCS 4 × 1 (one anode on C3, and four cathodes over Cz, F3, T7, and P3) and HD-tDCS 2 × 2 (two anodes over C3/C5 and two cathodes over FC3/FC5). M1-SO produced a large current flow in the PFC. Peaks of current flow also occurred in deeper brain structures, such as the cingulate cortex, insula, thalamus and brainstem. The same structures received significant amount of current with Cz-Oz and DLPFC tDCS. However, there were differences in the current flow to outer cortical regions. The visual cortex, cingulate and thalamus received the majority of the current flow with the Cz-Oz, while the anterior parts of the superior and middle frontal gyri displayed an intense amount of current with DLPFC montage. HD-tDCS montages enhanced the focality, producing peaks of current in subcortical areas at negligible levels. This study provides novel information regarding the neuroanatomical distribution and strength of the electric current using several tDCS montages applied for migraine and pain control. Such information may help clinicians and researchers in deciding the most appropriate tDCS montage to treat each pain disorder.

Frontiers in neuroanatomy

DaSilva, AF; Truong, DQ; DosSantos, MF; Toback, RL; Datta, A; Bikson, M

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The temporary and accumulated effects of transcranial direct current stimulation for the treatment of advanced Parkinson's disease monkeys.

2015

Transcranial direct current stimulation (tDCS) is a useful noninvasive technique of cortical brain stimulation for the treatment of neurological disorders. Clinical research has demonstrated tDCS with anodal stimulation of primary motor cortex (M1) in Parkinson's disease (PD) patients significantly improved their motor function. However, few studies have been focused on the optimization of parameters which contributed significantly to the treatment effects of tDCS and exploration of the underline neuronal mechanisms. Here, we used different stimulation parameters of anodal tDCS on M1 for the treatment of aged advanced PD monkeys induced with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) administration, and then analyzed the temporary and accumulated effects of tDCS treatment. The results indicated anodal tDCS on M1 very significantly improved motor ability temporarily; importantly, the treatment effects of anodal tDCS on M1 were quantitatively correlated to the accumulated stimulation instead of the stimuli intensity or duration respectively. In addition, c-fos staining showed tDCS treatment effects activated the neurons both in M1 and substantia nigra (SN). Therefore, we propose that long time and continue anodal tDCS on M1 is a better strategy to improve the motor symptoms of PD than individual manipulation of stimuli intensity or duration.

Scientific reports

Li, H; Lei, X; Yan, T; Li, H; Huang, B; Li, L; Xu, L; Liu, L; Chen, N; Lü, L; Ma, Y; Xu, L; Li, J; Wang, Z; Zhang, B; Hu, X

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Brain Plasticity Effects of Neuromodulation Against Multiple Sclerosis Fatigue.

2015

We recently reported on the efficacy of a personalized transcranial direct current stimulation (tDCS) treatment in reducing multiple sclerosis (MS) fatigue. The result supports the notion that interventions targeted at modifying abnormal excitability within the sensorimotor network could represent valid non-pharmacological treatments.The present work aimed at assessing whether the mentioned intervention also induces changes in the excitability of sensorimotor cortical areas.Two separate groups of fatigued MS patients were given a 5-day tDCS treatments targeting, respectively, the whole body somatosensory areas (S1wb) and the hand sensorimotor areas (SM1hand). The study had a double blind, sham-controlled, randomized, cross-over (Real vs. Sham) design. Before and after each treatment, we measured fatigue levels (by the modified fatigue impact scale, mFIS), motor evoked potentials (MEPs) in response to transcranial magnetic stimulation and somatosensory evoked potentials (SEPs) in response to median nerve stimulation. We took MEPs and SEPs as measures of the excitability of the primary motor area (M1) and the primary somatosensory area (S1), respectively.The Real S1wb treatment produced a 27% reduction of the mFIS baseline level, while the SM1hand treatment showed no difference between Real and Sham stimulations. M1 excitability increased on average 6% of the baseline in the S1wb group and 40% in the SM1hand group. Observed SEP changes were not significant and we found no association between M1 excitability changes and mFIS decrease.The tDCS treatment was more effective against MS fatigue when the electrode was focused on the bilateral whole body somatosensory area. Changes in S1 and M1 excitability did not correlate with symptoms amelioration.The neuromodulation treatment that proved effective against MS fatigue induced only minor variations of the motor cortex excitability, not enough to explain the beneficial effects of the intervention.

Frontiers in neurology

Tecchio, F; Cancelli, A; Cottone, C; Ferrucci, R; Vergari, M; Zito, G; Pasqualetti, P; Filippi, MM; Ghazaryan, A; Lupoi, D; Smits, FM; Giordani, A; Migliore, S; Porcaro, C; Salustri, C; Rossini, PM; Priori, A

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Anodal Transcranial Pulsed Current Stimulation: The Effects of Pulse Duration on Corticospinal Excitability.

2015

The aim is to investigate the effects of pulse duration (PD) on the modulatory effects of transcranial pulsed current (tPCS) on corticospinal excitability (CSE). CSE of the dominant primary motor cortex (M1) of right first dorsal interosseous muscle was assessed by motor evoked potentials, before, immediately, 10, 20 and 30 minutes after application of five experimental conditions: 1) anodal transcranial direct current stimulation (a-tDCS), 2) a-tPCS with 125 ms pulse duartion (a-tPCSPD = 125), 3) a-tPCS with 250 ms pulse duration (a-tPCSPD = 250), 4) a-tPCS with 500 ms pulse duration (a-tPCSPD = 500) and 5) sham a-tPCS. The total charges were kept constant in all experimental conditions except sham condition. Post-hoc comparisons indicated that a-tPCSPD = 500 produced larger CSE compared to a-tPCSPD = 125 (P<0.0001), a-tPCSPD = 250 (P = 0.009) and a-tDCS (P = 0.008). Also, there was no significant difference between a-tPCSPD = 250 and a-tDCS on CSE changes (P>0.05). All conditions except a-tPCSPD = 125 showed a significant difference to the sham group (P<0.006). All participants tolerated the applied currents. It could be concluded that a-tPCS with a PD of 500ms induces largest CSE changes, however further studies are required to identify optimal values.

PloS one

Jaberzadeh, S; Bastani, A; Zoghi, M; Morgan, P; Fitzgerald, PB

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Clinical utility of brain stimulation modalities following traumatic brain injury: current evidence.

2015

Traumatic brain injury (TBI) remains the main cause of disability and a major public health problem worldwide. This review focuses on the neurophysiology of TBI, and the rationale and current state of evidence of clinical application of brain stimulation to promote TBI recovery, particularly on consciousness, cognitive function, motor impairments, and psychiatric conditions. We discuss the mechanisms of different brain stimulation techniques including major noninvasive and invasive stimulations. Thus far, most noninvasive brain stimulation interventions have been nontargeted and focused on the chronic phase of recovery after TBI. In the acute stages, there is limited available evidence of the efficacy and safety of brain stimulation to improve functional outcomes. Comparing the studies across different techniques, transcranial direct current stimulation is the intervention that currently has the higher number of properly designed clinical trials, though total number is still small. We recognize the need for larger studies with target neuroplasticity modulation to fully explore the benefits of brain stimulation to effect TBI recovery during different stages of recovery.

Neuropsychiatric disease and treatment

Li, S; Zaninotto, AL; Neville, IS; Paiva, WS; Nunn, D; Fregni, F

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No Effects of Bilateral tDCS over Inferior Frontal Gyrus on Response Inhibition and Aggression.

2015

Response inhibition is defined as the capacity to adequately withdraw pre-planned responses. It has been shown that individuals with deficits in inhibiting pre-planned responses tend to display more aggressive behaviour. The prefrontal cortex is involved in both, response inhibition and aggression. While response inhibition is mostly associated with predominantly right prefrontal activity, the neural components underlying aggression seem to be left-lateralized. These differences in hemispheric dominance are conceptualized in cortical asymmetry theories on motivational direction, which assign avoidance motivation (relevant to inhibit responses) to the right and approach motivation (relevant for aggressive actions) to the left prefrontal cortex. The current study aimed to directly address the inverse relationship between response inhibition and aggression by assessing them within one experiment. Sixty-nine healthy participants underwent bilateral transcranial Direct Current Stimulation (tDCS) to the inferior frontal cortex. In one group we induced right-hemispheric fronto-cortical dominance by means of a combined right prefrontal anodal and left prefrontal cathodal tDCS montage. In a second group we induced left-hemispheric fronto-cortical dominance by means of a combined left prefrontal anodal and right prefrontal cathodal tDCS montage. A control group received sham stimulation. Response inhibition was assessed with a go/no-go task (GNGT) and aggression with the Taylor Aggression Paradigm (TAP). We revealed that participants with poorer performance in the GNGT displayed more aggression during the TAP. No effects of bilateral prefrontal tDCS on either response inhibition or aggression were observed. This is at odds with previous brain stimulation studies applying unilateral protocols. Our results failed to provide evidence in support of the prefrontal cortical asymmetry model in the domain of response inhibition and aggression. The absence of tDCS effects might also indicate that the methodological approach of shifting cortical asymmetry by means of bilateral tDCS protocols has failed.

PloS one

Dambacher, F; Schuhmann, T; Lobbestael, J; Arntz, A; Brugman, S; Sack, AT

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Task-concurrent anodal tDCS modulates bilateral plasticity in the human suprahyoid motor cortex.

2015

Transcranial direct current stimulation (tDCS) is a non-invasive method to modulate cortical excitability in humans. Here, we examined the effects of anodal tDCS on suprahyoid motor evoked potentials (MEP) when applied over the hemisphere with stronger and weaker suprahyoid/submental projections, respectively, while study participants performed a swallowing task. Thirty healthy volunteers were invited to two experimental sessions and randomly assigned to one of two different groups. While in the first group stimulation was targeted over the hemisphere with stronger suprahyoid projections, the second group received stimulation over the weaker suprahyoid projections. tDCS was applied either as anodal or sham stimulation in a random cross-over design. Suprahyoid MEPs were assessed immediately before intervention, as well as 5, 30, 60, and 90 min after discontinuation of stimulation from both the stimulated and non-stimulated contralateral hemisphere. We found that anodal tDCS (a-tDCS) had long-lasting effects on suprahyoid MEPs on the stimulated side in both groups (tDCS targeting the stronger projections: F (1,14) = 96.2, p < 0.001; tDCS targeting the weaker projections: F (1,14) = 37.45, p < 0.001). While MEPs did not increase when elicited from the non-targeted hemisphere after stimulation of the stronger projections (F (1,14) = 0.69, p = 0.42), we found increased MEPs elicited from the non-targeted hemisphere after stimulating the weaker projections (at time points 30-90 min) (F (1,14) = 18.26, p = 0.001). We conclude that anodal tDCS has differential effects on suprahyoid MEPs elicited from the targeted and non-targeted hemisphere depending on the site of stimulation. This finding may be important for the application of a-tDCS in patients with dysphagia, for example after stroke.

Frontiers in human neuroscience

Zhao, S; Dou, Z; Wei, X; Li, J; Dai, M; Wang, Y; Yang, Q; He, H

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Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity.

2015

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain-behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the br

NeuroImage. Clinical

Val-Laillet, D; Aarts, E; Weber, B; Ferrari, M; Quaresima, V; Stoeckel, LE; Alonso-Alonso, M; Audette, M; Malbert, CH; Stice, E

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Duration-dependent effects of the BDNF Val66Met polymorphism on anodal tDCS induced motor cortex plasticity in older adults: a group and individual perspective.

2015

The brain derived neurotrophic factor (BDNF) Val66Met polymorphism and stimulation duration are thought to play an important role in modulating motor cortex plasticity induced by non-invasive brain stimulation (NBS). In the present study we sought to determine whether these factors interact or exert independent effects in older adults. Fifty-four healthy older adults (mean age = 66.85 years) underwent two counterbalanced sessions of 1.5 mA anodal transcranial direct current stimulation (atDCS), applied over left M1 for either 10 or 20 min. Single pulse transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability (CSE) before and every 5 min for 30 min following atDCS. On a group level, there was an interaction between stimulation duration and BDNF genotype, with Met carriers (n = 13) showing greater post-intervention potentiation of CSE compared to Val66Val homozygotes homozygotes (n = 37) following 20 min (p = 0.002) but not 10 min (p = 0.219) of stimulation. Moreover, Met carriers, but not Val/Val homozygotes, exhibited larger responses to TMS (p = 0.046) after 20 min atDCS, than following 10 min atDCS. On an individual level, two-step cluster analysis revealed a considerable degree of inter-individual variability, with under half of the total sample (42%) showing the expected potentiation of CSE in response to atDCS across both sessions. Intra-individual variability in response to different durations of atDCS was also apparent, with one-third of the total sample (34%) exhibiting LTP-like effects in one session but LTD-like effects in the other session. Both the inter-individual (p = 0.027) and intra-individual (p = 0.04) variability was associated with BDNF genotype. In older adults, the BDNF Val66Met polymorphism along with stimulation duration appears to play a role in modulating tDCS-induced motor cortex plasticity. The results may have implications for the design of NBS protocols for healthy and diseased aged populations.

Frontiers in aging neuroscience

Puri, R; Hinder, MR; Fujiyama, H; Gomez, R; Carson, RG; Summers, JJ

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The relevance of aging-related changes in brain function to rehabilitation in aging-related disease.

2015

The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered.

Frontiers in human neuroscience

Crosson, B; McGregor, KM; Nocera, JR; Drucker, JH; Tran, SM; Butler, AJ

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Researchers' perspectives on scientific and ethical issues with transcranial direct current stimulation: An international survey.

2015

In the last decade, an increasing number of studies have suggested that transcranial direct current stimulation (tDCS) may enhance brain function in healthy individuals, and ameliorate cognitive and other symptoms in patients suffering from various medical conditions. This, along with its presumed safety, simplicity, and affordability, has generated great enthusiasm amongst researchers, clinicians, patient populations, and the public (including a growing "do-it-yourself" community). However, discussion about the effectiveness and ethics of tDCS thus far has been confined to small groups of tDCS researchers and bioethicists. We conducted an international online survey targeting the opinions of researchers using tDCS who were asked to rate the technique's efficacy in different contexts. We also surveyed opinions about ethical concerns, self-enhancement and public availability. 265 complete responses were received and analyzed statistically and thematically. Our results emphasize the potential uses of tDCS in clinical and research contexts, but also highlight a number of emerging methodological and safety concerns, ethical challenges and the need for improved communication between researchers and bioethicists with regard to regulation of the device. Neither the media reputation of tDCS as a "miracle device" nor concerns expressed in recent neuroethical publications were entirely borne out in expert opinion.

Scientific reports

Riggall, K; Forlini, C; Carter, A; Hall, W; Weier, M; Partridge, B; Meinzer, M

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A Randomized Placebo-Controlled Trial of Targeted Prefrontal Cortex Modulation with Bilateral tDCS in Patients with Crack-Cocaine Dependence.

2015

Transcranial direct current stimulation over the dorsolateral prefrontal cortex has been shown to be clinically useful in the treatment of drug addiction.We conducted a double-blind randomized clinical trial aiming to assess the effects of bilateral dorsolateral prefrontal cortex transcranial direct current stimulation (left cathodal/right anodal) on crack-cocaine addiction. We defined craving as the primary outcome, and other clinical measurements, including depressive and anxiety symtoms, and quality of life, as secondary outcomes. Seventeen male crack-cocaine users (mean age 30.4±9.8 SD) were randomized to receive 5 sessions of active transcranial direct current stimulation (2 mA, 35cm(2), for 20 minutes), every other day, and 19 males (mean age 30.3±8.4 SD) to receive sham-transcranial direct current stimulation (placebo) as control group.Craving scores were significantly reduced in the transcranial direct current stimulation group after treatment when compared with sham-transcranial direct current stimulation (P=.028) and baseline values (P=.003), and decreased linearly over 4 weeks (before, during, and after treatment) in the transcranial direct current stimulation group only (P=.047). Changes of anxiety scores towards increase in the sham-transcranial direct current stimulation and decrease in the transcranial direct current stimulation group (P=.03), and of the overall perception of quality of life (P=.031) and of health (P=.048) towards decrease in the sham-transcranial direct current stimulation group and increase in the transcranial direct current stimulation group differed significantly between groups.Repetitive bilateral transcranial direct current stimulation over the dorsolateral prefrontal cortex reduced craving for crack-cocaine use, decreased anxiety, and improved quality of life. We hypothesize that transcranial direct current stimulation effects may be associated with increased prefrontal processing and regulation of craving behavior.

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

Batista, EK; Klauss, J; Fregni, F; Nitsche, MA; Nakamura-Palacios, EM

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Blending transcranial direct current stimulations and physical exercise to maximize cognitive improvement.

2015

Frontiers in psychology

Moreau, D; Wang, CH; Tseng, P; Juan, CH

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Anodal transcranial direct current stimulation to the cerebellum improves handwriting and cyclic drawing kinematics in focal hand dystonia.

2015

There is increasing evidence that the cerebellum has a role in the pathophysiology of primary focal hand dystonia and might provide an intervention target for non-invasive brain stimulation to improve function of the affected hand. The primary objective of this study was to determine if cerebellar transcranial direct current stimulation (tDCS) improves handwriting and cyclic drawing kinematics in people with hand dystonia, by reducing cerebellar-brain inhibition (CBI) evoked by transcranial magnetic stimulation (TMS). Eight people with dystonia (5 writer's dystonia, 3 musician's dystonia) and eight age-matched controls completed the study and underwent cerebellar anodal, cathodal and sham tDCS in separate sessions. Dystonia severity was assessed using the Writer's Cramp Rating Scale (WRCS) and the Arm Dystonia Disability Scale (ADDS). The kinematic measures that differentiated the groups were; mean stroke frequency during handwriting and fast cyclic drawing and average pen pressure during light cyclic drawing. TMS measures of cortical excitability were no different between people with FHD and controls. There was a moderate, negative relationship between TMS-evoked CBI at baseline and the WRCS in dystonia. Anodal cerebellar tDCS reduced handwriting mean stroke frequency and average pen pressure, and increased speed and reduced pen pressure during fast cyclic drawing. Kinematic measures were not associated with a decrease in CBI within an individual. In conclusion, cerebellar anodal tDCS appeared to improve kinematics of handwriting and circle drawing tasks; but the underlying neurophysiological mechanism remains uncertain. A study in a larger homogeneous population is needed to further investigate the possible therapeutic benefit of cerebellar tDCS in dystonia.

Frontiers in human neuroscience

Bradnam, LV; Graetz, LJ; McDonnell, MN; Ridding, MC

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Polarity-specific transcranial direct current stimulation disrupts auditory pitch learning.

2015

Transcranial direct current stimulation (tDCS) is attracting increasing interest because of its potential for therapeutic use. While its effects have been investigated mainly with motor and visual tasks, less is known in the auditory domain. Past tDCS studies with auditory tasks demonstrated various behavioral outcomes, possibly due to differences in stimulation parameters, task-induced brain activity, or task measurements used in each study. Further research, using well-validated tasks is therefore required for clarification of behavioral effects of tDCS on the auditory system. Here, we took advantage of findings from a prior functional magnetic resonance imaging study, which demonstrated that the right auditory cortex is modulated during fine-grained pitch learning of microtonal melodic patterns. Targeting the right auditory cortex with tDCS using this same task thus allowed us to test the hypothesis that this region is causally involved in pitch learning. Participants in the current study were trained for 3 days while we measured pitch discrimination thresholds using microtonal melodies on each day using a psychophysical staircase procedure. We administered anodal, cathodal, or sham tDCS to three groups of participants over the right auditory cortex on the second day of training during performance of the task. Both the sham and the cathodal groups showed the expected significant learning effect (decreased pitch threshold) over the 3 days of training; in contrast we observed a blocking effect of anodal tDCS on auditory pitch learning, such that this group showed no significant change in thresholds over the 3 days. The results support a causal role for the right auditory cortex in pitch discrimination learning.

Frontiers in neuroscience

Matsushita, R; Andoh, J; Zatorre, RJ

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Non-invasive brain stimulation: an interventional tool for enhancing behavioral training after stroke.

2015

Stroke is the leading cause of disability among adults. Motor deficit is the most common impairment after stroke. Especially, deficits in fine motor skills impair numerous activities of daily life. Re-acquisition of motor skills resulting in improved or more accurate motor performance is paramount to regain function, and is the basis of behavioral motor therapy after stroke. Within the past years, there has been a rapid technological and methodological development in neuroimaging leading to a significant progress in the understanding of the neural substrates that underlie motor skill acquisition and functional recovery in stroke patients. Based on this and the development of novel non-invasive brain stimulation (NIBS) techniques, new adjuvant interventional approaches that augment the response to behavioral training have been proposed. Transcranial direct current, transcranial magnetic, and paired associative (PAS) stimulation are NIBS techniques that can modulate cortical excitability, neuronal plasticity and interact with learning and memory in both healthy individuals and stroke patients. These techniques can enhance the effect of practice and facilitate the retention of tasks that mimic daily life activities. The purpose of the present review is to provide a comprehensive overview of neuroplastic phenomena in the motor system during learning of a motor skill, recovery after brain injury, and of interventional strategies to enhance the beneficial effects of customarily used neurorehabilitation after stroke.

