Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah; Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah.
Functional Neurosurgery Unit, Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, United Kingdom.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Oct;6(10):961-972. doi: 10.1016/j.bpsc.2020.11.005. Epub 2020 Nov 24.
Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) can improve tics and comorbid obsessive-compulsive behavior (OCB) in patients with treatment-refractory Tourette syndrome (TS). However, some patients' symptoms remain unresponsive, the stimulation applied across patients is variable, and the mechanisms underlying improvement are unclear. Identifying the fiber pathways surrounding the GPi that are associated with improvement could provide mechanistic insight and refine targeting strategies to improve outcomes.
Retrospective data were collected for 35 patients who underwent bilateral GPi DBS for TS. Computational models of fiber tract activation were constructed using patient-specific lead locations and stimulation settings to evaluate the effects of DBS on basal ganglia pathways and the internal capsule. We first evaluated the relationship between activation of individual pathways and symptom improvement. Next, linear mixed-effects models with combinations of pathways and clinical variables were compared in order to identify the best-fit predictive models of tic and OCB improvement.
The best-fit model of tic improvement included baseline severity and the associative pallido-subthalamic pathway. The best-fit model of OCB improvement included baseline severity and the sensorimotor pallido-subthalamic pathway, with substantial evidence also supporting the involvement of the prefrontal, motor, and premotor internal capsule pathways. The best-fit models of tic and OCB improvement predicted outcomes across the cohort and in cross-validation.
Differences in fiber pathway activation likely contribute to variable outcomes of DBS for TS. Computational models of pathway activation could be used to develop novel approaches for preoperative targeting and selecting stimulation parameters to improve patient outcomes.
深部脑刺激（DBS）靶向苍白球 internus（GPi）可以改善治疗抵抗性妥瑞氏综合征（TS）患者的抽动和共病强迫行为（OCB）。然而，一些患者的症状仍然没有反应，应用于患者之间的刺激是不同的，改善的机制尚不清楚。确定与改善相关的围绕 GPi 的纤维通路可以提供机制见解，并改进靶向策略以改善结果。
回顾性收集了 35 名接受双侧 GPi DBS 治疗 TS 的患者数据。使用患者特异性导联位置和刺激设置构建纤维束激活的计算模型，以评估 DBS 对基底节通路和内囊的影响。我们首先评估了个体通路激活与症状改善之间的关系。接下来，比较了包含通路和临床变量的线性混合效应模型，以确定抽动和 OCB 改善的最佳拟合预测模型。
抽动改善的最佳拟合模型包括基线严重程度和关联苍白球丘脑底核通路。OCB 改善的最佳拟合模型包括基线严重程度和感觉运动苍白球丘脑底核通路，并且有大量证据表明还涉及前额叶、运动和运动前内囊通路。抽动和 OCB 改善的最佳拟合模型预测了整个队列和交叉验证中的结果。
纤维通路激活的差异可能导致 DBS 治疗 TS 的结果不同。通路激活的计算模型可用于开发新的术前靶向方法和选择刺激参数，以改善患者的结果。
