Bihemispheric Transcranial Direct Current Stimulation Research Articles

Brain complexity in stroke recovery after bihemispheric transcranial direct current stimulation in mice.

Stroke is one of the leading causes of disability worldwide. There are many different rehabilitation approaches aimed at improving clinical outcomes for stroke survivors. One of the latest therapeutic techniques is the non-invasive brain stimulation. Among non-invasive brain stimulation, transcranial direct current stimulation has shown promising results in enhancing motor and cognitive recovery both in animal models of stroke and stroke survivors. In this framework, one of the most innovative methods is the bihemispheric transcranial direct current stimulation that simultaneously increases excitability in one hemisphere and decreases excitability in the contralateral one. As bihemispheric transcranial direct current stimulation can create a more balanced modulation of brain activity, this approach may be particularly useful in counteracting imbalanced brain activity, such as in stroke. Given these premises, the aim of the current study has been to explore the recovery after stroke in mice that underwent a bihemispheric transcranial direct current stimulation treatment, by recording their electric brain activity with local field potential and by measuring behavioural outcomes of Grip Strength test. An innovative parameter that explores the complexity of signals, namely the Entropy, recently adopted to describe brain activity in physiopathological states, was evaluated to analyse local field potential data. Results showed that stroke mice had higher values of Entropy compared to healthy mice, indicating an increase in brain complexity and signal disorder due to the stroke. Additionally, the bihemispheric transcranial direct current stimulation reduced Entropy in both healthy and stroke mice compared to sham stimulated mice, with a greater effect in stroke mice. Moreover, correlation analysis showed a negative correlation between Entropy and Grip Strength values, indicating that higher Entropy values resulted in lower Grip Strength engagement. Concluding, the current evidence suggests that the Entropy index of brain complexity characterizes stroke pathology and recovery. Together with this, bihemispheric transcranial direct current stimulation can modulate brain rhythms in animal models of stroke, providing potentially new avenues for rehabilitation in humans.

Effects of bihemispheric transcranial direct current stimulation on motor recovery in subacute stroke patients: a double-blind, randomized sham-controlled trial

BackgroundBihemispheric transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) can simultaneously modulate bilateral corticospinal excitability and interhemispheric interaction. However, how tDCS affects subacute stroke recovery remains unclear. We investigated the effects of bihemispheric tDCS on motor recovery in subacute stroke patients.MethodsWe enrolled subacute inpatients who had first-ever ischemic stroke at subcortical regions and moderate-to-severe baseline Fugl-Meyer Assessment of Upper Extremity (FMA-UE) score 2–56. Participants between 14 and 28 days after stroke were double-blind, randomly assigned (1:1) to receive real (n = 13) or sham (n = 14) bihemispheric tDCS (with ipsilesional M1 anode and contralesional M1 cathode, 20 min, 2 mA) during task practice twice daily for 20 sessions in two weeks. Residual integrity of the ipsilesional corticospinal tract was stratified between groups. The primary efficacy outcome was the change in FMA-UE score from baseline (responder as an increase ≥ 10). The secondary measures included changes in the Action Research Arm Test (ARAT), FMA-Lower Extremity (FMA-LE) and explorative resting-state MRI functional connectivity (FC) of target regions after intervention and three months post-stroke.ResultsTwenty-seven participants completed the study without significant adverse effects. Nineteen patients (70%) had no recordable baseline motor-evoked potentials (MEP-negative) from the paretic forearm. Compared with the sham group, the real tDCS group showed enhanced improvement of FMA-UE after intervention (p < 0.01, effect size η2 = 0.211; responder rate: 77% vs. 36%, p = 0.031), which sustained three months post-stroke (p < 0.01), but not ARAT. Interestingly, in the MEP-negative subgroup analysis, the FMA-UE improvement remained but delayed. Additionally, the FMA-LE improvement after real tDCS was not significantly greater until three months post-stroke (p < 0.01). We found that the individual FMA-UE improvements after real tDCS were associated with bilateral intrahemispheric, rather than interhemispheric, FC strengths in the targeted cortices, while the improvements after sham tDCS were associated with predominantly ipsilesional FC changes after adjustment for age and sex (p < 0.01).ConclusionsBihemispheric tDCS during task-oriented training may facilitate motor recovery in subacute stroke patients, even with compromised corticospinal tract integrity. Further studies are warranted for tDCS efficacy and network-specific neuromodulation.Trial registration: This study is registered with ClinicalTrials.gov: (ID: NCT02731508).

