Hyper-influence of the orbitofrontal cortex over the ventral striatum in obsessive-compulsive disorder

Abstract

Dysfunction of the fronto-striato-thalamic circuit routing through the orbitofrontal cortex (OFC) is thought to play the main role in the pathophysiology of obsessive-compulsive disorder (OCD). Repetitious stimulation of the OFC-ventral striatum (VS) projections in mice has been shown to increase the firing of the postsynaptic VS cells and the frequency of OCD-like symptoms. Moreover, increased functional connectivity (FC) between the OFC and the VS has been reported in patients with OCD. While FC is a synchronous, non-directed correlation, the directed influence between these brain regions remains unclear in patients with OCD. We obtained resting state functional magnetic resonance imaging scans from 37 non-medicated patients with OCD and 38 matched healthy volunteers, and calculated bivariative voxel-wise Granger Causality (GC) to and from three striatal regions of interest (ROI) using a blind deconvolution procedure. Additionally, we conducted multivariative GC analysis to determine if the effect revealed by the bivariative voxel-wise GCA is mediated by another seed ROI. We found a significant hyper-influence of the OFC over the VS of subjects with OCD (p<.05, corrected). Multivariative GC analysis confirmed this effect (p<.05, corrected) and that it was not mediated by another brain area within the striatum. This is the first study investigating the directed influence of the fronto-striato-thalamic loop in non-medicated patients with OCD. We confirmed the hyperactive connection from the OFC to the VS that is consistent with previous animal studies. These findings provide evidence for the more detailed pathophysiology of OCD.

Keywords: Effective connectivity; Functional magnetic resonance imaging; Obsessive-compulsive disorder; Orbitofrontal cortex; Resting state; Striatum.