Task-based fMRI predicts response and remission to exposure therapy in obsessive-compulsive disorder

Abstract

Exposure and ritual prevention (EX/RP) is an effective first-line treatment for obsessive-compulsive disorder (OCD), but only some patients achieve minimal symptoms following EX/RP. Herein, we investigate whether task-based neural activity can predict who responds best to EX/RP. Unmedicated adult patients with OCD (n = 36) and healthy participants (n = 33) completed the Simon Spatial Incompatibility Task during high-resolution, multiband functional MRI (fMRI); patients were then offered twice-weekly EX/RP (17 sessions). Linear mixed-effects models were used to identify brain regions where conflict-related activity moderated the slope of change in Yale–Brown Obsessive-Compulsive Scale (Y-BOCS) scores across treatment. Conflict-related activity in the left pallidum and 35 cortical parcels/regions significantly predicted symptom improvement with EX/RP for patients with OCD (false discovery rate-corrected P < 0.05). Significant parcels/regions included cingulo-opercular and default mode network regions, specifically the anterior insula and anterior and posterior cingulate. Summarizing across these parcels/regions, greater conflict-related activity predicted greater EX/RP response and which patients achieved remission (Y-BOCS score ≤ 12; Cohen’s d = 1.68) with >80% sensitivity and specificity. The association between brain activity and treatment response was partially mediated by patient EX/RP adherence (b = −2.99; 43.61% of total effect; P = 0.02). Brain activity and adherence together were highly predictive of remission. Together, these findings suggest that cingulo-opercular and default mode regions typically implicated in task control and introspective processes, respectively, may be targets for novel treatments that augment the ability of persons with OCD to resolve cognitive conflict and thereby facilitate adherence to EX/RP, increasing the likelihood of remission.

Altered fronto‐amygdalar functional connectivity predicts response to cognitive behavioral therapy in pediatric obsessive‐compulsive disorder

“…This clinical trial was approved by the Institutional Review Board at the New York State Psychiatric Institute (NYSPI). Structural and functional imaging data from some of the same participants included in the present study have been reported in two previous publications (Cyr et al, 2020; Pagliaccio, Cha, et al, 2019; Pagliaccio, Middleton, et al, 2019).…”

“…Structural and functional imaging data from some of the same participants included in the present study have been reported in two previous publications (Cyr et al, 2020;Pagliaccio, Cha, et al, 2019;Pagliaccio, Middleton, et al, 2019).…”

“…Relationships between brain function and symptom change with treatment in adults with OCD have typically been assessed using univariate analyses such as correlations, univariate linear regressions, or logistic regression (Bernstein et al, 2018; Feusner et al, 2015; Fullana et al, 2017; Gottlich et al, 2015; Moody et al, 2017; Pagliaccio, Cha, et al, 2019; Pagliaccio, Middleton, et al, 2019). Such analytical approaches do not permit testing the directionality of relationships between brain measures (i.e., connectivity or activity) and symptoms, thereby precluding inferences about causality (Cole & Maxwell, 2003).…”

Much Ado About Missingness: A Demonstration of Full Information Maximum Likelihood Estimation to Address Missingness in Functional Magnetic Resonance Imaging Data

“…Functional magnetic resonance imaging (fMRI) paradigms can offer powerful insights into neural processes with particular relevance to health and well-being ( Insel et al, 2013 ). Given this potential, fMRI approaches are increasingly employed to address a wide variety of critical health research questions ranging from the neural underpinnings of disease risk to individual differences in response to clinical interventions (e.g., Pagliaccio et al, 2019 ; Stice and Burger, 2019 ). Despite notable progress in the collection and analysis of fMRI data, concerns regarding reproducibility and rigor in fMRI studies have arisen, with major potential implications for the field ( Poldrack et al, 2017 ).…”

Structural neural markers of response to cognitive behavioral therapy in pediatric obsessive‐compulsive disorder

“…Neuroscience could potentially aid in identifying robust pretreatment markers of treatment responsivity above and beyond severity/impairment and familial factors. However, extant studies have mainly focused on adults with OCD, for example, identifying task-based fMRI (Pagliaccio et al, 2019) or structural (orbitofrontal and cingulate cortex) predictors of treatment outcomes (Fullana et al, 2014;Hoexter et al, 2015;Hoexter et al, 2013). Data from youth suggest potential increases in orbitofrontal volume following CBT (Huyser et al, 2013;Huyser et al, 2014).…”