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.

Anatomically plausible networks of functionally inter-connected regions have been reliably demonstrated at rest, although the neurochemical basis of these ‘resting state networks’ is not well understood. In this study, we combined magnetic resonance spectroscopy (MRS) and resting state fMRI and demonstrated an inverse relationship between levels of the inhibitory neurotransmitter GABA within the primary motor cortex (M1) and the strength of functional connectivity across the resting motor network. This relationship was both neurochemically and anatomically specific. We then went on to show that anodal transcranial direct current stimulation (tDCS), an intervention previously shown to decrease GABA levels within M1, increased resting motor network connectivity. We therefore suggest that network-level functional connectivity within the motor system is related to the degree of inhibition in M1, a major node within the motor network, a finding in line with converging evidence from both simulation and empirical studies.DOI: http://dx.doi.org/10.7554/eLife.01465.001