Response inhibition activates distinct motor cortical inhibitory processes.

We routinely cancel preplanned movements that are no longer required. If stopping is forewarned, proactive processes are engaged to selectively decrease motor cortex excitability. However, without advance information there is a nonselective reduction in motor cortical excitability. In this study we examined modulation of human primary motor cortex inhibitory networks during response inhibition tasks with informative and uninformative cues using paired-pulse transcranial magnetic stimulation. Long- (LICI) and short-interval intracortical inhibition (SICI), indicative of GABA- and GABA-receptor mediated inhibition, respectively, were examined from motor evoked potentials obtained in task-relevant and task-irrelevant hand muscles when response inhibition was preceded by informative and uninformative cues. When the participants (10 men and 8 women) were cued to stop only a subcomponent of the bimanual response, the remaining response was delayed, and the extent of delay was greatest in the more reactive context, when cues were uninformative. For LICI, inhibition was reduced in both muscles during all types of response inhibition trials compared with the pre-task resting baseline. When cues were uninformative and left-hand responses were suddenly canceled, task-relevant LICI positively correlated with response times of the responding right hand. In trials where left-hand responding was highly probable or known (informative cues), task-relevant SICI was reduced compared with that when cued to rest, revealing a motor set indicative of responding. These novel findings indicate that the GABA-receptor-mediated pathway may set a default inhibitory tone according to task context, whereas the GABA-receptor-mediated pathways are recruited proactively with response certainty. NEW & NOTEWORTHY We examined how informative and uninformative cues that trigger both proactive and reactive processes modulate GABAergic inhibitory networks within human primary motor cortex. We show that GABA inhibition was released during the task regardless of cue type, whereas GABA inhibition was reduced when responding was highly probable or known compared with rest. GABA-receptor-mediated inhibition may set a default inhibitory tone, whereas GABA circuits may be modulated proactively according to response certainty.