Slepneva Natalya, Basich-Pease Genevieve, Reid Lee, Frank Adam C, Norbu Tenzin, Krystal Andrew D, Sugrue Leo P, Motzkin Julian C, Larson Paul S, Starr Philip A, Morrison Melanie A, Lee A Moses
Weill Institute for Neurosciences, University of California, San Francisco, California, USA.
Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, California, USA.
Hum Brain Mapp. 2024 Dec 15;45(18):e70106. doi: 10.1002/hbm.70106.
Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) is a circuit-based treatment for severe, refractory obsessive-compulsive disorder (OCD). The therapeutic effects of DBS are hypothesized to be mediated by direct modulation of a distributed cortico-striato-thalmo-cortical network underlying OCD symptoms. However, the exact underlying mechanism by which DBS exerts its therapeutic effects still remains unclear. In five participants receiving DBS for severe, refractory OCD (3 responders, 2 non-responders), we conducted a DBS On/Off cycling paradigm during the acquisition of functional MRI (23 fMRI runs) to determine the network effects of stimulation across a variety of bipolar configurations. We also performed tractography using diffusion-weighted imaging (DWI) to relate the functional impact of DBS to the underlying structural connectivity between active stimulation contacts and functional brain networks. We found that therapeutic DBS had a distributed effect, suppressing BOLD activity within regions such as the orbitofrontal cortex, dorsomedial prefrontal cortex, and subthalamic nuclei compared to non-therapeutic configurations. Many of the regions suppressed by therapeutic DBS were components of the default mode network (DMN). Moreover, the estimated stimulation field from the therapeutic configurations exhibited significant structural connectivity to core nodes of the DMN. Based upon these findings, we hypothesize that the suppression of the DMN by ALIC DBS is mediated by interruption of communication through structural white matter connections surrounding the DBS active contacts.
内囊前肢（ALIC）的深部脑刺激（DBS）是一种针对严重、难治性强迫症（OCD）的基于神经环路的治疗方法。DBS的治疗效果据推测是通过直接调节OCD症状背后的分布式皮质-纹状体-丘脑-皮质网络来介导的。然而，DBS发挥其治疗作用的确切潜在机制仍不清楚。在五名接受DBS治疗严重、难治性OCD的参与者（3名有反应者，2名无反应者）中，我们在功能磁共振成像（fMRI）采集期间（23次fMRI扫描）进行了DBS开/关循环范式，以确定在各种双极配置下刺激的网络效应。我们还使用扩散加权成像（DWI）进行了纤维束成像，以将DBS的功能影响与活跃刺激触点和功能性脑网络之间的潜在结构连接联系起来。我们发现，与非治疗性配置相比，治疗性DBS具有分布式效应，可抑制眶额叶皮质、背内侧前额叶皮质和丘脑底核等区域内的血氧水平依赖（BOLD）活动。许多被治疗性DBS抑制的区域是默认模式网络（DMN）的组成部分。此外，治疗性配置估计的刺激场与DMN的核心节点表现出显著的结构连接。基于这些发现，我们推测ALIC DBS对DMN的抑制是通过围绕DBS活跃触点的结构性白质连接中断通信来介导的。