Frontiers in human neuroscience

Wessel, MJ; Zimerman, M; Hummel, FC

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The effect of transcranial direct current stimulation on the expression of the flexor synergy in the paretic arm in chronic stroke is dependent on shoulder abduction loading.

2015

Reaching ability of the paretic upper extremity in individuals with stroke decreases with increased shoulder abduction (SABD) loads. Transcranial direct current stimulation (tDCS) has been implemented to improve movement ability following stroke. However, results from previous studies vary, perhaps due to the influence of impairment level and the type of motor tasks that were used to study the effects of tDCS. This study specifically examines the impact of SABD loading on the effects of tDCS in 9 individuals with moderate to severe chronic stroke. In 3 different sessions, participants repeated a reaching assessment with various SABD loads (supported on a haptic table, 25%, and 50% of maximum voluntary SABD torque) in random order, pre and post one of the following 15-min tDCS protocols: anodal stimulation of lesioned M1, cathodal stimulation of non-lesioned M1, or anodal stimulation of non-lesioned M1. Sham stimulation was also conducted preceding one of the tDCS sessions. The averaged maximum reaching distance over valid trials was calculated for each condition. We observed significant interactions between SABD load, tDCS protocol and time (i.e., pre or post-tDCS). Post hoc test showed that anodal stimulation of the lesioned M1 caused a clear trend (p = 0.058) of increasing the reaching ability at a medium level of SABD loading (25%), but not for higher loads (50%). This suggests that anodal stimulation increases residual corticospinal tract activity, which successfully increases reaching ability at moderate loads; however, is insufficient to make significant changes at higher SABD loads. We also found that cathodal stimulation of the non-lesioned M1 significantly (p = 0.018) decreased the reaching distance at a high level of SABD loading (50%). This study demonstrated, for the first time, that the effect of tDCS on the reaching ability is dependent on SABD loads in individuals with moderate to severe stroke.

Frontiers in human neuroscience

Yao, J; Drogos, J; Veltink, F; Anderson, C; Concha Urday Zaa, J; Hanson, LI; Dewald, JP

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The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies.

2015

There has been an explosion of research using transcranial direct current stimulation (tDCS) for investigating and modulating human cognitive and motor function in healthy populations. It has also been used in many studies seeking to improve deficits in disease populations. With the slew of studies reporting "promising results" for everything from motor recovery after stroke to boosting memory function, one could be easily seduced by the idea of tDCS being the next panacea for all neurological ills. However, huge variability exists in the reported effects of tDCS, with great variability in the effect sizes and even contradictory results reported. In this review, we consider the interindividual factors that may contribute to this variability. In particular, we discuss the importance of baseline neuronal state and features, anatomy, age and the inherent variability in the injured brain. We additionally consider how interindividual variability affects the results of motor-evoked potential (MEP) testing with transcranial magnetic stimulation (TMS), which, in turn, can lead to apparent variability in response to tDCS in motor studies.

Frontiers in cellular neuroscience

Li, LM; Uehara, K; Hanakawa, T

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Anodal tDCS over the Primary Motor Cortex Facilitates Long-Term Memory Formation Reflecting Use-Dependent Plasticity.

2015

Previous research suggests that anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) modulates NMDA receptor dependent processes that mediate synaptic plasticity. Here we test this proposal by applying anodal versus sham tDCS while subjects practiced to flex the thumb as fast as possible (ballistic movements). Repetitive practice of this task has been shown to result in performance improvements that reflect use-dependent plasticity resulting from NMDA receptor mediated, long-term potentiation (LTP)-like processes. Using a double-blind within-subject cross-over design, subjects (n=14) participated either in an anodal or a sham tDCS session which were at least 3 months apart. Sham or anodal tDCS (1 mA) was applied for 20 min during motor practice and retention was tested 30 min, 24 hours and one week later. All subjects improved performance during each of the two sessions (p < 0.001) and learning gains were similar. Our main result is that long term retention performance (i.e. 1 week after practice) was significantly better when practice was performed with anodal tDCS than with sham tDCS (p < 0.001). This effect was large (Cohen's d=1.01) and all but one subject followed the group trend. Our data strongly suggest that anodal tDCS facilitates long-term memory formation reflecting use-dependent plasticity. Our results support the notion that anodal tDCS facilitates synaptic plasticity mediated by an LTP-like mechanism, which is in accordance with previous research.

PloS one

Rroji, O; van Kuyck, K; Nuttin, B; Wenderoth, N

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Contribution of transcranial direct current stimulation on inhibitory control to assess the neurobiological aspects of attention deficit hyperactivity disorder: randomized controlled trial.

2015

The applicability of transcranial direct current stimulation (tDCS) in individuals with attention deficit hyperactivity disorder (ADHD) has not yet been investigated. This low-cost, non-invasive, and safe technique optimized to modulate the inhibitory response might be a useful treatment option for those affected by this condition.The aim of this single center, parallel, randomized, double-blinded, sham-controlled trial is to investigate the efficacy of transcranial direct current stimulation over the prefrontal cortex on the modulation of inhibitory control in adults with attention deficit hyperactivity disorder.A total of 60 individuals will be divided into 2 groups by block randomization to receive active or sham stimulation. Anodal stimulation over the left dorsolateral prefrontal cortex will be applied at 1 mA during a single 20-minute session. Before and after interventions, subjects will perform 2 go/no go tasks and the brain electrical activity will be recorded by electroencephalogram (EEG) with 32 channels, according to the 10-20 international EEG system.The trial began in May 2013 and we are currently performing the statistical analysis for the secondary outcomes.The findings from this study will provide preliminary results about the role of prefrontal cortex activation through tDCS on ADHD patients.Clinicaltrials.gov NCT01968512; http://clinicaltrials.gov/ct2/show/NCT01968512 (Archived by WebCite at www.webcitation.org/6YMSW2tkD).

JMIR research protocols

Cosmo, C; Baptista, AF; de Sena, EP

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Transcranial direct current stimulation of the left dorsolateral prefrontal cortex shifts preference of moral judgments.

2015

Attitude to morality, reflecting cultural norms and values, is considered unique to human social behavior. Resulting moral behavior in a social environment is controlled by a widespread neural network including the dorsolateral prefrontal cortex (DLPFC), which plays an important role in decision making. In the present study we investigate the influence of neurophysiological modulation of DLPFC reactivity by means of transcranial direct current stimulation (tDCS) on moral reasoning. For that purpose we administered anodal, cathodal, and sham stimulation of the left DLPFC while subjects judged the appropriateness of hard moral personal dilemmas. In contrast to sham and cathodal stimulation, anodal stimulation induced a shift in judgment of personal moral dilemmas towards more non-utilitarian actions. Our results demonstrate that alterations of left DLPFC activity can change moral judgments and, in consequence, provide a causal link between left DLPFC activity and moral reasoning. Most important, the observed shift towards non-utilitarian actions suggests that moral decision making is not a permanent individual trait but can be manipulated; consequently individuals with boundless, uncontrollable, and maladaptive moral behavior, such as found in psychopathy, might benefit from neuromodulation-based approaches.

PloS one

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

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Structural white matter changes in descending motor tracts correlate with improvements in motor impairment after undergoing a treatment course of tDCS and physical therapy.

2015

Motor impairment after stroke has been related to the structural and functional integrity of corticospinal tracts including multisynaptic motor fibers and tracts such as the cortico-rubral-spinal and the cortico-tegmental-spinal tract. Furthermore, studies have shown that the concurrent use of transcranial direct current stimulation (tDCS) with peripheral sensorimotor activities can improve motor impairment. We examined microstructural effects of concurrent non-invasive bihemispheric stimulation and physical/occupational therapy for 10 days on the structural components of the CST as well as other descending motor tracts which will be referred to here as alternate motor fibers (aMF). In this pilot study, ten chronic patients with a uni-hemispheric stroke underwent Upper-Extremity Fugl-Meyer assessments (UE-FM) and diffusion tensor imaging (DTI) for determining diffusivity measures such as fractional anisotropy (FA) before and after treatment in a section of the CST and aMF that spanned between the lower end of the internal capsule (below each patient's lesion) and the upper pons region on the affected and unaffected hemisphere. The treated group (tDCS + PT/OT) showed significant increases in the proportional UE-FM scores (+21%; SD 10%), while no significant changes were observed in an untreated comparison group. Significant increases in FA (+0.007; SD 0.0065) were found in the ipsilesional aMF in the treated group while no significant changes were found in the contralesional aMF, in either CST, or in any tracts in the untreated group. The FA changes in the ipsilesional aMF significantly correlated with the proportional change in the UE-FM (r = 0.65; p < 0.05). The increase in FA might indicate an increase in motor fiber alignment, myelination, and overall fiber integrity. Crossed and uncrossed fibers from multiple cortical regions might be one reason why the aMF fiber system showed more plastic structural changes that correlate with motor improvements than the CST.

Frontiers in human neuroscience

Zheng, X; Schlaug, G

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A meta-analysis of site-specific effects of cathodal transcranial direct current stimulation on sensory perception and pain.

2015

The primary aim of our meta-analysis was to evaluate the effects of cathodal transcranial direct current stimulation (c-tDCS) on sensory and pain thresholds (STh and PTh) in healthy individuals and pain level (PL) in patients with chronic pain. Electronic databases were searched for c-tDCS studies. Methodological quality was evaluated using the PEDro and Downs and Black (D&B) assessment tools. C-tDCS of the primary motor cortex (S1) increases both STh (P<0.001, effect size of 26.84%) and PTh (P<0.001, effect size of 11.62%). In addition, c-tDCS over M1 led to STh increase (P<0.005, effect size of 30.44%). Likewise, PL decreased significantly in the patient group following application of c-tDCS. The small number of studies precluded subgroup analysis. Nevertheless, meta-analysis showed that in all groups (except c-tDCS of S1) active c-tDCS and sham stimulation produced significant differences in STh/PTh in healthy and PL in patient group. This review provides evidence for the site-specific effectiveness of c-tDCS in increasing STh/PTh in healthy individuals and decreasing PL in patients with chronic pain. However, due to small sample sizes in the included studies, our results should be interpreted with caution. Given that the level of blinding was not considered in the inclusion criteria, the results of the current study should be interpreted with caution.

PloS one

Vaseghi, B; Zoghi, M; Jaberzadeh, S

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Inhibitory non-invasive brain stimulation to homologous language regions as an adjunct to speech and language therapy in post-stroke aphasia: a meta-analysis.

2015

Chronic communication impairment is common after stroke, and conventional speech and language therapy (SLT) strategies have limited effectiveness in post-stroke aphasia. Neurorehabilitation with non-invasive brain stimulation techniques (NIBS)-particularly repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS)-may enhance the effects of SLT in selected patients. Applying inhibitory NIBS to specific homologous language regions may induce neural reorganization and reduce interhemispheric competition. This mini review highlights randomized controlled trials (RCTs) and randomized cross-over trials using low-frequency rTMS or cathodal tDCS over the non-lesioned non-language dominant hemisphere and performs an exploratory meta-analysis of those trials considered combinable. Using a random-effects model, a meta-analysis of nine eligible trials involving 215 participants showed a significant mean effect size of 0.51 (95% CI = 0.24-0.79) for the main outcome "accuracy of naming" in language assessment. No heterogeneity was observed (I (2) = 0%). More multicenter RCTs with larger populations and homogenous intervention protocols are required to confirm these and the longer-term effects.

Frontiers in human neuroscience

Otal, B; Olma, MC; Flöel, A; Wellwood, I

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Understanding public (mis)understanding of tDCS for enhancement.

2015

In order to gain insight into the public's perspective on using the minimally invasive technique transcranial direct current stimulation (tDCS) as an enhancement tool, we analyzed and compared online comments in key popular press articles from two different periods (pre-commercialization and post-commercialization). The main conclusion drawn from this exploratory investigation is that public perception regarding tDCS has shifted from misunderstanding to cautionary realism. This change in attitude can be explained as moving from a focus on an emergent technology to a focus on its applications, benefits, and risks as the technology becomes more grounded within the public domain. Future governance of tDCS should include the concerns and enthusiasms of the public.

Frontiers in integrative neuroscience

Cabrera, LY; Reiner, PB

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Individualized treatment with transcranial direct current stimulation in patients with chronic non-fluent aphasia due to stroke.

2015

While evidence suggests that transcranial direct current stimulation (tDCS) may facilitate language recovery in chronic post-stroke aphasia, individual variability in patient response to different patterns of stimulation remains largely unexplored. We sought to characterize this variability among chronic aphasic individuals, and to explore whether repeated stimulation with an individualized optimal montage could lead to persistent reduction of aphasia severity. In a two-phase study, we first stimulated patients with four active montages (left hemispheric anode or cathode; right hemispheric anode or cathode) and one sham montage (Phase 1). We examined changes in picture naming ability to address (1) variability in response to different montages among our patients, and (2) whether individual patients responded optimally to at least one montage. During Phase 2, subjects who responded in Phase 1 were randomized to receive either real-tDCS or to receive sham stimulation (10 days); patients who were randomized to receive sham stimulation first were then crossed over to receive real-tDCS (10 days). In both phases, 2 mA tDCS was administered for 20 min per real-tDCS sessions and patients performed a picture naming task during stimulation. Patients' language ability was re-tested after 2-weeks and 2-months following real and sham tDCS in Phase 2. In Phase 1, despite considerable individual variability, the greatest average improvement was observed after left-cathodal stimulation. Seven out of 12 subjects responded optimally to at least one montage as demonstrated by transient improvement in picture-naming. In Phase 2, aphasia severity improved at 2-weeks and 2-months following real-tDCS but not sham. Despite individual variability with respect to optimal tDCS approach, certain montages result in consistent transient improvement in persons with chronic post-stroke aphasia. This preliminary study supports the notion that individualized tDCS treatment may enhance aphasia recovery in a persistent manner.

Frontiers in human neuroscience

Shah-Basak, PP; Norise, C; Garcia, G; Torres, J; Faseyitan, O; Hamilton, RH

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Transcranial Electrical Stimulation over Dorsolateral Prefrontal Cortex Modulates Processing of Social Cognitive and Affective Information.

2015

Recent neurofunctional studies suggested that lateral prefrontal cortex is a domain-general cognitive control area modulating computation of social information. Neuropsychological evidence reported dissociations between cognitive and affective components of social cognition. Here, we tested whether performance on social cognitive and affective tasks can be modulated by transcranial direct current stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC). To this aim, we compared the effects of tDCS on explicit recognition of emotional facial expressions (affective task), and on one cognitive task assessing the ability to adopt another person's visual perspective. In a randomized, cross-over design, male and female healthy participants performed the two experimental tasks after bi-hemispheric tDCS (sham, left anodal/right cathodal, and right anodal/left cathodal) applied over DLPFC. Results showed that only in male participants explicit recognition of fearful facial expressions was significantly faster after anodal right/cathodal left stimulation with respect to anodal left/cathodal right and sham stimulations. In the visual perspective taking task, instead, anodal right/cathodal left stimulation negatively affected both male and female participants' tendency to adopt another's point of view. These findings demonstrated that concurrent facilitation of right and inhibition of left lateral prefrontal cortex can speed-up males' responses to threatening faces whereas it interferes with the ability to adopt another's viewpoint independently from gender. Thus, stimulation of cognitive control areas can lead to different effects on social cognitive skills depending on the affective vs. cognitive nature of the task, and on the gender-related differences in neural organization of emotion processing.

PloS one

Conson, M; Errico, D; Mazzarella, E; Giordano, M; Grossi, D; Trojano, L

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Anodal transcranial direct current stimulation of parietal cortex enhances action naming in Corticobasal Syndrome.

2015

Corticobasal Syndrome (CBS) is a neurodegenerative disorder that overlaps both clinically and neuropathologically with Frontotemporal dementia (FTD) and is characterized by apraxia, alien limb phenomena, cortical sensory loss, cognitive impairment, behavioral changes and aphasia. It has been recently demonstrated that transcranial direct current stimulation (tDCS) improves naming in healthy subjects and in subjects with language deficits.The aim of the present study was to explore the extent to which anodal tDCS over the parietal cortex (PARC) could facilitate naming performance in CBS subjects.Anodal tDCS was applied to the left and right PARC during object and action naming in seventeen patients with a diagnosis of possible CBS. Participants underwent two sessions of anodal tDCS (left and right) and one session of placebo tDCS. Vocal responses were recorded and analyzed for accuracy and vocal Reaction Times (vRTs).A shortening of naming latency for actions was observed only after active anodal stimulation over the left PARC, as compared to placebo and right stimulations. No effects have been reported for accuracy.Our preliminary finding demonstrated that tDCS decreased vocal reaction time during action naming in a sample of patients with CBS. A possible explanation of our results is that anodal tDCS over the left PARC effects the brain network implicated in action observation and representation. Further studies, based on larger patient samples, should be conducted to investigate the usefulness of tDCS as an additional treatment of linguistic deficits in CBS patients.

Frontiers in aging neuroscience

Manenti, R; Bianchi, M; Cosseddu, M; Brambilla, M; Rizzetti, C; Padovani, A; Borroni, B; Cotelli, M

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Transcranial random noise stimulation-induced plasticity is NMDA-receptor independent but sodium-channel blocker and benzodiazepines sensitive.

2015

Application of transcranial random noise stimulation (tRNS) between 0.1 and 640 Hz of the primary motor cortex (M1) for 10 min induces a persistent excitability increase lasting for at least 60 min. However, the mechanism of tRNS-induced cortical excitability alterations is not yet fully understood.The main aim of this study was to get first efficacy data with regard to the possible neuronal effect of tRNS.Single-pulse transcranial magnetic stimulation (TMS) was used to measure levels of cortical excitability before and after combined application of tRNS at an intensity of 1 mA for 10 min stimulation duration and a pharmacological agent (or sham) on eight healthy male participants.The sodium channel blocker carbamazepine showed a tendency toward inhibiting MEPs 5-60 min poststimulation. The GABA A agonist lorazepam suppressed tRNS-induced cortical excitability increases at 0-20 and 60 min time points. The partial NMDA receptor agonist D-cycloserine, the NMDA receptor antagonist dextromethorphan and the D2/D3 receptor agonist ropinirole had no significant effects on the excitability increases seen with tRNS.In contrast to transcranial direct current stimulation (tDCS), aftereffects of tRNS are seem to be not NMDA receptor dependent and can be suppressed by benzodiazepines suggesting that tDCS and tRNS depend upon different mechanisms.

Frontiers in neuroscience

Chaieb, L; Antal, A; Paulus, W

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Impact of Anodal and Cathodal Transcranial Direct Current Stimulation over the Left Dorsolateral Prefrontal Cortex during Attention Bias Modification: An Eye-Tracking Study.

2015

People with anxiety disorders show an attentional bias for threat (AB), and Attention Bias Modification (ABM) procedures have been found to reduce this bias. However, the underlying processes accounting for this effect remain poorly understood. One explanation suggests that ABM requires the modification of attention control, driven by the recruitment of the dorsolateral prefrontal cortex (DLPFC). In the present double-blind study, we examined whether modifying left DLPFC activation influences the effect of ABM on AB. We used transcranial direct current stimulation (tDCS) to directly modulate cortical excitability of the left DLPFC during an ABM procedure designed to reduce AB to threat. Anodal tDCS increases excitability, whereas cathodal tDCS decreases it. We randomly assigned highly trait-anxious individuals to one of three conditions: 1) ABM combined with cathodal tDCS, 2) ABM combined with anodal tDCS, or 3) ABM combined with sham tDCS. We assessed the effects of these manipulations on both reaction times and eye-movements on a task indexing AB. Results indicate that combining ABM and anodal tDCS over the left DLPFC reduces the total duration that participants' gaze remains fixated on threat, as assessed using eye-tracking measurement. However, in contrast to previous studies, there were no changes in AB from baseline to post-training for participants that received ABM without tDCS. As the tendency to maintain attention to threat is known to play an important role in the maintenance of anxiety, the present findings suggest that anodal tDCS over the left DLPFC may be considered as a promising tool to reduce the maintenance of gaze to threat. Implications for future translational research combining ABM and tDCS are discussed.

PloS one

Heeren, A; Baeken, C; Vanderhasselt, MA; Philippot, P; de Raedt, R

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Evaluation of a home-based transcranial direct current stimulation (tDCS) treatment device for chronic pain: study protocol for a randomised controlled trial.

