Differential connectivity of frontolimbic circuit induced by individualized disorder-specific stimuli in distinct symptom profiles of obsessive-compulsive disorder

Background: Emotional processing deficits in obsessive-compulsive disorder (OCD) are reportedly caused by an aberrant frontolimbic circuit activation with inconsistent evidence, possibly due to symptom heterogeneity. We compared the activation and connectivity patterns of the frontolimbic structures during symptom provocation between patients with distinct symptom profiles of OCD. Methods: We recruited 37 symptomatic OCD subjects categorized based on predominant symptom profiles, i.e., 19 with contamination/washing symptoms (OCD-C) and 18 with taboo thoughts (OCD-T), along with 17 healthy controls (HC). All subjects were evaluated with comprehensive clinical assessments and functional magnetic resonance imaging (fMRI) while appraising personalized disorder-specific visual stimuli with contrasting neutral stimuli as part of an individualized symptom provocation (ISP) task. Results: OCD-C subjects had decreased task-dependent mean activation of left amygdala and right hippocampus compared to the other groups during symptom induction. Task-modulated functional connectivity analyses during ISP task revealed that HC had increased connectivity between right hippocampus and bilateral supplementary motor cortex, right insula and left cerebellum, left insula and inferior temporal gyrus than OCD-C. OCD-T subjects had greater connectivity between right insula and left cerebellum than OCD-C and increased connectivity of medial frontal cortex with right lateral occipital cortex than HC. Conclusions: Contamination-related symptoms had decreased activation and altered connectivity of frontolimbic circuit during emotional provocation. Replicating these findings on larger samples with other symptom profiles might help develop personalized, targeted interventions for this heterogeneous disorder.