Transcranial Direct Current Stimulation Enhances Neuroplasticity and Accelerates Motor Recovery in a Stroke Mouse Model.

More effective strategies are needed to promote poststroke functional recovery. Here, we evaluated the impact of bihemispheric transcranial direct current stimulation (tDCS) on forelimb motor function recovery and the underlying mechanisms in mice subjected to focal ischemia of the motor cortex. Photothrombotic stroke was induced in the forelimb brain motor area, and tDCS was applied once per day for 3 consecutive days, starting 72 hours after stroke. Grid-walking, single pellet reaching, and grip strength tests were conducted to assess motor function. Local field potentials were recorded to evaluate brain connectivity. Western immunoblotting, ELISA, quantitative real-time polymerase chain reaction, and Golgi-Cox staining were used to uncover tDCS-mediated stroke recovery mechanisms. Among our results, tDCS increased the rate of motor recovery, anticipating it at the early subacute stage. In this window, tDCS enhanced BDNF (brain-derived neurotrophic factor) expression and dendritic spine density in the peri-infarct motor cortex, along with increasing functional connectivity between motor and somatosensory cortices. Treatment with the BDNF TrkB (tropomyosin-related tyrosine kinase B) receptor inhibitor, ANA-12, prevented tDCS effects on motor recovery and connectivity as well as the increase of spine density, pERK (phosphorylated extracellular signal-regulated kinase), pCaMKII (phosphorylated calcium/calmodulin-dependent protein kinase II), pMEF (phosphorylated myocyte-enhancer factor), and PSD (postsynaptic density)-95. The tDCS-promoted rescue was paralleled by enhanced plasma BDNF level, suggesting its potential role as circulating prognostic biomarker. The rate of motor recovery is accelerated by tDCS applied in the subacute phase of stroke. Anticipation of motor recovery via vicariate pathways or neural reserve recruitment would potentially enhance the efficacy of standard treatments, such as physical therapy, which is often delayed to a later stage when plastic responses are progressively lower.

Limited Add-On Effects of Unilateral and Bilateral Transcranial Direct Current Stimulation on Visuo-Motor Grip Force Tracking Task Training Outcome in Chronic Stroke. A Randomized Controlled Trial

Background: This randomized controlled trial investigated if uni- and bihemispheric transcranial direct current stimulation (tDCS) of the motor cortex can enhance the effects of visuo-motor grip force tracking task training and transfer to clinical assessments of upper extremity motor function.Methods: In a randomized, double-blind, sham-controlled trial, 40 chronic stroke patients underwent 5 days of visuo-motor grip force tracking task training of the paretic hand with either unilateral or bilateral (N = 15/group) or placebo tDCS (N = 10). Immediate and long-term (3 months) effects on training outcome and motor recovery (Upper Extremity Fugl-Meyer, UE-FM, Wolf Motor Function Test, and WMFT) were investigated.Results: Trained task performance significantly improved independently of tDCS in a curvilinear fashion. In the anodal stimulation group UE-FM scores were higher than in the sham group at day 5 (adjusted mean difference: 2.6, 95%CI: 0.6–4.5, p = 0.010) and at 3 months follow up (adjusted mean difference: 2.8, 95%CI: 0.8–4.7, p = 0.006). Neither training alone, nor the combination of training and tDCS improved WMFT performance.Conclusions: Visuo-motor grip force tracking task training can facilitate recovery of upper extremity function. Only minimal add-on effects of anodal but not dual tDCS were observed.Clinical Trial Registration: https://clinicaltrials.gov/ct2/results?recrs=&cond=&term=NCT01969097&cntry=&state=&city=&dist=, identifier: NCT01969097, retrospectively registered on 25/10/2013.

