Mechanisms underlying long-interval cortical inhibition in the human motor cortex: a TMS-EEG study

Long-interval cortical inhibition (LICI) refers to suppression of neuronal activity following paired-pulse transcranial magnetic stimulation (TMS) with interstimulus intervals (ISIs) between 50 and 200 ms. LICI can be measured either from motor-evoked potentials (MEPs) in small hand muscles or directly from the cortex using concurrent electroencephalography (EEG). However, it remains unclear whether EEG inhibition reflects similar mechanisms to MEP inhibition. Eight healthy participants received single- and paired-pulse TMS (ISI = 100 ms) over the motor cortex. MEPs were measured from a small hand muscle (first dorsal interosseus), whereas early (P30, P60) and late (N100) TMS-evoked cortical potentials (TEPs) were measured over the motor cortex using EEG. Conditioning and test TMS intensities were altered, and modulation of LICI strength was measured using both methods. LICI of MEPs and both P30 and P60 TEPs increased in strength with increasing conditioning intensities and decreased with increasing test intensities. LICI of N100 TEPs remained unchanged across all conditions. In addition, MEP and P30 LICI strength correlated with the slope of the N100 evoked by the conditioning pulse. LICI of early and late TEP components was differentially modulated with altered TMS intensities, suggesting independent underlying mechanisms. LICI of P30 is consistent with inhibition of cortical excitation similar to MEPs, whereas LICI of N100 may reflect presynaptic autoinhibition of inhibitory interneurons. The N100 evoked by the conditioning pulse is consistent with the mechanism responsible for LICI, most likely GABAB-mediated inhibition of cortical activity.