2015

Stimulation of the primary motor cortex (M1) has been shown to reduce the pain of neuropathy in multiple studies. There are several methods of stimulation both invasive and non-invasive. Recent work by this laboratory has seen that 40% of a sample of chronic neuropathic pain patients responded positively to non-invasive repetitive transcranial magnetic stimulation (rTMS) to the motor cortex with a reduction in pain levels by at least 20%. The effect however is short lived and multiple return visits are necessary to maintain this response. Transcranial direct current stimulation (tDCS) offers a more mobile method of motor cortex stimulation and is similarly non-invasive. The protocol described is designed to assess the analgesic effect of a home-based tDCS treatment device on chronic neuropathic pain in both responders and non-responders to previous TMS treatment.This article reports the protocol for a randomised, sham-controlled, double-blinded crossover study in which patients with chronic neuropathic pain (n = 24) will receive anodal, cathodal and sham tDCS over M1. All patients will have previously completed a study of rTMS of the motor cortex and have been designated as responders or non-responders to this modality. Patients receive all three tDCS stimulation types by self-administration. We assess the effect on pain scores [numerical rating scale (NRS)], self reported health status (Short Form-36 Health Survey) and anxiety/depression (Hospital Anxiety and Depression Scale). A linear mixed model with fixed effects will analyse changes in pain scores from pre- to post- interventions. Analysis will be carried out on an intention-to-treat basis. A proportion analysis will also be carried out with patients separated into either responders or non-responders to previous TMS. Safety will be assessed throughout the study by monitoring of adverse events.The result of this trial will assess the efficacy of self-administered tDCS of the motor cortex in the treatment of chronic neuropathic pain and also provide insight into whether a potential differential effect is seen in patients that have previously been shown to be either responsive or non-responsive to rTMS over the same area.ISRCTN56839387 date 27 January 2014. First patient randomised to trial 30 October 2012.

Trials

O'Neill, F; Sacco, P; Nurmikko, T

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Neuromodulation and antenatal depression: a review.

2015

Depression during pregnancy affects 5%-8% of women. While the percentage of women in the US taking serotonin reuptake inhibitors during pregnancy has risen over the last decade, pregnant women continue to report that they prefer non-pharmacologic interventions.We review the literature regarding neuromodulation techniques for major depressive disorder during pregnancy. The rationale for their use in this population, new developments, and future directions are discussed.A literature search was conducted in PubMed Plus, Ovid Medline, and Embase to collect all articles on neuromodulation for the treatment of depression during pregnancy. Key search words included electroconvulsive therapy, transcranial magnetic stimulation, deep brain stimulation, transcranial direct current stimulation, neuromodulation, depression, and pregnancy. Given the sparse literature, all articles from 1960 to 2014 that addressed the use of neuromodulation in pregnancy were included.The data support the use of electroconvulsive therapy in all trimesters of pregnancy for major depressive disorder. New data are emerging for the use of transcranial magnetic stimulation in pregnancy, which is likely safe, but more data are needed before it can be recommended as a primary treatment modality during pregnancy. Other neuromodulation techniques have not been well studied in this population.

Neuropsychiatric disease and treatment

Kim, DR; Snell, JL; Ewing, GC; O'Reardon, J

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Effectiveness of transcranial direct current stimulation preceding cognitive behavioural management for chronic low back pain: sham controlled double blinded randomised controlled trial.

2015

To evaluate the effectiveness of transcranial direct current stimulation alone and in combination with cognitive behavioural management in patients with non-specific chronic low back pain.Double blind parallel group randomised controlled trial with six months' follow-up conducted May 2011-March 2013. Participants, physiotherapists, assessors, and analyses were blinded to group allocation.Interdisciplinary chronic pain centre.135 participants with non-specific chronic low back pain >12 weeks were recruited from 225 patients assessed for eligibility.Participants were randomised to receive anodal (20 minutes to motor cortex at 2 mA) or sham transcranial direct current stimulation (identical electrode position, stimulator switched off after 30 seconds) for five consecutive days immediately before cognitive behavioural management (four week multidisciplinary programme of 80 hours).Two primary outcome measures of pain intensity (0-100 visual analogue scale) and disability (Oswestry disability index) were evaluated at two primary endpoints after stimulation and after cognitive behavioural management.Analyses of covariance with baseline values (pain or disability) as covariates showed that transcranial direct current stimulation was ineffective for the reduction of pain (difference between groups on visual analogue scale 1 mm (99% confidence interval -8.69 mm to 6.3 mm; P=0.68)) and disability (difference between groups 1 point (-1.73 to 1.98; P=0.86)) and did not influence the outcome of cognitive behavioural management (difference between group 3 mm (-10.32 mm to 6.73 mm); P=0.58; difference between groups on Oswestry disability index 0 point (-2.45 to 2.62); P=0.92). The stimulation was well tolerated with minimal transitory side effects.This results of this trial on the effectiveness of transcranial direct current stimulation for the reduction of pain and disability do not support its clinical use for managing non-specific chronic low back pain.Trial registration Current controlled trials ISRCTN89874874.

BMJ (Clinical research ed.)

Luedtke, K; Rushton, A; Wright, C; Jürgens, T; Polzer, A; Mueller, G; May, A

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The bipolar depression electrical treatment trial (BETTER): design, rationale, and objectives of a randomized, sham-controlled trial and data from the pilot study phase.

2015

Bipolar depression (BD) is a prevalent condition, with poor therapeutic options and a high degree of refractoriness. This justifies the development of novel treatment strategies, such as transcranial direct current stimulation (tDCS) that showed promising results in unipolar depression.We describe a randomized, sham-controlled, double-blinded trial using tDCS for refractory, acutely symptomatic BD (the bipolar depression electrical treatment trial, BETTER). Sixty patients will be enrolled and assessed with clinical and neuropsychological tests. The primary outcome is change (over time and across groups) in the scores of the Hamilton Depression Rating Scale (17 items). Biological markers such as blood neurotrophins and interleukins, genetic polymorphisms, heart rate variability, and motor cortical excitability will be assessed. Twelve anodal-left/cathodal-right 2 mA tDCS sessions over the dorsolateral prefrontal cortex will be performed in 6 weeks.In the pilot phase, five patients received active tDCS and were double-blindly assessed, two presenting clinical response. TDCS was well-tolerated, with no changes in cognitive scores.This upcoming clinical trial will address the efficacy of tDCS for BD on different degrees of refractoriness. The evaluation of biological markers will also help in understanding the pathophysiology of BD and the mechanisms of action of tDCS.

Neural plasticity

Pereira Junior, Bde S; Tortella, G; Lafer, B; Nunes, P; Benseñor, IM; Lotufo, PA; Machado-Vieira, R; Brunoni, AR

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Combined neuromodulatory interventions in acute experimental pain: assessment of melatonin and non-invasive brain stimulation.

2015

Transcranial direct current stimulation (tDCS) and melatonin can effectively treat pain. Given their potentially complementary mechanisms of action, their combination could have a synergistic effect. Thus, we tested the hypothesis that compared to the control condition and melatonin alone, tDCS combined with melatonin would have a greater effect on pain modulatory effect, as assessed by quantitative sensory testing (QST) and by the pain level during the Conditioned Pain Modulation (CPM)-task. Furthermore, the combined treatment would have a greater cortical excitability effect as indicated by the transcranial magnetic stimulation (TMS) and on the serum BDNF level. Healthy males (n = 20), (aged 18-40 years), in a blinded, placebo-controlled, crossover, clinical trial, were randomized into three groups: sublingual melatonin (0.25 mg/kg) + a-tDCS, melatonin (0.25 mg/kg) + sham-(s)-tDCS, or sublingual placebo+sham-(s)-tDCS. Anodal stimulation (2 mA, 20 min) was applied over the primary motor cortex. There was a significant difference in the heat pain threshold (°C) for melatonin+a-tDCS vs. placebo+s-tDCS (mean difference: 4.86, 95% confidence interval [CI]: 0.9 to 8.63) and melatonin+s-tDCS vs. placebo+s-tDCS (mean: 5.16, 95% CI: 0.84 to 8.36). There was no difference between melatonin+s-tDCS and melatonin+a-tDCS (mean difference: 0.29, 95% CI: -3.72 to 4.23). The mean change from the baseline on amplitude of motor evocate potential (MEP) was significantly higher in the melatonin+a-tDCS (-19.96% ± 5.2) compared with melatonin+s-tDCS group (-1.36% ± 5.35) and with placebo+s-tDCS group (3.61% ± 10.48), respectively (p < 0.05 for both comparisons). While melatonin alone or combined with a-tDCS did not significantly affect CPM task result, and serum BDNF level. The melatonin effectively reduced pain; however, its association with a-tDCS did not present an additional modulatory effect on acute induced pain.

Frontiers in behavioral neuroscience

da Silva, NR; Laste, G; Deitos, A; Stefani, LC; Cambraia-Canto, G; Torres, IL; Brunoni, AR; Fregni, F; Caumo, W

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Direct electric stimulation to increase cerebrovascular function.

2015

Frontiers in systems neuroscience

Pulgar, VM

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Efficacy and interindividual variability in motor-cortex plasticity following anodal tDCS and paired-associative stimulation.

2015

Interindividual response variability to various motor-cortex stimulation protocols has been recently reported. Comparative data of stimulation protocols with different modes of action is lacking. We aimed to compare the efficacy and response variability of two LTP-inducing stimulation protocols in the human motor cortex: anodal transcranial direct current stimulation (a-tDCS) and paired-associative stimulation (PAS25). In two experiments 30 subjects received 1mA a-tDCS and PAS25. Data analysis focused on motor-cortex excitability change and response defined as increase in MEP applying different cut-offs. Furthermore, the predictive pattern of baseline characteristics was explored. Both protocols induced a significant increase in motor-cortical excitability. In the PAS25 experiments the likelihood to develop a MEP response was higher compared to a-tDCS, whereas for intracortical facilitation (ICF) the likelihood for a response was higher in the a-tDCS experiments. Baseline ICF (12 ms) correlated positively with an increase in MEPs only following a-tDCS and responders had significantly higher ICF baseline values. Contrary to recent studies, we showed significant group-level efficacy following both stimulation protocols confirming older studies. However, we also observed a remarkable amount of nonresponders. Our findings highlight the need to define sufficient physiological read-outs for a given plasticity protocol and to develop predictive markers for targeted stimulation.

Neural plasticity

Strube, W; Bunse, T; Malchow, B; Hasan, A

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The short-term effects of transcranial direct current stimulation on electroencephalography in children with autism: a randomized crossover controlled trial.

2015

Abnormal synaptic maturation and connectivity are possible etiologies of autism. Previous studies showed significantly less alpha activity in autism than normal children. Therefore, we studied the effects of anodal tDCS on peak alpha frequency (PAF) related to autism treatment evaluation checklist (ATEC). Twenty male children with autism were randomly assigned in a crossover design to receive a single session of both active and sham tDCS stimulation (11 mA) over F3 (left dorsolateral prefrontal cortex). Pre- to postsession changes in a measure of cortical activity impacted by tDCS (PAF) and ATEC were compared between groups. We also examined the associations between pre- and postsession changes in the PAF and ATEC. The results show significant pre- to postsession improvements in two domains of ATEC (social and health/behavior domains) following active tDCS, relative to sham treatment. PAF also significantly increased at the stimulation site, and an increase in PAF was significantly associated with improvements in the two domains of ATEC impacted by tDCS. The findings suggest that a single session of anodal tDCS over the F3 may have clinical benefits in children with autism and that those benefits may be related to an increase in PAF.

Behavioural neurology

Amatachaya, A; Jensen, MP; Patjanasoontorn, N; Auvichayapat, N; Suphakunpinyo, C; Janjarasjitt, S; Ngernyam, N; Aree-uea, B; Auvichayapat, P

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Shaping pseudoneglect with transcranial cerebellar direct current stimulation and music listening.

2015

Non-invasive brain stimulation modulates cortical excitability depending on the initial activation state of the structure being stimulated. Combination of cognitive with neurophysiological stimulations has been successfully employed to modulate responses of specific brain regions. The present research combined a neurophysiological pre-conditioning with a cognitive conditioning stimulation to modulate behavior. We applied this new state-dependency approach to investigate the cerebellar role in musical and spatial information processing, given that a link between musical perception and visuo-spatial abilities and a clear cerebellar involvement in music perception and visuo-spatial tasks have been reported. Cathodal, anodal or sham transcranial cerebellar Direct Current Stimulation (tcDCS) pre-conditioning was applied on the left cerebellar hemisphere followed by conditioning stimulation through music or white noise listening in a sample of healthy subjects performing a Line Bisection Task (LBT). The combination of the cathodal stimulation with music listening resulted in a marked attentional shift toward the right hemispace, compensating thus the natural leftward bias of the baseline condition (pseudoneglect). Conversely, the anodal or sham pre-conditioning stimulations combined with either music and white noise conditioning listening did not modulate spatial attention. The efficacy of the combined stimulation (cathodal pre-conditioning and music conditioning) and the absence of any effect of the single stimulations provide a strong support to the state-dependency theory. They propose that tcDCS in combination with music listening could act as a rehabilitative tool to improve cognitive functions in the presence of neglect or other spatial disorders.

Frontiers in human neuroscience

Picazio, S; Granata, C; Caltagirone, C; Petrosini, L; Oliveri, M

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Effects of transcranial direct current stimulation on the control of finger force during dexterous manipulation in healthy older adults.

2015

The contribution of poor finger force control to age-related decline in manual dexterity is above and beyond ubiquitous behavioral slowing. Altered control of the finger forces can impart unwanted torque on the object affecting its orientation, thus impairing manual performance. Anodal transcranial direct current stimulation (tDCS) over primary motor cortex (M1) has been shown to improve the performance speed on manual tasks in older adults. However, the effects of anodal tDCS over M1 on the finger force control during object manipulation in older adults remain to be fully explored. Here we determined the effects of anodal tDCS over M1 on the control of grip force in older adults while they manipulated an object with an uncertain mechanical property. Eight healthy older adults were instructed to grip and lift an object whose contact surfaces were unexpectedly made more or less slippery across trials using acetate and sandpaper surfaces, respectively. Subjects performed this task before and after receiving anodal or sham tDCS over M1 on two separate sessions using a cross-over design. We found that older adults used significantly lower grip force following anodal tDCS compared to sham tDCS. Friction measured at the finger-object interface remained invariant after anodal and sham tDCS. These findings suggest that anodal tDCS over M1 improved the control of grip force during object manipulation in healthy older adults. Although the cortical networks for representing objects and manipulative actions are complex, the reduction in grip force following anodal tDCS over M1 might be due to a cortical excitation yielding improved processing of object-specific sensory information and its integration with the motor commands for production of manipulative forces. Our findings indicate that tDCS has a potential to improve the control of finger force during dexterous manipulation in older adults.

PloS one

Parikh, PJ; Cole, KJ

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Transcranial direct current stimulation modulates efficiency of reading processes.

2015

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that offers promise as an investigative method for understanding complex cognitive operations such as reading. This study explores the ability of a single session of tDCS to modulate reading efficiency and phonological processing performance within a group of healthy adults. Half the group received anodal or cathodal stimulation, on two separate days, of the left temporo-parietal junction while the other half received anodal or cathodal stimulation of the right homologue area. Pre- and post-stimulation assessment of reading efficiency and phonological processing was carried out. A larger pre-post difference in reading efficiency was found for participants who received right anodal stimulation compared to participants who received left anodal stimulation. Further, there was a significant post-stimulation increase in phonological processing speed following right hemisphere anodal stimulation. Implications for models of reading and reading impairment are discussed.

Frontiers in human neuroscience

Thomson, JM; Doruk, D; Mascio, B; Fregni, F; Cerruti, C

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Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for technology and protocols.

2015

The effect of transcranial direct current stimulation (tDCS) is cumulative. Treatment protocols typically require multiple consecutive sessions spanning weeks or months. However, traveling to clinic for a tDCS session can present an obstacle to subjects and their caregivers. With modified devices and headgear, tDCS treatment can be administered remotely under clinical supervision, potentially enhancing recruitment, throughput, and convenience. Here we propose standards and protocols for clinical trials utilizing remotely-supervised tDCS with the goal of providing safe, reproducible and well-tolerated stimulation therapy outside of the clinic. The recommendations include: (1) training of staff in tDCS treatment and supervision; (2) assessment of the user's capability to participate in tDCS remotely; (3) ongoing training procedures and materials including assessments of the user and/or caregiver; (4) simple and fail-safe electrode preparation techniques and tDCS headgear; (5) strict dose control for each session; (6) ongoing monitoring to quantify compliance (device preparation, electrode saturation/placement, stimulation protocol), with corresponding corrective steps as required; (7) monitoring for treatment-emergent adverse effects; (8) guidelines for discontinuation of a session and/or study participation including emergency failsafe procedures tailored to the treatment population's level of need. These guidelines are intended to provide a minimal level of methodological rigor for clinical trials seeking to apply tDCS outside a specialized treatment center. We outline indication-specific applications (Attention Deficit Hyperactivity Disorder, Depression, Multiple Sclerosis, Palliative Care) following these recommendations that support a standardized framework for evaluating the tolerability and reproducibility of remote-supervised tDCS that, once established, will allow for translation of tDCS clinical trials to a greater size and range of patient populations.

Frontiers in systems neuroscience

Charvet, LE; Kasschau, M; Datta, A; Knotkova, H; Stevens, MC; Alonzo, A; Loo, C; Krull, KR; Bikson, M

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Keep calm and carry on: improved frustration tolerance and processing speed by transcranial direct current stimulation (tDCS).

2015

Cognitive control (CC) of attention is a major prerequisite for effective information processing. Emotional distractors can bias and impair goal-directed deployment of attentional resources. Frustration-induced negative affect and cognition can act as internal distractors with negative impact on task performance. Consolidation of CC may thus support task-oriented behavior under challenging conditions. Recently, transcranial direct current stimulation (tDCS) has been put forward as an effective tool to modulate CC. Particularly, anodal, activity enhancing tDCS to the left dorsolateral prefrontal cortex (dlPFC) can increase insufficient CC in depression as indicated by a reduction of attentional biases induced by emotionally salient stimuli. With this study, we provide first evidence that, compared to sham stimulation, tDCS to the left dlPFC enhances processing speed measured by an adaptive version of the Paced Auditory Serial Addition Task (PASAT) that is typically thwarted by frustration. Notably, despite an even larger amount of error-related negative feedback, the task-induced upset was suppressed in the group receiving anodal tDCS. Moreover, inhibition of task-related negative affect was correlated with performance gains, suggesting a close link between enhanced processing speed and consolidation of CC by tDCS. Together, these data provide first evidence that activity enhancing anodal tDCS to the left dlPFC can support focused cognitive processing particularly when challenged by frustration-induced negative affect.

PloS one

Plewnia, C; Schroeder, PA; Kunze, R; Faehling, F; Wolkenstein, L

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Cerebellar transcranial direct current stimulation effects on saccade adaptation.

2015

Saccade adaptation is a cerebellar-mediated type of motor learning in which the oculomotor system is exposed to repetitive errors. Different types of saccade adaptations are thought to involve distinct underlying cerebellar mechanisms. Transcranial direct current stimulation (tDCS) induces changes in neuronal excitability in a polarity-specific manner and offers a modulatory, noninvasive, functional insight into the learning aspects of different brain regions. We aimed to modulate the cerebellar influence on saccade gains during adaptation using tDCS. Subjects performed an inward (n = 10) or outward (n = 10) saccade adaptation experiment (25% intrasaccadic target step) while receiving 1.5 mA of anodal cerebellar tDCS delivered by a small contact electrode. Compared to sham stimulation, tDCS increased learning of saccadic inward adaptation but did not affect learning of outward adaptation. This may imply that plasticity mechanisms in the cerebellum are different between inward and outward adaptation. TDCS could have influenced specific cerebellar areas that contribute to inward but not outward adaptation. We conclude that tDCS can be used as a neuromodulatory technique to alter cerebellar oculomotor output, arguably by engaging wider cerebellar areas and increasing the available resources for learning.

Neural plasticity

Avila, E; van der Geest, JN; Kengne Kamga, S; Verhage, MC; Donchin, O; Frens, MA

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Transcranial direct current stimulation improves ipsilateral selective muscle activation in a frequency dependent manner.

2015

Failure to suppress antagonist muscles can lead to movement dysfunction, such as the abnormal muscle synergies often seen in the upper limb after stroke. A neurophysiological surrogate of upper limb synergies, the selectivity ratio (SR), can be determined from the ratio of biceps brachii (BB) motor evoked potentials to transcranial magnetic stimulation prior to forearm pronation versus elbow flexion. Surprisingly, cathodal transcranial direct current stimulation (c-TDCS) over ipsilateral primary motor cortex (M1) reduces (i.e. improves) the SR in healthy adults, and chronic stroke patients. The ability to suppress antagonist muscles may be exacerbated at high movement rates. The aim of the present study was to investigate whether the selective muscle activation of the biceps brachii (BB) is dependent on altering frequency demands, and whether the c-tDCS improvement of SR is dependent on task frequency. Seventeen healthy participants performed repetitive isometric elbow flexion and forearm pronation at three rates, before and after c-tDCS or sham delivered to ipsilateral left M1. Ipsilateral c-tDCS improved the SR in a frequency dependent manner by selectively suppressing BB antagonist excitability. Our findings confirm that c-tDCS is an effective tool for improving selective muscle activation, and provide novel evidence for its efficacy at rates of movement where it is most likely to benefit task performance.

PloS one

Uehara, K; Coxon, JP; Byblow, WD

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Wearable functional near infrared spectroscopy (fNIRS) and transcranial direct current stimulation (tDCS): expanding vistas for neurocognitive augmentation.