Effects of tDCS on Language Recovery in Post-Stroke Aphasia: A Pilot Study Investigating Clinical Parameters and White Matter Change with Diffusion Imaging.

Objectives: In this pilot study we investigated the effects of transcranial direct current stimulation (tDCS) on language recovery in the subacute stage of post-stroke aphasia using clinical parameters and diffusion imaging with constrained spherical deconvolution-based tractography. Methods: The study included 21 patients with subacute post-stroke aphasia. Patients were randomly classified into two groups with a ratio of 2:1 to receive real tDCS or sham tDCS as placebo control. Patients received 10 sessions (5/week) bi-hemispheric tDCS treatments over the left affected Broca’s area (anodal electrode) and over the right unaffected Broca’s area (cathodal stimulation). Aphasia score was assessed clinically using the language section of the Hemispheric Stroke Scale (HSS) before and after treatment sessions. Diffusion imaging and tractography were performed for seven patients of the real group, both before and after the 10th session. Dissection of language-related white matter tracts was achieved, and diffusion measures were extracted. A paired Student’s t-test was used to compare the clinical recovery and diffusion measures of the dissected tracts both pre- and post- treatment. The partial correlation between changes in diffusion measures and the language improvements was calculated. Results: At baseline assessment, there were no significant differences between groups in demographic and clinical HSS language score. No significant clinical recovery in HSS was evident in the sham group. However, significant improvements in the different components of HSS were only observed in patients receiving real tDCS. Associated significant increase in the fractional anisotropy of the right uncinate fasciculus and a significant reduction in the mean diffusivity of the right frontal aslant tract were reported. A significant positive correlation was found between the changes in the right uncinate fasciculus and fluency improvement. Conclusions: Aphasia recovery after bi-hemispheric transcranial direct current stimulation was associated with contralesional right-sided white matter changes at the subacute stage. These changes probably reflect neuroplasticity that could contribute to the recovery. Both the right uncinate fasciculus and right frontal aslant tract seem to be involved in aphasia recovery.

Ergogenic Effects of Bihemispheric Transcranial Direct Current Stimulation on Fitness: a Randomized Cross-over Trial.

Several types of routines and methods have been experimented to gain neuromuscular advantages, in terms of exercise performance, in athletes and fitness enthusiasts. The aim of the present study was to evaluate the impact of biemispheric transcranial direct current stimulation on physical fitness indicators of healthy, physically active, men. In a randomized, single-blinded, crossover fashion, seventeen subjects (age: 30.9 ± 6.5 years, BMI: 24.8±3.1 kg/m2) underwent either stimulation or sham, prior to: vertical jump, sit & reach, and endurance running tests. Mixed repeated measures anova revealed a large main effect of stimulation for any of the three physical fitness measures. Stimulation determined increases of lower limb power (+ 5%), sit & reach amplitude (+ 9%) and endurance running capacity (+ 12%) with respect to sham condition (0.16<ηp2 < 0.41; p<0.05). Ratings-of-perceived-exertion, recorded at the end of each test session, did not change across all performances. However, in the stimulated-endurance protocol, an average lower rate-of-perceived-exertion at iso-time was inferred. A portable transcranial direct current stimulation headset could be a valuable ergogenic resource for individuals seeking to improve physical fitness in daily life or in athletic training.

