Non-technical summaryInter-individual differences in regional GABA as assessed by magnetic resonance spectroscopy (MRS) relate to behavioural variation in humans. However, it is not clear what the relationship is between MRS measures of the concentration of neurotransmitters in a region and synaptic activity. Transcranial magnetic stimulation (TMS) techniques provide physiological measures of cortical excitation or inhibition. Here, we investigated the relationship between MRS and TMS measures of glutamatergic and GABAergic activity within the same individuals. We demonstrated a relationship between MRS-assessed glutamate levels and a TMS measure of global cortical excitability, suggesting that MRS measures of glutamate do reflect glutamatergic activity. However, there was no clear relationship between MRS-assessed GABA levels and TMS measures of synaptic GABAA or GABAB activity. A relationship was found between MRS-assessed GABA and a TMS protocol with less clearly understood physiological underpinnings. We speculate that this protocol may therefore reflect extrasynaptic GABA tone.

Anodal transcranial direct current stimulation (tDCS) can boost the effects of motor training and facilitate plasticity in the healthy brain. Motor rehabilitation depends on learning and plasticity, and motor learning can occur after stroke. Here, we tested whether brain stimulation using anodal tDCS added to motor training could improve rehabilitation outcomes in patients after stroke. We performed a randomized, controlled trial in 24 patients at least 6 months after a first unilateral stroke not directly involving the primary motor cortex. Patients received either anodal tDCS (n=11) or sham treatment (n=13) paired with daily motor training for 9 days. We observed improvements that persisted for at least 3 months post-intervention after anodal tDCS but not sham treatment on the Action Research Arm Test (ARAT) and Wolf Motor Function Test (WMFT) but not on the Fugl-Meyer upper extremity score (UEFM). Functional MRI showed increased activity during movement of the affected hand in the ipsilesional motor and premotor cortex in the anodal tDCS group compared to the sham treatment group. Structural MRI revealed intervention-related increases in gray matter volume in cortical areas including ipsilesional motor and premotor cortex after anodal tDCS but not sham treatment. The addition of ipsilesional anodal tDCS to a 9-day motor training program improved long-term clinical outcomes relative to sham treatment in patients after stroke.