2015

Contemporary studies with transcranial direct current stimulation (tDCS) provide a growing base of evidence for enhancing cognition through the non-invasive delivery of weak electric currents to the brain. The main effect of tDCS is to modulate cortical excitability depending on the polarity of the applied current. However, the underlying mechanism of neuromodulation is not well understood. A new generation of functional near infrared spectroscopy (fNIRS) systems is described that are miniaturized, portable, and include wearable sensors. These developments provide an opportunity to couple fNIRS with tDCS, consistent with a neuroergonomics approach for joint neuroimaging and neurostimulation investigations of cognition in complex tasks and in naturalistic conditions. The effects of tDCS on complex task performance and the use of fNIRS for monitoring cognitive workload during task performance are described. Also explained is how fNIRS + tDCS can be used simultaneously for assessing spatial working memory. Mobile optical brain imaging is a promising neuroimaging tool that has the potential to complement tDCS for realistic applications in natural settings.

Frontiers in systems neuroscience

McKendrick, R; Parasuraman, R; Ayaz, H

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Transcranial direct current stimulation as a treatment for auditory hallucinations.

2015

Auditory hallucinations (AH) are a symptom of several psychiatric disorders, such as schizophrenia. In a significant minority of patients, AH are resistant to antipsychotic medication. Alternative treatment options for this medication resistant group are scarce and most of them focus on coping with the hallucinations. Finding an alternative treatment that can diminish AH is of great importance. Transcranial direct current stimulation (tDCS) is a safe and non-invasive technique that is able to directly influence cortical excitability through the application of very low electric currents. A 1-2 mA direct current is applied between two surface electrodes, one serving as the anode and the other as the cathode. Cortical excitability is increased in the vicinity of the anode and reduced near the cathode. The technique, which has only a few transient side effects and is cheap and portable, is increasingly explored as a treatment for neurological and psychiatric symptoms. It has shown efficacy on symptoms of depression, bipolar disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, epilepsy, and stroke. However, the application of tDCS as a treatment for AH is relatively new. This article provides an overview of the current knowledge in this field and guidelines for future research.

Frontiers in psychology

Koops, S; van den Brink, H; Sommer, IE

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Differential influences of unilateral tDCS over the intraparietal cortex on numerical cognition.

2015

Recent neuro-imaging research identified the bilateral intraparietal sulcus (IPS) to be a key area associated with number processing. However, causal structure-function relationships are hard to evaluate from neuro-imaging techniques such as fMRI. Nevertheless, brain stimulation methods like transcranial direct current stimulation (tDCS) allow for investigating the functional relevance of the IPS for number processing. Following up on a study using bilateral bi-cephalic tDCS over the IPS, the current study aimed at evaluating the differential lateralized functional contributions of the left and right IPS to number processing using unilateral bi-cephalic tDCS over either the left or right IPS. Results indicated a right lateralization for the processing of the place-value structure of the Arabic number system. Importantly, the processing of number magnitude information was not affected by unilateral IPS corroborating the assumption that number magnitude is processed in the bilateral IPS. Taken together, these data suggest that even though number magnitude is represented bilaterally, the left and right IPS seem to contribute differentially to numerical cognition with respect to the processing of specific other aspects of numerical information.

Frontiers in human neuroscience

Artemenko, C; Moeller, K; Huber, S; Klein, E

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When problem size matters: differential effects of brain stimulation on arithmetic problem solving and neural oscillations.

2015

The problem size effect is a well-established finding in arithmetic problem solving and is characterized by worse performance in problems with larger compared to smaller operand size. Solving small and large arithmetic problems has also been shown to involve different cognitive processes and distinct electroencephalography (EEG) oscillations over the left posterior parietal cortex (LPPC). In this study, we aimed to provide further evidence for these dissociations by using transcranial direct current stimulation (tDCS). Participants underwent anodal (30min, 1.5 mA, LPPC) and sham tDCS. After the stimulation, we recorded their neural activity using EEG while the participants solved small and large arithmetic problems. We found that the tDCS effects on performance and oscillatory activity critically depended on the problem size. While anodal tDCS improved response latencies in large arithmetic problems, it decreased solution rates in small arithmetic problems. Likewise, the lower-alpha desynchronization in large problems increased, whereas the theta synchronization in small problems decreased. These findings reveal that the LPPC is differentially involved in solving small and large arithmetic problems and demonstrate that the effects of brain stimulation strikingly differ depending on the involved neuro-cognitive processes.

PloS one

Rütsche, B; Hauser, TU; Jäncke, L; Grabner, RH

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Modulating cognition using transcranial direct current stimulation of the cerebellum.

2015

Numerous studies have emerged recently that demonstrate the possibility of modulating, and in some cases enhancing, cognitive processes by exciting brain regions involved in working memory and attention using transcranial electrical brain stimulation. Some researchers now believe the cerebellum supports cognition, possibly via a remote neuromodulatory effect on the prefrontal cortex. This paper describes a procedure for investigating a role for the cerebellum in cognition using transcranial direct current stimulation (tDCS), and a selection of information-processing tasks of varying task difficulty, which have previously been shown to involve working memory, attention and cerebellar functioning. One task is called the Paced Auditory Serial Addition Task (PASAT) and the other a novel variant of this task called the Paced Auditory Serial Subtraction Task (PASST). A verb generation task and its two controls (noun and verb reading) were also investigated. All five tasks were performed by three separate groups of participants, before and after the modulation of cortico-cerebellar connectivity using anodal, cathodal or sham tDCS over the right cerebellar cortex. The procedure demonstrates how performance (accuracy, verbal response latency and variability) could be selectively improved after cathodal stimulation, but only during tasks that the participants rated as difficult, and not easy. Performance was unchanged by anodal or sham stimulation. These findings demonstrate a role for the cerebellum in cognition, whereby activity in the left prefrontal cortex is likely dis-inhibited by cathodal tDCS over the right cerebellar cortex. Transcranial brain stimulation is growing in popularity in various labs and clinics. However, the after-effects of tDCS are inconsistent between individuals and not always polarity-specific, and may even be task- or load-specific, all of which requires further study. Future efforts might also be guided towards neuro-enhancement in cerebellar patients presenting with cognitive impairment once a better understanding of brain stimulation mechanisms has emerged.

Journal of visualized experiments : JoVE

Pope, PA

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Effects of anodal transcranial direct current stimulation on visually guided learning of grip force control.

2015

Anodal transcranial Direct Current Stimulation (tDCS) has been shown to be an effective non-invasive brain stimulation method for improving cognitive and motor functioning in patients with neurological deficits. tDCS over motor cortex (M1), for instance, facilitates motor learning in stroke patients. However, the literature on anodal tDCS effects on motor learning in healthy participants is inconclusive, and the effects of tDCS on visuo-motor integration are not well understood. In the present study we examined whether tDCS over the contralateral motor cortex enhances learning of grip-force output in a visually guided feedback task in young and neurologically healthy volunteers. Twenty minutes of 1 mA anodal tDCS were applied over the primary motor cortex (M1) contralateral to the dominant (right) hand, during the first half of a 40 min power-grip task. This task required the control of a visual signal by modulating the strength of the power-grip for six seconds per trial. Each participant completed a two-session sham-controlled crossover protocol. The stimulation conditions were counterbalanced across participants and the sessions were one week apart. Performance measures comprised time-on-target and target-deviation, and were calculated for the periods of stimulation (or sham) and during the afterphase respectively. Statistical analyses revealed significant performance improvements over the stimulation and the afterphase, but this learning effect was not modulated by tDCS condition. This suggests that the form of visuomotor learning taking place in the present task was not sensitive to neurostimulation. These null effects, together with similar reports for other types of motor tasks, lead to the proposition that tDCS facilitation of motor learning might be restricted to cases or situations where the motor system is challenged, such as motor deficits, advanced age, or very high task demand.

Biology

Minarik, T; Sauseng, P; Dunne, L; Berger, B; Sterr, A

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How does anodal transcranial direct current stimulation of the pain neuromatrix affect brain excitability and pain perception? A randomised, double-blind, sham-control study.

2015

Integration of information between multiple cortical regions of the pain neuromatrix is thought to underpin pain modulation. Although altered processing in the primary motor (M1) and sensory (S1) cortices is implicated in separate studies, the simultaneous changes in and the relationship between these regions are unknown yet. The primary aim was to assess the effects of anodal transcranial direct current stimulation (a-tDCS) over superficial regions of the pain neuromatrix on M1 and S1 excitability. The secondary aim was to investigate how M1 and S1 excitability changes affect sensory (STh) and pain thresholds (PTh).Twelve healthy participants received 20 min a-tDCS under five different conditions including a-tDCS of M1, a-tDCS of S1, a-tDCS of DLPFC, sham a-tDCS, and no-tDCS. Excitability of dominant M1 and S1 were measured before, immediately, and 30 minutes after intervention respectively. Moreover, STh and PTh to peripheral electrical and mechanical stimulation were evaluated. All outcome measures were assessed at three time-points of measurement by a blind rater.A-tDCS of M1 and dorsolateral prefrontal cortex (DLPFC) significantly increased brain excitability in M1 (p < 0.05) for at least 30 min. Following application of a-tDCS over the S1, the amplitude of the N20-P25 component of SEPs increased immediately after the stimulation (p < 0.05), whilst M1 stimulation decreased it. Compared to baseline values, significant STh and PTh increase was observed after a-tDCS of all three stimulated areas. Except in M1 stimulation, there was significant PTh difference between a-tDCS and sham tDCS.a-tDCS of M1 is the best spots to enhance brain excitability than a-tDCS of S1 and DLPFC. Surprisingly, a-tDCS of M1 and S1 has diverse effects on S1 and M1 excitability. A-tDCS of M1, S1, and DLPFC increased STh and PTh levels. Given the placebo effects of a-tDCS of M1 in pain perception, our results should be interpreted with caution, particularly with respect to the behavioural aspects of pain modulation.Australian New Zealand Clinical Trials, ACTRN12614000817640, http://www.anzctr.org.au/.

PloS one

Vaseghi, B; Zoghi, M; Jaberzadeh, S

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A framework for categorizing electrode montages in transcranial direct current stimulation.

2015

Frontiers in human neuroscience

Nasseri, P; Nitsche, MA; Ekhtiari, H

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Enhancing multiple object tracking performance with noninvasive brain stimulation: a causal role for the anterior intraparietal sulcus.

2015

Multiple object tracking (MOT) is a complex task recruiting a distributed network of brain regions. There are also marked individual differences in MOT performance. A positive causal relationship between the anterior intraparietal sulcus (AIPS), an integral region in the MOT attention network and inter-individual variation in MOT performance has not been previously established. The present study used transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, in order to examine such a causal link. Active anodal stimulation was applied to the right AIPS and the left dorsolateral prefrontal cortex (DLPFC) (and sham stimulation), an area associated with working memory (but not MOT) while participants completed a MOT task. Stimulation to the right AIPS significantly improved MOT accuracy more than the other two conditions. The results confirm a causal role of the AIPS in the MOT task and illustrate that tDCS has the ability to improve MOT performance.

Frontiers in systems neuroscience

Blumberg, EJ; Peterson, MS; Parasuraman, R

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Analgesic efficacy of cerebral and peripheral electrical stimulation in chronic nonspecific low back pain: a randomized, double-blind, factorial clinical trial.

2015

Chronic non-specific low back pain is a major socioeconomic public health issue worldwide and, despite the volume of research in the area, it is still a difficult-to-treat condition. The conservative analgesic therapy usually comprises a variety of pharmacological and non-pharmacological strategies, such as transcutaneous electrical nerve stimulation. The neuromatrix pain model and the new findings on the process of chronicity of pain point to a higher effectiveness of treatments that address central rather than peripheral structures. The transcranial direct current stimulation is a noninvasive technique of neuromodulation that has made recent advances in the treatment of chronic pain. The simultaneous combination of these two electrostimulation techniques (cerebral and peripheral) can provide an analgesic effect superior to isolated interventions. However, all the evidence on the analgesic efficacy of these techniques, alone or combined, is still fragmented. This is a protocol for a randomized clinical trial to investigate whether cerebral electrical stimulation combined with peripheral electrical stimulation is more effective in relieving pain than the isolated application of electrical stimulations in patients with chronic nonspecific low back pain.Ninety-two patients will be randomized into four groups to receive transcranial direct current stimulation (real/sham) + transcutaneous electrical nerve stimulation (real/sham) for 12 sessions over a period of four weeks. The primary clinical outcome (pain intensity) and the secondary ones (sensory and affective aspects of pain, physical functioning and global perceived effect) will be recorded before treatment, after four weeks, in Month 3 and in Month 6 after randomization. Confounding factors such as anxiety and depression, the patient's satisfaction with treatment and adverse effects will also be listed. Data will be collected by an examiner unaware of (blind to) the treatment allocation.The results of this study may assist in clinical decision-making about the combined use of cerebral and peripheral electrical stimulation for pain relief in patients with chronic low back pain.NCT01896453.

BMC musculoskeletal disorders

Hazime, FA; de Freitas, DG; Monteiro, RL; Maretto, RL; Carvalho, NA; Hasue, RH; João, SM

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Modulating brain oscillations to drive brain function.

2014 Dec

Do neuronal oscillations play a causal role in brain function? In a study in this issue of PLOS Biology, Helfrich and colleagues address this long-standing question by attempting to drive brain oscillations using transcranial electrical current stimulation. Remarkably, they were able to manipulate visual perception by forcing brain oscillations of the left and right visual hemispheres into synchrony using oscillatory currents over both hemispheres. Under this condition, human observers more often perceived an inherently ambiguous visual stimulus in one of its perceptual instantiations. These findings shed light on the mechanisms underlying neuronal computation. They show that it is the neuronal oscillations that drive the visual experience, not the experience driving the oscillations. And they indicate that synchronized oscillatory activity groups brain areas into functional networks. This points to new ways for controlled experimental and possibly also clinical interventions for the study and modulation of brain oscillations and associated functions.

PLoS biology

Thut, G

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Selective modulation of interhemispheric functional connectivity by HD-tACS shapes perception.

2014 Dec

Oscillatory neuronal synchronization between cortical areas has been suggested to constitute a flexible mechanism to coordinate information flow in the human cerebral cortex. However, it remains unclear whether synchronized neuronal activity merely represents an epiphenomenon or whether it is causally involved in the selective gating of information. Here, we combined bilateral high-density transcranial alternating current stimulation (HD-tACS) at 40 Hz with simultaneous electroencephalographic (EEG) recordings to study immediate electrophysiological effects during the selective entrainment of oscillatory gamma-band signatures. We found that interhemispheric functional connectivity was modulated in a predictable, phase-specific way: In-phase stimulation enhanced synchronization, anti-phase stimulation impaired functional coupling. Perceptual correlates of these connectivity changes were found in an ambiguous motion task, which strongly support the functional relevance of long-range neuronal coupling. Additionally, our results revealed a decrease in oscillatory alpha power in response to the entrainment of gamma band signatures. This finding provides causal evidence for the antagonistic role of alpha and gamma oscillations in the parieto-occipital cortex and confirms that the observed gamma band modulations were physiological in nature. Our results demonstrate that synchronized cortical network activity across several spatiotemporal scales is essential for conscious perception and cognition.

PLoS biology

Helfrich, RF; Knepper, H; Nolte, G; Strüber, D; Rach, S; Herrmann, CS; Schneider, TR; Engel, AK

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Cognitive enhancement or cognitive cost: trait-specific outcomes of brain stimulation in the case of mathematics anxiety.

2014 Dec

The surge in noninvasive brain stimulation studies investigating cognitive enhancement has neglected the effect of interindividual differences, such as traits, on stimulation outcomes. Using the case of mathematics anxiety in a sample of healthy human participants in a placebo-controlled, double-blind, crossover experiment, we show that identical transcranial direct current stimulation (tDCS) exerts opposite behavioral and physiological effects depending on individual trait levels. Mathematics anxiety is the negative emotional response elicited by numerical tasks, impairing mathematical achievement. tDCS was applied to the dorsolateral prefrontal cortex, a frequent target for modulating emotional regulation. It improved reaction times on simple arithmetic decisions and decreased cortisol concentrations (a biomarker of stress) in high mathematics anxiety individuals. In contrast, tDCS impaired reaction times for low mathematics anxiety individuals and prevented a decrease in cortisol concentration compared with sham stimulation. Both groups showed a tDCS-induced side effect-impaired executive control in a flanker task-a cognitive function subserved by the stimulated region. These behavioral and physiological double dissociations have implications for brain stimulation research by highlighting the role of individual traits in experimental findings. Brain stimulation clearly does not produce uniform benefits, even applied in the same configuration during the same tasks, but may interact with traits to produce markedly opposed outcomes.

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

Sarkar, A; Dowker, A; Cohen Kadosh, R

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Pain reduction in myofascial pain syndrome by anodal transcranial direct current stimulation combined with standard treatment: a randomized controlled study.

2014 Dec

Myofascial pain syndrome (MPS) in the shoulder is among the most prevalent pain problems in the middle-aged population worldwide. Evidence suggests that peripheral and central sensitization may play an important role in the development and maintenance of shoulder MPS. Given previous research supporting the potential efficacy of anodal transcranial direct current stimulation (tDCS) for modulating pain-related brain activity in individuals with refractory central pain, we hypothesized that anodal tDCS when applied over the primary motor cortex (M1) combined with standard treatment will be more effective for reducing pain in patients with MPS than standard treatment alone.Study participants were randomized to receive either (1) standard treatment with 5 consecutive days of 1 mA anodal tDCS over M1 for 20 minutes; or (2) standard treatment plus sham tDCS. Measures of pain intensity, shoulder passive range of motion (PROM), analgesic medication use, and self-reported physical functioning were administered before treatment and again at posttreatment and 1-, 2-, 3-, and 4-week follow-up.Thirty-one patients with MPS were enrolled. Participants assigned to the active tDCS condition reported significantly more pretreatment to posttreatment reductions in pain intensity that were maintained at 1-week posttreatment, and significant improvement in shoulder adduction PROM at 1-week follow-up than participants assigned to the sham tDCS condition.Five consecutive days of anodal tDCS over M1 combined with standard treatment appears to reduce pain intensity and may improve PROM, faster than standard treatment alone. Further tests on the efficacy and duration of effects of tDCS in the treatment of MPS are warranted.

The Clinical journal of pain

Sakrajai, P; Janyacharoen, T; Jensen, MP; Sawanyawisuth, K; Auvichayapat, N; Tunkamnerdthai, O; Keeratitanont, K; Auvichayapat, P

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Baseline brain activity predicts response to neuromodulatory pain treatment.

2014 Dec

The objective of this study was to examine the associations between baseline electroencephalogram (EEG)-assessed brain oscillations and subsequent response to four neuromodulatory treatments. Based on available research, we hypothesized that baseline theta oscillations would prospectively predict response to hypnotic analgesia. Analyses involving other oscillations and the other treatments (meditation, neurofeedback, and both active and sham transcranial direct current stimulation) were viewed as exploratory, given the lack of previous research examining brain oscillations as predictors of response to these other treatments.Randomized controlled study of single sessions of four neuromodulatory pain treatments and a control procedure.Thirty individuals with spinal cord injury and chronic pain had their EEG recorded before each session of four active treatments (hypnosis, meditation, EEG biofeedback, transcranial direct current stimulation) and a control procedure (sham transcranial direct stimulation).As hypothesized, more presession theta power was associated with greater response to hypnotic analgesia. In exploratory analyses, we found that less baseline alpha power predicted pain reduction with meditation.The findings support the idea that different patients respond to different pain treatments and that between-person treatment response differences are related to brain states as measured by EEG. The results have implications for the possibility of enhancing pain treatment response by either 1) better patient/treatment matching or 2) influencing brain activity before treatment is initiated in order to prepare patients to respond. Research is needed to replicate and confirm the findings in additional samples of individuals with chronic pain.

Pain medicine (Malden, Mass.)

Jensen, MP; Sherlin, LH; Fregni, F; Gianas, A; Howe, JD; Hakimian, S

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Enhanced long-term memory encoding after parietal neurostimulation.

2014 Dec

Neurostimulation, e.g., transcranial direct current stimulation (tDCS), shows promise as an effective cognitive intervention. In spite of low spatial resolution, limited penetration, and temporary influence, evidence highlights tDCS-linked cognitive benefits in a range of cognitive domains. The left posterior parietal cortex (PPC) is an accessible node in frontoparietal networks engaged during long-term memory (LTM). Here, we tested the hypothesis that tDCS can facilitate LTM by pairing LTM encoding and retrieval with PPC stimulation. Healthy young adults performed a verbal LTM task (California Verbal Learning Task) with four different stimulation parameters. In Experiment 1, we applied tDCS to left PPC during LTM encoding. In Experiment 2, we applied tDCS just prior to retrieval to test the temporal specificity of tDCS during a LTM task. In later experiments, we tested hemispheric specificity by replicating Experiment 1 while stimulating the right PPC. Experiment 1 showed that tDCS applied during LTM encoding improved the pace of list learning and enhanced retrieval after a short delay. Experiment 2 indicated anodal left PPC tDCS only improved LTM when applied during encoding, and not during maintenance. Experiments 3 and 4 confirmed that tDCS effects were hemisphere specific and that no effects were found after right PPC stimulation during encoding. These findings indicate that anodal tDCS to the PPC helps verbal LTM in healthy young adults under certain conditions. First, when it is applied to the left, not the right, PPC and second, when it is applied during encoding.

