PMID- 36380526 OWN - NLM STAT- MEDLINE DCOM- 20230421 LR - 20231117 IS - 1460-2156 (Electronic) IS - 0006-8950 (Print) IS - 0006-8950 (Linking) VI - 146 IP - 4 DP - 2023 Apr 19 TI - Mechanisms of imbalanced frontostriatal functional connectivity in obsessive-compulsive disorder. PG - 1322-1327 LID - 10.1093/brain/awac425 [doi] AB - The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is lacking, and the mechanistic understanding of these effects is incomplete. To confirm and advance knowledge on changes in frontostriatal functional connectivity in OCD, participants with OCD and matched healthy controls underwent resting-state functional, structural and diffusion neuroimaging. Functional connectivity changes in frontostriatal systems were here replicated in individuals with OCD (n = 52) compared with controls (n = 45). OCD participants showed greater functional connectivity (t = 4.3, PFWE = 0.01) between the nucleus accumbens (NAcc) and the orbitofrontal cortex (OFC) but lower functional connectivity between the dorsal putamen and lateral prefrontal cortex (t = 3.8, PFWE = 0.04) relative to controls. Computational modelling suggests that NAcc-OFC connectivity changes reflect an increased influence of NAcc over OFC activity and reduced OFC influence over NAcc activity (posterior probability, Pp > 0.66). Conversely, dorsal putamen showed reduced modulation over lateral prefrontal cortex activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalizing frontostriatal dynamics in OCD. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Naze, Sebastien AU - Naze S AUID- ORCID: 0000-0003-0367-402X AD - Department of Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. FAU - Hearne, Luke J AU - Hearne LJ AD - Department of Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. FAU - Roberts, James A AU - Roberts JA AD - Department of Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. FAU - Sanz-Leon, Paula AU - Sanz-Leon P AD - Department of Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. FAU - Burgher, Bjorn AU - Burgher B AD - Department of Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. FAU - Hall, Caitlin AU - Hall C AD - Department of Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. FAU - Sonkusare, Saurabh AU - Sonkusare S AUID- ORCID: 0000-0002-4439-0579 AD - Department of Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. FAU - Nott, Zoie AU - Nott Z AD - Department of Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. FAU - Marcus, Leo AU - Marcus L AD - Department of Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. FAU - Savage, Emma AU - Savage E AD - Department of Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. FAU - Robinson, Conor AU - Robinson C AD - Department of Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. FAU - Tian, Ye Ella AU - Tian YE AD - Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Melbourne 3053, Australia. FAU - Zalesky, Andrew AU - Zalesky A AD - Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Melbourne 3053, Australia. FAU - Breakspear, Michael AU - Breakspear M AD - College of Engineering Science and Environment, College of Health and Medicine, University of Newcastle, Callaghan 2308, Australia. FAU - Cocchi, Luca AU - Cocchi L AUID- ORCID: 0000-0003-3651-2676 AD - Department of Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. LA - eng GR - U54 MH091657/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Brain JT - Brain : a journal of neurology JID - 0372537 SB - IM MH - Humans MH - *Magnetic Resonance Imaging MH - Prefrontal Cortex/diagnostic imaging MH - *Obsessive-Compulsive Disorder/diagnostic imaging MH - Nucleus Accumbens MH - Putamen/diagnostic imaging MH - Brain Mapping PMC - PMC10396323 OTO - NOTNLM OT - DCM OT - OCD OT - connectivity OT - cortico-striatal OT - nucleus accumbens COIS- L.C., B.B., L.J.H, C.R. and A.Z. are involved in a not-for-profit clinical neuromodulation centre (Qld. Neurostimulation Centre). This centre had no role in the present trial. EDAT- 2022/11/17 06:00 MHDA- 2023/04/21 06:41 PMCR- 2023/11/16 CRDT- 2022/11/16 01:02 PHST- 2022/08/11 00:00 [received] PHST- 2022/10/13 00:00 [revised] PHST- 2022/10/30 00:00 [accepted] PHST- 2023/04/21 06:41 [medline] PHST- 2022/11/17 06:00 [pubmed] PHST- 2022/11/16 01:02 [entrez] PHST- 2023/11/16 00:00 [pmc-release] AID - 6830574 [pii] AID - awac425 [pii] AID - 10.1093/brain/awac425 [doi] PST - ppublish SO - Brain. 2023 Apr 19;146(4):1322-1327. doi: 10.1093/brain/awac425.