Using TMS-EEG to study the intricate interplay between GABAergic inhibition and glutamatergic excitation during reactive and proactive motor inhibition

Transcranial magnetic stimulation (TMS) studies have provided insight into the neurotransmission underlying motor inhibition but are limited to the primary motor cortex (M1). To investigate {gamma}-aminobutyric acid (GABA) and glutamatergic neurotransmission across the broader motor inhibition network, we combined TMS with electroencephalography (EEG). The N45 and N100 components of the TMS-evoked potentials (TEPs) have been liked to GABAa and GABAb signaling, respectively, whereas the N15, P30 and P60 TEPs are believed to reflect glutamatergic neurotransmission. This study investigates how these components are modulated during reactive and proactive motor inhibition. Twenty-four healthy participants completed two TMS-EEG sessions targeting either the left M1 or the pre-supplementary motor area (preSMA) at rest and during a stop-signal task. We compared TEP amplitudes across TMS conditions (active/sham) and trial types and assessed their relationship with task performance. Participants with a higher N45 amplitude over M1 at rest demonstrated a faster stop-signal reaction time. Active TMS during successful motor inhibition evoked higher N15 amplitudes over preSMA than during uncertain go trials, suggesting that an early excitatory signal from preSMA is crucial for reactive inhibition. In contrast, proactive inhibition was linked to lower P30 amplitudes in M1, possibly reflecting reduced motor facilitation. These findings provide novel empirical insights into the neurophysiological mechanisms underpinning motor inhibition, emphasizing the importance of a coordinated balance between inhibitory processes in M1 and early glutamatergic excitatory signals from preSMA for effective inhibition.