Response preparation involves a release of intracortical inhibition in task-irrelevant muscles.

Action preparation involves widespread modulation of motor system excitability, but the precise mechanisms are unknown. In this study, we investigated whether intracortical inhibition changes in task-irrelevant muscle representations during action preparation. We used transcranial magnetic stimulation (TMS) combined with electromyography in healthy human adults to measure motor-evoked potentials (MEPs) and cortical silent periods (CSPs) in task-irrelevant muscles during the preparatory period of simple delayed response tasks. In , participants responded with the left index finger in one task condition and the right index finger in another task condition, whereas MEPs and CSPs were measured from the contralateral nonresponding and tonically contracted index finger. During , participants responded with the right pinky finger whereas MEPs and CSPs were measured from the tonically contracted left index finger. In both experiments, MEPs and CSPs were compared between the task preparatory period and a resting intertrial baseline. The CSP duration during response preparation decreased from baseline in every case. A laterality difference was also observed in , with a greater CSP reduction during the preparation of left finger responses compared to right finger responses. Despite reductions in CSP duration, consistent with a release of intracortical inhibition, MEP amplitudes were smaller during action preparation when accounting for background levels of muscle activity, consistent with earlier studies that reported decreased corticospinal excitability. These findings indicate that intracortical inhibition associated with task-irrelevant muscles is transiently released during action preparation and implicate a novel mechanism for the controlled and coordinated release of motor cortex inhibition. In this study, we observed the first evidence of a release of intracortical inhibition in task-irrelevant muscle representations during response preparation. We applied transcranial magnetic stimulation to elicit cortical silent periods in task-irrelevant muscles during response preparation, and observed a consistent decrease in the silent period duration relative to a resting baseline. These findings address the question of whether cortical mechanisms underlie widespread modulation in motor excitability during response preparation.