Dual Transcranial Direct Current Stimulation Research Articles

Dual-tDCS Ameliorates Cerebral Injury and Promotes Motor Function Recovery via cGAS-STING Signaling Pathway in a Rat Model of Ischemic Stroke.

Ischemic stroke is one of the leading causes of death and disability. Dual transcranial direct current stimulation (dual-tDCS) is a promising intervention to treat ischemic stroke, but its efficacy and underlying mechanism remain to be verified. Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has recently emerged as a key mediator in cerebral injury. However, little is known about the effect of cGAS-STING on neuronal damage in ischemic stroke, and it remains to be studied whether the cGAS-STING pathway is involved in tDCS intervention for ischemic stroke. Therefore, we aimed to investigate whether dual-tDCS can alleviate ischemic brain injury in a rat model of ischemic stroke and if so, whether via cGAS-STING pathway. Middle cerebral artery occlusion (MCAO) was employed to induce a rat model of ischemic stroke. Male SD rats weighing 250-280g were randomly assigned to the Sham, MCAO, Dual-tDCS, Dual-tDCS + RU.521, and Dual-tDCS + 2'3'-cGAMP groups, with 10 rats in each group completing the experiment. Behavioral, morphological, MRI, and molecular biological methods were performed. We found that the cGAS-STING pathway was activated and expressed in neurons after MCAO. Dual-tDCS improved motor function and infarct volume, inhibited neuronal apoptosis, promoted the expression of neurotrophins (BDNF and NGF), CD31, and VEGF, and suppressed inflammation reaction after MCAO via the cGAS-STING pathway. Taken together, dual-tDCS may improve MCAO-induced brain injury and promote the recovery of motor function, resulting from the inhibition of neuronal apoptosis and inflammation reaction, as well as promotion of the expression of nerve plasticity- and angiogenesis-related proteins, via cGAS-STING pathway.

The Effects of Single and Dual Transcranial Direct Current Stimulation on Motor and Cognitive Functions in Male Gymnasts

Background: The better performance of elite athletes than others may be due to their better mental and psychological advantages. Transcranial direct current stimulation (tDCS) is an attractive technique to improve the physical and mental functions in recent years. Objectives: This study aimed to examine the effects of single and dual tDCS of M1 and DLPFC regions on motor and cognitive functions in male gymnasts. Methods: Sixteen male gymnasts (age mean = 21.70 ± 0.66 years) who were selected randomly, exposed to 4 different intervention conditions in 4 separate sessions with a one-week interval between the sessions, including (1) anodal stimulation of the M1 area; (2) anodal stimulation of the left DLPFC area; (3) simultaneous stimulation of M1 and DLPFC areas; (4) sham stimulation. After ensuring the normal distribution using shapiro-whilk test, gathered data were analyzed with two- way repeated measures ANOVA. Results: The results showed that single and dual tDCS of M1 and DLPFC regions had a significant effect on improving bimanual coordination, eye-hand coordination, reaction time, working memory, and selective attention of male gymnasts. Also, considering the observed effect size, the M1& DLPFC stimulation condition had a greater effect than other stimulation conditions. Conclusions: Based on present findings coaches and sports physiologists can improve the performance of their athletes with inclusion single and dual tDCS into their training routines.

Combining Transcranial Direct Current Stimulation With Hand Robotic Rehabilitation in Chronic Stroke Patients: A Double-Blind Randomized Clinical Trial.

This study aimed to assess the impact of combining transcranial direct current stimulation with end-effector robot-assisted treatment on upper limb function, spasticity, and hand dexterity in chronic stroke patients. This was a prospective, double-blind randomized trial with 20 equally allocated stroke patients. The experimental group received dual transcranial direct current stimulation (anode over affected M1, cathode over contralateral M1) alongside robot-assisted treatment, while the control group received sham transcranial direct current stimulation with the same electrode placement + robot-assisted treatment. Each patient underwent 20 combined transcranial direct current stimulation and robot-assisted treatment sessions. The primary outcome measure was the Fugl-Meyer Upper Limb motor score, with secondary outcomes including AMADEO kinematic measures, Action Research Arm Test, and Functional Independence Measure. Assessments were conducted at baseline, after rehabilitation, and 3 mos later. Combining bilateral transcranial direct current stimulation with robot-assisted treatment did not yield additional improvements in Fugl-Meyer Upper Limb motor score, Functional Independence Measure, or Action Research Arm Test scores among stroke patients. However, the real transcranial direct current stimulation group showed enhanced finger flexion in the affected hand based on AMADEO kinematic measures. The addition of transcranial direct current stimulation to robot-assisted treatment did not result in significant overall functional improvements in chronic stroke patients. However, a benefit was observed in finger flexion of the affected hand.

