Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Nat Commun. 2023 Sep 4;14(1):5385. doi: 10.1038/s41467-023-41026-x.
Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of action. To gain mechanistic insight, we monitored neuronal activity in cortico-striatal regions in a mouse model for compulsive behavior, while systematically varying clinically-relevant parameters of internal-capsule DBS. DBS showed dose-dependent effects on both brain and behavior: An increasing, yet balanced, number of excited and inhibited neurons was recruited, scattered throughout cortico-striatal regions, while excessive grooming decreased. Such neuronal recruitment did not alter basic brain function such as resting-state activity, and only occurred in awake animals, indicating a dependency on network activity. In addition to these widespread effects, we observed specific involvement of the medial orbitofrontal cortex in therapeutic outcomes, which was corroborated by optogenetic stimulation. Together, our findings provide mechanistic insight into how DBS exerts its therapeutic effects on compulsive behaviors.
脑深部刺激（DBS）是一种治疗其他治疗方法抵抗性精神障碍的有效方法，包括强迫症。皮质纹状体回路的调制被认为是一种作用机制。为了获得机制上的见解，我们在强迫行为的小鼠模型中监测皮质纹状体区域的神经元活动，同时系统地改变内部囊 DBS 的临床相关参数。DBS 对大脑和行为表现出剂量依赖性影响：招募了越来越多但平衡的兴奋和抑制神经元，分布在皮质纹状体区域，而过度梳理减少。这种神经元募集不会改变静息状态活动等基本大脑功能，并且仅在清醒动物中发生，表明对网络活动的依赖性。除了这些广泛的影响外，我们还观察到内侧眶额皮层在治疗结果中的特定参与，这一点得到了光遗传学刺激的证实。总的来说，我们的发现为 DBS 如何对强迫症行为产生治疗效果提供了机制上的见解。