Modulating dream experience: Noninvasive brain stimulation over the sensorimotor cortex reduces dream movement

Recently, cortical correlates of specific dream contents have been reported, such as the activation of the sensorimotor cortex during dreamed hand clenching. Yet, despite a close resemblance of such activation patterns to those seen during the corresponding wakeful behaviour, the causal mechanisms underlying specific dream contents remain largely elusive. Here, we aimed to investigate the causal role of the sensorimotor cortex in generating movement and bodily sensations during REM sleep dreaming. Following bihemispheric transcranial direct current stimulation (tDCS) or sham stimulation, guided by functional mapping of the primary motor cortex, naive participants were awakened from REM sleep and responded to a questionnaire on bodily sensations in dreams. Electromyographic (EMG) and electroencephalographic (EEG) recordings were used to quantify physiological changes during the preceding REM period. We found that tDCS, compared to sham stimulation, significantly decreased reports of dream movement, especially of repetitive actions. Other types of bodily experiences, such as tactile or vestibular sensations, were not affected by tDCS, confirming the specificity of stimulation effects to movement sensations. In addition, tDCS reduced EEG interhemispheric coherence in parietal areas and affected the phasic EMG correlation between both arms. These findings show that a complex temporal reorganization of the motor network co-occurred with the reduction of dream movement, revealing a link between central and peripheral motor processes and movement sensations of the dream self. tDCS over the sensorimotor cortex interferes with dream movement during REM sleep, which is consistent with a causal contribution to dream experience and has broader implications for understanding the neural basis of self-experience in dreams.

Abstract TMP43: Differential Cortical Effect Modulated by Anodal, Cathodal and Bihemispheric Transcranial Direct Current Stimulation (tDCS) in Patients With Ischemic Stroke

Introduction: The differential brain modulatory effects across hemispheres from different montages in stroke patients is not well established. We aimed to investigate the cortical excitability on lesional and contra-lesional hemisphere modulated by anodal, cathodal and bihemispheric montage at 4 mA tDCS strengths. Hypothesis: Bihemispheric tDCS montage induces more cortical excitability on the lesional hemisphere. Methods: Eighteen aging stroke patients with unilateral ischemic stroke of 6 or more months and inducible motor evoked potentials (MEP) underwent 3 sessions of 30 minutes 4 mA tDCS combined with occupational therapy. Each session was at least 2 days apart and consisted of one of the 3 different montages: anodal (Anode: lesional C3/C4, Cathode: non-lesional FP1/FP2), cathodal (Anode: lesional FP1/FP2, Cathode: non-lesional C3/C4), or bihemispheric (Anode: lesional C3/C4, Cathode: non-lesional C3/C4). We collected MEP size, short intracortical inhibition (SICI, 3 ms) and intracortical facilitation (ICF, 15 ms) on bilateral abductor pollicis brevis (APB) muscles using single or paired pulse TMS at 5 timepoints (baseline and four post-tDCS 12 minutes apart sessions). Results: All 18 subjects had comparable resting motor threshold (rMT) across 3 montages (see A). Bihemispheric tDCS montage offered significantly larger peak-to-peak MEP responses on the lesioned cortex (ANOVA, F=8.97, P&lt;0.01) but not on the non-lesioned cortex (ANOVA, F=0.86, P=0.42). These differences were apparent in single pulse, SICI and ICF (see B). Conclusion: Our findings support that bihemispheric montage is better suited in post-stroke motor recovery tDCS applications.

Effects of Bihemispheric Transcranial Direct Current Stimulation on Upper Extremity Function in Stroke Patients: A randomized Double-Blind Sham-Controlled Study

