Motor cortex excitability and inhibitory imbalance in autism spectrum disorder assessed with transcranial magnetic stimulation: a systematic review

Cortical excitation/inhibition (E/I) imbalances contribute to various clinical symptoms observed in autism spectrum disorder (ASD). However, the detailed pathophysiologic underpinning of E/I imbalance remains uncertain. Transcranial magnetic stimulation (TMS) motor-evoked potentials (MEP) are a non-invasive tool for examining cortical inhibition in ASD. Here, we conducted a systematic review on TMS neurophysiology in motor cortex (M1) such as MEPs and short-interval intracortical inhibition (SICI) between individuals with ASD and controls. Out of 538 initial records, we identified six articles. Five studies measured MEP, where four studies measured SICI. There were no differences in MEP amplitudes between the two groups, whereas SICI was likely to be reduced in individuals with ASD compared with controls. Notably, SICI largely reflects GABA(A) receptor-mediated function. Conversely, other magnetic resonance spectroscopy and postmortem methodologies assess GABA levels. The present review demonstrated that there may be neurophysiological deficits in GABA receptor-mediated function in ASD. In conclusion, reduced GABAergic function in the neural circuits could underlie the E/I imbalance in ASD, which may be related to the pathophysiology of clinical symptoms of ASD. Therefore, a novel treatment that targets the neural circuits related to GABA(A) receptor-mediated function in regions involved in the pathophysiology of ASD may be promising.