Mechanisms and interventions promoting healthy frontostriatal dynamics in obsessive-compulsive disorder

Sebastien Naze (), Luke J. Hearne, Paula Sanz-Leon, Conor Robinson, Caitlin V. Hall, Saurabh Sonkusare, Bjorn Burgher, Andrew Zalesky, James A. Roberts and Luca Cocchi ()
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Sebastien Naze: QIMR Berghofer
Luke J. Hearne: QIMR Berghofer
Paula Sanz-Leon: QIMR Berghofer
Conor Robinson: QIMR Berghofer
Caitlin V. Hall: QIMR Berghofer
Saurabh Sonkusare: QIMR Berghofer
Bjorn Burgher: QIMR Berghofer
Andrew Zalesky: The University of Melbourne
James A. Roberts: QIMR Berghofer
Luca Cocchi: QIMR Berghofer

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Changes in the frontostriatal system activity support individuals’ perseverance in distressful thoughts and rigid, repetitive behaviours that define obsessive-compulsive disorder (OCD). Converging evidence from preclinical and clinical work suggests that OCD maps onto a functional imbalance in the ventral and dorsal frontostriatal circuits. However, the neural mechanisms supporting these dysregulations remain elusive, their association with symptom severity is unclear, and therapeutic interventions are limited. To address these gaps, we combined neuroimaging and behavioural data from individuals with OCD and controls with computational modelling. We found that bidirectionally decreasing spontaneous neural coupling in the ventromedial circuit while concurrently increasing dorsolateral cortico-striatal coupling delivered the highest functional improvements in OCD. The analysis of longitudinal changes in obsessions and compulsions with respect to modelled neural interventions supported our predictions. By highlighting behaviourally meaningful neural mechanisms hidden from traditional neuroimaging analysis, this study advances knowledge on the neural basis of OCD and provides new therapeutic targets for obsessions and compulsions.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62190-2

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DOI: 10.1038/s41467-025-62190-2

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