Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects.

BACKGROUND: Rapid-rate repetitive transcranial magnetic stimulation (rTMS) can produce a lasting increase in cortical excitability in healthy subjects or induce beneficial effects in patients with neuropsychiatric disorders; however, the conditioning effects of rTMS are often subtle and variable, limiting therapeutic applications. Here we show that magnitude and direction of after-effects induced by rapid-rate rTMS depend on the state of cortical excitability before stimulation and can be tuned by preconditioning with transcranial direct current stimulation (tDCS). METHODS: Ten healthy volunteers received a 20-sec train of 5-Hz rTMS given at an intensity of individual active motor threshold to the left primary motor hand area. This interventional protocol was preconditioned by 10 min of anodal, cathodal, or sham tDCS. We used single-pulse TMS to assess corticospinal excitability at rest before, between, and after the two interventions. RESULTS: The 5-Hz rTMS given after sham tDCS failed to produce any after-effect, whereas 5-Hz rTMS led to a marked shift in corticospinal excitability when given after effective tDCS. The direction of rTMS-induced plasticity critically depended on the polarity of tDCS conditioning. CONCLUSIONS: Preconditioning with tDCS enhances cortical plasticity induced by rapid-rate rTMS and can shape the direction of rTMS-induced after-effects.     

Parietal transcranial direct current stimulation modulates primary motor cortex excitability

The posterior parietal cortex is part of the cortical network involved in motor learning and is structurally and functionally connected with the primary motor cortex (M1). Neuroplastic alterations of neuronal connectivity might be an important basis for learning processes. These have however not been explored for parieto‐motor connections in humans by transcranial direct current stimulation (tDCS). Exploring tDCS effects on parieto‐motor cortical connectivity might be functionally relevant, because tDCS has been shown to improve motor learning. We aimed to explore plastic alterations of parieto‐motor cortical connections by tDCS in healthy humans. We measured neuroplastic changes of corticospinal excitability via motor evoked potentials (MEP) elicited by single‐pulse transcranial magnetic stimulation (TMS) before and after tDCS over the left posterior parietal cortex (P3), and 3 cm posterior or lateral to P3, to explore the spatial specificity of the effects. Furthermore, short‐interval intracortical inhibition/intracortical facilitation (SICI/ICF) over M1, and parieto‐motor cortical connectivity were obtained before and after P3 tDCS. The results show polarity‐dependent M1 excitability alterations primarily after P3 tDCS. Single‐pulse TMS‐elicited MEPs, M1 SICI/ICF at 5 and 7 ms and 10 and 15 ms interstimulus intervals (ISIs), and parieto‐motor connectivity at 10 and 15 ms ISIs were all enhanced by anodal stimulation. Single pulse‐TMS‐elicited MEPs, and parieto‐motor connectivity at 10 and 15 ms ISIs were reduced by cathodal tDCS. The respective corticospinal excitability alterations lasted for at least 120 min after stimulation. These results show an effect of remote stimulation of parietal areas on M1 excitability. The spatial specificity of the effects and the impact on parietal cortex–motor cortex connections suggest a relevant connectivity‐driven effect.     

Anodal transcranial direct current stimulation enhances the effects of motor imagery training in a finger tapping task

Motor imagery (MI) training and anodal transcranial direct current stimulation (tDCS) applied over the primary motor cortex can independently improve hand motor function. The main objective of this double‐blind, sham‐controlled study was to examine whether anodal tDCS over the primary motor cortex could enhance the effects of MI training on the learning of a finger tapping sequence. Thirty‐six right‐handed young human adults were assigned to one of three groups: (i) who performed MI training combined with anodal tDCS applied over the primary motor cortex; (ii) who performed MI training combined with sham tDCS; and (iii) who received tDCS while reading a book. The MI training consisted of mentally rehearsing an eight‐item complex finger sequence for 13 min. Before (Pre‐test), immediately after (Post‐test 1), and at 90 min after (Post‐test 2) MI training, the participants physically repeated the sequence as fast and as accurately as possible. An anova showed that the number of sequences correctly performed significantly increased between Pre‐test and Post‐test 1 and remained stable at Post‐test 2 in the three groups (P < 0.001). Furthermore, the percentage increase in performance between Pre‐test and Post‐test 1 and Post‐test 2 was significantly greater in the group that performed MI training combined with anodal tDCS compared with the other two groups (P < 0.05). As a potential physiological explanation, the synaptic strength within the primary motor cortex could have been reinforced by the association of MI training and tDCS compared with MI training alone and tDCS alone.     

