Investigating TMS-EEG Indices of Long-Interval Intracortical Inhibition at Different Interstimulus Intervals

Long-interval intracortical inhibition (LICI) is a transcranial magnetic stimulation (TMS) paradigm that uses paired magnetic stimuli separated by 100-200 ms to investigate the activity of cortical GABAergic interneurons. While commonly applied, the mechanisms contributing to LICI are not well understood, and growing evidence suggests that inhibition observed at different interstimulus intervals (ISI) may involve non-identical processes.

This study aims to utilise combined TMS-EEG to more thoroughly characterise LICI at different ISIs, as the TMS-evoked EEG potential (TEP) can provide more direct insight into the cortical response to stimulation that is not subject to variations in spinal cord excitability that can confound the motor evoked potential (MEP).

In 12 subjects (22.6 ± 0.9 years), LICI was applied using two ISIs of 100 ms (LICI₁₀₀) and 150 ms (LICI₁₅₀), while TEPs were recorded using simultaneous high-definition EEG.

Analysis of EEG data within a region of interest (C3 electrode) showed that test alone stimulation produced three consistent TEP peaks (corresponding to P30, N100 and P180) that were all significantly inhibited following paired-pulse stimulation. However, for P30, inhibition varied between LICI conditions, with reduced amplitude following LICI₁₀₀ (P = 0.03) but not LICI₁₅₀ (P = 0.3). In contrast, the N100 and P180 were significantly reduced by LICI at both intervals (all P-values < 0.05). In addition, topographical analyses suggested that the global change in P30, N40 and P180 differed between LICI conditions.

These findings suggest that LICI₁₀₀ and LICI₁₅₀ reflect complex measurements of cortical inhibition with differential contributions from comparable circuits.