489. Task-based fMRI investigation of neural changes following acceptance and commitment therapy in major depressive disorder

Abstract

Abstract Background Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric condition worldwide, and a substantial proportion of patients fail to achieve full remission with antidepressant pharmacotherapy or cognitive behavioral therapy (CBT). Acceptance and Commitment Therapy (ACT), a third-wave behavioral therapy grounded in relational frame theory, targets maladaptive processes such as cognitive fusion and experiential avoidance to enhance psychological flexibility rather than directly modifying cognitive content. Although accumulating evidence supports the clinical efficacy of ACT for depression, its underlying neural mechanisms remain largely unexplored. Aims & Objectives The present study investigated the neural correlates of ACT in patients with MDD using task-based functional magnetic resonance imaging (fMRI) designed to elicit cognitive fusion. Method This study was embedded within a randomized controlled trial, including 42 adults diagnosed with MDD (ACT group: n = 21; waitlist control group: n = 21). Participants underwent fMRI scanning and psychological assessments at baseline and after an 8-week interval. Clinical and process-related measures included depressive symptoms (Center for Epidemiologic Studies Depression Scale), brooding rumination (Rumination Response Scale–Revised), psychological inflexibility (Acceptance and Action Questionnaire–II), cognitive fusion (Cognitive Fusion Questionnaire), and thought–action fusion beliefs (Thought–Action Fusion Scale). During fMRI, participants completed a thought–action fusion induction task involving negative or neutral statements about close or neutral individuals. Results Behaviorally, the ACT group showed significant reductions in reaction time and emotional intensity in response to negative statements involving close persons following treatment, whereas no significant changes were observed in the waitlist control group. Neuroimaging results revealed significant group-by-time interactions during the cognitive fusion condition, with the ACT group exhibiting increased activation in the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and insula after intervention. In addition, ACT was associated with enhanced functional connectivity between the mPFC and posterior cingulate cortex/precuneus. Changes in mPFC and ACC activity were negatively correlated with reaction time during the task, depressive symptom severity, brooding rumination, and ACT process measures, including cognitive fusion and experiential avoidance. Increased mPFC–PCC connectivity was also associated with reductions in brooding rumination. Discussion & Conclusions This study provides the first task-based fMRI evidence linking ACT-related clinical improvements in MDD to neural changes elicited by cognitive fusion–specific stimuli. The findings suggest that ACT modulates midline cortical regions involved in emotional regulation and self-referential processing, potentially facilitating reductions in ruminative thinking through enhanced cognitive defusion and acceptance. These results offer neurobiological support for ACT mechanisms in depression and highlight its potential transdiagnostic relevance.