Background and PurposeTranscranial direct current stimulation (tDCS) is a treatment used in the rehabilitation of stroke patients aiming to improve functionality of the plegic upper extremity. Currently, tDCS is not routinely used in post stroke rehabilitation. The aim of this study was to establish the effects of bihemspheric tDCS combined with physical therapy (PT) and occupational therapy (OT) on upper extremity motor function. MethodsThirty-two stroke inpatients were randomised into 2 groups. All patients received 15 sessions of conventional upper extremity PT and OT over 3 weeks. The tDCS group (n = 16) also received 30 minutes of bihemispheric tDCS and the sham group (n = 16) 30 minutes of sham bihemispheric tDCS simultaneously to OT. Patients were evaluated before and after treatment using the Fugl Meyer upper extremity (FMUE), functional independence measure (FIM), and Brunnstrom stages of stroke recovery (BSSR) by a physiatrist blind to the treatment group ResultsThe improvement in FIM was higher in the tDCS group compared to the sham group (P = .001). There was a significant within group improvement in FMUE, FIM and BSSR in those receiving tDCS (P = .001). There was a significant improvement in FIM in the chronic (> 6months) stroke sufferers who received tDCS when compared to those who received sham tDCS and when compared to subacute stroke (3-6 months) sufferers who received tDCS/sham. ConclusionsUpper extremity motor function in hemiplegic stroke patients improves when bihemispheric tDCS is used alongside conventional PT and OT. The improvement in functionality is greater in chronic stroke patients.

Acute effects of bi-hemispheric transcranial direct current stimulation on the neuromuscular function of patients with chronic stroke: A randomized controlled study

BackgroundMuscle weakness in patients with chronic stroke is due to neuromuscular disorders such as muscle atrophy, loss of voluntary activation or weak muscle contractile properties which are majored by the imbalance of interhemispheric inhibition following stroke. In patients with chronic stroke, unilateral transcranial direct current stimulation improved the maximal isometric strength of paretic knee extensors, but bilateral transcranial direct current stimulation failed to improve concentric strength. This study aimed to assess if a bilateral current stimulation improves isometric maximal strength, voluntary activation and contractile properties of knee extensors in patients with chronic stroke. MethodsThirteen patients with chronic stroke and eight young healthy individuals participated in this randomized, simple-blinded, crossover study that included two experimental sessions: one with sham bilateral transcranial direct current stimulation and another with effective bilateral transcranial direct current stimulation (20 min, 2 mA). In the stroke patients, the anode was placed over the primary motor cortex of the affected hemisphere and the cathode over the contralateral primary motor cortex. In healthy participants, the brain side targeted by the anode and the cathode was randomly assigned. In each session, participants performed three assessments of strength, voluntary activation and contractile properties: before, during and after effective/sham bilateral transcranial direct current stimulation. FindingsBilateral transcranial direct current stimulation had no effect on any neuromuscular assessments in both groups (All P values > 0.05, partial eta-squares varied from 0.02 to 0.06). InterpretationA single session of bilateral transcranial direct current stimulation did not compensate muscular weakness of knee extensors in patients with chronic stroke.

Cooperation Not Competition: Bihemispheric tDCS and fMRI Show Role for Ipsilateral Hemisphere in Motor Learning.

What is the role of ipsilateral motor and premotor areas in motor learning? One view is that ipsilateral activity suppresses contralateral motor cortex and, accordingly, that inhibiting ipsilateral regions can improve motor learning. Alternatively, the ipsilateral motor cortex may play an active role in the control and/or learning of unilateral hand movements. We approached this question by applying double-blind bihemispheric transcranial direct current stimulation (tDCS) over both contralateral and ipsilateral motor cortex in a between-group design during 4 d of unimanual explicit sequence training in human participants. Independently of whether the anode was placed over contralateral or ipsilateral motor cortex, bihemispheric stimulation yielded substantial performance gains relative to unihemispheric or sham stimulation. This performance advantage appeared to be supported by plastic changes in both hemispheres. First, we found that behavioral advantages generalized strongly to the untrained hand, suggesting that tDCS strengthened effector-independent representations. Second, functional imaging during speed-matched execution of trained sequences conducted 48 h after training revealed sustained, polarity-independent increases in activity in both motor cortices relative to the sham group. These results suggest a cooperative rather than competitive interaction of the two motor cortices during skill learning and suggest that bihemispheric brain stimulation during unimanual skill learning may be beneficial because it harnesses plasticity in the ipsilateral hemisphere.SIGNIFICANCE STATEMENT Many neurorehabilitation approaches are based on the idea that is beneficial to boost excitability in the contralateral hemisphere while attenuating that of the ipsilateral cortex to reduce interhemispheric inhibition. We observed that bihemispheric transcranial direct current stimulation (tDCS) with the excitatory anode either over contralateral or ipsilateral motor cortex facilitated motor learning nearly twice as strongly as unihemispheric tDCS. These increases in motor learning were accompanied by increases in fMRI activation in both motor cortices that outlasted the stimulation period, as well as increased generalization to the untrained hand. Collectively, our findings suggest a cooperative rather than a competitive role of the hemispheres and imply that it is most beneficial to harness plasticity in both hemispheres in neurorehabilitation of motor deficits.

