Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, United Kingdom; The National Hospital for Neurology and Neurosurgery, London, United Kingdom.
Department of Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
Biol Psychiatry. 2019 May 1;85(9):726-734. doi: 10.1016/j.biopsych.2019.01.017. Epub 2019 Jan 30.
Deep brain stimulation (DBS) is an emerging treatment for severe obsessive-compulsive disorder (OCD). We compared the efficacy of ventral capsule/ventral striatal (VC/VS) and anteromedial subthalamic nucleus (amSTN) DBS in the same patients and tested for mechanistic differences on mood and cognitive flexibility and associated neural circuitry. The possible synergistic benefit of DBS at both sites and cognitive behavioral therapy was explored.
Six patients with treatment-refractory OCD (5 men; Yale-Brown Obsessive Compulsive Scale score >32) entered double-blind counterbalanced phases of 12-week amSTN or VC/VS DBS, followed by 12-week open phases when amSTN and VC/VS were stimulated together, in which optimal stimulation parameters were achieved and adjunctive inpatient cognitive behavioral therapy was delivered. OCD and mood were assessed with standardized scales and cognitive flexibility with the Cambridge Neuropsychological Test Automated Battery Intra-Extra Dimensional Set-Shift task. Diffusion-weighted and intraoperative magnetic resonance imaging scans were performed for tractography from optimally activated electrode contacts.
DBS at each site significantly and equivalently reduced OCD symptoms with little additional gain following combined stimulation. amSTN but not VC/VS DBS significantly improved cognitive flexibility, whereas VC/VS DBS had a greater effect on mood. The VC/VS effective site was within the VC. VC DBS connected primarily to the medial orbitofrontal cortex, and amSTN DBS to the lateral orbitofrontal cortex, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex. No further improvement followed cognitive behavioral therapy, reflecting a floor effect of DBS on OCD.
Both the VC/VS and amSTN are effective targets for severe treatment-refractory OCD. Differential improvements in mood and cognitive flexibility and their associated connectivity suggest that DBS at these sites modulates distinct brain networks.
深部脑刺激（DBS）是一种治疗重度强迫症（OCD）的新兴方法。我们比较了腹侧壳核/腹侧纹状体（VC/VS）和前内侧苍白球（amSTN）DBS 在同一患者中的疗效，并测试了其对情绪和认知灵活性以及相关神经回路的机制差异。还探索了这两个部位的 DBS 与认知行为疗法相结合的协同益处。
6 名治疗抵抗性 OCD 患者（5 名男性；耶鲁-布朗强迫症量表评分>32）进入 12 周 amSTN 或 VC/VS DBS 的双盲对照阶段，随后进入 12 周的开放阶段，此时 amSTN 和 VC/VS 同时刺激，以达到最佳刺激参数，并提供附加的住院认知行为疗法。使用标准化量表评估 OCD 和情绪，使用剑桥神经心理学测试自动化电池内外维度转换任务评估认知灵活性。进行弥散加权和术中磁共振成像扫描，以进行来自最佳激活电极触点的轨迹追踪。
每个部位的 DBS 均显著且等效地降低了 OCD 症状，而联合刺激后几乎没有额外获益。amSTN 但不是 VC/VS DBS 显著改善了认知灵活性，而 VC/VS DBS 对情绪的影响更大。VC/VS 的有效部位位于 VC 内。VC/VS DBS 主要连接内侧眶额皮质，amSTN DBS 连接外侧眶额皮质、背侧前扣带回皮质和背外侧前额皮质。认知行为疗法后没有进一步改善，反映了 DBS 对 OCD 的疗效下限。
VC/VS 和 amSTN 都是治疗重度治疗抵抗性 OCD 的有效靶点。情绪和认知灵活性的改善及其相关连接的差异表明，这些部位的 DBS 调节了不同的大脑网络。
