Changes in motor cortex GABA in children with perinatal stroke after transcranial direct current stimulation and intensive motor rehabilitation

Introduction Perinatal stroke (PS) often damages the motor system, leading to hemiparetic cerebral palsy. Current treatment is limited to rehabilitation therapy, but non-invasive brain stimulation is a promising adjuvant. Magnetic resonance spectroscopy (MRS) has demonstrated motor cortex metabolite level differences in PS but the effects of therapy and neuromodulation on γ-aminobutyric acid (GABA) levels are unknown. We aim to determine if GABA is altered in bilateral primary motor cortex (M1) of children with PS, and how levels change following transcranial direct current stimulation (tDCS) and motor therapy interventions. Methods Participants (6-18 yrs) with PS and hemiparesis were recruited to the Stimulation for Perinatal Stroke Optimizing Recovery Trajectories (SPORT) trial. Participants attended a 10-day camp and were randomized to receive active or sham cathodal tDCS over non-lesioned M1. At baseline, 1-week post-camp, and 6-month follow-up, MRI was performed, and motor function was assessed. Task-fMRI localized bilateral M1 for MRS voxel placement. GABA-edited MEGA-PRESS quantified GABA+ levels. Results Forty-nine participants were included. Motor function increased for all groups (p<0.001). At baseline, GABA+ was lower in the lesioned hemisphere and lesioned M1 GABA+ was positively associated with subjective motor function measures. Interhemispheric differences in GABA+ equalized by 6 months. No effect of therapy or tDCS on GABA+ was observed. Discussion M1 GABA levels are altered in children with PS but do not appear to change with intensive motor learning or tDCS. MRS measures of neurochemical changes may inform mechanisms of interventional plasticity in children with disabilities.