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

Abstract 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 casual regulation within this inhibitory circuit in humans remains controversial. Methods Here, we capitalize on the recent progress in robust and biologically plausible directed causal modelling (DCM-PEB) and a large response inhibition dataset (n=250) acquired with concomitant functional fMRI 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 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.