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Peter L. Remijnse, MD; Marjan M. A. Nielen, PhD; Anton J. L. M. van Balkom, MD, PhD; Daniëlle C. Cath, MD, PhD; Patricia van Oppen, PhD; Harry B. M. Uylings, PhD; Dick J. Veltman, MD, PhD

Arch Gen Psychiatry. 2006;63:1225-1236.

Context  The orbitofrontal cortex (OFC)–striatal circuit, which is important for motivational behavior, is assumed to be involved in the pathophysiology of obsessive-compulsive disorder (OCD) according to current neurobiological models of this disorder. However, the engagement of this neural loop in OCD has not been tested directly in a cognitive activation imaging paradigm so far.

Objective  To determine whether the OFC and the ventral striatum show abnormal neural activity in OCD during cognitive challenge.

Design  A reversal learning task was employed in 20 patients with OCD who were not receiving medication and 27 healthy controls during an event-related functional magnetic resonance imaging experiment using a scanning sequence sensitive to OFC signal. This design allowed investigation of the neural correlates of reward and punishment receipt as well as of "affective switching," ie, altering behavior on reversing reinforcement contingencies.

Results  Patients with OCD exhibited an impaired task end result reflected by a reduced number of correct responses relative to control subjects but showed adequate behavior on receipt of punishment and with regard to affective switching. On reward outcome, patients showed decreased responsiveness in right medial and lateral OFC as well as in the right caudate nucleus (border zone ventral striatum) when compared with controls. During affective switching, patients recruited the left posterior OFC, bilateral insular cortex, bilateral dorsolateral, and bilateral anterior prefrontal cortex to a lesser extent than control subjects. No areas were found for which patients exhibited increased activity relative to controls, and no differential activations were observed for punishment in a direct group comparison.

Conclusions  These data show behavioral impairments accompanied by aberrant OFC-striatal and dorsal prefrontal activity in OCD on a reversal learning task that addresses this circuit's function. These findings not only confirm previous reports of dorsal prefrontal dysfunction in OCD but also provide evidence for the involvement of the OFC-striatal loop in the pathophysiology of OCD.

Author Affiliations: Departments of Psychiatry (Drs Remijnse, Nielen, van Balkom, Cath, van Oppen, and Veltman) and Anatomy (Dr Uylings), VU University Medical Center, Amsterdam, the Netherlands; Graduate School of Neurosciences, Amsterdam (Drs Remijnse and Uylings); Outpatient Academic Clinic for Anxiety Disorders, GGZ Buitenamstel, Amsterdam (Drs van Balkom, Cath, van Oppen, and Veltman); and Netherlands Institute for Brain Research, KNAW, Amsterdam (Dr Uylings).

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