An initial investigation of the orbitofrontal cortex hyperactivity in obsessive-compulsive disorder: exaggerated representations of anticipated aversive events?

Orbitofrontal cortical (OFC) dysfunction has been repeatedly involved in obsessive-compulsive disorder, but the precise significance of this abnormality is still unclear. Current neurocognitive models propose that specific areas of the OFC contribute to behavioral regulation by representing the anticipated affective value of future events. This leads to the hypothesis that these OFC areas are hyperactive in patients, reflecting ruminative preoccupation with future aversive events. In experimental situations, such hyperactivity should be triggered by negative affect in response to high likelihood of events such as the conflict between simultaneously active incompatible responses, which can potentially lead to poor task performance. We tested this hypothesis by examining fMRI indices of brain activity of 15 OCD patients and 15 matched controls. Subjects were scanned while performing a cognitive task which involved responding to cues and subsequent probes, and some of the probes elicited response conflict. Relative to controls, the lateral OFC of patients was specifically hyperactive to cues associated with high proportion of subsequent high-conflict probes. The level of OFC hyperactivity correlated directly with the severity of anxiety symptoms. These results support the hypothesis that OCD is characterized by exaggerated OFC representations of anticipated aversive events.