Common and differential connectivity profiles of deep brain stimulation and capsulotomy in refractory obsessive-compulsive disorder

Abstract

Neurosurgical interventions including deep brain stimulation (DBS) and capsulotomy have been demonstrated effective for refractory obsessive-compulsive disorder (OCD), although treatment-shared/-specific network mechanisms remain largely unclear. We retrospectively analyzed resting-state fMRI data from three cohorts: a cross-sectional dataset of 186 subjects (104 OCD and 82 healthy controls), and two longitudinal datasets of refractory patients receiving ventral capsule/ventral striatum DBS (14 OCD) and anterior capsulotomy (27 OCD). We developed a machine learning model predictive of OCD symptoms (indexed by the Yale-Brown Obsessive Compulsive Scale, Y-BOCS) based on functional connectivity profiles and used graphic measures of network communication to characterize treatment-induced profile changes. We applied a linear model on 2 levels treatments (DBS or capsulotomy) and outcome to identify whether pre-surgical network communication was associated with differential treatment outcomes. We identified 54 functional connectivities within fronto-subcortical networks significantly predictive of Y-BOCS score in patients across 3 independent cohorts, and observed a coexisting pattern of downregulated cortico-subcortical and upregulated cortico-cortical network communication commonly shared by DBS and capsulotomy. Furthermore, increased cortico-cortical communication at ventrolateral and centrolateral prefrontal cortices induced by DBS and capsulotomy contributed to improvement of mood and anxiety symptoms, respectively (p < 0.05). Importantly, pretreatment communication of ventrolateral and centrolateral prefrontal cortices were differentially predictive of mood and anxiety improvements by DBS and capsulotomy (effect sizes = 0.45 and 0.41, respectively). These findings unravel treatment-shared and treatment-specific network characteristics induced by DBS and capsulotomy, which may facilitate the search of potential evidence-based markers for optimally selecting among treatment options for a patient.