May Dual Transcranial Direct Current Stimulation Enhance the Efficacy of Robot-Assisted Therapy for Promoting Upper Limb Recovery in Chronic Stroke?

Objective To assess whether dual transcranial direct current stimulation (tDCS) may enhance the efficacy of exoskeleton robotic training on upper limb motor functions in patients with chronic stroke. Methods A prospective, bi-center, double-blind, randomized clinical trial study was performed. Patients with moderate-to-severe stroke (according to The National Institute of Health Stroke Scale) were randomly assigned to receive dual or sham tDCS immediately before robotic therapy (10 sessions, 2 weeks). The primary outcome was the Fugl–Meyer for Upper Extremity, assessed before, after, and at the 12-week follow-up. Neurophysiological evaluation of corticospinal projections to upper limb muscles was performed by recording motor evoked potentials (MEPs). ClinicalTrials.gov-NCT03026712. Results Two hundred and sixty individuals were tested for eligibility, of which 80 were enrolled and agreed to participate. Excluding 14 dropouts, 66 patients were randomly assigned into the 2 groups. Results showed that chronic patients were stable before treatment and significantly improved after that. The records within subject improvements were not significantly different between the 2 groups. However, a post-hoc analysis subdividing patients in 2 subgroups based on the presence or absence of MEPs at the baseline showed a significantly higher effect of real tDCS in patients without MEPs when compared to patients with MEPs (F = 4.6, P = .007). Conclusion The adjunction of dual tDCS to robotic arm training did not further enhance recovery in the treated sample of patients with chronic stroke. However, a significant improvement in the subgroup of patients with a severe corticospinal dysfunction (as suggested by the absence of MEPs) suggests that they could benefit from such a treatment combination.

Five-Session Dual-Transcranial Direct Current Stimulation With Task-Specific Training Does Not Improve Gait and Lower Limb Performance Over Training Alone in Subacute Stroke: A Pilot Randomized Controlled Trial

ObjectiveTo determine the effect of five-session dual-transcranial direct current stimulation (dual-tDCS) combined with task-specific training on gait and lower limb motor performance in individuals with subacute stroke. Materials and MethodsTwenty-five participants who had a stroke in the subacute phase with mild motor impairment were recruited, randomized, and allocated into two groups. The active group (n = 13) received dual-tDCS with anodal over the lesioned hemisphere M1 and cathodal over the nonlesioned hemisphere, at 2 mA for 20 min before training for five consecutive days, while the sham group (n = 12) received sham mode before training. Gait speed as a primary outcome, temporospatial gait variables, lower-limb functional tasks (sit-to-stand and walking mobility), and muscle strength as secondary outcomes were collected at preintervention and postintervention (day 5), one-week follow-up, and one-month follow-up. ResultsThe primary outcome and most of the secondary outcomes were improved in both groups, with no significant difference between the two groups, and most of the results indicated small to moderate effect sizes of active tDCS compared to sham tDCS. ConclusionThe combined intervention showed no benefit over training alone in improving gait variables and lower-limb performance. However, some performances were saturated at some point, as moderate to high function participants were recruited in the present study. Future studies should consider recruiting participants with more varied motor impairment levels and may need to determine the optimal stimulation protocols and parameters to improve gait and lower-limb performance.