Experimental brain research

Jones, KT; Gözenman, F; Berryhill, ME

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Reduced short interval cortical inhibition correlates with atomoxetine response in children with attention-deficit hyperactivity disorder (ADHD).

2014 Dec

Clinical trials in children with attention-deficit hyperactivity disorder (ADHD) show variability in behavioral responses to the selective norepinephrine reuptake inhibitor atomoxetine. The objective of this study was to determine whether transcranial magnetic stimulation-evoked short interval cortical inhibition might be a biomarker predicting, or correlating with, clinical atomoxetine response. At baseline and after 4 weeks of atomoxetine treatment in 7- to 12-year-old children with ADHD, transcranial magnetic stimulation short interval cortical inhibition was measured, blinded to clinical improvement. Primary analysis was by multivariate analysis of covariance. Baseline short interval cortical inhibition did not predict clinical responses. However, paradoxically, after 4 weeks of atomoxetine, mean short interval cortical inhibition was reduced 31.9% in responders and increased 6.1% in nonresponders (analysis of covariance t 41 = 2.88; P = .0063). Percentage reductions in short interval cortical inhibition correlated with reductions in the ADHD Rating Scale (r = 0.50; P = .0005). In children ages 7 to 12 years with ADHD treated with atomoxetine, improvements in clinical symptoms are correlated with reductions in motor cortex short interval cortical inhibition.

Journal of child neurology

Chen, TH; Wu, SW; Welge, JA; Dixon, SG; Shahana, N; Huddleston, DA; Sarvis, AR; Sallee, FR; Gilbert, DL

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Electrifying the motor engram: effects of tDCS on motor learning and control.

2014 Nov

Learning to control our movements is accompanied by neuroplasticity of motor areas of the brain. The mechanisms of neuroplasticity are diverse and produce what is referred to as the motor engram, i.e., the neural trace of the motor memory. Transcranial direct current stimulation (tDCS) alters the neural and behavioral correlates of motor learning, but its precise influence on the motor engram is unknown. In this review, we summarize the effects of tDCS on neural activity and suggest a few key principles: (1) Firing rates are increased by anodal polarization and decreased by cathodal polarization, (2) anodal polarization strengthens newly formed associations, and (3) polarization modulates the memory of new/preferred firing patterns. With these principles in mind, we review the effects of tDCS on motor control, motor learning, and clinical applications. The increased spontaneous and evoked firing rates may account for the modulation of dexterity in non-learning tasks by tDCS. The facilitation of new association may account for the effect of tDCS on learning in sequence tasks while the ability of tDCS to strengthen memories of new firing patterns may underlie the effect of tDCS on consolidation of skills. We then describe the mechanisms of neuroplasticity of motor cortical areas and how they might be influenced by tDCS. We end with current challenges for the fields of brain stimulation and motor learning.

Experimental brain research

Orban de Xivry, JJ; Shadmehr, R

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

2014 Nov

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

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

2014 Nov

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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Visualizing simulated electrical fields from electroencephalography and transcranial electric brain stimulation: a comparative evaluation.

2014 Nov

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

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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

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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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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

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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

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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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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

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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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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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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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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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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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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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Activation and inhibition of posterior parietal cortex have bi-directional effects on spatial errors following interruptions.

2014

Interruptions to ongoing mental activities are omnipresent in our modern digital world, but the brain networks involved in interrupted performance are not known, nor have the activation of those networks been modulated. Errors following interruptions reflect failures in spatial memory, whose maintenance is supported by a brain network including the right posterior parietal cortex (PPC). The present study therefore used bi-directional transcranial Direct Current Stimulation (tDCS) of right PPC to examine the neuromodulation of spatial errors following interruptions, as well as performance on another PPC-dependent task, mental rotation. Anodal stimulation significantly reduced the number of interruption-based errors and increased mental rotation accuracy whereas cathodal stimulation significantly increased errors and reduced mental rotation accuracy. The results provide evidence for a causal role of the PPC in the maintenance of spatial representations during interrupted task performance.

Frontiers in systems neuroscience

Foroughi, CK; Blumberg, EJ; Parasuraman, R

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Prefronto-cerebellar transcranial direct current stimulation improves sleep quality in euthymic bipolar patients: a brief report.

2014

Sleep problems are common in bipolar disorder (BD) and may persist during the euthymic phase of the disease. The aim of the study was to improve sleep quality of euthymic BD patients through the administration of prefronto-cerebellar transcranial direct current stimulation (tDCS).25 euthymic outpatients with a diagnosis of BD Type I or II have been enrolled in the study. tDCS montage was as follows: cathode on the right cerebellar cortex and anode over the left dorsolateral prefrontal cortex (DLPFC); the intensity of stimulation was set at 2 mA and delivered for 20 min/die for 3 consecutive weeks. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality at baseline and after the tDCS treatment.PSQI total score and all PSQI subdomains, with the exception of "sleep medication," significantly improved after treatment.This is the first study where a positive effect of tDCS on the quality of sleep in euthymic BD patients has been reported. As both prefrontal cortex and cerebellum may play a role in regulating sleep processes, concomitant cathodal (inhibitory) stimulation of cerebellum and anodal (excitatory) stimulation of DLPFC may have the potential to modulate prefrontal-thalamic-cerebellar circuits leading to improvements of sleep quality.

Behavioural neurology

Minichino, A; Bersani, FS; Spagnoli, F; Corrado, A; De Michele, F; Calò, WK; Primavera, M; Yang, B; Bernabei, L; Macrì, F; Vergnani, L; Biondi, M; Delle Chiaie, R

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Electrical stimulation over bilateral occipito-temporal regions reduces N170 in the right hemisphere and the composite face effect.

2014

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate cortical excitability. Although the clinical value of tDCS has been advocated, the potential of tDCS in cognitive rehabilitation of face processing deficits is less understood. Face processing has been associated with the occipito-temporal cortex (OT). The present study investigated whether face processing in healthy adults can be modulated by applying tDCS over the OT. Experiment 1 investigated whether tDCS can affect N170, a face-sensitive ERP component, with a face orientation judgment task. The N170 in the right hemisphere was reduced in active stimulation conditions compared with the sham stimulation condition for both upright faces and inverted faces. Experiment 2 further demonstrated that tDCS can modulate the composite face effect, a type of holistic processing that reflects the obligatory attention to all parts of a face. The composite face effect was reduced in active stimulation conditions compared with the sham stimulation condition. Additionally, the current polarity did not modulate the effect of tDCS in the two experiments. The present study demonstrates that N170 can be causally manipulated by stimulating the OT with weak currents. Furthermore, our study provides evidence that obligatory attention to all parts of a face can be affected by the commonly used tDCS parameter setting.

PloS one

Yang, LZ; Zhang, W; Shi, B; Yang, Z; Wei, Z; Gu, F; Zhang, J; Cui, G; Liu, Y; Zhou, Y; Zhang, X; Rao, H

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The role of pulse shape in motor cortex transcranial magnetic stimulation using full-sine stimuli.

2014

A full-sine (biphasic) pulse waveform is most commonly used for repetitive transcranial magnetic stimulation (TMS), but little is known about how variations in duration or amplitude of distinct pulse segments influence the effectiveness of a single TMS pulse to elicit a corticomotor response. Using a novel TMS device, we systematically varied the configuration of full-sine pulses to assess the impact of configuration changes on resting motor threshold (RMT) as measure of stimulation effectiveness with single-pulse TMS of the non-dominant motor hand area (M1). In young healthy volunteers, we (i) compared monophasic, half-sine, and full-sine pulses, (ii) applied two-segment pulses consisting of two identical half-sines, and (iii) manipulated amplitude, duration, and current direction of the first or second full-sine pulse half-segments. RMT was significantly higher using half-sine or monophasic pulses compared with full-sine. Pulses combining two half-sines of identical polarity and duration were also characterized by higher RMT than full-sine stimuli resulting. For full-sine stimuli, decreasing the amplitude of the half-segment inducing posterior-anterior oriented current in M1 resulted in considerably higher RMT, whereas varying the amplitude of the half-segment inducing anterior-posterior current had a smaller effect. These findings provide direct experimental evidence that the pulse segment inducing a posterior-anterior directed current in M1 contributes most to corticospinal pathway excitation. Preferential excitation of neuronal target cells in the posterior-anterior segment or targeting of different neuronal structures by the two half-segments can explain this result. Thus, our findings help understanding the mechanisms of neural stimulation by full-sine TMS.

PloS one

Delvendahl, I; Gattinger, N; Berger, T; Gleich, B; Siebner, HR; Mall, V

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The use of magnetic resonance spectroscopy as a tool for the measurement of bi-hemispheric transcranial electric stimulation effects on primary motor cortex metabolism.

2014

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of neurological and psychiatric disorders such as stroke and depression. Yet, the mechanisms underlying its ability to modulate brain excitability to improve clinical symptoms remains poorly understood. To help improve this understanding, proton magnetic resonance spectroscopy ((1)H-MRS) can be used as it allows the in vivo quantification of brain metabolites such as γ-aminobutyric acid (GABA) and glutamate in a region-specific manner. In fact, a recent study demonstrated that (1)H-MRS is indeed a powerful means to better understand the effects of tDCS on neurotransmitter concentration. This article aims to describe the complete protocol for combining tDCS (NeuroConn MR compatible stimulator) with (1)H-MRS at 3 T using a MEGA-PRESS sequence. We will describe the impact of a protocol that has shown great promise for the treatment of motor dysfunctions after stroke, which consists of bilateral stimulation of primary motor cortices. Methodological factors to consider and possible modifications to the protocol are also discussed.

Journal of visualized experiments : JoVE

Tremblay, S; Beaulé, V; Proulx, S; Lafleur, LP; Doyon, J; Marjańska, M; Théoret, H

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Polarity specific effects of transcranial direct current stimulation on interhemispheric inhibition.

2014

Transcranial direct current stimulation (tDCS) has been used as a useful interventional brain stimulation technique to improve unilateral upper-limb motor function in healthy humans, as well as in stroke patients. Although tDCS applications are supposed to modify the interhemispheric balance between the motor cortices, the tDCS after-effects on interhemispheric interactions are still poorly understood. To address this issue, we investigated the tDCS after-effects on interhemispheric inhibition (IHI) between the primary motor cortices (M1) in healthy humans. Three types of tDCS electrode montage were tested on separate days; anodal tDCS over the right M1, cathodal tDCS over the left M1, bilateral tDCS with anode over the right M1 and cathode over the left M1. Single-pulse and paired-pulse transcranial magnetic stimulations were given to the left M1 and right M1 before and after tDCS to assess the bilateral corticospinal excitabilities and mutual direction of IHI. Regardless of the electrode montages, corticospinal excitability was increased on the same side of anodal stimulation and decreased on the same side of cathodal stimulation. However, neither unilateral tDCS changed the corticospinal excitability at the unstimulated side. Unilateral anodal tDCS increased IHI from the facilitated side M1 to the unchanged side M1, but it did not change IHI in the other direction. Unilateral cathodal tDCS suppressed IHI both from the inhibited side M1 to the unchanged side M1 and from the unchanged side M1 to the inhibited side M1. Bilateral tDCS increased IHI from the facilitated side M1 to the inhibited side M1 and attenuated IHI in the opposite direction. Sham-tDCS affected neither corticospinal excitability nor IHI. These findings indicate that tDCS produced polarity-specific after-effects on the interhemispheric interactions between M1 and that those after-effects on interhemispheric interactions were mainly dependent on whether tDCS resulted in the facilitation or inhibition of the M1 sending interhemispheric volleys.

PloS one

Tazoe, T; Endoh, T; Kitamura, T; Ogata, T

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Transcranial magnetic stimulation and transcranial direct current stimulation: treatments for cognitive and neuropsychiatric symptoms in the neurodegenerative dementias?

2014

Two methods of non-invasive brain stimulation, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have demonstrable positive effects on cognition and can ameliorate neuropsychiatric symptoms such as depression. Less is known about the efficacy of these approaches in common neurodegenerative diseases. In this review, we evaluate the effects of TMS and tDCS upon cognitive and neuropsychiatric symptoms in the major dementias, including Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), and frontotemporal dementia (FTD), as well as the potential pre-dementia states of Mild Cognitive Impairment (MCI) and Parkinson's disease (PD).PubMed (until 7 February 2014) and PsycINFO (from 1967 to January Week 3 2014) databases were searched in a semi-systematic manner in order to identify relevant treatment studies. A total of 762 studies were identified and 32 studies (18 in the dementias and 14 in PD populations) were included.No studies were identified in patients with PDD, FTD or VaD. Of the dementias, 13 studies were conducted in patients with AD, one in DLB, and four in MCI. A total of 16 of the 18 studies showed improvements in at least one cognitive or neuropsychiatric outcome measure. Cognitive or neuropsychiatric improvements were observed in 12 of the 14 studies conducted in patients with PD.Both TMS and tDCS may have potential as interventions for the treatment of symptoms associated with dementia and PD. These results are promising; however, available data were limited, particularly within VaD, PDD and FTD, and major challenges exist in order to maximise the efficacy and clinical utility of both techniques. In particular, stimulation parameters vary considerably between studies and are likely to subsequently impact upon treatment efficacy.

Alzheimer's research & therapy

Elder, GJ; Taylor, JP

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A simultaneous modulation of reactive and proactive inhibition processes by anodal tDCS on the right inferior frontal cortex.

2014

Proactive and reactive inhibitory processes are a fundamental part of executive functions, allowing a person to stop inappropriate responses when necessary and to adjust performance in in a long term in accordance to the goals of a task. In the current study, we manipulate, in a single task, both reactive and proactive inhibition mechanisms, and we investigate the within-subjects effect of increasing, by means of anodal transcranial direct current stimulation (tDCS), the involvement of the right inferior frontal cortex (rIFC). Our results show a simultaneous enhancement of these two cognitive mechanisms when modulating the neural activity of rIFC. Thus, the application of anodal tDCS increased reaction times on Go trials, indicating a possible increase in proactive inhibition. Concurrently, the stop-signal reaction time, as a covert index of the inhibitory process, was reduced, demonstrating an improvement in reactive inhibition. In summary, the current pattern of results validates the engagement of the rIFC in these two forms of inhibitory processes, proactive and reactive inhibition and it provides evidence that both processes can operate concurrently in the brain.

PloS one

Cunillera, T; Fuentemilla, L; Brignani, D; Cucurell, D; Miniussi, C

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Patient-conducted anodal transcranial direct current stimulation of the motor cortex alleviates pain in trigeminal neuralgia.

2014

Transcranial direct current stimulation (tDCS) of the primary motor cortex has been shown to modulate pain and trigeminal nociceptive processing.Ten patients with classical trigeminal neuralgia (TN) were stimulated daily for 20 minutes over two weeks using anodal (1 mA) or sham tDCS over the primary motor cortex (M1) in a randomized double-blind cross-over design. Primary outcome variable was pain intensity on a verbal rating scale (VRS 0-10). VRS and attack frequency were assessed for one month before, during and after tDCS. The impact on trigeminal pain processing was assessed with pain-related evoked potentials (PREP) and the nociceptive blink reflex (nBR) following electrical stimulation on both sides of the forehead before and after tDCS.Anodal tDCS reduced pain intensity significantly after two weeks of treatment. The attack frequency reduction was not significant. PREP showed an increased N2 latency and decreased peak-to-peak amplitude after anodal tDCS. No severe adverse events were reported.Anodal tDCS over two weeks ameliorates intensity of pain in TN. It may become a valuable treatment option for patients unresponsive to conventional treatment.

The journal of headache and pain

Hagenacker, T; Bude, V; Naegel, S; Holle, D; Katsarava, Z; Diener, HC; Obermann, M

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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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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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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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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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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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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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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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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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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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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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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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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

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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

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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

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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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

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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

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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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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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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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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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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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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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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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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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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 transcranial direct current stimulation of prefrontal cortex.

2013

The midbrain lies deep within the brain and has an important role in reward, motivation, movement and the pathophysiology of various neuropsychiatric disorders such as Parkinson's disease, schizophrenia, depression and addiction. To date, the primary means of acting on this region has been with pharmacological interventions or implanted electrodes. Here we introduce a new noninvasive brain stimulation technique that exploits the highly interconnected nature of the midbrain and prefrontal cortex to stimulate deep brain regions. Using transcranial direct current stimulation (tDCS) of the prefrontal cortex, we were able to remotely activate the interconnected midbrain and cause increases in participants' appraisals of facial attractiveness. Participants with more enhanced prefrontal/midbrain connectivity following stimulation exhibited greater increases in attractiveness ratings. These results illustrate that noninvasive direct stimulation of prefrontal cortex can induce neural activity in the distally connected midbrain, which directly effects behavior. Furthermore, these results suggest that this tDCS protocol could provide a promising approach to modulate midbrain functions that are disrupted in neuropsychiatric disorders.

Translational psychiatry

Chib, VS; Yun, K; Takahashi, H; Shimojo, S

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tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli.

2013

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

PloS one

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

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

2013

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

Frontiers in human neuroscience

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

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

2013

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

Frontiers in systems neuroscience

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

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

2013

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

Neural plasticity

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

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

2013

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

Stroke research and treatment

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

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High-frequency TRNS reduces BOLD activity during visuomotor learning.

2013

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

PloS one

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

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

2013

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

Frontiers in neurology

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

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

2013

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

BMC neuroscience

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

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

2013

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

PloS one

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

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

2013

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

Stroke research and treatment

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

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Enhancing social ability by stimulating right temporoparietal junction.

2012 Dec

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

Current biology : CB

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

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

2012 Dec

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

Annals of physical and rehabilitation medicine

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

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

2012 Dec

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

Brain research

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

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

2012 Dec

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

Journal of neurophysiology

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

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

2012 Nov

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

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

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

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Wolf Motor Function Test for characterizing moderate to severe hemiparesis in stroke patients.

2012 Nov

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

Archives of physical medicine and rehabilitation

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

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

2012 Oct

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

Annals of rehabilitation medicine

Jeon, SY; Han, SJ

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

2012 Sep

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

Psychiatria Danubina

Herremans, SC; Baeken, C

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Can tDCS enhance treatment of aphasia after stroke?

2012 Sep

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

Aphasiology

Holland, R; Crinion, J

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

2012 Aug

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

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

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

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Modulation of soleus H reflex by spinal DC stimulation in humans.

2012 Aug

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

Journal of neurophysiology

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

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Modulation of training by single-session transcranial direct current stimulation to the intact motor cortex enhances motor skill acquisition of the paretic hand.

2012 Aug

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

Stroke; a journal of cerebral circulation

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

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

2012 Aug

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

European archives of psychiatry and clinical neuroscience

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

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

2012 Aug

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

Journal of sleep research

Jakobson, AJ; Fitzgerald, PB; Conduit, R

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

2012 Jul

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

Discovery medicine

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

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High-resolution modeling assisted design of customized and individualized transcranial direct current stimulation protocols.

2012 Jul

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

Neuromodulation : journal of the International Neuromodulation Society

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

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Temporal profile of functional visual rehabilitative outcomes modulated by transcranial direct current stimulation.

2012 Jul

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

Neuromodulation : journal of the International Neuromodulation Society

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

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Left lateralizing transcranial direct current stimulation improves reading efficiency.

2012 Jul

Poor reading efficiency is the most persistent problem for adults with developmental dyslexia. Previous research has demonstrated a relationship between left posterior temporal cortex (pTC) function and reading ability, regardless of dyslexia status.In this study, we tested whether enhancing left lateralization of pTC using transcranial direct current stimulation (tDCS) improves reading efficiency in adults without dyslexia.Twenty-five right-handed adults with no history of learning disorder participated. Real and sham "Left lateralizing" tDCS were applied to the pTC in separate sessions. Standardized word and nonword reading tests were given immediately after stimulation.Modeling of the induced electrical field confirmed that tDCS was likely to increase left pTC excitability and reduce right pTC excitability as intended. Relative to sham, real tDCS induced improvements in word reading efficiency in below average readers.Enhancing left lateralization of the pTC using tDCS improves word reading efficiency in below-average readers. This demonstrates that left lateralization of the pTC plays a role in reading ability, and provides stimulation parameters that could be used for a trial of tDCS in adults with developmental dyslexia. Such short-term gains could amplify the effect of appropriate reading interventions when performed in conjunction with them.

Brain stimulation

Turkeltaub, PE; Benson, J; Hamilton, RH; Datta, A; Bikson, M; Coslett, HB

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Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions.

2012 Jul

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past 10 years, tDCS physiologic mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodologic, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them.We convened a workgroup of researchers in the field to review, discuss, and provide updates and key challenges of tDCS use in clinical research.We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (1) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (2) methodologic aspects related to the clinical research of tDCS as divided according to study phase (ie, preclinical, phase I, phase II, and phase III studies); (3) ethical and regulatory concerns; and (4) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS.

