Inhibitory control in children and adolescents with paediatric-onset obsessive-compulsive disorder - An fMRI study

Background The pathophysiology of obsessive-compulsive disorder (OCD) appears to involve dysfunctions in brain circuits underlying sensorimotor, cognitive, affective, and motivational processes. One area of dysfunction observed is disruption in inhibitory motor control. While functional magnetic resonance imaging (fMRI) has revealed associated alterations at the brain network level in adults, studies in pediatric OCD has yielded inconsistent results.

This task-based fMRI study examined executive motor control in 65 unmedicated paediatric OCD patients and 58 age- and sex-matched healthy controls. Participants were aged eight to 17 years and performed a stop-signal task during whole-brain 3 Tesla fMRI. In addition to whole-brain analyses, we performed a region-of-interest analysis, focusing on brain regions subserving inhibitory motor control during the stop-signal task.

The paediatric patients with OCD showed comparable task performance and inhibition abilities to healthy controls. However, during successful inhibition, patients with paediatric OCD showed increased activation in the superior frontal sulcus, dorsomedial prefrontal cortex and dorsal anterior cingulate cortex as compared to healthy controls.

Our behavioural findings indicate typical inhibitory motor control proficiency in paediatric OCD patients. This proficiency in completing a stop-signal task was associated with increased brain activation pattern in brain areas resembling patterns observed in adult patients with OCD, suggesting compensatory mechanisms. These findings, obtained in a large sample of unmedicated children and adolescents, contribute to the notion of early neural impairment in paediatric OCD. Competing Interest Statement Hartwig R. Siebner has received honoraria as speaker and consultant from Lundbeck AS, Denmark, and as editor (Neuroimage Clinical) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany, Oxford University Press, Oxford, UK, and from Gyldendal Publishers, Copenhagen, Denmark. Clinical Trial NCT03595098 Funding Statement This study was funded by the Lundbeck Foundation, Capital Region Mental Health Services Research Foundation, Gangsted Foundation, Psychiatric Research Foundation of 1967, Holms Memorial Scholarship, Doctor Sofus Carl Emil Friis and wife Olga Friis Scholarship, Network for Research and Quality Assurance in Psychotherapy, Rosalie Petersens Foundation, Independent Research Fund Denmark. HRS is supported by a Grand Solutions grant from Innovation Fund Denmark (9068-00025B) and a grant from the Lundbeck Foundation (grant nr. R336-2020-1035). HRS were supported by a grant from Novo Nordisk foundation (NNF17OC0027872). KML received funding from the Lundbeck Foundation (R322-2019-2311). 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 study was approved by the National Research Ethics Committee (H-18010607) and The Knowledge Centre on Data Protection Compliance in The Capital Region of Denmark (VD-2018-263, l-suite 6502), and followed the Helsinki Declaration (World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects, 2013). 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 Data Availability Data is not publicly available, but can be retrieved during collaborations.