Dual transcranial direct current stimulation for subacute stroke patients with compromised corticospinal integrity: a randomized, double-blind, sham-controlled study

Dual transcranial direct current stimulation for subacute stroke patients with compromised corticospinal integrity: a randomized, double-blind, sham-controlled study

Effects of Dual Transcranial Direct Current Stimulation and Modified Constraint-Induced Movement Therapy to Improve Upper-Limb Function after Stroke: A Double-Blinded, Pilot Randomized Controlled Trial

BackgroundDual transcranial direct current stimulation (dual tDCS) can be combined with stroke rehabilitation interventions to promote excitatory changes in the cerebral cortex. ObjectiveTo investigate how the combined intervention of dual tDCS and modified constraint-induced movement therapy (mCIMT) using both anodal and cathodal stimulation affects on the recovery of upper limb function in chronic stroke patients. MethodsThis study was a double-blind randomized controlled trial. A total of 30 patients were randomly assigned to the experimental group (dual tDCS and mCIMT) or control group (sham dual tDCS and mCIMT). The experimental and control group performed mCIMT immediately after applying dual tDCS for 20 min, but the control group also performed mCIMT after applying sham tDCS for 20 min in a state where no current flows. The total intervention period was performed 5 times a week for 4 weeks. The outcome was assessed using Fugle-Meyer Assessment (FMA) Motor Activity Log (MAL) Accelerometer. ResultsThere was a significant improvement in AOU of MAL and usage of unaffected side in the experimental group compared to the control group, and the experimental group showed more than a small effect difference compared to the control group in the effect size of all evaluations. ConclusionsThis study has clinical significance in that it presents the possibility of convergence intervention that considers the therapeutic efficiency in clinical practice.

DUAL-tDCS Treatment over the Temporo-Parietal Cortex Enhances Writing Skills: First Evidence from Chronic Post-Stroke Aphasia.

The learning of writing skills involves the re-engagement of previously established independent procedures. Indeed, the writing deficit an adult may acquire after left hemispheric brain injury is caused by either an impairment to the lexical route, which processes words as a whole, to the sublexical procedure based on phoneme-to-grapheme conversion rules, or to both procedures. To date, several approaches have been proposed for writing disorders, among which, interventions aimed at restoring the sub-lexical procedure were successful in cases of severe agraphia. In a randomized double-blind crossover design, fourteen chronic Italian post-stroke aphasics underwent dual transcranial direct current stimulation (tDCS) (20 min, 2 mA) with anodal and cathodal current simultaneously placed over the left and right temporo-parietal cortex, respectively. Two different conditions were considered: (1) real, and (2) sham, while performing a writing task. Each experimental condition was performed for ten workdays over two weeks. After real stimulation, a greater amelioration in writing with respect to the sham was found. Relevantly, these effects generalized to different language tasks not directly treated. This evidence suggests, for the first time, that dual tDCS associated with training is efficacious for severe agraphia. Our results confirm the critical role of the temporo-parietal cortex in writing skills.

Neurophysiological signatures of hand motor response to dual-transcranial direct current stimulation in subacute stroke: a TMS and MEG study

BackgroundDual transcranial direct current stimulation (tDCS) to the bilateral primary motor cortices (M1s) has potential benefits in chronic stroke, but its effects in subacute stroke, when behavioural effects might be expected to be greater, have been relatively unexplored. Here, we examined the neurophysiological effects and the factors influencing responsiveness of dual-tDCS in subacute stroke survivors.MethodsWe conducted a randomized sham-controlled crossover study in 18 survivors with first-ever, unilateral subcortical ischaemic stroke 2–4 weeks after stroke onset and 14 matched healthy controls. Participants had real dual-tDCS (with an ipsilesional [right for controls] M1 anode and a contralesional M1 [left for controls] cathode; 2 mA for 20mins) and sham dual-tDCS on separate days, with concurrent paretic [left for controls] hand exercise. Using transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), we recorded motor evoked potentials (MEPs), the ipsilateral silent period (iSP), short-interval intracortical inhibition, and finger movement-related cortical oscillations before and immediately after tDCS.ResultsStroke survivors had decreased excitability in ipsilesional M1 with a relatively excessive transcallosal inhibition from the contralesional to ipsilesional hemisphere at baseline compared with controls, as quantified by decreased MEPs and increased iSP duration. Dual-tDCS led to increased MEPs and decreased iSP duration in ipsilesional M1. The magnitude of the tDCS-induced MEP increase in stroke survivors was predicted by baseline contralesional-to-ipsilesional transcallosal inhibition (iSP) ratio. Baseline post-movement synchronization in α-band activity in ipsilesional M1 was decreased after stroke compared with controls, and its tDCS-induced increase correlated with upper limb score in stroke survivors. No significant adverse effects were observed during or after dual-tDCS.ConclusionsTask-concurrent dual-tDCS in subacute stroke can safely and effectively modulate bilateral M1 excitability and inter-hemispheric imbalance and also movement-related α-activity.

