  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.
