Differential Functional Connectivity of Frontolimbic Circuit During Symptom Provocation in Distinct Symptom Profiles of Obsessive-Compulsive Disorder: Connectivité fonctionnelle différentielle du circuit frontolimbique durant la provocation de symptômes dans des profils symptomatiques distincts du trouble obsessionnel-compulsif

Abstract

Background: Emotional processing deficits and frontolimbic dysfunction have been observed in patients with obsessive-compulsive disorder (OCD), with inconsistent evidence possibly due to symptom heterogeneity. We compared the functional activation and connectivity patterns of the frontolimbic structures during symptom provocation between patients with distinct symptom profiles of OCD. Methods: Thirty-seven symptomatic OCD subjects were recruited and categorized based on predominant symptom profiles to contamination/washing symptom group (OCD-C, n = 19) and taboo thoughts group (OCD-T, n = 18), along with 17 healthy controls (HCs). All subjects were evaluated with comprehensive clinical assessments and functional magnetic resonance imaging while appraising personalized disorder-specific stimuli with contrasting neutral stimuli as part of an individualized symptom provocation task. Region of interest analyses and task-dependent seed-to-voxel connectivity of the frontolimbic circuit were compared between the groups, with correction employed for multiple comparisons. Results: OCD-C subjects had decreased task-dependent mean activation of the left amygdala (adjusted mean difference = 13.48, p= 0.03) and right hippocampus (adjusted mean difference = 13.48, p = 0.04) compared to HC. Task-modulated functional connectivity analyses revealed that OCD-C had decreased connectivity of the right hippocampus with bilateral supplementary motor cortex and anterior cingulate gyrus (T = -5.11, p = 0.04); right insula with left cerebellum (T = -5.47, p = 0.02); and left insula with inferior temporal gyrus (T = -6.27, p = 0.03) than HC. OCD-T subjects had greater connectivity of right insula with left cerebellum (T = 6.64, p < 0.001) than OCD-C and increased connectivity of medial frontal cortex with right lateral occipital cortex (T = 5.08, p < 0.001) than HC. Conclusions: Contamination-related symptoms were associated with decreased activation and connectivity of amygdala and hippocampus during symptom provocation, while the taboo thoughts were associated with increased connectivity of the insular cortex and medial frontal cortex. These findings suggest that distinct neurobiological markers may underlie the clinical heterogeneity of OCD.