Enhancing Human Action Inhibition Through Cortico–Cortical Paired Associative Stimulation

Reactive inhibition is crucial for preventing inappropriate actions, and impairments in this ability are common in various disorders, with the underlying neural mechanisms poorly understood. To explore the neural dynamics of such an ability, we used a novel transcranial magnetic stimulation (TMS) protocol, cortico-cortical paired associative stimulation (ccPAS), to induce Hebbian spike-timing-dependent plasticity (STDP). Our goal was to investigate the functional relevance of key brain regions in the action inhibition network (AIN). Healthy participants underwent ccPAS targeting functional connectivity between AIN regions: pre/supplementary motor area (preSMA/SMA) to the left motor cortex (lM1), right inferior frontal gyrus (rIFG) to lM1, or right M1 (rM1) to lM1. Participants completed a stop signal task (SST) before and after ccPAS stimulation. Motor evoked potentials (MEP) were recorded during ccPAS to assess network plasticity, and resting motor threshold (rMT) was measured for global motor excitability. Reactive inhibition improved selectively in the preSMA/SMA-lM1 group, with MEPs increasing after preSMA/SMA-lM1 and rM1-lM1 stimulation, suggesting facilitatory modulations. rMT correlated with behavioral improvement in the preSMA/SMA group. These findings demonstrate that ccPAS improved reactive inhibition, enhancing plasticity between preSMA/SMA and lM1, providing insights into the AIN's functional mechanism.