Mechanisms of imbalanced frontostriatal functional connectivity in obsessive-compulsive disorder.

The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is lacking and the mechanistic understanding of these effects is incomplete. To confirm and advance knowledge on changes in frontostriatal functional connectivity in OCD, participants with OCD and matched healthy controls underwent resting-state functional, structural, and diffusion neuroimaging. Functional connectivity changes in frontostriatal systems were here replicated in individuals with OCD (n = 52) compared to controls (n = 45). OCD participants showed greater functional connectivity (T = 4.3, pFWE = 0.01) between the nucleus accumbens (NAcc) and the orbitofrontal cortex (OFC), but lower functional connectivity between the dorsal putamen (dPut) and lateral prefrontal cortex (lPFC) (T = 3.8, pFWE = 0.04) relative to controls. Computational modelling suggest that NAcc-OFC connectivity changes reflect an increased influence of NAcc over OFC activity and reduced OFC influence over NAcc activity (posterior probability, Pp > 0.66). Conversely, dPut showed reduced modulation over lPFC activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalising frontostriatal dynamics in OCD.