Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex

Non-technical summary Inter-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.