Theta‐burst stimulation over primary motor cortex degrades early motor learning

Theta‐burst stimulation (TBS) is currently used for inducing long‐lasting changes in primary motor cortex (M1) excitability. More information is needed on how M1 is involved in early motor learning (practice‐related improvement in motor performance, motor retention and motor consolidation). We investigated whether inhibitory continuous TBS (cTBS) is an effective experimental approach for modulating early motor learning of a simple finger movement in healthy humans. In a short task, 11 subjects practised 160 movements, and in a longer task also testing motor consolidation ten subjects practised 600 movements. During both experiments subjects randomly received real or sham cTBS over the left M1. Motor evoked potentials were tested at baseline and 7 min after cTBS. In the 160‐movement experiment to test motor retention, 20 movements were repeated 30 min after motor practice ended. In the 600‐movement experiment motor retention was assessed 15 and 30 min after motor practice ended, motor consolidation was tested by performing 20 movements 24 h after motor practice ended. Kinematic variables – movement amplitude, peak velocity and peak acceleration – were measured. cTBS significantly reduced the practice‐related improvement in motor performance of finger movements in the experiment involving 160 movements and in the first part of the experiment involving 600 movements. After cTBS, peak velocity and peak acceleration of the 20 movements testing motor retention decreased whereas those testing motor consolidation remained unchanged. cTBS over M1 degrades practice‐related improvement in motor performance and motor retention, but not motor consolidation of a voluntary finger movement.     

Multisession anodal transcranial direct current stimulation induces motor cortex plasticity enhancement and motor learning generalization in an aging population

Objectives

The present aging study investigated the impact of a multisession anodal-tDCS protocol applied over the primary motor cortex (M1) during motor sequence learning on generalization of motor learning and plasticity-dependent measures of cortical excitability.

Effects of anodal transcranial direct current stimulation over lower limb primary motor cortex on motor learning in healthy individuals

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which alters motor functions in healthy humans and in neurological patients. Most studies so far investigated the effects of tDCS on mechanisms underlying improvements in upper limb performance. To investigate the effect of anodal tDCS over the lower limb motor cortex (M1) on lower limb motor learning in healthy volunteers, we conducted a randomized, single‐blind and sham‐controlled study. Thirty‐three (25.81 ± 3.85, 14 female) volunteers were included, and received anodal or sham tDCS over the left M1 (M1‐tDCS); 0.0625 mA/cm² anodal tDCS was applied for 15 min during performance of a visuo‐motor task (VMT) with the right leg. Motor learning was monitored for performance speed and accuracy based on electromyographic recordings. We also investigated the influence of electrode size and baseline responsivity to transcranial magnetic stimulation (TMS) on the stimulation effects. Relative to baseline measures, only M1‐tDCS applied with small electrodes and in volunteers with high baseline sensitivity to TMS significantly improved VMT performance. The computational analysis showed that the small anode was more specific to the targeted leg motor cortex volume when compared to the large anode. We conclude that anodal M1‐tDCS modulates VMT performance in healthy subjects. As these effects critically depend on sensitivity to TMS and electrode size, future studies should investigate the effects of intensified tDCS and/or model‐based different electrode positions in low‐sensitivity TMS individuals.     

Noninvasive cortical stimulation with transcranial direct current stimulation in Parkinson's disease.

