Whether transcranial direct current stimulation (tDCS) benefits stroke rehabilitation remains unclear. To investigate how tDCS reorganizes brain circuitry, nineteen post-stroke patients underwent rehabilitation sessions with bi-hemispheric real vs sham tDCS intervention. Resting motor threshold measurements showed tDCS evoked higher excitability in the motor cortex that enhanced the descending conduction from the lesioned primary motor cortex to the target hand muscle. Granger causality analysis further revealed brain circuitry rewiring among the lesioned cerebellum, premotor, and primary motor cortex in the tDCS group compared to the sham owing to the newly formed connections close to the anodal electrode. Rebuilding of these critical pathways was clear via the increase of event related desynchronisation (ERD) and white matter integrity in the same lesioned region. Furthermore, only the tDCS group demonstrated a positive recovery trend in the penumbra regions by the longitudinal functional magnetic resonance imaging (fMRI) analysis. To interpret tDCS mechanism, we introduce a polarized gamma-aminobutyric acid (GABA) theory, where GABAA receptor activity depends on the orientation of dipolar GABA that can be manipulated by tDCS field. Results suggest that tDCS intervention lowers motor excitability via re-orienting GABA, leading to reorganization of the lesioned cortical network, and the motor descending pathway, finally the recovery of motor function.
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