Dissociable Frontostriatal Connectivity: Mechanism and Predictor of the Clinical Efficacy of Capsulotomy in Obsessive-Compulsive Disorder

Background: Little is known about the neural mechanism and response variability underlying neurosurgical interventions for intractable obsessive-compulsive disorder (OCD). Methods: Of 81 OCD patients screened for capsulotomy identified in our institutional database, 36 patients with clinical assessment before and after capsulotomy and imaging data (9 of 36 patients without postoperative imaging data used as an independent test group), and 29 healthy control subjects were retrospectively recruited. Twenty of 36 patients (56%) responded to the lesion procedure (determined as a ≥35% reduction in Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score). Seed-based (i.e., ventral and dorsal caudate, medial dorsal thalamus, and ventral and dorsal putamen) resting-state functional connectivity was used to examine alterations in frontostriatal circuitry after capsulotomy. Results: The Y-BOCS score significantly decreased (p <.001) after capsulotomy in OCD patients. Functional connectivity between the ventral striatum/nucleus accumbens and the dorsal anterior cingulate cortex was reduced (p <.05, corrected) after the surgical procedure. Moreover, change in connectivity significantly correlated with alteration in Y-BOCS score (r =.41, p =.033). In addition, preoperative connectivity between the dorsal caudate and the dorsal anterior cingulate cortex could differentiate nonresponders from responders and predict changes in Y-BOCS score (R² =.23, F_1,25 = 7.56, p =.011), which was generalized in an independent test group. Conclusions: We demonstrated that restoration of ventral frontostriatal connectivity was associated with clinical improvement in refractory OCD, suggesting a therapeutic mechanism of capsulotomy. Moreover, preoperative variations in dorsal frontostriatal connectivity predicted clinical response, which may offer a predictor of treatment outcome.