Obsessive-compulsive disorder (OCD) is a debilitating and chronic disorder with a lifetime prevalence of near 1%. Characterized as recurrent, intrusive thoughts (obsessions) and repetitive behaviors (compulsions), it heavily affects work and life of patients and causes large burden for the family and society. It is reported that 30%~40% of OCD patients fail to respond adequately to the first-line treatments (i.e., medication and cognitive-behavioral therapies).

Psychosurgical interventions, such as capsulotomy and cingulotomy, have been used as “last-resort” treatments for patients with treatment-refractory OCD. However, evidence of the neural circuit mechanisms through which therapeutic effects are achieved and what underlies response variability remains scarce.

In a study published in Biological Psychiatry, Dr. WANG Zheng’s lab at the Institute of Neuroscience of Chinese Academy of Sciences, and Dr. SUN Bomin’s team at Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, used resting-state functional magnetic resonance imaging (fMRI) to investigate neural mechanism and response variability underlying neurosurgical interventions for severe OCD. They revealed that two dissociable frontostriatal circuits underlie mechanism and predictor of the clinical efficacy of capsulotomy.

Through the resting-state functional connectivity approach, the researchers examined alterations in frontostriatal circuitry before and after capsulotomy. In OCD patients, functional connectivity between ventral striatum and dorsal anterior cingulate cortex (dACC) was reduced after the surgical procedure. The change in connectivity significantly correlated with clinical improvement.

To explore the response predictors of capsulotomy for OCD patients, the preoperative frontostriatal connectivity that could differentiate responders and non-responders were firstly identified. Then, a linear regression model was applied between the strength of identified connectivity and changes in Y-BOCS scores. The results showed that preoperative connectivity between dorsal caudate and dACC predicted changes in Y-BOCS score, which was further validated in an independent group of patients.

Collectively, the findings demonstrated restoration of ventral frontostriatal connectivity was associated with clinical improvement in severe 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.

This study was funded by National Key R&D Program of China, the Strategic Priority Research Program (B) of the Chinese Academy of Sciences, National Natural Science Foundation of China, Shanghai Jiao Tong University School of Medicine–Institute of Neuroscience (SHSMU-ION) Research Center for Brain Disorders, and Natural Science Foundation and Major Basic Research Program of Shanghai.