Are response inhibition failures in OCD related to abnormal fronto-striatal circuits?

Neurobiological studies using a range of techniques are now being actively pursued in several laboratories to clarify the pathophysiology of OCD. The most widely accepted neurobiological model of OCD is that abnormalities in orbital prefrontal cortex and its ventral striatal target fields are involved in causing obsessive and compulsive symptoms. In animal models and studies of patients with lesions to this brain circuitry, a selective disturbance in the ability to suppress responses to irrelevant stimuli has been demonstrated. Such a deficit in response suppression might underlie the apparent inhibitory deficit suggested by the symptomatology of OCD. To date, little direct evidence of such a deficit has been reported. Oculomotor tests were administered to 13 medication-naive, non-depressed young-adult OCD patients 18-40 years of age, and 13 age and sex case-matched healthy comparison subjects, to assess three well-delineated aspects of prefrontal cortical function: the ability to suppress responses, to volitionally execute delayed responses, and to anticipate predictable events. Oculomotor paradigms have some advantage for assessing neuorcognitive processes, mainly the relative reflexive nature of basic eye movements, and the fact that the main regions subserving different aspects of oculomotor control have been well delineated in single cell studies of rhesus monkey and human functional imaging studies. OCD patients made significantly more oculomotor response suppression failures than controls on a task where they were instructed to look away from rather than toward lights that flashed close to their point of gaze (hardest part of task), while no significant differences on the task were observed when a light flashed further from their point of gaze. No significant differences between adult OCD patients and controls were observed on other prefrontal cortical functions. A basic disturbance of neurobehavioral inhibition in OCD may underlie the repetitive symptomatic behavior that characterizes the illness. Behavioral response inhibition abnormalities in OCD may be related to failures in fronto-striatal circuitry, particularly orbital prefrontal-ventral striatal circuits.