Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands; Maastricht Brain Imaging Centre, Maastricht, the Netherlands.
Neuroimage. 2024 Mar;288:120527. doi: 10.1016/j.neuroimage.2024.120527. Epub 2024 Jan 28.
Treatment-resistant obsessive-compulsive disorder (OCD) generally improves with deep-brain stimulation (DBS), thought to modulate neural activity at both the implantation site and in connected brain regions. However, its invasive nature, side-effects, and lack of customization, make non-invasive treatments preferable. Harnessing the established remote effects of cortical transcranial magnetic stimulation (TMS), connectivity-based approaches have emerged for depression that aim at influencing distant regions connected to the stimulation site. We here investigated whether effective OCD DBS targets (here subthalamic nucleus [STN] and nucleus accumbens [NAc]) could be modulated non-invasively with TMS. In a proof-of-concept study with nine healthy individuals, we used 7T magnetic resonance imaging (MRI) and probabilistic tractography to reconstruct the fiber tracts traversing manually segmented STN/NAc. Two TMS targets were individually selected based on the strength of their structural connectivity to either the STN, or both the STN and NAc. In a sham-controlled, within-subject cross-over design, TMS was administered over the personalized targets, located around the precentral and middle frontal gyrus. Resting-state functional 3T MRI was acquired before, and at 5 and 25 min after stimulation to investigate TMS-induced changes in the functional connectivity of the STN and NAc with other regions of the brain. Static and dynamic seed-to-voxel correlation analyses were conducted. TMS over both targets was able to modulate the functional connectivity of the STN and NAc, engaging both overlapping and distinct regions, and unfolding following different temporal dynamics. Given the relevance of the engaged connected regions to OCD pathology, we argue that a personalized, connectivity-based procedure is worth investigating as potential treatment for refractory OCD.
治疗抵抗性强迫症（OCD）通常随着深部脑刺激（DBS）而改善，被认为可调节植入部位和连接脑区的神经活动。然而，其侵入性、副作用和缺乏定制化使其更倾向于使用非侵入性治疗。皮质经颅磁刺激（TMS）的既定远程效应已被利用，用于旨在影响与刺激部位相连的远距离区域的连接性方法已应用于抑郁症。我们在此研究了是否可以用 TMS 非侵入性地调节有效的 OCD DBS 靶点（这里是丘脑底核[STN]和伏隔核[NAc]）。在一项具有 9 名健康个体的概念验证研究中，我们使用 7T 磁共振成像（MRI）和概率追踪来重建手动分割的 STN/NAc 穿过的纤维束。根据其与 STN 的结构连接强度，或者与 STN 和 NAc 的结构连接强度，分别选择两个 TMS 靶点。在一项假刺激对照、个体内交叉设计中，将 TMS 施加于个性化靶点，位于中央前回和额中回周围。在刺激前、刺激后 5 分钟和 25 分钟采集静息状态功能 3T MRI，以研究 TMS 对 STN 和 NAc 与大脑其他区域的功能连接的诱导变化。进行了静态和动态种子到体素相关分析。对两个靶点的 TMS 都能够调节 STN 和 NAc 的功能连接，涉及重叠和不同的区域，并具有不同的时间动态。鉴于所涉及的连接区域与 OCD 病理的相关性，我们认为个性化、基于连接的程序值得作为难治性 OCD 的潜在治疗方法进行研究。