Effector-independent reduction in choice reaction time following bi-hemispheric transcranial direct current stimulation over motor cortex.

Increased reaction times (RT) during choice-RT tasks stem from a requirement for additional processing as well as reduced motor-specific preparatory activation. Transcranial direct current stimulation (tDCS) can modulate primary motor cortex excitability, increasing (anodal stimulation) or decreasing (cathodal stimulation) excitability in underlying cortical tissue. The present study investigated whether lateralized differences in choice-RT would result from the concurrent modulation of left and right motor cortices using bi-hemispheric tDCS. Participants completed a choice-RT task requiring either a left or right wrist extension. In forced-choice trials an illuminated target indicated the required response, whereas in free-choice trials participants freely selected either response upon illumination of a central fixation. Following a pre-test trial block, offline bi-hemispheric tDCS (1 mA) was applied over the left and right motor cortices for 10 minutes, which was followed by a post-tDCS block of RT trials. Twelve participants completed three experimental sessions, two with real tDCS (anode right, anode left), as well as a sham tDCS session. Post-tDCS results showed faster RTs for both right and left responses irrespective of tDCS polarity during forced-choice trials, while sham tDCS had no effect. In contrast, no stimulation-related RT or response selection differences were observed in free-choice trials. The present study shows evidence of an effector-independent speeding of response initiation in a forced-choice RT task following bi-hemispheric tDCS and yields novel information regarding the functional effect of bi-hemispheric tDCS.

P040 Restoration of abnormal muscular cramping in musicians’ dystonia through bihemispheric transcranial direct current stimulation and bimanual motor retraining

Question Task-specific focal dystonia (TSFD) is typically characterized by involuntary and abnormal muscular cramping, which compromises fine motor control. Previous neurophysiological studies have identified loss of inhibitory control at the motor cortex as a possible pathophysiology of the dystonic cramping. A recent study demonstrated that bi-hemispheric transcranial direct current stimulation (tDCS) over the motor cortices during performing bimanual mirrored finger movements ameliorated impairment of dexterous finger movements in pianists with TSFD. However, little has been uncovered about its underlying neurophysiological mechanism. Here we tested a hypothesis that the bi-hemispheric tDCS with motor retraining normalizes abnormal co-contraction between antagonistic pairs of extrinsic finger muscles in pianists with TSFD. Methods Eight pianists suffering from TSFD at the right hand and eight healthy pianists performed the bimanual mirrored finger movements for twenty-four minutes with two conditions; either with 2 mA tDCS over the motor cortices (cathodal over the left and anodal over the right) for twenty-four minutes (real condition) or thirty seconds (sham condition). Results The results demonstrated changes in pattern of muscular co-contraction only following the real stimulation condition, in which tonic activity turned into more phasic pattern. In addition, the amount of muscular co-contraction was significantly decreased after the real stimulation in the patients, which was the case neither at the sham condition of the patients nor at both conditions of the healthy controls. Conclusions The results provide physiological evidences of restoration of both abnormal pattern and amount of muscular co-activation of musicians’ dystonia through the bi-hemispheric tDCS with bimanual motor retraining.

