The right inferior frontal gyrus as pivotal node and effective regulator of the basal ganglia-thalamocortical response inhibition circuit

Background:The involvement of specific basal ganglia-thalamocortical circuits in response inhibition has been extensively mapped in animal models.However,the pivotal nodes and directed causal regulation within this inhibitory circuit in humans remains con-troversial.Objective:The main aim of the present study was to determine the causal information flow and critical nodes in the basal ganglia-thalamocortical inhibitory circuits and also to examine whether these are modulated by biological factors(i.e.sex)and behavioral performance.Methods:Here,we capitalize on the recent progress in robust and biologically plausible directed causal modeling(DCM-PEB)and a large response inhibition dataset(n=250)acquired with concomitant functional magnetic resonance imaging to determine key nodes,their causal regulation and modulation via biological variables(sex)and inhibitory performance in the inhibitory circuit encompassing the right inferior frontal gyrus(rIFG),caudate nucleus(rCau),globus pallidum(rGP),and thalamus(rThal).Results:The entire neural circuit exhibited high intrinsic connectivity and response inhibition critically increased causal projections from the rIFG to both rCau and rThal.Direct comparison further demonstrated that response inhibition induced an increasing rIFG inflow and increased the causal regulation of this region over the rCau and rThal.In addition,sex and performance influenced the functional architecture of the regulatory circuits such that women displayed increased rThal self-inhibition and decreased rThal to GP modulation,while better inhibitory performance was associated with stronger rThal to rIFG communication.Furthermore,control analyses did not reveal a similar key communication in a left lateralized model.Conclusions:Together,these findings indicate a pivotal role of the rIFG as input and causal regulator of subcortical response inhibition nodes.