Timing-dependent interaction effects of tDCS with mirror therapy on upper extremity motor recovery in patients with chronic stroke: A randomized controlled pilot study

This study was a randomized, controlled pilot trial to investigate the timing-dependent interaction effects of dual transcranial direct current stimulation (tDCS) in mirror therapy (MT) for hemiplegic upper extremity in patients with chronic stroke. Thirty patients with chronic stroke were randomly assigned to three groups: tDCS applied before MT (prior-tDCS group), tDCS applied during MT (concurrent-tDCS group), and sham tDCS applied randomly prior to or concurrent with MT (sham-tDCS group). Dual tDCS at 1 mA was applied bilaterally over the ipsilesional M1 (anodal electrode) and the contralesional M1 (cathodal electrode) for 30 min. The intervention was delivered five days per week for two weeks. Upper extremity motor performance was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT), and the Box and Block Test (BBT). Assessments were administered at baseline, post-intervention, and two weeks follow-up. The results indicated that concurrent-tDCS group showed significant improvements in the ARAT in relation to the prior-tDCS group and sham-tDCS group at post-intervention. Besides, a trend toward greater improvement was also found in the FMA-UE for the concurrent-tDCS group. However, no statistically significant difference in the FMA-UE and BBT was identified among the three groups at either post-intervention or follow-up. The concurrent-tDCS seems to be more advantageous and time-efficient in the context of clinical trials combining with MT. The timing-dependent interaction factor of tDCS to facilitate motor recovery should be considered in future clinical application.

Effects of Dual-transcranial Direct Current Stimulation During Physical Therapy in Sub-acute Stroke

Effects of Dual-transcranial Direct Current Stimulation During Physical Therapy in Sub-acute Stroke

Dual Transcranial Direct Current Stimulation (dTDCS)-Enhanced Therapy After Hemorrhagic Strokes and VEGF

Dual Transcranial Direct Current Stimulation (dTDCS)-Enhanced Therapy After Hemorrhagic Strokes and VEGF

Dual Transcranial Direct Current Stimulation for Poststroke Dysphagia: A Randomized Controlled Trial

Background. Poststroke dysphagia is associated with considerable morbidity and has high health care cost implications. Objective. To evaluate whether anodal transcranial direct current stimulation (tDCS) over the lesioned hemisphere and cathodal tDCS to the contralateral one during the early stage of rehabilitation can improve poststroke dysphagia. Methods. A total of 40 patients referred to our neurorehabilitation department were randomized to receive anodal tDCS over the damaged hemisphere plus cathodal stimulation over the contralateral one versus sham stimulation during swallowing maneuvers over the course of 10 sessions of treatment. Swallowing function was evaluated before and after stimulation using the Dysphagia Outcome and Severity Scale (DOSS). Results. The percentage of patients who reached various thresholds of improvement was higher in the tDCS group than in the sham group, but the differences were not significant (eg, DOSS score ≥ 20% increase from baseline: 55% in the tDCS group vs 40% in the sham group; P = .53). Among all variables recorded at baseline, only a subgroup of patients without nasogastric tube showed a significantly higher improvement with tDCS treatment versus sham (DOSS score ≥10% and ≥20% from baseline: 64.29% vs 0%, P = .01). Conclusions. In patients with poststroke dysphagia, treatment with dual tDCS in the early phase of rehabilitation does not significantly increase the probability of recovery compared with sham stimulation.

Effectiveness of a single session of dual-transcranial direct current stimulation in combination with upper limb robotic-assisted rehabilitation in chronic stroke patients: a randomized, double-blind, cross-over study.

