Dissociating the role of the pre-SMA in response inhibition and switching: a combined online and offline TMS approach

The pre-supplementary motor area (pre-SMA) is considered to be a key node in the cognitive control of actions that require rapid updating, inhibition, or switching, as well as working memory. It is now recognized that the pre-SMA is part of a 'cognitive control' network involving the inferior frontal gyrus (IFG) and subcortical regions, such as the striatum and subthalamic nucleus. However, two important questions remain to be addressed. First, it is not clear if the main role of the pre-SMA in cognitive control lies in inhibition or switching of actions. From imaging evidence, the right pre-SMA is consistently recruited during inhibition and switching, but the extent to which it participates specifically in either of these processes is unknown. Secondly, the pre-SMA may perform inhibition and switching alone or as part of a larger brain network. The present study used online and offline transcranial magnetic stimulation (TMS) to dissociate the roles of pre-SMA in cognitive control, but also to investigate the potential contribution of connectivity between the pre-SMA and IFG. We applied continuous theta burst stimulation (cTBS) over the right IFG before participants performed a stop switching task while receiving single TMS pulses over the right pre-SMA. The results were compared to a sham cTBS session and pulses applied over the vertex region. Significant worsening of inhibition as well as response adaptation during inhibition was found when applying pulses over the pre-SMA. However, no such worsening was observed in switch trials. Additionally, after cTBS over the IFG, inhibition was also delayed, suggesting its critical necessity in stopping of actions. The results reveal a key contribution of the pre-SMA in inhibition and could suggest a dissociative role in the switching of actions. These findings indicate there is an essential union between IFG and pre-SMA during inhibition