Advances in neuroimaging have led to a greater understanding of brain-behavior relationships in obsessive-compulsive disorder (OCD). This article provides an updated review and analysis of the structural and functional neuroimaging studies in OCD published to date and discusses how evidence from various types of neuroimaging studies has been synthesized to generate and test hypotheses regarding these relationships. We also review the basic science literature on the functional neuroanatomy of cortico-basal ganglia-thalamo-cortical circuits and integrate this information with neuroimaging data in OCD, to present a theoretical model of brain mediation of OCD symptoms and response to treatment. Taken together, neuroimaging studies indicate that OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, which may be attributable to an imbalance of tone between direct and indirect striato-pallidal pathways. Serotonergic drugs may ameliorate OCD symptoms by changing the relative balance of tone through the indirect versus direct orbitofrontal-subcortical pathways, thereby decreasing activity in the overall circuit that exists in the symptomatic state.

Obsessive-compulsive disorder (OCD) has a long history of speculations concerning its cause. This article reviews human functional neuroimaging studies of OCD, then presents data from a study in the nonhuman primate that concerns the localization of brain systems that may mediate the expression of OCD symptoms. We use these lines of evidence to argue that increased "neural tone" through a section of the behaviorally disinhibiting "direct" basal ganglia pathway, relative to tone in the behaviorally inhibiting or moderating "indirect" basal ganglia system, may mediate the expression of OCD symptoms. The limbic orbital prefrontal cortex, the involvement of which is highly implicated in OCD, may have a greater influence on neural tone in the direct pathway than in the indirect, whereas more dorsal neocortical prefrontal regions may have the opposite effects on these two basal ganglia subsystems. Effective OCD treatments may obtain their results by preferentially decreasing neural tone through the direct relative to the indirect basal ganglia system.