Deep brain stimulation modulates directional frontolimbic connectivity in obsessive-compulsive disorder

Deep brain stimulation (DBS) is effective for patients with treatment-refractory obsessive-compulsive disorder. DBS of the ventral anterior limb of the internal capsule (vALIC) rapidly improves mood and anxiety with optimal stimulation parameters. To understand these rapid effects of vALIC-DBS, we studied functional interactions within the affective amygdala circuit. We compared resting state functional magnetic resonance imaging data during chronic stimulation versus one week of stimulation discontinuation in patients, and obtained two resting state scans from matched healthy volunteers to account for test-retest effects. Imaging data were analyzed using functional connectivity analysis and dynamic causal modelling. Improvement in mood and anxiety following DBS was associated with reduced amygdala-insula functional connectivity. Directional connectivity analysis revealed that DBS increased the impact of the ventromedial prefrontal cortex on the amygdala, and decreased the impact of the amygdala on the insula. These results highlight the importance of the amygdala circuit in the pathophysiology of OCD, and suggest a neural systems model through which negative mood and anxiety are modulated by vALIC-DBS for OCD and possibly other psychiatric disorders.