Brain stimulation

Brunoni, AR; Nitsche, MA; Bolognini, N; Bikson, M; Wagner, T; Merabet, L; Edwards, DJ; Valero-Cabre, A; Rotenberg, A; Pascual-Leone, A; Ferrucci, R; Priori, A; Boggio, PS; Fregni, F

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Modulation of large-scale brain networks by transcranial direct current stimulation evidenced by resting-state functional MRI.

2012 Jul

Brain areas interact mutually to perform particular complex brain functions such as memory or language. Furthermore, under resting-state conditions several spatial patterns have been identified that resemble functional systems involved in cognitive functions. Among these, the default-mode network (DMN), which is consistently deactivated during task periods and is related to a variety of cognitive functions, has attracted most attention. In addition, in resting-state conditions some brain areas engaged in focused attention (such as the anticorrelated network, AN) show a strong negative correlation with DMN; as task demand increases, AN activity rises, and DMN activity falls.We combined transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) to investigate these brain network dynamics.Ten healthy young volunteers underwent four blocks of resting-state fMRI (10-minutes), each of them immediately after 20 minutes of sham or active tDCS (2 mA), on two different days. On the first day the anodal electrode was placed over the left dorsolateral prefrontal cortex (DLPFC) (part of the AN) with the cathode over the contralateral supraorbital area, and on the second day, the electrode arrangement was reversed (anode right-DLPFC, cathode left-supraorbital).After active stimulation, functional network connectivity revealed increased synchrony within the AN components and reduced synchrony in the DMN components.Our study reveals a reconfiguration of intrinsic brain activity networks after active tDCS. These effects may help to explain earlier reports of improvements in cognitive functions after anodal-tDCS, where increasing cortical excitability may have facilitated reconfiguration of functional brain networks to address upcoming cognitive demands.

Brain stimulation

Peña-Gómez, C; Sala-Lonch, R; Junqué, C; Clemente, IC; Vidal, D; Bargalló, N; Falcón, C; Valls-Solé, J; Pascual-Leone, Á; Bartrés-Faz, D

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Modulating locomotor adaptation with cerebellar stimulation.

2012 Jun

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

Journal of neurophysiology

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

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Combined central and peripheral stimulation to facilitate motor recovery after stroke: the effect of number of sessions on outcome.

2012 Jun

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

Neurorehabilitation and neural repair

Lindenberg, R; Zhu, LL; Schlaug, G

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

2012 May

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

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

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

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Cerebellar modulation of human associative plasticity.

2012 May

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

The Journal of physiology

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

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Enhanced locomotor adaptation aftereffect in the "broken escalator" phenomenon using anodal tDCS.

2012 May

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

Journal of neurophysiology

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

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

2012 Apr

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

Brain stimulation

Pope, PA; Miall, RC

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

2012 Apr

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

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

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

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Modulation of LTP at rat hippocampal CA3-CA1 synapses by direct current stimulation.

2012 Apr

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

Journal of neurophysiology

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

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

2012 Apr

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

Journal of neurophysiology

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

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Differences in the experience of active and sham transcranial direct current stimulation.

2012 Apr

A limited number of studies have shown that modulation of cortical excitability using transcranial direct current stimulation (tDCS) is safe and tolerable. Few have directly evaluated whether sham and active stimulation are indistinguishable.We aimed to demonstrate tDCS safety and tolerability in a large cohort, and to compare the occurrence and severity of side effects between sham and active stimulation sessions.One hundred thirty-one healthy subjects undergoing 277 tDCS sessions rated on a 1 to 5 scale the perception of side effects during and after stimulation. Proportions of active and sham sessions associated with side effects were compared using Fisher exact test, and distributions of severity ratings were compared using the Kruskal-Wallis test.No serious adverse effects occurred. Side effects most commonly reported were tingling (76%), itching (68%), burning (54%), and pain (25%). Side effect severity was mild, with fewer than 2% of responses indicating a severity > 3 on all questions except tingling (15%), itching (20%), burning (7%), pain (5%), and fatigue (3%) during stimulation. Rates of sensory side effects were statistically significantly higher in active stimulation sessions compared with sham sessions. No other stimulation parameters had a statistically significant impact on side effect occurrence.TDCS is a safe well-tolerated technique with no evidence of risk for serious adverse effects. Sensory side effects are common, but the severity is typically low. Because sensory side effects are more frequent and more severe in active compared with sham tDCS, the current method of sham stimulation may not be an adequate control condition for some studies.

Brain stimulation

Kessler, SK; Turkeltaub, PE; Benson, JG; Hamilton, RH

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

2012 Mar

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

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

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

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

2012 Mar

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

Experimental brain research

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

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When anger leads to aggression: induction of relative left frontal cortical activity with transcranial direct current stimulation increases the anger-aggression relationship.

2012 Mar

The relationship between anger and aggression is imperfect. Based on work on the neuroscience of anger, we predicted that anger associated with greater relative left frontal cortical activation would be more likely to result in aggression. To test this hypothesis, we combined transcranial direct current stimulation (tDCS) over the frontal cortex with interpersonal provocation. Participants received insulting feedback after 15 min of tDCS and were able to aggress by administering noise blasts to the insulting participant. Individuals who received tDCS to increase relative left frontal cortical activity behaved more aggressively when they were angry. No relation between anger and aggression was observed in the increase relative right frontal cortical activity or sham condition. These results concur with the motivational direction model of frontal asymmetry, in which left frontal activity is associated with anger. We propose that anger with approach motivational tendencies is more likely to result in aggression.

Social cognitive and affective neuroscience

Hortensius, R; Schutter, DJ; Harmon-Jones, E

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

2012 Feb

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

Annals of rehabilitation medicine

Sohn, MK; Kim, BO; Song, HT

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The neuroethics of non-invasive brain stimulation.

2012 Feb

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

Current biology : CB

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

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

2012 Jan

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

The British journal of psychiatry : the journal of mental science

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

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

2012 Jan

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

Journal of neurophysiology

Venkatakrishnan, A; Sandrini, M

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

2012 Jan

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

NeuroImage

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

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

2012

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

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

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

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

2012

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

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

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

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

2012

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

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

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

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

2012

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

Frontiers in human neuroscience

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

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Neurobiological effects of transcranial direct current stimulation: a review.

2012

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

Frontiers in psychiatry

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

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

2012

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

PloS one

Luedtke, K; May, A; Jürgens, TP

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

2012

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

Frontiers in psychiatry

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

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

2012

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

Frontiers in pharmacology

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

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

2012

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

TheScientificWorldJournal

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

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

2012

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

Frontiers in psychiatry

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

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

2012

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

Frontiers in psychiatry

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

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Target optimization in transcranial direct current stimulation.

2012

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

Frontiers in psychiatry

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

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

2012

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

Frontiers in psychiatry

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

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

2012

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

PloS one

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

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EEG Driven tDCS Versus Bifrontal tDCS for Tinnitus.

2012

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

Frontiers in psychiatry

De Ridder, D; Vanneste, S

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

2012

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

Frontiers in psychiatry

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

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

2012

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

Frontiers in psychiatry

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

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Parietal contributions to visual working memory depend on task difficulty.

2012

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

Frontiers in psychiatry

Jones, KT; Berryhill, ME

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Learning, memory, and transcranial direct current stimulation.

2012

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

Frontiers in psychiatry

Brasil-Neto, JP

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Transcranial direct current stimulation and behavioral models of smoking addiction.

2012

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

Frontiers in psychiatry

Fraser, PE; Rosen, AC

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

2012

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

BMC neuroscience

Coffman, BA; Trumbo, MC; Clark, VP

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

2012

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

PloS one

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

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

2012

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

Frontiers in psychiatry

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

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Altering automatic verbal processes with transcranial direct current stimulation.

2012

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

Frontiers in psychiatry

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

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

2012

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

Frontiers in psychiatry

Madhavan, S; Shah, B

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Pharmacological modulation of the short-lasting effects of antagonistic direct current-stimulation over the human motor cortex.

2012

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

Frontiers in psychiatry

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

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Transcutaneous spinal direct current stimulation.

2012

In the past 10 years renewed interest has centered on non-invasive transcutaneous weak direct currents applied over the scalp to modulate cortical excitability ("brain polarization" or transcranial direct current stimulation, tDCS). Extensive literature shows that tDCS induces marked changes in cortical excitability that outlast stimulation. Aiming at developing a new, non-invasive, approach to spinal cord neuromodulation we assessed the after-effects of thoracic transcutaneous spinal DC stimulation (tsDCS) on somatosensory potentials (SEPs) evoked in healthy subjects by posterior tibial nerve (PTN) stimulation. Our findings showed that thoracic anodal tsDCS depresses the cervico-medullary PTN-SEP component (P30) without eliciting adverse effects. tsDCS also modulates post-activation H-reflex dynamics. Later works further confirmed that transcutaneous electric fields modulate spinal cord function. Subsequent studies in our laboratory showed that tsDCS modulates the flexion reflex in the human lower limb. Besides influencing the laser evoked potentials (LEPs), tsDCS increases pain tolerance in healthy subjects. Hence, though the underlying mechanisms remain speculative, tsDCS modulates activity in lemniscal, spinothalamic, and segmental motor systems. Here we review currently available experimental evidence that non-invasive spinal cord stimulation (SCS) influences spinal function in humans and argue that, by focally modulating spinal excitability, tsDCS could provide a novel therapeutic tool complementary to drugs and invasive SCS in managing various pathologic conditions, including pain.

Frontiers in psychiatry

Cogiamanian, F; Ardolino, G; Vergari, M; Ferrucci, R; Ciocca, M; Scelzo, E; Barbieri, S; Priori, A

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

2012

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

Frontiers in psychiatry

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

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

2012

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

Frontiers in psychiatry

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

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

2012

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

Frontiers in psychiatry

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

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

2012

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

Frontiers in psychiatry

Hansen, N

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

2012

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

Frontiers in psychiatry

Kanai, R; Muggleton, N; Walsh, V

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

2012

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

PloS one

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

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

2012

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

PloS one

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

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Reorganizing the intrinsic functional architecture of the human primary motor cortex during rest with non-invasive cortical stimulation.

2012

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

PloS one

Polanía, R; Paulus, W; Nitsche, MA

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Modulation of untruthful responses with non-invasive brain stimulation.

2012

Deceptive abilities have long been studied in relation to personality traits. More recently, studies explored the neural substrates associated with deceptive skills suggesting a critical role of the prefrontal cortex. Here we investigated whether non-invasive brain stimulation over the dorsolateral prefrontal cortex (DLPFC) could modulate generation of untruthful responses about subject's personal life across contexts (i.e., deceiving on guilt-free questions on daily activities; generating previously memorized lies about past experience; and producing spontaneous lies about past experience), as well as across modality responses (verbal and motor responses). Results reveal that real, but not sham, transcranial direct current stimulation (tDCS) over the DLPFC can reduce response latency for untruthful over truthful answers across contexts and modality responses. Also, contexts of lies seem to incur a different hemispheric laterality. These findings add up to previous studies demonstrating that it is possible to modulate some processes involved in generation of untruthful answers by applying non-invasive brain stimulation over the DLPFC and extend these findings by showing a differential hemispheric contribution of DLPFCs according to contexts.

Frontiers in psychiatry

Fecteau, S; Boggio, P; Fregni, F; Pascual-Leone, A

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

2012

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

International journal of Alzheimer's disease

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

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

2011 Dec

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

Journal of neural engineering

Faria, P; Hallett, M; Miranda, PC

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

2011 Nov

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

Journal of neurology

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

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

2011 Oct

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

International review of psychiatry (Abingdon, England)

Jorge, RE; Robinson, RG

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

2011 Oct

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

Brain stimulation

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

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Random noise stimulation improves neuroplasticity in perceptual learning.

2011 Oct

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

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

Fertonani, A; Pirulli, C; Miniussi, C

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

2011 Oct

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

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

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

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

2011 Oct

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

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

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

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Bilateral transcranial direct current stimulation modulates activation-induced regional blood flow changes during voluntary movement.

2011 Oct

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that induces changes in cortical excitability: anodal stimulation increases while cathodal stimulation reduces excitability. Imaging studies performed after unilateral stimulation have shown conflicting results regarding the effects of tDCS on surrogate markers of neuronal activity. The aim of this study was to directly measure these effects on activation-induced changes in regional cerebral blood flow (ΔrCBF) using positron emission tomography (PET) during bilateral tDCS. Nine healthy subjects underwent repeated rCBF measurements with (15)O-water and PET during a simple motor task while receiving tDCS or sham stimulation over the primary motor cortex (M1). Motor evoked potentials (MEPs) were also assessed before and after real and sham stimulation. During tDCS with active movement, ΔrCBF in M1 was significantly lower on the cathodal than the anodal side when compared with sham stimulation. This decrease in ΔrCBF was accompanied by a decrease in MEP amplitude on the cathodal side. No effect was observed on resting or activated rCBF relative to sham stimulation. We thus conclude that it is the interaction of cathodal tDCS with activation-induced ΔrCBF rather than the effect on resting or activated rCBF itself which constitutes the physiological imaging correlate of tDCS.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Paquette, C; Sidel, M; Radinska, BA; Soucy, JP; Thiel, A

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The use of non-invasive brain stimulation techniques to facilitate recovery from post-stroke aphasia.

2011 Sep

Aphasia is a common symptom after left hemispheric stroke. Neuroimaging techniques over the last 10-15 years have described two general trends: Patients with small left hemisphere strokes tend to recruit perilesional areas, while patients with large left hemisphere lesions recruit mainly homotopic regions in the right hemisphere. Non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been employed to facilitate recovery by stimulating lesional and contralesional regions. The majority of these brain stimulation studies have attempted to block homotopic regions in the right posterior inferior frontal gyrus (IFG) to affect a presumed disinhibited right IFG (triangular portion). Other studies have used anodal or excitatory tDCS to stimulate the contralesional (right) fronto-temporal region or parts of the intact left IFG and perilesional regions to improve speech-motor output. It remains unclear whether the interhemispheric disinhibition model, which is the basis for motor cortex stimulation studies, also applies to the language system. Future studies could address a number of issues, including: the effect of lesion location on current density distribution, timing of the intervention with regard to stroke onset, whether brain stimulation should be combined with behavioral therapy, and whether multiple brain sites should be stimulated. A better understanding of the predictors of recovery from natural outcome studies would also help to inform study design, and the selection of clinically meaningful outcome measures in future studies.

Neuropsychology review

Schlaug, G; Marchina, S; Wan, CY

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Effects of transcranial direct current stimulation (tDCS) on human regional cerebral blood flow.

2011 Sep

Transcranial direct current stimulation (tDCS) can up- and down-regulate cortical excitability depending on current direction, however our abilities to measure brain-tissue effects of the stimulation and its after-effects have been limited so far. We used regional cerebral blood flow (rCBF), a surrogate measure of brain activity, to examine regional brain-tissue and brain-network effects during and after tDCS. We varied the polarity (anodal and cathodal) as well as the current strength (0.8 to 2.0mA) of the stimulation. Fourteen healthy subjects were randomized into receiving either anodal or cathodal stimulation (two subjects received both, one week apart) while undergoing Arterial Spin Labeling (ASL) in the MRI scanner with an alternating off-on sampling paradigm. The stimulating, MRI-compatible electrode was placed over the right motor region and the reference electrode over the contralateral supra-orbital region. SPM5 was used to process and extract the rCBF data using a 10mm spherical volume of interest (VOI) placed in the motor cortex directly underneath the stimulating scalp electrode. Anodal stimulation induced a large increase (17.1%) in rCBF during stimulation, which returned to baseline after the current was turned off, but exhibited an increase in rCBF again in the post-stimulation period. Cathodal stimulation induced a smaller increase (5.6%) during stimulation, a significant decrease compared to baseline (-6.5%) after cessation, and a continued decrease in the post-stimulation period. These changes in rCBF were all significant when compared to the pre-stimulation baseline or to a control region. Furthermore, for anodal stimulation, there was a significant correlation between current strength and the increase in rCBF in the on-period relative to the pre-stimulation baseline. The differential rCBF after-effects of anodal (increase in resting state rCBF) and cathodal (decrease in resting state rCBF) tDCS support findings of behavioral and cognitive after-effects after cathodal and anodal tDCS. We also show that tDCS not only modulates activity in the brain region directly underlying the stimulating electrode but also in a network of brain regions that are functionally related to the stimulated area. Our results indicate that ASL may be an excellent tool to investigate the effects of tDCS and its stimulation parameters on brain activity.

NeuroImage

Zheng, X; Alsop, DC; Schlaug, G

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D2 receptor block abolishes θ burst stimulation-induced neuroplasticity in the human motor cortex.

2011 Sep

Dopamine (DA) is a neurotransmitter with an important influence on learning and memory, which is thought to be due to its modulatory effect on plasticity at central synapses, which in turn depends on activation of D1 and D2 receptors. Methods of brain stimulation (transcranial direct current stimulation, tDCS; paired associative stimulation, PAS) lead to after-effects on cortical excitability that are thought to resemble long-term potentization (LTP)/long-term depression (LTD) in reduced preparations. In a previous study we found that block of D2 receptors abolished plasticity induced by tDCS but had no effect on the facilitatory plasticity induced by PAS. We postulated that the different effect of D2 receptor block on tDCS- and PAS-induced plasticity may be due to the different focality and associativity of the stimulation techniques. However, alternative explanations for this difference could not be ruled out. tDCS also differs from PAS in other aspects, as tDCS induces plasticity by subthreshold neuronal activation, modulating spontaneous activity, whereas PAS induces plasticity via phasic suprathreshold stimulation. The present study in 12 volunteers examined effects of D2 receptor blockade (sulpiride (SULP) 400 mg), on the LTP/LTD-like effects of theta burst transcranial magnetic stimulation (TBS), which has less restricted effects on cortical synapses than that of PAS, and does not induce associative plasticity, similar to tDCS, but on the other hand induces cortical excitability shifts by suprathreshold (rhythmic) activation of cortical neurons similarly to PAS. Administration of SULP blocked both the excitatory and inhibitory effects of intermittent (iTBS) and continuous TBS (cTBS), respectively. As the reduced response to TBS following SULP resembles its effect on tDCS, the results support an effect of DA on plasticity, which might be related to the focality and associativity of the plasticity induced.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Monte-Silva, K; Ruge, D; Teo, JT; Paulus, W; Rothwell, JC; Nitsche, MA

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Suppression of seizure by cathodal transcranial direct current stimulation in an epileptic patient - a case report -.

2011 Aug

Epilepsy is an intractable disease, though many treatment modalities have been developed. Recently, noninvasive transcranial direct current stimulation (tDCS), which can change brain excitability, was introduced and has been applied for therapeutic purposes regarding epilepsy. A suppression of seizures was experienced by cathodal tDCS in a medication refractory pediatric epileptic patient. The patient was an 11-year-old female who had focal cortical dysplasia of the cerebral hemisphere. The patient was treated with antiepileptic drugs but the mean seizure frequency was still eight episodes per month. The tDCS cathode was placed at the midpoint of P4 and T4 in the 10-20 EEG system where the abnormal wave was observed on a sleep EEG. Two mA of tDCS was applied 20 minutes a day, five days a week for two weeks. During a two-month period after treatment termination, only six seizure attacks occurred, and the duration of each seizure episode also decreased. tDCS was applied under the same conditions for another two weeks. For two months after the second treatment session, only one seizure attack occurred, and it showed great improvement compared to the eight seizure attacks per month before the tDCS treatment. The medications were not changed, and there were no notable side effects that were caused by tDCS.

Annals of rehabilitation medicine

Yook, SW; Park, SH; Seo, JH; Kim, SJ; Ko, MH

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The Factors Associated with Good Responses to Speech Therapy Combined with Transcranial Direct Current Stimulation in Post-stroke Aphasic Patients.

2011 Aug

To determine factors associated with good responses to speech therapy combined with transcranial direct current stimulation (tDCS) in aphasic patients after stroke.The language function was evaluated using Korean version of Western aphasia battery (K-WAB) before and after speech therapy with tDCS in 37 stroke patients. Patients received speech therapy for 30 minutes over 2 to 3 weeks (10 sessions) while the cathodal tDCS was performed to the Brodmann area 45 with 1 mA for 20 minutes. We compared the improvement of aphasia quotient % (AQ%) between two evaluation times according to age, sex, days after onset, stroke type, aphasia type, brain lesion confirmed by magnetic resonance image and initial severity of aphasia. The factors related with good responses were also checked.AQ% improved from pre- to post-therapy (14.94±6.73%, p<0.001). AQ% improvement was greater in patients with less severe, fluent type of aphasia who received treatment before 30 days since stroke was developed (p<0.05). The adjusted logistic regression model revealed that patients with hemorrhagic stroke were more likely to achieve good responses (odds ratio=4.897, p<0.05) relative to infarction. Initial severity over 10% in AQ% was also found to be significantly associated with good improvement (odds ratio=8.618, p<0.05).Speech therapy with tDCS was established as a treatment tool for aphasic patients after stroke. Lower initial severity was associated with good responses.

Annals of rehabilitation medicine

Jung, IY; Lim, JY; Kang, EK; Sohn, HM; Paik, NJ

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Speech facilitation by left inferior frontal cortex stimulation.