Electrical stimulation of deep brain structures, such as globus pallidus and subthalamic nucleus, is widely accepted as a therapeutic tool for patients with Parkinson's disease (PD). Cortical stimulation either with epidural implanted electrodes or repetitive transcranial magnetic stimulation can be associated with motor function enhancement in PD. We aimed to study the effects of another noninvasive technique of cortical brain stimulation, transcranial direct current stimulation (tDCS), on motor function and motor-evoked potential (MEP) characteristics of PD patients. We tested tDCS using different electrode montages [anodal stimulation of primary motor cortex (M1), cathodal stimulation of M1, anodal stimulation of dorsolateral prefrontal cortex (DLPFC), and sham-stimulation] and evaluated the effects on motor function--as indexed by Unified Parkinson's Disease Rating Scale (UPDRS), simple reaction time (sRT) and Purdue Pegboard test--and on corticospinal motor excitability (MEP characteristics). All experiments were performed in a double-blinded manner. Anodal stimulation of M1 was associated with a significant improvement of motor function compared to sham-stimulation in the UPDRS (P < 0.001) and sRT (P = 0.019). This effect was not observed for cathodal stimulation of M1 or anodal stimulation of DLPFC. Furthermore, whereas anodal stimulation of M1 significantly increased MEP amplitude and area, cathodal stimulation of M1 significantly decreased them. There was a trend toward a significant correlation between motor function improvement after M1 anodal-tDCS and MEP area increase. These results confirm and extend the notion that cortical brain stimulation might improve motor function in patients with PD.     

Unihemispheric concurrent dual‐site cathodal transcranial direct current stimulation: the effects on corticospinal excitability

We aimed to assess the effects of concurrent cathodal transcranial direct current stimulation (c‐tDCS) of two targets in a hemisphere, termed unihemispheric concurrent dual‐site cathodal tDCS (c‐tDCS_UHCDS), on the size of M1 corticospinal excitability and its lasting effect. Secondary aims were to identify the mechanisms behind the efficacy of c‐tDCS_UHCDS and to evaluate the side effects of this new technique. Twelve healthy volunteers received 20 min c‐tDCS under five conditions in a random order: M1 c‐tDCS, c‐tDCS_UHCDS of M1–dorsolateral prefrontal cortex (DLPFC), M1–primary sensory cortex (S1), M1–primary visual cortex (V1) and sham. The M1 corticospinal excitability of the first dorsal interossei muscle was assessed before, immediately after, and 30 min, 60 min and 24 h after the interventions. Short‐interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were also assessed, using a paired‐pulse paradigm. Compared to conventional M1 c‐tDCS, corticospinal excitability significantly increased following c‐tDCS_UHCDS of M1‐DLPFC and M1‐V1 for up to 24 h (P = 0.001). Significant increases in ICF were observed following c‐tDCS_UHCDS of M1‐DLPFC (P = 0.005) and M1‐V1 (P = 0.002). Compared to baseline values, ICF and SICI increased significantly at T₆₀ (P < 0.001) and T_24 h (P < 0.001) following the concurrent c‐tDCS of M1 and V1. Sham c‐tDCS_UHCDS did not induce any significant alteration. The corticospinal excitability increase was mainly accompanied by ICF increase, which indirectly indicates the activity of glutamergic mechanisms. The findings may help us to more fully understand the brain function and develop future motor learning studies. No significant excitability change induced by sham c‐tDCS_UHCDS suggests that there is no placebo effect associated with this new tDCS technique.     

Anodal transcranial direct current stimulation over premotor cortex facilitates observational learning of a motor sequence

Motor skills, including complex movement sequences, can be acquired by observing a model without physical practice of the skill, a phenomenon known as observational learning. Observational learning of motor skills engages the same memory substrate as physical practice, and is thought to be mediated by the action observation network, a bilateral fronto‐parietal circuit with mirror‐like properties. We examined the effects of anodal transcranial direct current stimulation (tDCS) over premotor cortex, a key node of the action observation network, on observational learning of a serial response time task. Results showed that anodal tDCS during observation of the to‐be‐learned sequence facilitated reaction times in the subsequent behavioral test. The study provides evidence that increasing excitability of the action observation network during observation can facilitate later motor skill acquisition.     

