Background: Obsessive-compulsive disorder (OCD) may develop following brain lesions, but lesion distribution and connectivity patterns are unknown. Methods: OCD-associated lesions, identified from systematic literature search, were traced on common brain space and compared to control lesions (N=608). Topography was analyzed using brain atlases, and lesion location networks computed using normative functional connectivity (N=1000). Lesional network maps (LNMs) were contrasted to data from primary OCD. Results: Among 129 case-descriptions of lesional OCD, traced lesions (n=40) were more specifically located in orbitofrontal cortex bilaterally and right temporal pole, and more connected to orbitofrontal cortex and ventral basal ganglia, bilaterally. LNMs overlapped with primary OCD functional peaks from Neurosynth, revealed abnormal functional connectivity in patients with primary OCD (n=54) compared to controls (n=61), and aligned with brain stimulation targets. Conclusions: Lesional OCD has specific patterns of brain lesion topography and functional connectivity, with LNMs associated to brain functional patterns in primary OCD.

NL was affiliated to Philips Healthcare, Portugal. JBB-C received honoraria in 2018 as member of the local Advisory Board for Trevicta from Janssen-Cilag, Ltd. AJO-M is recipient of a grant from Schuhfried GmBH for norming and validation of cognitive tests, and was national coordinator for Portugal of trials of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd (EudraCT number 2017-003288-36 and 2020-001348-25), and of esketamine for treatment-resistant depression, sponsored by Janssen-Cilag, Ltd (EudraCT NUMBER: 2019-002992-33); has received payment, honoraria, or support for attending meetings and participating in advisory boards from MSD, Neurolite AG, Janssen Pharmaceuticals, Angelini Pharma, and the European Monitoring Centre for Drugs and Drug Addiction; has received consultancy fees from Bioprojet Pharma and NaturalX Health Ventures (all outside the submitted work); is Vice President of the Portuguese Society for Psychiatry and Mental Health; is head of the Psychiatry Working Group for the National Board of Medical Examination at the Portuguese Medical Association and Portuguese Ministry of Health; is President of the Ethics Committee for the Public Institute for Addictive Behaviors and Dependence; and is President of the Scientific Council of the Portuguese Obsessive Compulsive Disorder Foundation. The remaining authors declare that they have no potential conflicts of interest involving this work, including relevant financial activities outside the submitted work and any other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing what is written. None of these agencies had a role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the abstract, nor in the decision to submit the abstract.

This work was supported by a NARSAD 2023 Young Investigator Grant (31379) to GC. AJO-M is supported by the European Research Council (grant agreement number 950357). JBB-C and AJO-M were supported by grant FCT-PTDC/MEC-PSQ/30302/2017-IC&DT-LISBOA-01-0145-FEDER, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020 - Programa Operacional Regional de Lisboa. JO was supported by a NARSAD 2018 Young Investigator Grant (27595). ND and AM are supported by FCT through PhD Scholarships (2022.12871.BD and SFRH/BD/144508/2019, respectively). SHS was funded by the Sidney R. Baer and Brain & Behavior Research Foundations. MDF was supported by grants from the Sidney R. Baer Jr. Foundation, the NIH (R01MH113929 R01MH113929, R21MH126271, R56AG069086, R21NS123813), the Nancy Lurie Marks Foundation, the Kaye Family Research Fund, the Ellison/Baszucki Foundation, and the Mather s Foundation. None of the funding agencies had a role in the design and conduct of the study, in the collection, management, analysis and interpretation of the data, in the preparation, review or approval of the manuscript, nor in the decision to submit the manuscript for publication.

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