2011 Aug

Electrophysiological studies in humans and animals suggest that noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting [1], polarity-dependent [2] changes in neocortical excitability. Application of tDCS can have significant and selective behavioral consequences that are associated with the cortical location of the stimulation electrodes and the task engaged during stimulation [3-8]. However, the mechanism by which tDCS affects human behavior is unclear. Recently, functional magnetic resonance imaging (fMRI) has been used to determine the spatial topography of tDCS effects [9-13], but no behavioral data were collected during stimulation. The present study is unique in this regard, in that both neural and behavioral responses were recorded using a novel combination of left frontal anodal tDCS during an overt picture-naming fMRI study. We found that tDCS had significant behavioral and regionally specific neural facilitation effects. Furthermore, faster naming responses correlated with decreased blood oxygen level-dependent (BOLD) signal in Broca's area. Our data support the importance of Broca's area within the normal naming network and as such indicate that Broca's area may be a suitable candidate site for tDCS in neurorehabilitation of anomic patients, whose brain damage spares this region.

Current biology : CB

Holland, R; Leff, AP; Josephs, O; Galea, JM; Desikan, M; Price, CJ; Rothwell, JC; Crinion, J

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[The use of noninvasive brain stimulation in childhood psychiatric disorders: new diagnostic and therapeutic opportunities and challenges].

2011 Aug

Novel diagnostic and therapeutic approaches based on noninvasive brain stimulation offer some promise in the field of childhood psychiatric disorders. There are two primary methods of noninvasive brain stimulation currently available: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Both noninvasive neuromodulation techniques appear to rely on modulating brain plasticity and thus open new hopes in the treatment of brain circuit and plasticity disorders. Since many childhood psychiatric disorders involve disturbances in the timing or mechanisms of plasticity within frontostriatal circuits, and the developing brain shows a greater capacity of brain plasticity, noninvasive brain stimulation might induce greater benefits in this population than in adults. Although the utilization of TMS and tDCS remains limited in children, there is enough evidence for their rational, safe use in this population. In this paper, we review the principles of noninvasive brain stimulation and the diagnostic and therapeutic applications in child-hood psychiatric disorders in order to inform its development into safe and reliable diagnostic and effective therapeutic approaches in pediatric psychiatry.

Revista de neurologia

Rubio-Morell, B; Rotenberg, A; Hernández-Expósito, S; Pascual-Leone, Á

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Neuroplastic changes following rehabilitative training correlate with regional electrical field induced with tDCS.

2011 Aug

Transcranial direct current stimulation (tDCS) has recently emerged as a promising approach to enhance neurorehabilitative outcomes. However, little is known about how the local electrical field generated by tDCS relates to underlying neuroplastic changes and behavior. To address this question, we present a case study analysis of an individual with hemianopia due to stroke and who benefited from a combined visual rehabilitation training and tDCS treatment program. Activation associated with a visual motion perception task (obtained by functional magnetic resonance imaging; fMRI) was used to characterize local changes in brain activity at baseline and after training. Individualized, high-resolution electrical field modeling reproducing precise cerebral and lesioned tissue geometry, predicted distortions of current flow in peri-lesional areas and diffuse clusters of peak electric fields. Using changes in fMRI signal as an index of cortical recovery, correlations to the electrical field map were determined. Significant correlations between the electrical field and change in fMRI signal were region specific including cortical areas under the anode electrode and peri-lesional visual areas. These patterns were consistent with effective tDCS facilitated rehabilitation. We describe the methodology used to analyze tDCS mechanisms through combined fMRI and computational modeling with the ultimate goal of developing a rationale for individualized therapy.

NeuroImage

Halko, MA; Datta, A; Plow, EB; Scaturro, J; Bikson, M; Merabet, LB

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Probing for hemispheric specialization for motor skill learning: a transcranial direct current stimulation study.

2011 Aug

Convergent findings point to a left-sided specialization for the representation of learned actions in right-handed humans, but it is unknown whether analogous hemispheric specialization exists for motor skill learning. In the present study, we explored this question by comparing the effects of anodal transcranial direct current stimulation (tDCS) over either left or right motor cortex (M1) on motor skill learning in either hand, using a tDCS montage to better isolate stimulation to one hemisphere. Results were compared with those previously found with a montage more commonly used in the field. Six groups trained for three sessions on a visually guided sequential pinch force modulation task with their right or left hand and received right M1, left M1, or sham tDCS. A linear mixed-model analysis for motor skill showed a significant main effect for stimulation group (left M1, right M1, sham) but not for hand (right, left) or their interaction. Left M1 tDCS induced significantly greater skill learning than sham when hand data were combined, a result consistent not only with the hypothesized left hemisphere specialization for motor skill learning but also with possible increased left M1 responsiveness to tDCS. The unihemispheric montage effect size was one-half that of the more common montage, and subsequent power analysis indicated that 75 subjects per group would be needed to detect differences seen with only 12 subjects with the customary bihemispheric montage.

Journal of neurophysiology

Schambra, HM; Abe, M; Luckenbaugh, DA; Reis, J; Krakauer, JW; Cohen, LG

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Noninvasive brain stimulation in Alzheimer's disease: systematic review and perspectives for the future.

2011 Aug

A number of studies have applied transcranial magnetic stimulation (TMS) to physiologically characterize Alzheimer's disease (AD) and to monitor effects of pharmacological agents, while others have begun to therapeutically use TMS and transcranial direct current stimulation (tDCS) to improve cognitive function in AD. These applications are still very early in development, but offer the opportunity of learning from them for future development.We performed a systematic search of all studies using noninvasive stimulation in AD and reviewed all 29 identified articles. Twenty-four focused on measures of motor cortical reactivity and (local) plasticity and functional connectivity, with eight of these studies assessing also effects of pharmacological agents. Five studies focused on the enhancement of cognitive function in AD.Short-latency afferent inhibition (SAI) and resting motor threshold are significantly reduced in AD patients as compared to healthy elders. Results on other measures of cortical reactivity, e.g. intracortical inhibition (ICI), are more divergent. Acetylcholine-esterase inhibitors and dopaminergic drugs may increase SAI and ICI in AD. Motor cortical plasticity and connectivity are impaired in AD. TMS/tDCS can induce acute and short-duration beneficial effects on cognitive function, but the therapeutic clinical significance in AD is unclear. Safety of TMS/tDCS is supported by studies to date.TMS/tDCS appears safe in AD, but longer-term risks have been insufficiently considered. TMS holds promise as a physiologic biomarker in AD to identify therapeutic targets and monitor pharmacologic effects. In addition, TMS/tDCS may have therapeutic utility in AD, though the evidence is still very preliminary and cautious interpretation is warranted.

Experimental gerontology

Freitas, C; Mondragón-Llorca, H; Pascual-Leone, A

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Dissociating the roles of the cerebellum and motor cortex during adaptive learning: the motor cortex retains what the cerebellum learns.

2011 Aug

Adaptation to a novel visuomotor transformation has revealed important principles regarding learning and memory. Computational and behavioral studies have suggested that acquisition and retention of a new visuomotor transformation are distinct processes. However, this dissociation has never been clearly shown. Here, participants made fast reaching movements while unexpectedly a 30-degree visuomotor transformation was introduced. During visuomotor adaptation, subjects received cerebellar, primary motor cortex (M1) or sham anodal transcranial direct current stimulation (tDCS), a noninvasive form of brain stimulation known to increase excitability. We found that cerebellar tDCS caused faster adaptation to the visuomotor transformation, as shown by a rapid reduction of movement errors. These findings were not present with similar modulation of visual cortex excitability. In contrast, tDCS over M1 did not affect adaptation, but resulted in a marked increase in retention of the newly learnt visuomotor transformation. These results show a clear dissociation in the processes of acquisition and retention during adaptive motor learning and demonstrate that the cerebellum and primary motor cortex have distinct functional roles. Furthermore, they show that is possible to enhance cerebellar function using tDCS.

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

Galea, JM; Vazquez, A; Pasricha, N; de Xivry, JJ; Celnik, P

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Individualized model predicts brain current flow during transcranial direct-current stimulation treatment in responsive stroke patient.

2011 Jul

Although numerous published reports have demonstrated the beneficial effects of transcranial direct-current stimulation (tDCS) on task performance, fundamental questions remain regarding the optimal electrode configuration on the scalp. Moreover, it is expected that lesioned brain tissue will influence current flow and should therefore be considered (and perhaps leveraged) in the design of individualized tDCS therapies for stroke. The current report demonstrates how different electrode configurations influence the flow of electrical current through brain tissue in a patient who responded positively to a tDCS treatment targeting aphasia. The patient, a 60-year-old man, sustained a left hemisphere ischemic stroke (lesion size = 87.42 mL) 64 months before his participation. In this study, we present results from the first high-resolution (1 mm(3)) model of tDCS in a brain with considerable stroke-related damage; the model was individualized for the patient who received anodal tDCS to his left frontal cortex with the reference cathode electrode placed on his right shoulder. We modeled the resulting brain current flow and also considered three additional reference electrode positions: right mastoid, right orbitofrontal cortex, and a "mirror" configuration with the anode over the undamaged right cortex. Our results demonstrate the profound effect of lesioned tissue on resulting current flow and the ability to modulate current pattern through the brain, including perilesional regions, through electrode montage design. The complexity of brain current flow modulation by detailed normal and pathologic anatomy suggest: (1) That computational models are critical for the rational interpretation and design of individualized tDCS stroke-therapy; and (2) These models must accurately reproduce head anatomy as shown here.

Brain stimulation

Datta, A; Baker, JM; Bikson, M; Fridriksson, J

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Mechanisms of aphasia recovery after stroke and the role of noninvasive brain stimulation.

2011 Jul

One of the most frequent symptoms of unilateral stroke is aphasia, the impairment or loss of language functions. Over the past few years, behavioral and neuroimaging studies have shown that rehabilitation interventions can promote neuroplastic changes in aphasic patients that may be associated with the improvement of language functions. Following left hemisphere strokes, the functional reorganization of language in aphasic patients has been proposed to involve both intrahemispheric interactions between damaged left hemisphere and perilesional sites and transcallosal interhemispheric interactions between the lesioned left hemisphere language areas and homotopic regions in the right hemisphere. A growing body of evidence for such reorganization comes from studies using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), two safe and noninvasive procedures that can be applied clinically to modulate cortical excitability during post-stroke language recovery. We discuss a hierarchical model for the plastic changes in language representation that occur in the setting of dominant hemisphere stroke and aphasia. We further argue that TMS and tDCS are potentially promising tools for enhancing functional recovery of language and for further elucidating mechanisms of plasticity in patients with aphasia.

Brain and language

Hamilton, RH; Chrysikou, EG; Coslett, B

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Transcranial direct current stimulation influences the cardiac autonomic nervous control.

2011 Jun

To investigate whether the manipulation of brain excitability by transcranial direct current stimulation (tDCS) modulates the heart rate variability (HRV), the effect of tDCS applied at rest on the left temporal lobe in athletes (AG) and non-athletes (NAG) was evaluated. The HRV parameters (natural logarithms of LF, HF, and LF/HF) was assessed in 20 healthy men before, and immediately after tDCS and sham stimulation. After anodal tDCS in AG the parasympathetic activity (HF(log)) increased (P<0.01) and the sympathetic activity (LF(log)) and sympatho-vagal balance (LF/HF(log)) decreased (P<0.01), whereas no significant effects were detected in NAG (P>0.05). No significant changes in HRV indexes were provoked by sham stimulation in both AG and NAG (P>0.05). In conclusion, tDCS applied on the left temporal lobe significantly increased the overall HRV in AG, enhancing the parasympathetic and decreasing the sympathetic modulation of heart rate. Consequently the sympatho-vagal balance decreased at rest in AG but not in NAG. Releasing a weak electric current to stimulate selected brain areas may induce favorable effects on the autonomic control to the heart in highly fit subjects.

Neuroscience letters

Montenegro, RA; Farinatti, Pde T; Fontes, EB; Soares, PP; Cunha, FA; Gurgel, JL; Porto, F; Cyrino, ES; Okano, AH

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Cathodal transcranial direct current stimulation of the primary motor cortex improves selective muscle activation in the ipsilateral arm.

2011 Jun

Proximal upper limb muscles are represented bilaterally in primary motor cortex. Goal-directed upper limb movement requires precise control of proximal and distal agonist and antagonist muscles. Failure to suppress antagonist muscles can lead to abnormal movement patterns, such as those commonly experienced in the proximal upper limb after stroke. We examined whether noninvasive brain stimulation of primary motor cortex could be used to improve selective control of the ipsilateral proximal upper limb. Thirteen healthy participants performed isometric left elbow flexion by contracting biceps brachii (BB; agonist) and left forearm pronation (BB antagonist) before and after 20 min of cathodal transcranial direct current stimulation (c-tDCS) or sham tDCS of left M1. During the tasks, motor evoked potentials (MEPs) in left BB were acquired using single-pulse transcranial magnetic stimulation of right M1 150-270 ms before muscle contraction. As expected, left BB MEPs were facilitated before flexion and suppressed before pronation. After c-tDCS, left BB MEP amplitudes were reduced compared with sham stimulation, before pronation but not flexion, indicating that c-tDCS enhanced selective muscle activation of the ipsilateral BB in a task-specific manner. The potential for c-tDCS to improve BB antagonist control correlated with BB MEP amplitude for pronation relative to flexion, expressed as a selectivity ratio. This is the first demonstration that selective muscle activation in the proximal upper limb can be improved after c-tDCS of ipsilateral M1 and that the benefits of c-tDCS for selective muscle activation may be most effective in cases where activation strategies are already suboptimal. These findings may have relevance for the use of tDCS in rehabilitation after stroke.

Journal of neurophysiology

McCambridge, AB; Bradnam, LV; Stinear, CM; Byblow, WD

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Effects of anodal transcranial direct current stimulation over the leg motor area on lumbar spinal network excitability in healthy subjects.

2011 Jun

In recent years, two techniques have become available for the non-invasive stimulation of human motor cortex: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). The effects of TMS and tDCS when applied over motor cortex should be considered with regard not only to cortical circuits but also to spinal motor circuits. The different modes of action and specificity of TMS and tDCS suggest that their effects on spinal network excitability may be different from that in the cortex. Until now, the effects of tDCS on lumbar spinal network excitability have never been studied. In this series of experiments, on healthy subjects, we studied the effects of anodal tDCS over the lower limb motor cortex on (i) reciprocal Ia inhibition projecting from the tibialis anterior muscle (TA) to the soleus (SOL), (ii) presynaptic inhibition of SOL Ia terminals, (iii) homonymous SOL recurrent inhibition, and (iv) SOL H-reflex recruitment curves. The results show that anodal tDCS decreases reciprocal Ia inhibition, increases recurrent inhibition and induces no modification of presynaptic inhibition of SOL Ia terminals and of SOL-H reflex recruitment curves. Our results indicate therefore that the effects of tDCS are the opposite of those previously described for TMS on spinal network excitability. They also indicate that anodal tDCS induces effects on spinal network excitability similar to those observed during co-contraction suggesting that anodal tDCS activates descending corticospinal projections mainly involved in co-contractions.

The Journal of physiology

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

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Transcranial direct current stimulation effects on I-wave activity in humans.

2011 Jun

Transcranial direct current stimulation (tDCS) of the human cerebral cortex modulates cortical excitability noninvasively in a polarity-specific manner: anodal tDCS leads to lasting facilitation and cathodal tDCS to inhibition of motor cortex excitability. To further elucidate the underlying physiological mechanisms, we recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation of the primary motor cortex before and after a 5-min period of anodal or cathodal tDCS in eight conscious patients who had electrodes implanted in the cervical epidural space for the control of pain. The effects of anodal tDCS were evaluated in six subjects and the effects of cathodal tDCS in five subjects. Three subjects were studied with both polarities. Anodal tDCS increased the excitability of cortical circuits generating I waves in the corticospinal system, including the earliest wave (I1 wave), whereas cathodal tDCS suppressed later I waves. The motor evoked potential (MEP) amplitude changes immediately following tDCS periods were in agreement with the effects produced on intracortical circuitry. The results deliver additional evidence that tDCS changes the excitability of cortical neurons.

Journal of neurophysiology

Lang, N; Nitsche, MA; Dileone, M; Mazzone, P; De Andrés-Arés, J; Diaz-Jara, L; Paulus, W; Di Lazzaro, V; Oliviero, A

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Stimulation of the human motor cortex alters generalization patterns of motor learning.

2011 May

It has been hypothesized that the generalization patterns that accompany learning carry the signatures of the neural systems that are engaged in that learning. Reach adaptation in force fields has generalization patterns that suggest primary engagement of a neural system that encodes movements in the intrinsic coordinates of joints and muscles, and lesser engagement of a neural system that encodes movements in the extrinsic coordinates of the task. Among the cortical motor areas, the intrinsic coordinate system is most prominently represented in the primary sensorimotor cortices. Here, we used transcranial direct current stimulation (tDCS) to alter mechanisms of synaptic plasticity and found that when it was applied to the motor cortex, it increased generalization in intrinsic coordinates but not extrinsic coordinates. However, when tDCS was applied to the posterior parietal cortex, it had no effects on learning or generalization in the force field task. The results suggest that during force field adaptation, the component of learning that produces generalization in intrinsic coordinates depends on the plasticity in the sensorimotor cortex.

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

Orban de Xivry, JJ; Marko, MK; Pekny, SE; Pastor, D; Izawa, J; Celnik, P; Shadmehr, R

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Cathodal transcranial direct current stimulation suppresses ipsilateral projections to presumed propriospinal neurons of the proximal upper limb.

2011 May

This study investigated whether cathodal transcranial direct current stimulation (c-tDCS) of left primary motor cortex (M1) modulates excitability of ipsilateral propriospinal premotoneurons (PNs) in healthy humans. Transcranial magnetic stimulation (TMS) of the right motor cortex was used to obtain motor evoked potentials (MEPs) from the left biceps brachii (BB) while participants maintained contraction of the left BB. To examine presumed PN excitability, left BB MEPs were compared with those conditioned by median nerve stimulation (MNS) at the left elbow. Interstimulus intervals between TMS and MNS were set to produce summation at the C3-C4 level of the spinal cord. MNS facilitated BB MEPs elicited at TMS intensities near active motor threshold but inhibited BB MEPs at slightly higher intensities, indicative of putative PN modulation. c-tDCS suppressed the facilitatory and inhibitory effects of MNS. Sham tDCS did not alter either component. There was no effect of c-tDCS and sham tDCS on nonconditioned left BB MEPs or on the ipsilateral silent period of left BB. Right first dorsal interosseous MEPs were suppressed by c-tDCS. These results indicate that M1 c-tDCS can be used to modulate excitability of ipsilateral projections to presumed PNs controlling the proximal arm muscle BB. This technique may hold promise for promoting motor recovery of proximal upper limb function after stroke.

Journal of neurophysiology

Bradnam, LV; Stinear, CM; Byblow, WD

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Noninvasive brain stimulation may improve stroke-related dysphagia: a pilot study.

2011 Apr

Treatment options for stroke-related dysphagia are currently limited. In this study, we investigated whether noninvasive brain stimulation in combination with swallowing maneuvers facilitates swallowing recovery in dysphagic stroke patients during early stroke convalescence.Fourteen patients with subacute unilateral hemispheric infarction were randomized to anodal transcranial direct current stimulation (tDCS) versus sham stimulation to the sensorimotor cortical representation of swallowing in the unaffected hemisphere over the course of 5 consecutive days with concurrent standardized swallowing maneuvers. Severity of dysphagia was measured using a validated swallowing scale, Dysphagia Outcome and Severity scale, before the first and after the last session of tDCS or sham. The effect of tDCS was analyzed in a multivariate linear regression model using changes in Dysphagia Outcome and Severity Scale as the outcome variable after adjusting for the effects of other potential confounding variables such as the National Institutes of Health Stroke Scale and Dysphagia Outcome and Severity scale scores at baseline, acute ischemic lesion volumes, patient age, and time from stroke onset to stimulation.Patients who received anodal tDCS gained 2.60 points of improvement in Dysphagia Outcome and Severity scale scores compared to patients in the sham stimulation group who showed an improvement of 1.25 points (P=0.019) after controlling for the effects of other aforementioned variables. Six out 7 (86%) patients in tDCS stimulation group gained at least 2 points of improvement compared with 3 out 7 (43%) patients in the sham group (P=0.107).Because brain stem swallowing centers have bilateral cortical innervations, measures that enhance cortical input and sensorimotor control of brain stem swallowing may be beneficial for dysphagia recovery.

Stroke; a journal of cerebral circulation

Kumar, S; Wagner, CW; Frayne, C; Zhu, L; Selim, M; Feng, W; Schlaug, G

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Polarity and timing-dependent effects of transcranial direct current stimulation in explicit motor learning.

