Neuroanatomical Substrates and Predictors of Response to Capsulotomy in Intractable Obsessive-Compulsive Disorder

Background: Anterior capsulotomy that surgically targets fiber tracts connecting prefrontal cortex and subcortical nuclei is a therapeutic option for a subgroup of patients with treatment-refractory obsessive-compulsive disorder. The goal of this study was to investigate neural correlates to anterior capsulotomy and find predictors of clinical improvement following this procedure. Methods: Structural and diffusion imaging data and clinical evaluation were acquired from 31 patients with refractory obsessive-compulsive disorder who underwent anterior capsulotomy. Of the 31 patients, 16 were clinical responders defined by a ≥35% reduction in the Yale-Brown Obsessive Compulsive Scale scores. Analysis of variance was applied on 2 levels (surgery and response) to examine alterations of gray matter volume and fiber tract integrity (measured by generalized fractional anisotropy). The correlation between preoperative data and clinical response was further investigated. Results: After surgery, generalized fractional anisotropy was significantly decreased in the bilateral anterior limb of the internal capsule and anterior thalamic radiation, accompanied by a decrease in gray matter volume in the prefrontal cortex, anterior cingulate cortex, striatum, thalamus, and cerebellum. Moreover, atrophy of the right caudate was greater in responders than in nonresponders, which correlated with alteration in Yale-Brown Obsessive Compulsive Scale score. In addition, preoperative gray matter volume in the right inferior frontal gyrus and generalized fractional anisotropy in the left superior longitudinal fasciculus and right cingulum predicted improved response. More anterior location of the lesion area predicted better clinical response. Conclusions: These results demonstrate that reduced volume of the right caudate might be associated with therapeutic response of capsulotomy and might offer a potential predictor of treatment outcome and a guide for lesion site.