Neurochemical profiles of the anterior temporal lobe predict response of repetitive transcranial magnetic stimulation on semantic processing

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique used to modulate cortical excitability in the human brain. However, one major challenge with rTMS is that the responses to stimulation are highly variable across individuals. The underlying reasons why responses to rTMS are highly variable between individuals still remain unclear. Here, we investigated whether the response to continuous theta-burst stimulation (cTBS) - an effective rTMS protocol for decreasing cortical excitability - is related to individual differences in glutamate and GABA neurotransmission. We acquired resting-state magnetic resonance spectroscopy (MRS) and functional magnetic resonance imaging (fMRI) during semantic processing. Then, we applied cTBS over the anterior temporal lobe (ATL), a hub for semantic representation, to explore the relationship between the baseline neurochemical profiles in this region and the response to cTBS. We found that the baseline excitation-inhibition balance (glutamate + glutamine/GABA ratio) in the ATL was associated with individual cTBS responsiveness during semantic processing. Specifically, individuals with lower excitation-inhibition balance showed stronger inhibitory effect - poorer semantic performance. Our results revealed that non-responders (subjects who did not show an inhibitory effect of cTBS on subsequent semantic performance) had higher excitatory-inhibitory balance in the ATL, which led to up-regulated task-induced regional activity as well as increased ATL-connectivity with other semantic regions compared to responders. These results disclose that the baseline neurochemical state of a cortical region can be a significant factor in predicting responses to cTBS.