2011 Apr

Transcranial direct current stimulation (tDCS) is attracting increasing interest as a therapeutic tool for neurorehabilitation, particularly after stroke, because of its potential to modulate local excitability and therefore promote functional plasticity. Previous studies suggest that timing is important in determining the behavioural effects of brain stimulation. Regulatory metaplastic mechanisms exist to modulate the effects of a stimulation intervention in a manner dependent on prior cortical excitability, thereby preventing destabilization of existing cortical networks. The importance of such timing dependence has not yet been fully explored for tDCS. Here, we describe the results of a series of behavioural experiments in healthy controls to determine the importance of the relative timing of tDCS for motor performance. Application of tDCS during an explicit sequence-learning task led to modulation of behaviour in a polarity specific manner: relative to sham stimulation, anodal tDCS was associated with faster learning and cathodal tDCS with slower learning. Application of tDCS prior to performance of the sequence-learning task led to slower learning after both anodal and cathodal tDCS. By contrast, regardless of the polarity of stimulation, tDCS had no significant effect on performance of a simple reaction time task. These results are consistent with the idea that anodal tDCS interacts with subsequent motor learning in a metaplastic manner and suggest that anodal stimulation modulates cortical excitability in a manner similar to motor learning.

Neuropsychologia

Stagg, CJ; Jayaram, G; Pastor, D; Kincses, ZT; Matthews, PM; Johansen-Berg, H

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The role of GABA in human motor learning.

2011 Mar

GABA modification plays an important role in motor cortical plasticity. We therefore hypothesized that interindividual variation in the responsiveness of the GABA system to modification influences learning capacity in healthy adults. We assessed GABA responsiveness by transcranial direct current stimulation (tDCS), an intervention known to decrease GABA. The magnitude of M1 GABA decrease induced by anodal tDCS correlated positively with both the degree of motor learning and the degree of fMRI signal change within the left M1 during learning. This study therefore suggests that the responsiveness of the GABAergic system to modification may be relevant to short-term motor learning behavior and learning-related brain activity.

Current biology : CB

Stagg, CJ; Bachtiar, V; Johansen-Berg, H

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Transcranial direct current stimulation improves naming reaction time in fluent aphasia: a double-blind, sham-controlled study.

2011 Mar

Previous evidence suggests that anodal transcranial direct current stimulation (A-tDCS) applied to the left hemisphere can improve aphasic participants' ability to name common objects. The current study further examined this issue in a more tightly controlled experiment in participants with fluent aphasia.We examined the effect of A-tDCS on reaction time during overt picture naming in 8 chronic stroke participants. Anode electrode placement targeted perilesional brain regions that showed the greatest activation on a pretreatment functional MRI scan administered during overt picture naming with the reference cathode electrode placed on the contralateral forehead. A-tDCS (1 mA; 20-minute) was compared with sham tDCS (S-tDCS) in a crossover design. Participants received 10 sessions of computerized anomia treatment; 5 sessions included A-tDCS and 5 included S-tDCS.Coupling A-tDCS with behavioral language treatment reduced reaction time during naming of trained items immediately posttreatment (Z=1.96, P=0.025) and at subsequent testing 3 weeks later (Z=2.52, P=0.006).A-tDCS administered during language treatment decreased processing time during picture naming by fluent aphasic participants. Additional studies combining A-tDCS, an inexpensive method with no reported serious side effects, with behavioral language therapy are recommended.

Stroke; a journal of cerebral circulation

Fridriksson, J; Richardson, JD; Baker, JM; Rorden, C

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Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex.

2011 Mar

Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent "homeostatic-like" rule governing the response of the human motor cortex to plasticity probing protocols.

Journal of neurophysiology

Fricke, K; Seeber, AA; Thirugnanasambandam, N; Paulus, W; Nitsche, MA; Rothwell, JC

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Nicotinergic impact on focal and non-focal neuroplasticity induced by non-invasive brain stimulation in non-smoking humans.

2011 Mar

Nicotine improves cognitive performance and modulates neuroplasticity in brain networks. The neurophysiological mechanisms underlying nicotine-induced behavioral changes have been sparsely studied, especially in humans. Global cholinergic activation focuses on plasticity in humans. However, the specific contribution of nicotinic receptors to these effects is unclear. Henceforth, we explored the impact of nicotine on non-focal neuroplasticity induced by transcranial direct current stimulation (tDCS) and focal, synapse-specific plasticity induced by paired associative stimulation (PAS) in healthy non-smoking individuals. Forty-eight subjects participated in the study. Each subject received placebo and nicotine patches combined with one of the stimulation protocols to the primary motor cortex in different sessions. Transcranial magnetic stimulation (TMS)-elicited motor-evoked potential (MEP) amplitudes were recorded as a measure of corticospinal excitability until the evening of the second day following the stimulation. Nicotine abolished or reduced both PAS- and tDCS-induced inhibitory neuroplasticity. Non-focal facilitatory plasticity was also abolished, whereas focal facilitatory plasticity was slightly prolonged by nicotine. Thus, nicotinergic influence on facilitatory, but not inhibitory plasticity mimics that of global cholinergic enhancement. Therefore, activating nicotinic receptors has clearly discernable effects from global cholinergic activation. These nicotine-generated plasticity alterations might be important for the effects of the drug on cognitive function.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

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

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Reducing procedural pain and discomfort associated with transcranial direct current stimulation.

2011 Jan

Transcranial direct current stimulation (tDCS) appears to have modulatory effects on the excitability of cortical brain tissue. Though tDCS as presently applied causes no apparent harm to brain structure or function, a number of uncomfortable sensations can occur beneath the electrodes during stimulation, including tingling, pain, itching, and burning sensations. Therefore, we investigated the effect of topically applied Eutectic mixture of local anesthetics (EMLA) on tDCS-related discomfort.Nine healthy adults received both anodal and cathodal 2.0 mA tDCS for 5 minutes over the prefrontal cortex with the skin pretreated for 20 minutes with either EMLA or placebo cream. Participants rated procedural discomfort six times across eight dimensions of sensation.On average, the mean sensation ratings for EMLA-associated tDCS stimulation were significantly lower than placebo-associated stimulation for every cutaneous sensation evaluated. Cathodal stimulation was associated with higher ratings of "sharpness" and intolerability than anodal stimulation.Topical EMLA may reduce tDCS-related discomfort.

Brain stimulation

McFadden, JL; Borckardt, JJ; George, MS; Beam, W

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[New neurostimulation techniques in adicctions].

2011

Addiction is associated with changes in brain activation patterns. In recent years new techniques of neurostimulation that can alter the activity of brain circuits have been developed, and are being explored in the treatment of addictions. The most important of these techniques are Transcranial Magnetic Stimulation (TMS), Transcranial Direct Electrical Stimulation (tDCS), Vagus Nerve Stimulation (VNS) and Deep Brain Stimulation (DBS). The findings reported are clearly still insufficient for them to be considered as therapeutic alternatives in substance use disorders.

Adicciones

García-Toro, M; Gili, M; Roca, M

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Modulation of event-related desynchronization during motor imagery with transcranial direct current stimulation in a patient with severe hemiparetic stroke: a case report.

2011

Recently, surface electroencephalogram (EEG)-based brain-machine interfaces (BMI) have been used for people with disabilities. As a BMI signal source, event-related desynchronization of alpha-band EEG (8-13 Hz) during motor imagery (mu ERD), which is interpreted as desynchronized activities of the activated neurons, is commonly used. However, it is often difficult for patients with severe hemiparesis to produce mu ERD of sufficient strength to activate BMI. Therefore, whether it is possible to modulate mu ERD during motor imagery with anodal transcranial direct-current stimulation (tDCS) was assessed in a severe left hemiparetic stroke patient. EEG was recorded over the primary motor cortex (M1), and mu ERD during finger flexion imagery was measured before and after a 5-day course of tDCS applied to M1. The ERD recorded over the affected M1 increased significantly after tDCS intervention. Anodal tDCS may increase motor cortex excitability and potentiate ERD during motor imagery in patients with severe hemiparetic stroke.

The Keio journal of medicine

Tohyama, T; Fujiwara, T; Matsumoto, J; Honaga, K; Ushiba, J; Tsuji, T; Hase, K; Liu, M

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Efficacy of transcranial direct current stimulation coupled with a multidisciplinary rehabilitation program for the treatment of fibromyalgia.

2011

Pain control in fibromyalgia patients is limited no matter the therapeutic regimens used. Recent data have shown that daily sessions of anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) in patients with fibromyalgia (FM) are associated with reduction of pain perception.We aimed to test whether active tDCS, as compared with sham tDCS, combined with multidisciplinary rehabilitation is associated with significant clinical gains in fibromyalgia.This was a randomized, double-blinded controlled trial.23 patients were randomized to receive weekly sessions of multidisciplinary rehabilitation approach combined with sham or anodal tDCS of M1. Patients were evaluated for pain with VAS and for quality of life with SF-36, fibromyalgia pain questionnaire and health assessment questionnaire by a blinded rater before and after the 4 month period of rehabilitation.Patients tolerated tDCS treatment well, without adverse effects. Patients who received active treatment had a significantly greater reduction of SF-36 pain domain scores (F((2,21))=6.57; p=0.006) and a tendency of higher improvement in Fibromyalgia Impact Questionnaire (FIQ) scores after (p=0.056) as compared with sham tDCS/standard treatment, but no differences were observed in the other domains.Although active tDCS was associated with superior results in one domain (SF-36 pain domain), the lack of significance in the other domains does not fully support this strategy (weekly tDCS) combined with a multidisciplinary approach.

The open rheumatology journal

Riberto, M; Marcon Alfieri, F; Monteiro de Benedetto Pacheco, K; Dini Leite, V; Nemoto Kaihami, H; Fregni, F; Rizzo Battistella, L

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Improved proper name recall in aging after electrical stimulation of the anterior temporal lobes.

2011

Evidence from neuroimaging and neuropsychology suggests that portions of the anterior temporal lobes (ATLs) play a critical role in proper name retrieval. We previously found that anodal transcranial direct current stimulation (tDCS) to the ATLs improved retrieval of proper names in young adults (Ross et al., 2010). Here we extend that finding to older adults who tend to experience greater proper-naming deficits than young adults. The task was to look at pictures of famous faces or landmarks and verbally recall the associated proper name. Our results show a numerical improvement in face naming after left or right ATL stimulation, but a statistically significant effect only after left-lateralized stimulation. The magnitude of the enhancing effect was similar in older and younger adults but the lateralization of the effect differed depending on age. The implications of these findings for the use of tDCS as tool for rehabilitation of age-related loss of name recall are discussed.

Frontiers in aging neuroscience

Ross, LA; McCoy, D; Coslett, HB; Olson, IR; Wolk, DA

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Non-invasive brain stimulation enhances the effects of melodic intonation therapy.

2011

Research has suggested that a fronto-temporal network in the right hemisphere may be responsible for mediating melodic intonation therapy's (MIT) positive effects on speech recovery. We investigated the potential for a non-invasive brain stimulation technique, transcranial direct current stimulation (tDCS), to augment the benefits of MIT in patients with non-fluent aphasia by modulating neural activity in the brain during treatment with MIT. The polarity of the current applied to the scalp determines the effects of tDCS on the underlying tissue: anodal-tDCS increases excitability, whereas cathodal tDCS decreases excitability. We applied anodal-tDCS to the posterior inferior frontal gyrus of the right hemisphere, an area that has been shown both to contribute to singing through the mapping of sounds to articulatory actions and to serve as a key region in the process of recovery from aphasia, particularly in patients with large left hemisphere lesions. The stimulation was applied while patients were treated with MIT by a trained therapist. Six patients with moderate to severe non-fluent aphasia underwent three consecutive days of anodal-tDCS + MIT, and an equivalent series of sham-tDCS + MIT. The two treatment series were separated by 1 week, and the order in which the treatments were administered was randomized. Compared to the effects of sham-tDCS + MIT, anodal-tDCS + MIT led to significant improvements in fluency of speech. These results support the hypothesis that, as the brain seeks to reorganize and compensate for damage to left hemisphere language centers, combining anodal-tDCS with MIT may further recovery from post-stroke aphasia by enhancing activity in a right hemisphere sensorimotor network for articulation.

Frontiers in psychology

Vines, BW; Norton, AC; Schlaug, G

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Polarity-dependent transcranial direct current stimulation effects on central auditory processing.

2011

Given the polarity dependent effects of transcranial direct current stimulation (tDCS) in facilitating or inhibiting neuronal processing, and tDCS effects on pitch perception, we tested the effects of tDCS on temporal aspects of auditory processing. We aimed to change baseline activity of the auditory cortex using tDCS as to modulate temporal aspects of auditory processing in healthy subjects without hearing impairment. Eleven subjects received 2mA bilateral anodal, cathodal and sham tDCS over auditory cortex in a randomized and counterbalanced order. Subjects were evaluated by the Random Gap Detection Test (RGDT), a test measuring temporal processing abilities in the auditory domain, before and during the stimulation. Statistical analysis revealed a significant interaction effect of time vs. tDCS condition for 4000 Hz and for clicks. Post-hoc tests showed significant differences according to stimulation polarity on RGDT performance: anodal improved 22.5% and cathodal decreased 54.5% subjects' performance, as compared to baseline. For clicks, anodal also increased performance in 29.4% when compared to baseline. tDCS presented polarity-dependent effects on the activity of the auditory cortex, which results in a positive or negative impact in a temporal resolution task performance. These results encourage further studies exploring tDCS in central auditory processing disorders.

PloS one

Ladeira, A; Fregni, F; Campanhã, C; Valasek, CA; De Ridder, D; Brunoni, AR; Boggio, PS

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Task-specific effects of tDCS-induced cortical excitability changes on cognitive and motor sequence set shifting performance.

2011

In this study, we tested the effects of transcranial Direct Current Stimulation (tDCS) on two set shifting tasks. Set shifting ability is defined as the capacity to switch between mental sets or actions and requires the activation of a distributed neural network. Thirty healthy subjects (fifteen per site) received anodal, cathodal and sham stimulation of the dorsolateral prefrontal cortex (DLPFC) or the primary motor cortex (M1). We measured set shifting in both cognitive and motor tasks. The results show that both anodal and cathodal single session tDCS can modulate cognitive and motor tasks. However, an interaction was found between task and type of stimulation as anodal tDCS of DLPFC and M1 was found to increase performance in the cognitive task, while cathodal tDCS of DLPFC and M1 had the opposite effect on the motor task. Additionally, tDCS effects seem to be most evident on the speed of changing sets, rather than on reducing the number of errors or increasing the efficacy of irrelevant set filtering.

PloS one

Leite, J; Carvalho, S; Fregni, F; Gonçalves, ÓF

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Cortico-Cortical Connectivity between Right Parietal and Bilateral Primary Motor Cortices during Imagined and Observed Actions: A Combined TMS/tDCS Study.

2011

Previous transcranial magnetic stimulation (TMS) studies showed functional connections between the parietal cortex (PC) and the primary motor cortex (M1) during tasks of different reaching-to-grasp movements. Here, we tested whether the same network is involved in cognitive processes such as imagined or observed actions. Single pulse TMS of the right and left M1 during rest and during a motor imagery and an action observation task (i.e., an index-thumb pinch grip in both cases) was used to measure corticospinal excitability changes before and after conditioning of the right PC by 10 min of cathodal, anodal, or sham transcranial direct current stimulation (tDCS). Corticospinal excitability was indexed by the size of motor-evoked potentials (MEPs) from the contralateral first dorsal interosseous (FDI; target) and abductor digiti minimi muscle (control) muscles. Results showed selective ipsilateral effects on the M1 excitability, exclusively for motor imagery processes: anodal tDCS enhanced the MEPs' size from the FDI muscle, whereas cathodal tDCS decreased it. Only cathodal tDCS impacted corticospinal facilitation induced by action observation. Sham stimulation was always uneffective. These results suggest that motor imagery, differently from action observation, is sustained by a strictly ipsilateral parieto-motor cortex circuits. Results might have implication for neuromodulatory rehabilitative purposes.

Frontiers in neural circuits

Feurra, M; Bianco, G; Polizzotto, NR; Innocenti, I; Rossi, A; Rossi, S

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Down-regulation of negative emotional processing by transcranial direct current stimulation: effects of personality characteristics.

2011

Evidence from neuroimaging and electrophysiological studies indicates that the left dorsolateral prefrontal cortex (DLPFC) is a core region in emotional processing, particularly during down-regulation of negative emotional conditions. However, emotional regulation is a process subject to major inter-individual differences, some of which may be explained by personality traits. In the present study we used transcranial direct current stimulation (tDCS) over the left DLPFC to investigate whether transiently increasing the activity of this region resulted in changes in the ratings of positive, neutral and negative emotional pictures. Results revealed that anodal, but not cathodal, tDCS reduced the perceived degree of emotional valence for negative stimuli, possibly due to an enhancement of cognitive control of emotional expression. We also aimed to determine whether personality traits (extraversion and neuroticism) might condition the impact of tDCS. We found that individuals with higher scores on the introversion personality dimension were more permeable than extraverts to the modulatory effects of the stimulation. The present study underlines the role of the left DLPFC in emotional regulation, and stresses the importance of considering individual personality characteristics as a relevant variable, although replication is needed given the limited sample size of our study.

PloS one

Peña-Gómez, C; Vidal-Piñeiro, D; Clemente, IC; Pascual-Leone, Á; Bartrés-Faz, D

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Investigating the Role of Current Strength in tDCS Modulation of Working Memory Performance in Healthy Controls.

2011

Transcranial direct current stimulation (tDCS) is a brain stimulation technique that has the potential to improve working memory (WM) deficits in many clinical disorders. The aim of this study was to investigate the role of current strength on the ability of anodal tDCS to improve WM, and secondly to investigate the time course of effects. Twelve healthy participants underwent three stimulation sessions consisting of 20 min of either 1 mA anodal tDCS, 2 mA anodal tDCS, or sham tDCS to the left dorsolateral prefrontal cortex (DLPFC) localized via F3, all whilst completing a WM task. Intra-stimulation and post-stimulation WM performances were measured using the n-back and Sternberg tasks respectively. Results revealed no significant improvements in participants' accuracy, but a significant interaction was found with respect to current strength and time for accurate reaction time. The finding provides partial support for the hypothesis, in that it appears current strength may affect aspects of WM performance. However, more research is needed, and a higher difficulty level of WM tasks is one of the suggestions discussed for future research.

Frontiers in psychiatry

Teo, F; Hoy, KE; Daskalakis, ZJ; Fitzgerald, PB

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Errorless and errorful learning modulated by transcranial direct current stimulation.

2011

Errorless learning is advantageous over trial and error learning (errorful learning) as errors are avoided during learning resulting in increased memory performance. Errorful learning challenges the executive control system of memory processes as the erroneous items compete with the correct items during retrieval. The left dorsolateral prefrontal cortex (DLPFC) is a core region involved in this executive control system. Transcranial direct current stimulation (tDCS) can modify the excitability of underlying brain functioning.In a single blinded tDCS study one group of young healthy participants received anodal and another group cathodal tDCS of the left DLPFC each compared to sham stimulation. Participants had to learn words in an errorless and an errorful manner using a word stem completion paradigm. The results showed that errorless compared to errorful learning had a profound effect on the memory performance in terms of quality. Anodal stimulation of the left DLPFC did not modulate the memory performance following errorless or errorful learning. By contrast, cathodal stimulation hampered memory performance after errorful learning compared to sham, whereas there was no modulation after errorless learning.Concluding, the study further supports the advantages of errorless learning over errorful learning. Moreover, cathodal stimulation of the left DLPFC hampered memory performance following the conflict-inducing errorful learning as compared to no modulation after errorless learning emphasizing the importance of the left DLPFC in executive control of memory.

BMC neuroscience

Hammer, A; Mohammadi, B; Schmicker, M; Saliger, S; Münte, TF

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Uncovering Multisensory Processing through Non-Invasive Brain Stimulation.

2011

Most of current knowledge about the mechanisms of multisensory integration of environmental stimuli by the human brain derives from neuroimaging experiments. However, neuroimaging studies do not always provide conclusive evidence about the causal role of a given area for multisensory interactions, since these techniques can mainly derive correlations between brain activations and behavior. Conversely, techniques of non-invasive brain stimulation (NIBS) represent a unique and powerful approach to inform models of causal relations between specific brain regions and individual cognitive and perceptual functions. Although NIBS has been widely used in cognitive neuroscience, its use in the study of multisensory processing in the human brain appears a quite novel field of research. In this paper, we review and discuss recent studies that have used two techniques of NIBS, namely transcranial magnetic stimulation and transcranial direct current stimulation, for investigating the causal involvement of unisensory and heteromodal cortical areas in multisensory processing, the effects of multisensory cues on cortical excitability in unisensory areas, and the putative functional connections among different cortical areas subserving multisensory interactions. The emerging view is that NIBS is an essential tool available to neuroscientists seeking for causal relationships between a given area or network and multisensory processes. With its already large and fast increasing usage, future work using NIBS in isolation, as well as in conjunction with different neuroimaging techniques, could substantially improve our understanding of multisensory processing in the human brain.

Frontiers in psychology

Bolognini, N; Maravita, A

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Electrode positioning and montage in transcranial direct current stimulation.

2011

Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a non-invasive and safe alternative to change cortical excitability. The effects of one session of tDCS can last for several minutes, and its effects depend on polarity of stimulation, such as that cathodal stimulation induces a decrease in cortical excitability, and anodal stimulation induces an increase in cortical excitabil