Motivational Tuning of Fronto-Subthalamic Connectivity Facilitates Control of Action Impulses

Abstract

It is critical for survival to quickly respond to environmental stimuli with the most appropriate action. This task becomes most challenging when response tendencies induced by relevant and irrelevant stimulus features are in conflict, and have to be resolved in real time. Inputs from the pre-supplementary motor area (pre-SMA) and inferior frontal gyrus (IFG) to the subthalamic nucleus (STN) are thought to support this function, but the connectivity and causality of these regions in calibrating motor control has not been delineated. In this study, we combined off-line noninvasive brain stimulation and functional magnetic resonance imaging, while young healthy human participants performed a modified version of the Simon task. We show that impairing pre-SMA function by noninvasive brain stimulation improved control over impulsive response tendencies, but only when participants were explicitly rewarded for fast and accurate responses. These effects were mediated by enhanced activation and connectivity of the IFG-STN pathway. These results provide causal evidence for a pivotal role of the IFG-STN pathway during action control. Additionally, they suggest a parallel rather than hierarchical organization of the pre-SMA-STN and IFG-STN pathways, since interruption of pre-SMA function can enhance IFG-STN connectivity and improve control over inappropriate responses.

Theta burst magnetic stimulation over the pre-supplementary motor area improves motor inhibition

“…Imaging suggested that the pre-SMA is part of the brain "inhibitory network" [3,8,10,11,34] and here we provide direct 'causal' evidence to indicate that the pre-SMA is a structure with a primarily inhibitory function. Amongst the various processes by which the pre-SMA is considered to exert top-down control [34][35][36][37], our results suggest a predominant role in reactive motor inhibition, without a significant contribution to conflict resolution (see next section for interpretation).…”

“…It appears that experimental manipulation of its normal activity by means of brain stimulation alters the functioning of the right hemispheric inhibitory network, but based on our behavioural results and combined TMS and imaging data [8,10,11], it seems that the brain adapts to this 'perturbation' of the right hemispheric inhibitory network in such a way that motor inhibition improves. The seemingly 'paradoxical' enhancement of motor inhibition may be related to compensation from distant sites with connectivity to the right pre-SMA across the left hemisphere network (i.e.…”

“…This interpretation is supported by results showing increased activity following TMS over homologous regions in the left hemisphere "inhibitory network". After 1Hz rTMS of the pre-SMA, connectivity between the left IFG and STN was strengthened [10]. Similarly, the left pre-SMA showed increased activation following TMS over the right pre-SMA and new functional connections linked the left IFG with the left pre-SMA [8].…”

“…Similarly, the findings with regard to the effects of rTMS over the pre-SMA are also inconsistent, as improved [8,10,11] but also impaired inhibition [21] have been reported, while others noted involvement of the pre-SMA in conflict resolution [13].…”

“…Subsequent studies [8,10,11] using transcranial magnetic stimulation (TMS) and imaging show direct involvement of the pre-SMA in inhibition, although its involvement in related functions of action monitoring [12] and conflict resolution during action selection [13] have also been proposed.…”