Brain transcranial direct current stimulation modulates motor excitability in mice

Shortly after the application of weak transcranial direct current stimulation (tDCS) to the animal and human brain, changes in corticospinal excitability, which mainly depend on polarity, duration and current density of the stimulation protocol, have been reported. In humans, anodal tDCS has been reported to enhance motor‐evoked potentials (MEPs) elicited by transcranial brain stimulation while cathodal tDCS has been shown to decrease them. Here we investigated the effects produced by tDCS on mice motor cortex. MEPs evoked by transcranial electric stimulation were recorded from forelimbs of 12 C57BL/6 mice, under sevofluorane anaesthesia, before and after (0, 5 and 10 min) anodal and cathodal tDCS (tDCS duration 10 min). With respect to sham condition stimulation (anaesthesia), MEP size was significantly increased immediately after anodal tDCS, and was reduced after cathodal tDCS (～20% vs. sham). Both effects declined towards basal levels in the following 10 min. Although the site and mechanisms of action of tDCS need to be more clearly identified, the directionality of effects of tDCS on mice MEPs is consistent with previous findings in humans. The feasibility of tDCS in mice suggests the potential applicability of this technique to assess the potential therapeutic options of brain polarization in animal models of neurological and neuropsychiatric diseases.     

Anodal transcranial direct current stimulation of the motor cortex increases cortical voluntary activation and neural plasticity

Introduction: We examined the cumulative effect of 4 consecutive bouts of noninvasive brain stimulation on corticospinal plasticity and motor performance, and whether these responses were influenced by the brain‐derived neurotrophic factor (BDNF) polymorphism. Methods: In a randomized double‐blinded cross‐over design, changes in strength and indices of corticospinal plasticity were analyzed in 14 adults who were exposed to 4 consecutive sessions of anodal and sham transcranial direct current stimulation (tDCS). Participants also undertook a blood sample for BDNF genotyping (N = 13). Results: We observed a significant increase in isometric wrist flexor strength with transcranial magnetic stimulation revealing increased corticospinal excitability, decreased silent period duration, and increased cortical voluntary activation compared with sham tDCS. Conclusions: The results show that 4 consecutive sessions of anodal tDCS increased cortical voluntary activation manifested as an improvement in strength. Induction of corticospinal plasticity appears to be influenced by the BDNF polymorphism. Muscle Nerve 54 : 903–913, 2016     

Neuroplasticity and network connectivity of the motor cortex following stroke: A transcranial direct current stimulation study

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has potential for clinical utility in neurorehabilitation. However, recent evidence indicates that the responses to tDCS are highly variable. This study investigated whether electroencephalographic (EEG) measures of functional connectivity of the target network were associated with the response to ipsilesional anodal tDCS in stroke survivors. Ten chronic stroke patients attended two experimental sessions in a randomized cross‐over trial and received anodal or sham tDCS. Single‐pulse transcranial magnetic stimulation was used to quantify change in corticospinal excitability following tDCS. At the beginning of each session, functional connectivity was estimated using the debiased‐weighted phase lag index from EEG recordings at rest. Magnetic resonance imaging identified lesion location and lesion volume. Partial least squares regression identified models of connectivity which maximally accounted for variance in anodal tDCS responses. Stronger connectivity of a network with a seed approximating the stimulated ipsilesional motor cortex, and clusters of electrodes approximating the ipsilesional parietal cortex and contralesional frontotemporal cortex in the alpha band (8–13 Hz) was strongly associated with a greater increase of corticospinal excitability following anodal tDCS. This association was not observed following sham stimulation. Addition of a structural measure(s) of injury (lesion volume) provided an improved model fit for connectivity between the seed electrode and ipsilesional parietal cortex, but not the contralesional frontotemporal cortex. TDCS has potential to greatly assist stroke rehabilitation and functional connectivity appears a robust and specific biomarker of response which may assist clinical translation of this therapy.     

