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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Source of funding: This work was carried out as a doctoral thesis of NST funded by the Indian Council of Medical Research (ICMR) and research bursary from the TSS foundation (TVSB/002/208/2020/01378). Acknowledgements: NST acknowledges the salary support received from the Department of Biotechnology, Ministry of Science and Technology, Government of India funded project- Accelerator Program for Discovery in Brain disorders using Stem cells (ADBS) (BT/PR17316/MED/31/326/2015). SSA has received a research grant from DBT/Wellcome Trust India Alliance (IA/CPHI/18/1/503931). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Ethics Committee of National Institute of Mental Health and Neurosciences (India) gave ethical approval for this research work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The imaging and clinical data in the present study will be available upon reasonable request to the corresponding author.