Network-based functional connectivity predicts response to exposure therapy in unmedicated adults with obsessive-compulsive disorder

Abstract

Obsessive-compulsive disorder (OCD) is associated with alterations in cortico-striato-thalamo-cortical brain networks, but some resting-state functional magnetic resonance imaging studies report more diffuse alterations in brain connectivity. Few studies have assessed functional connectivity within or between networks across the whole brain in unmedicated OCD patients or how patterns of connectivity predict response to exposure and ritual prevention (EX/RP) therapy, a first-line treatment for OCD. Herein, multiband resting-state functional MRI scans were collected from unmedicated, adult patients with OCD (n = 41) and healthy participants (n = 36); OCD patients were then offered twice weekly EX/RP (17 sessions). A whole-brain-network-based statistic approach was used to identify group differences in resting-state connectivity. We detected altered pre-treatment functional connectivity between task-positive regions in the temporal gyri (middle and superior) and regions of the cingulo-opercular and default networks in individuals with OCD. Signal extraction was performed using a reconstruction independent components analysis and isolated two independent subcomponents (IC1 and IC2) within this altered connectivity. In the OCD group, linear mixed-effects models tested whether IC1 or IC2 values predicted the slope of change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores across EX/RP treatment. Lower (more different from controls) IC2 score significantly predicted greater symptom reduction with EX/RP (Bonferroni-corrected p = 0.002). Collectively, these findings suggest that an altered balance between task-positive and task-negative regions centered around temporal gyri may contribute to difficulty controlling intrusive thoughts or urges to perform ritualistic behaviors.

Trial registration: ClinicalTrials.gov NCT02221518.

Figures

Fig. 1. Resting-state functional connectivity group differences.

Visualization of the 23 edges comprising the NBS component that differed significantly across patients with OCD and healthy controls (details in Table 2). Nodes (endpoints of edges) are plotted by center of mass. Edges (21) with greater average connectivity in healthy controls (HC) compared to the OCD group are represented in blue. Edges (2) with greater average connectivity in the OCD group are represented in red.

Fig. 2. Visualization of the largest weights (loadings) generated by reconstruction independent components analysis (RICA) for independent subcomponents 1 and 2 (see also Table 3).

Nodes (endpoints of edges) are plotted by center of mass. Edges are color-coded according to the subcomponent(s) for which they have a suprathreshold RICA weighting. An edge is defined as “suprathreshold” for a subcomponent(s) if the absolute value of its RICA weight in the subcomponent is >0.2. A auditory, CO cingulo-opercular, DM default mode, V visual, VA ventral attention.