Naze Sebastien, Hearne Luke J, Sanz-Leon Paula, Robinson Conor, Hall Caitlin V, Sonkusare Saurabh, Burgher Bjorn, Zalesky Andrew, Roberts James A, Cocchi Luca
QIMR Berghofer, Brisbane, Queensland, Australia.
School of Physics, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia.
Nat Commun. 2025 Aug 11;16(1):7400. doi: 10.1038/s41467-025-62190-2.
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.
前额叶纹状体系统活动的变化支持个体在痛苦想法以及定义强迫症（OCD）的刻板、重复行为中坚持不懈。来自临床前和临床研究的越来越多的证据表明，强迫症与腹侧和背侧前额叶纹状体回路的功能失衡有关。然而，支持这些失调的神经机制仍然难以捉摸，它们与症状严重程度的关联尚不清楚，并且治疗干预措施有限。为了填补这些空白，我们将强迫症患者和对照组的神经影像学和行为数据与计算模型相结合。我们发现，双向降低腹内侧回路中的自发神经耦合，同时增加背外侧皮质 - 纹状体耦合，能在强迫症中带来最大的功能改善。对强迫观念和强迫行为相对于模拟神经干预的纵向变化分析支持了我们的预测。通过突出传统神经影像学分析中隐藏的具有行为意义的神经机制，本研究推进了对强迫症神经基础的认识，并为强迫观念和强迫行为提供了新的治疗靶点。