Effects of carotid endarterectomy on motor evoked potentials elicited by transcranial magnetic stimulation

Purpose To investigate the within 3 days effects of carotid endarterectomy (CEA) on functional status of the central motor system in patients with carotid stenosis by means of transcranial magnetic stimulation (TMS). Patients and method We studied 30 consecutive patients, 20 males and 10 females with a mean age of 69.2 ± 7.1 years, who underwent CEA for symptomatic carotid stenosis. All patients had suffered an ischemic attack 6 months prior to the operation. Two TMS studies, one before and one shortly after CEA were performed on both sides in each of the patients. Resting motor threshold, motor evoked potentials (MEP) amplitude at rest, MEP latency at rest and during contraction and silent period duration (SPD) were recorded and analyzed. Two groups of data were collected. Group 1 consisted of data from the operated side in all 30 patients. Group 2 consisted of data from the contralateral side and served as a control. Results Motor resting thresholds were similar in the two groups. Intragroup pre and post CEA comparisons showed no difference in the operated group and significant increased threshold after CEA on the non-operated side. There was no significant difference of TMS intensity for maximal MEP in either side before or after CEA. Latency at rest and during voluntary contraction and amplitude at rest showed no significant differences between or within groups’ comparisons. In group 1 SPD showed a statistically significant increase after CEA as opposed to baseline. In group 2 SPD showed a non significant increase after CEA. Conclusion In the absence of other MEP changes, our finding of prolonged SPD post–operatively suggests preferential influence of the inhibitory cortical circuits. The potential favorable effect of CEA in patients with hyperexcitability such as disabling spasticity after stroke should be further studied.     

Motion‐induced disturbance of auditory–motor synchronization and its modulation by transcranial direct current stimulation

The timing of personal movement with respect to external events has previously been investigated using a synchronized finger‐tapping task with a sequence of auditory or visual stimuli. While visuomotor synchronization is more accurate with moving stimuli than with stationary stimuli, it remains unclear whether the same principle holds true in the auditory domain. Although the right inferior–superior parietal lobe (IPL/SPL), a center of auditory motion processing, is expected to be involved in auditory–motor synchronization with moving sounds, its functional relevance has not yet been investigated. The aim of the present study was thus to clarify whether horizontal auditory motion affects the accuracy of finger‐tapping synchronized with sounds, as well as whether the application of transcranial direct current stimulation (tDCS) to the right IPL/SPL affects this. Nineteen healthy right‐handed participants performed a task in which tapping was synchronized with both stationary sounds and sounds that created apparent horizontal motion. This task was performed before and during anodal, cathodal and sham tDCS application to the right IPL/SPL in separate sessions. The time difference between the onset of the sounds and tapping was larger with apparently moving sounds than with stationary sounds. Cathodal tDCS decreased this difference, anodal tDCS increased the variance of the difference and sham stimulation had no effect. These results supported the hypothesis that auditory motion disturbs efficient auditory–motor synchronization and that the right IPL/SPL plays an important role in tapping in synchrony with moving sounds via auditory motion processing.     

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

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

Effects on motor learning of transcranial alternating current stimulation applied over the primary motor cortex and cerebellar hemisphere

Transcranial alternating current stimulation (tACS) is a non-invasive method of brain stimulation that modulates oscillatory neural activity in the cortical area under the electrodes. Gamma (γ)-tACS applied over the primary motor cortex (M1) and cerebellar hemisphere is known to improve motor performance; however, it is not yet known whether it affects motor learning. Thus, here we investigated whether γ-tACS applied over the M1 and cerebellar hemisphere affects motor learning. This study involved 30 healthy subjects (14 females, 16 males) performing a visuomotor control task (eight trials) during an administration of either γ-tACS or a sham stimulation (15 subjects per condition) over their right M1 and left cerebellar hemisphere. Each subject performed five trials after 24 h. The motor learning efficiency, motor learning retention and re-motor learning efficiency in each condition were compared. The motor learning retention in the γ-tACS condition was significantly higher than that in the sham condition (p = 0.031). Thus, subjects who were administered γ-tACS maintained their motor performance the next day better than sham-stimulated subjects. There was no significant difference between the conditions in the motor learning efficiency and those in the re-motor learning efficiency. Our results demonstrate that γ-tACS administered over the M1 and cerebellar hemisphere during a motor learning task can enhance motor learning retention.     

