Translational Research in OCD: Circuitry and Mechanisms

Abstract

Although the pathophysiology of obsessive-compulsive disorder (OCD) remains unknown, converging lines of evidence point to abnormalities in the orbital (OFC), ventromedial (vmPFC-subgenual cingulate and medial OFC), and dorsal anterior cingulate (dACC) cortical-basal ganglia circuits. OCD-linked patterns of activity in these PFC regions are accentuated during provocation of symptoms and can predict treatment response; they tend to normalize following successful treatment (Greenberg et al, 2010). Moreover, neurosurgical interventions (lesions or deep brain stimulation-DBS) within the ventral internal capsule (VC), ventral striatum (VS), or dACC (treatments for intractable OCD) all act on subcomponents of the vmPFC/OFC/dACC-basal ganglia network (Greenberg et al, 2010). Indeed, DBS interventions specifically affect vmPFC, OFC, and possibly dACC connections with striatum, thalamus, and/or brainstem (Figure 1) (Lehman et al, 2011). The efficacy of VC/VS DBS (or lesions) for OCD likely requires modulating the OFC/vmPFC/dACC-basal ganglia circuit. Interestingly, high frequency stimulation (HFS) in a rat homolog of the VC/VS DBS target reduces OFC activity, enhances local field potential delta band activity in OFC, and enhances synchrony between specific regions within this prefrontal network (McCracken and Grace, 2009). Thus, OCD pathophysiology likely represents dysfunctional network interactions rather than only disruption within specific structures.