The impact of transcranial direct current stimulation (tDCS) is controversial in the neurorehabilitation literature. It has been suggested that tDCS should be combined with other therapy to improve their efficacy. To assess the effectiveness of a single session of upper limb robotic-assisted therapy (RAT) combined with real or sham-tDCS in chronic stroke patients. Twenty-one hemiparetic chronic stroke patients were included in a randomized, controlled, cross-over double-blind study. Each patient underwent two sessions 7 days apart in a randomized order: (a) 20 min of real dual-tDCS associated with RAT (REAL+RAT) and (b) 20 min of sham dual-tDCS associated with RAT (SHAM+RAT). Patient dexterity (Box and Block and Purdue Pegboard tests) and upper limb kinematics were evaluated before and just after each intervention. The assistance provided by the robot during the intervention was also recorded. Gross manual dexterity (1.8±0.7 blocks, P=0.008) and straightness of movement (0.01±0.03, P<0.05) improved slightly after REAL+RAT compared with before the intervention. There was no improvement after SHAM+RAT. The post-hoc analyses did not indicate any difference between interventions: REAL+RAT and SHAM+RAT (P>0.05). The assistance provided by the robot was similar during both interventions (P>0.05). The results showed a slight improvement in hand dexterity and arm movement after the REAL+RAT tDCS intervention. The observed effect after a single session was small and not clinically relevant. Repetitive sessions could increase the benefits of this combined approach.

Effect of single-session dual-tDCS before physical therapy on lower-limb performance in sub-acute stroke patients: A randomized sham-controlled crossover study.

Anodal stimulation increases cortical excitably, whereas cathodal stimulation decreases cortical excitability. Dual transcranial direct current stimulation (tDCS; anodal over the lesioned hemisphere, cathodal over the non-lesioned hemisphere) was found to enhance motor learning. The corresponding tDCS-induced changes were reported to reduce the inhibition exerted by the unaffected hemisphere on the affected hemisphere and restore the normal balance of the interhemispheric inhibition. Most studies were devoted to the possible modification of upper-limb motor function after tDCS; however, almost no study has demonstrated its effects on lower-limb function and gait, which are also commonly disordered in stroke patients with motor deficits. In this randomized sham-controlled crossover study, we included 19 patients with sub-acute stroke. Participants were randomly allocated to receive real or sham dual-tDCS followed by conventional physical therapy with an intervention interval of at least 1 week. Dual-tDCS was applied over the lower-limb M1 at 2-mA intensity for 20min. Lower-limb performance was assessed by the Timed Up and Go (TUG) and Five-Times-Sit-To-Stand (FTSTS) tests and muscle strength was assessed by peak knee torque of extension. We found a significant increase in time to perform the FTSST for the real group, with improvements significantly greater than for the sham group; the TUG score was significantly increased but not higher than for the sham group. An after-effect on FTSTS was found at approximately 1 week after the real intervention. Muscle strength was unchanged in both limbs for both real and sham groups. Our results suggest that a single session of dual-tDCS before conventional physical therapy could improve sit-to-stand performance, which appeared to be improved over conventional physical therapy alone. However, strength performance was not increased after the combination treatment.

Neuromodulation by task-concurrent dual transcranial direct current stimulation over the motor cortex in subacute stroke (P4.218)

Neuromodulation by task-concurrent dual transcranial direct current stimulation over the motor cortex in subacute stroke (P4.218)

Increased functional connectivity one week after motor learning and tDCS in stroke patients

Recent studies using resting-state functional magnetic resonance imaging (rs-fMRI) demonstrated that changes in functional connectivity (FC) after stroke correlate with recovery. The aim of this study was to explore whether combining motor learning to dual transcranial direct current stimulation (dual-tDCS, applied over both primary motor cortices (M1)) modulated FC in stroke patients. Twenty-two chronic hemiparetic stroke patients participated in a baseline rs-fMRI session. One week later, dual-tDCS/sham was applied during motor skill learning (intervention session); one week later, the retention session started with the acquisition of a run of rs-fMRI imaging. The intervention+retention sessions were performed once with dual-tDCS and once with sham in a randomized, cross-over, placebo-controlled, double-blind design. A whole-brain independent component analysis based analysis of variance (ANOVA) demonstrated no changes between baseline and sham sessions in the somatomotor network, whereas a FC increase was observed one week after dual-tDCS compared to baseline (qFDR <0.05, t63=4.15). A seed-based analysis confirmed specific stimulation-driven changes within a network of motor and premotor regions in both hemispheres. At baseline and one week after sham, the strongest FC was observed between the M1 and dorsal premotor cortex (PMd) of the undamaged hemisphere. In contrast, one week after dual-tDCS, the strongest FC was found between the M1 and PMd of the damaged hemisphere. Thus, a single session of dual-tDCS combined with motor skill learning increases FC in the somatomotor network of chronic stroke patients for one week.