Neural correlates of unihemispheric and bihemispheric motor cortex stimulation in healthy young adults

Bihemispheric non-invasive motor cortex stimulation has shown promise for facilitating motor learning and recovery after stroke. However, previous studies yielded mixed results that can primarily be attributed to inter-individual variability in response. We therefore aimed at investigating neural correlates of bihemispheric transcranial direct current stimulation (tDCS) effects using multimodal magnetic resonance imaging (MRI). Twenty-four young healthy adults underwent diffusion tensor imaging (DTI), resting state and task-related functional MRI in a randomized sham-controlled, double-blind study using a triple cross-over design. We compared two active stimulation conditions—bihemispheric (or “dual”) and unihemispheric anodal tDCS—with sham tDCS. The anode was placed over the left primary motor cortex in all conditions, and subgroups of responders were defined according to task-related activity in this area while subjects pressed a response button with their right index fingers during a choice reaction time task. Compared to sham, “dual responders” and “anodal responders” were characterized by mean beta value increases of 86±55% and 126±55%, respectively. In line with electrophysiological studies, tDCS effects on motor cortex activation appeared to be highly variable across the group. At rest, dual tDCS caused widespread bihemispheric alterations of functional connectivity, possibly mediating its most striking effect, which consisted of bilateral motor cortex disinhibition during the task-related functional MRI. In contrast, unihemispheric anodal tDCS was characterized by more local modulations of functional motor networks. As in aging and after stroke, the impact of dual tDCS on the motor system in young adults seems to depend on the microstructural status of transcallosal motor tracts as well. In sum, these results shed light on the neural correlates of dual and anodal tDCS effects in young adults and help in explaining the great inter-individual variability in response.

Enhanced motor learning with bilateral transcranial direct current stimulation: Impact of polarity or current flow direction?

Bilateral transcranial direct current stimulation (TDCS) is superior to unilateral TDCS when targeting motor learning. This effect could be related to either the current flow direction or additive polarity-specific effects on each hemisphere. This sham-controlled randomized study included fifty right-handed healthy subjects in a parallel-group design who performed an exoskeleton-based motor task of the proximal left arm on three consecutive days. Prior to training, we applied either sham, right anodal (a-TDCS), left cathodal (c-TDCS), concurrent a-TDCS and c-TDCS with two independent current sources and return electrodes (double source (ds)-TDCS) or classical bilateral stimulation (bi-TDCS). Motor performance improved over time for both unilateral (a-TDCS, c-TDCS) and bilateral (bi-TDCS, ds-TDCS) TDCS montages. However, only the two bilateral paradigms led to an improvement of the final motor performance at the end of the training period as compared to the sham condition. There was no difference between the two bilateral stimulation conditions (bi-TDCS, ds-TDCS). Bilateral TDCS is more effective than unilateral stimulation due to its polarity-specific effects on each hemisphere rather than due to its current flow direction. This study is the first systematic evaluation of stimulation polarity and current flow direction of bi-hemispheric motor cortex TDCS on motor learning of proximal upper limb muscles.

Bihemispheric Transcranial Direct Current Stimulation Acutely Improves Strength And Force Steadiness In Post-stroke Hemiparetic Patients

Transcranial direct current stimulation (tDCS) has been applied within rehabilitation programs in post-stroke patients. Two approaches have been used to minimize inter-hemispheric unbalance: cathodal tDCS upon the contralesional hemisphere to reduce inhibition of the ipsilesional hemisphere, and anodal tDCS upon the ipsilesional hemisphere to increase its excitability. PURPOSE: The purpose of present study was to investigate whether bihemisferic tDCS in both ipsilesional and contralesional motor cortex modulate the maximal strength and force steadiness of lower limbs in chronic stroke patients. METHODS: In a double blind, crossover, randomized sham-controlled experimental design, 10 chronic stroke patients performed bilateral knee extension and flexion isokinetic tests at submaximal and maximal workloads [2 sets of 10 repetitions at 50% peak torque and 1 set of 3 reps at 100% peak torque, respectively] with and without bihemispheric tDCS. RESULTS: After tDCS the peak torque increased only for the knee extension in the non-paretic limb (P = 0.008), while no difference was found in the paretic limb (P > 0.05). The force steadiness reflected by the coefficient of variation during the extension phase of the knee extension decreased in tDCS vs. sham condition in both paretic (P = 0.01) and non-paretic limbs (P = 0.04). However, in the knee flexion phase, the coefficient of variation after tDCS decreased only in paretic limb (P = 0.05). CONCLUSION: A single session of bihemispheric tDCS might enhance the maximal strength and force steadiness in chronic stroke patients. These findings warrant additional research to ratify the potential role of bihemispheric tDCS to improve motor performance in stroke patients. Supported by Supported by the Brazilian Council for the Technological and Research Development (CNPq) and Carlos Chagas Foundation for the Research Development in the State of Rio de Janeiro (FAPERJ)

