Modulating regional motor cortical excitability with non-invasive brain stimulation results in neurochemical changes in bilateral motor cortices

Learning a novel motor skill is dependent both on regional changes within the primary motor cortex (M1) contralateral to the active hand, and also on modulation between and within anatomically-distant but functionally-connected brain regions. Inter-regional changes are particularly important in functional recovery after stroke, where critical plastic changes underpinning behavioural improvements are observed in both ipsilesional and contralesional M1s. It is increasingly understood that reduction in γ-aminobutyric acid (GABA) in the contralateral M1 is necessary to allow learning of a motor task. However, the physiological mechanisms underpinning plasticity within other brain regions, most importantly the ipsilateral M1, are not well understood. Here, we used concurrent two-voxel magnetic resonance spectroscopy (MRS) to simultaneously quantify changes in neurochemicals within left and right M1s, in healthy humans of both sexes, in response to transcranial direct current stimulation (tDCS) applied to left M1. We demonstrated a decrease in GABA in both the stimulated (left) and non-stimulated (right) M1 after anodal tDCS, whereas a decrease in GABA was only observed in non-stimulated M1 after cathodal stimulation. This GABA decrease in the non-stimulated M1 during cathodal tDCS was negatively correlated with microstructure of M1:M1 callosal fibres, as quantified by diffusion MRI, suggesting that structural features of these fibres may mediate GABA decrease in the unstimulated region. We found no significant changes in glutamate. Taken together, these findings shed light on interactions between the two major network nodes underpinning motor plasticity, offering a potential framework from which to optimise future interventions to improve motor function after stroke.