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Background and Objective: We aim to assess the cortical excitability under three montages with single session of transcranial direct current stimulation (tDCS) at 4 mA on ischemic stroke patients. Methods: Adult subjects with first-ever unilateral ischemic stroke ≥6 months and inducible motor evoked potentials (MEP) underwent 3 sessions (washed out ≥2 days apart) of 30 minutes 4 mA tDCS in anodal, cathodal or bihemispheric montage (in pseudorandom order) combined with t upper extremity repetitive task training administered by an Occupational Therapist. We collected MEP responses to transcranial magnetic stimulation (TMS) single pulse, short intracortical inhibition (SICI, 3 ms) and intracortical facilitation (ICF, 15 ms) on bilateral abductor pollicis brevis (APB) muscles at baseline and four post-stimulation timepoints 12 minutes apart. We also monitored safety by recording adverse events, surveying subjects with a questionnaire on tolerability issues and collecting biometric measures (body resistance, skin temperature under the tDCS electrode). Results: Eighteen subjects completed 54 tDCS sessions in total. We observed montage ( P P P >0.949) suggested sufficient washout interval across the visits. No subjects experienced any adverse events. Biometric measures and tolerability were comparable across the three montages. The most common tolerability issue was transient redness under the tDCS electrodes (70% at anode, 48% at cathode). Conclusions: The bihemispheric montage increased ipsilateral cortical excitability the most in a single session of 4 mA tDCS in chronic ischemic stroke patients. Additionally, a current level of 4 mA is safe and tolerable over multiple sessions.

Introduction: By the proof of concept, a phase I tDCS current escalation safety study established the safety and tolerability of up to 4 mA with single session application in ischemic stroke patients; however, the sample size is relatively small with only 3 subjects received 4 mA dose in the 3+3 design. We aim to further investigate the safety and tolerability of tDCS at 4 mA currents with multiple sessions. Hypothesis: tDCS in 4 mA strength is safe and tolerable in three montage conditions (anodal, cathodal and bihemispheric) Methods: Eighteen aging stroke patients underwent 3 sessions of 4 mA tDCS that are at least 2 days apart: 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 monitored safety by looking for any adverse event (AE) or serious adverse event (SAE). We measured tolerability using questionnaire/examination. We implemented biometric monitoring (body resistance, skin temperature at tDCS application sites) to ensure the patient safety. Results: All 18 patients completed all 54 sessions of tDCS (3 sessions per subject) without any adverse event or serious adverse event. Per Questionnaire, the most common tolerability issue was transient redness at tDCS application sites (70% at anode, 48% at cathode, see A). Body resistance was comparable across montages and skin temperature was below body temperature in all tDCS sessions (see B). Conclusion: Our findings provide further evidence that tDCS at 4 mA is safe and tolerable. The efficacy of 4 mA tDCS is being investigated by NIH StrokeNet-funded study called TRANSPORT2.

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 Conclusion: Our findings support that bihemispheric montage is better suited in post-stroke motor recovery tDCS applications.