Contralesional Cathodal versus Dual Transcranial Direct Current Stimulation for Decreasing Upper Limb Spasticity in Chronic Stroke Individuals: A Clinical and Neurophysiological Study

Different transcranial direct current stimulation (tDCS) paradigms have been implemented to treat poststroke spasticity, but discordant results have been reported. This study aimed to determine the efficacy and persistence of dual tDCS (anode over affected motor cortex [M1] and cathode over contralateral M1) compared with cathodal tDCS (cathode over contralateral M1) on upper limb (UL) functional, behavioral, and neurophysiological measures in chronic poststroke individuals. Ten subjects with UL spasticity (7 men; mean 62 years; 8 ischemic stroke; years from event: 2.3 years) were enrolled in a cross-over, double-blinded study. Cathodal and dual tDCS, both preceded by 1 week of sham stimulation 1 month before real stimulation, were applied with 3 months interval. Stimulating paradigm was 20 minutes for five consecutive days in each block. Evaluations were performed before (T1), after real or sham treatment (T2), and after 1 (T3), 4 (T4), and 8 weeks (T5). Functional, behavioral, and neurophysiological tests were performed at each time. Both tDCS paradigms decreased spasticity, increased strength, and ameliorated behavioral scales. Cathodal tDCS was superior to dual tDCS in reducing UL distal spasticity immediately after treatment (T2: cathodal > dual: P = .023) and provided a higher and longer lasting reduction at proximal districts (T3: cathodal > dual: P = .042; T4: cathodal > dual: P = .028; T5: cathodal > dual: P = .05). These findings are supported by an H-reflex modulation (overall time effect P > .002). Cathodal tDCS is slightly more effective than dual tDCS in reducing distal UL spasticity in chronic poststroke subjects. A modulation of spinal inhibitory mechanisms, demonstrated by H-reflex modifications, supports this finding.

Abstract T P113: Structural Changes In The Corticospinal Tract After 10 Days Of Combined Physical Therapy And Transcranial Direct Current Stimulation

A few studies have shown that long-term skill acquisition can lead to changes in white matter tracts. Studies examining structural changes in the corticospinal tract in patients recovering from a stroke have yielded mixed results. The current study examines whether 10 days of combined physical therapy (PT) and non-invasive brain-stimulation (using dual transcranial direct current stimulation) can lead to changes in the corticospinal tract (CST) on the affected hemisphere. Seven stroke patients participated in an intense 10-day long treatment of physical therapy (1 hour/day) and tDCS (30 minutes per session) with anodal stimulation applied over the affected motor cortex and cathodal stimulation over the unaffected motor cortex. Each patient also underwent Fugl-Meyer assessments (UE-FM) and diffusion tensor imaging (DTI) before and after the treatment phase. A control group of seven patients were also scanned at two time points and assessed without any intervening therapy. The DTI images were processed using the standard algorithms provided by FSL and normalized to FSL's FA template. We used a section of the CST derived from the JHU atlas, between the internal capsule (below each patient’s lesion) and upper brain stem as our region of interest to extract FA and other diffusivity values before and after therapy. All patients showed an increase in proportional UE-FM scores (+21%; SD 10%) and an increase in average FA (+0.013; SD 0.01) of the descending CST below the lesion after the intervention and no significant change was seen in the patient that were assessed two times but had no treatment. In addition, we found a strong correlation between the change in FA and a proportional improvement in the UE-FM score (r=0.689). These findings support the notion that focal white matter changes can be detected with DTI and that an intense course of an experimental treatment (2x5 days of combined PT+tDCS) induced structural changes in the descending CST that were not seen in patients scanned twice without treatment.

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

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.