Hemispheric dorsolateral prefrontal cortex lateralization in the regulation of empathy for pain

The dorsolateral prefrontal cortex (DLPFC) is involved in the cognitive appraisal and modulation of the pain experience. In this sham-controlled study, with healthy volunteers, we used bi-hemispheric transcranial direct current stimulation (tDCS) over the DLPFC to assess emotional reactions elicited by pain observation. Left-cathodal/right-anodal tDCS decreased valence and arousal evaluations compared to other tDCS conditions. Compared to sham condition, both left-cathodal/right-anodal and left-anodal/right-cathodal tDCS decreased hostility, sadness and self-pain perception. These decreased sensations after both active tDCS suggest a common role for left and right DLPFC in personal distress modulation. However, the differences in arousal and valence evaluations point to distinct roles of lateralized DLPFC in cognitive empathy, probably through distinct emotion regulation mechanisms.

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

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.

P 171. Bihemispheric motor cortex stimulation in older adults induces modulations of resting state and task-related activity

Bihemispheric transcranial direct current stimulation (“dual” tDCS) of primary motor cortices has been described to enhance motor learning in healthy subjects and to facilitate motor recovery after stroke. In order to investigate the neural correlates of its mode of action, we compared different tDCS montages in a group of healthy older adults in a cross-over design (‘dual’ vs. ‘anodal’ vs. ‘sham’). 20 subjects (mean age 68.7 ± 4.7 years, all right-handed) underwent tDCS and simultaneous MRI at 3T, including resting state fMRI and a choice reaction time task. In the task, subjects were presented with different symbols in a randomized order and required to respond with button presses using either left or right index fingers. In both active stimulation conditions, the anode was placed over left primary motor cortex (M1). The cathode was positioned over right M1 (dual) or the contralateral supraorbital region (anodal). The current was constantly delivered during resting state and task-related fMRI. Task-related fMRI analysis was carried out with SPM8; resting state data were analyzed with Lipsia using low-frequency spectral Eigenvector Centrality Mapping (ECM). Task-specific analyses revealed differential effects of the two active tDCS conditions. Compared with anodal tDCS, dual tDCS yielded stronger activations in bilateral primary motor cortices when either the left or right index fingers were used. In the resting state analysis, ECM values in left prefrontal and cingulate cortices were higher in the dual condition as compared to sham. Anodal yielded higher ECM values in the left prefrontal as well as left ventral premotor cortex when compared with sham; lower values were found in right M1 and the left precuneus. Comparing the two active tDCS conditions, increased connectivity of the cingulate cortex and decreased connectivity in the right cerebellum was found under dual compared to anodal tDCS (all p < .001, Monte Carlo-corrected). In conclusion, tDCS induced specific changes of M1 activation in task-specific activations, dependent on the electrode set-up. As a complement, the resting state analysis demonstrated altered connectivity within a multimodal network including motor cortices as well as prefrontal regions, indicating that the previously documented stronger behavioral effects of dual as compared to anodal tDCS may not be merely mediated by a “simple” add-on effect of cathodal stimulation, but rather due to complex bihemispheric network modulations.

Differential Effects of Dual and Unihemispheric Motor Cortex Stimulation in Older Adults

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.