Inhibition-Related Cortical Hypoconnectivity as a Candidate Vulnerability Marker for Obsessive-Compulsive Disorder
Bullmore, Edward T.
Robbins, Trevor W.
Sahakian, Barbara J.
Chamberlain, Samuel R.
BACKGROUND: Obsessive-compulsive disorder (OCD) is a prevalent neuropsychiatric condition, with biological models implicating disruption of cortically mediated inhibitory control pathways, ordinarily serving to regulate our environmental responses and habits. The aim of this study was to evaluate inhibition-related cortical dysconnectivity as a novel candidate vulnerability marker of OCD. METHODS: In total, 20 patients with OCD, 18 clinically asymptomatic first-degree relatives of patients with OCD, and 20 control participants took part in a neuroimaging study comprising a functional magnetic resonance imaging stop signal task. Brain activations during the contrasts of interest were cluster thresholded, and a three-dimensional watershed algorithm was used to decompose activation maps into discrete clusters. Functional connections between these key neural nodes were examined using a generalized psychophysiological interaction model. RESULTS: The three groups did not differ in terms of age, education level, gender, IQ, or behavioral task parameters. Patients with OCD exhibited hyperactivation of the bilateral occipital cortex during the task versus the other groups. Compared with control participants, patients with OCD and their relatives exhibited significantly reduced connectivity between neural nodes, including frontal cortical, middle occipital cortical, and cerebellar regions, during the stop signal task. CONCLUSIONS: These findings indicate that hypoconnectivity between anterior and posterior cortical regions during inhibitory control represents a candidate vulnerability marker for OCD. Such vulnerability markers, if found to generalize, may be valuable to shed light on etiological processes contributing not only to OCD but also obsessive-compulsive-related disorders more widely.