GABA Modulates Frequency-Dependent Plasticity in Humans

Frequency-dependent reorganization of the primary somatosensory cortex, together with perceptual changes, arises following repetitive sensory stimulation. Here, we investigate the role of GABA in this process. We co-stimulated two finger tips and measured GABA and Glx using magnetic resonance (MR) spectroscopy at the beginning and end of the stimulation. Participants performed a perceptual learning task before and after stimulation. There were 2 sessions with stimulation frequency either at or above the resonance frequency of the primary somatosensory cortex (23 and 39 Hz, respectively). Perceptual learning occurred following above resonance stimulation only, while GABA reduced during this condition. Lower levels of early GABA were associated with greater perceptual learning. One possible mechanism underlying this finding is that cortical disinhibition "unmasks" lateral connections within the cortex to permit adaptation to the sensory environment. These results provide evidence in humans for a frequency-dependent inhibitory mechanism underlying learning and suggest a mechanism-based approach for optimizing neurostimulation frequency.