Background: Dual 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. Methods: We 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 movementrelated cortical oscillations before and immediately after tDCS. Results: Stroke 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.

Background Bihemispheric 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. Methods We 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. Results Twenty-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). Conclusions Bihemispheric 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).

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Introduction: Non-invasive transcranial direct current stimulation (tDCS) can induce polarity-specific changes in cortical excitability. Compared to unilateral anodal tDCS over the non-dominant motor cortex (M1), dual-hemispheric tDCS to the M1 may further accelerate motor reaction of the target hand and alter excitability of the corticospinal tract (CST). However, the effects and individual variability of bi-hemispheric tDCS to the M1 during motor training remain largely unclear in healthy and stroke subjects. Purpose: We assessed the hypothesis that bi-hemispheric tDCS during single-session motor training alter inter-hemispheric inhibition, CST excitability and bilateral cortical oscillations. Methods: We enrolled first-time, unilateral ischemic stroke patients between two and four weeks after stroke and matched healthy controls. They were subjected to two 20 min-sessions of dual-hemispheric tDCS (anode over non-dominant or ipsilesional M1, cathode over dominant or contralesional M1; 2mA for 20 mins) and sham tDCS (2mA for 2 mins) in a randomized crossover design during repetitive extension of the non-dominant or paretic extensor carpi radialis muscle. We compared the post-stimulation changes of motor evoked potentials (MEPs), ipsilateral silent period (iSP), short interval intracoritcal inhibition (SICI), as well as resting and unilateral finger lifting-related cortical oscillations by magnetoencephalography (MEG). Results: Compared to the sham tDCS, the dual-hemispheric tDCS significantly increased MEP amplitudes and reduced SICI at the anodal-stimulated M1, as well as decreased inter-hemispheric inhibition from the cathodal-stimulated M1 with shortened iSP for about 30 mins in healthy controls (n=8). In contrast, reduced MEP amplitudes were observed at the cathodal-stimulated M1. The tDCS effects on cortical oscillations and in stroke patients are currently under investigation. Conclusions: Task-concurrent dual tDCS may enhance activity-dependent motor plasticity in subacute stroke.