Resting state functional connectivity measures correlate with the response to anodal transcranial direct current stimulation

Responses to non‐invasive brain stimulation are highly variable between subjects. Resting state functional connectivity was investigated as a marker of plasticity induced by anodal transcranial direct current stimulation (tDCS). Twenty‐six healthy adults (15 male, 26.4 ± 6.5 years) were tested. Experiment 1 investigated whether functional connectivity could predict modulation of corticospinal excitability following anodal tDCS. Experiment 2 determined test – retest reliability of connectivity measures. Three minutes of electroencephalography was recorded and connectivity was quantified with the debiased weighted phase lag index. Anodal (1 mA, 20 min) or sham tDCS was applied to the left primary motor cortex (M1), with a change in motor evoked potential amplitude recorded from the right first dorsal interosseous used as a marker of tDCS response. Connectivity in the high beta frequency (20–30 Hz) between an electrode approximating the left M1 (C3) and electrodes overlying the left parietal cortex was a strong predictor of tDCS response (cross‐validated R² = 0.69). Similar relationships were observed for alpha (8–13 Hz; R² = 0.64), theta (4–7 Hz; R² = 0.53), and low beta (14–19 Hz; R² = 0.58) frequencies, however, test – retest reliability of connectivity measures was strongest for the high beta frequency model (ICC = 0.65; good reliability). Further investigation of the high beta model found that greater connectivity between C3 and a cluster of electrodes approximately overlying the left parietal cortex was associated with stronger responses to anodal (rho = 0.61, P = 0.03), but not sham tDCS (rho = 0.43, P = 0.14). Functional connectivity is a strong predictor of the neuroplastic response to tDCS and may be one important characteristic to assist targeted tDCS application.     

Modulation of movement-associated cortical activation by transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is currently attracting increasing interest as a tool for neurorehabilitation. However, local and distant effects of tDCS on motor-related cortical activation patterns remain poorly defined, limiting the rationale for its use. Here we describe the results of a functional magnetic resonance imaging (MRI) experiment designed to characterize local and distant effects on cortical motor activity following excitatory anodal stimulation and inhibitory cathodal stimulation. Fifteen right-handed subjects performed a visually cued serial reaction time task with their right hand in a 3-T MRI scanner both before and after 10 min of 1-mA tDCS applied to the left primary motor cortex (M1). Relative to sham stimulation, anodal tDCS led to short-lived activation increases in the M1 and the supplementary motor area (SMA) within the stimulated hemisphere. The increase in activation in the SMA with anodal stimulation was found also when directly comparing anodal with cathodal stimulation. Relative to sham stimulation, cathodal tDCS led to an increase in activation in the contralateral M1 and dorsal premotor cortex (PMd), as well as an increase in functional connectivity between these areas and the stimulated left M1. These increases were also found when directly comparing cathodal with anodal stimulation. Significant within-session linear decreases in activation occurred in all scan sessions. The after-effects of anodal tDCS arose primarily from a change in the slope of these decreases. In addition, following sham stimulation compared with baseline, a between-session decrease in task-related activity was found. The effects of cathodal tDCS arose primarily from a reduction of this normal decrease.     

Facilitation of visuo-motor learning by transcranial direct current stimulation of the motor and extrastriate visual areas in humans

Performance of visuo-motor tasks requires the transfer of visual data to motor performance and depends highly on visual perception and cognitive processing, mainly during the learning phase. The primary aim of this study was to determine if the human middle temporal (MT)+/V5, an extrastriate visual area that is known to mediate motion processing, and the primary motor cortex are involved in learning of visuo-motor coordination tasks. To pursue this, we increased or decreased MT+/V5, primary contralateral motor (M1) and primary visual cortex excitability by 10 min of anodal or cathodal transcranial direct current stimulation in healthy human subjects during the learning phase of a visually guided tracking task. The percentage of correct tracking movements increased significantly in the early learning phase during anodal stimulation, but only when the left V5 or M1 was stimulated. Cathodal stimulation had no significant effect. Also, stimulation of the primary visual cortex was not effective for this kind of task. Our data suggest that the areas V5 and M1 are involved in the early phase of learning of visuo-motor coordination.