The role of GABA in semantic memory and its neuroplasticity

Abstract

A fundamental challenge in neuroscience is understanding neural functioning and plasticity of the brain. The anterior temporal lobe (ATL) is a hub for semantic memory, which generates coherent conceptual representations. GABAergic inhibition plays a crucial role in shaping human cognition and plasticity, but it is unclear how this inhibition relates to human semantic memory and its plasticity. Here, we employed a combination of continuous theta burst stimulation (cTBS), MR spectroscopy and fMRI to investigate the role of GABA in semantic memory and its neuroplasticity. We found that inhibitory cTBS increased GABA concentrations in the ATL and reduced blood-oxygen level-dependent (BOLD) activation during semantic tasks. Crucially, changes in GABA were tightly linked to changes in regional activity, suggesting that GABA mediates cTBS-induced plasticity. Individuals with better semantic performance exhibited selective activity in the ATL, attributable to higher GABA levels, which can sharpen distributed semantic representations. Our results revealed a non-linear, inverted-U-shape relationship between GABA levels in the ATL and semantic performance, thus offering an explanation for the individual differences in semantic memory function and neuromodulation outcomes. These findings offer a neurochemical explanation for individual variability in neuromodulation and provide insights for developing targeted interventions for semantic impairments.