Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, USA.
Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah, USA.
Brain. 2020 Aug 1;143(8):2607-2623. doi: 10.1093/brain/awaa188.
Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate 'reverse' tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P < 0.017). For centromedial thalamus, connectivity to sensorimotor networks, parietal-temporal-occipital networks, putamen, and cerebellum was positively correlated with tic improvement; the model predicted clinical improvement scores (P = 0.012) and was robust to cross-validation. Regions in the anterior/lateral centromedial thalamus exhibited higher connectivity to the positively correlated networks, but volume of tissue activated overlap with this map did not predict improvement (P > 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.
深部脑刺激可能是治疗某些严重、治疗抵抗性抽动秽语综合征的有效方法;然而,患者的反应各不相同,并且没有可靠的方法来预测临床结果。本回顾性研究的目的是确定与 tic 和共患强迫症行为改善相关的刺激依赖性结构网络,比较不同手术靶点的网络,并确定连接是否可用于预测临床结果。使用为双侧植入苍白球内(n=34)或中央中脑(n=32)的大的多部位队列患者(n=66)的组织激活体积生成概率轨迹以形成规范结构连接组。轨迹图用于识别与 tic 或共患强迫症行为改善相关的网络,并预测整个队列的临床结果。然后,使用相关网络生成“反向”轨迹以将所有患者的总刺激体积划分为局部区域以进行靶向或避免。结果表明,对于苍白球内,与边缘网络、联合网络、尾状核、丘脑和小脑的连接与 tic 的改善呈正相关;该模型预测了临床改善评分(P=0.003),并且对交叉验证具有鲁棒性。前内侧苍白球附近的区域与正相关网络的连接性高于后腹侧苍白球,并且与该图重叠的组织激活体积与 tic 改善显著相关(P<0.017)。对于中央中脑,与感觉运动网络、顶叶颞叶枕叶网络、壳核和小脑的连接与 tic 改善呈正相关;该模型预测了临床改善评分(P=0.012),并且对交叉验证具有鲁棒性。前/外侧中央中脑的区域与正相关网络的连接性较高,但与该图重叠的组织激活体积不能预测改善(P>0.23)。对于强迫症行为,两个靶点都显示与前额叶皮层、眶额皮层和扣带皮层的连接呈正相关与改善相关;然而,只有中央中脑的地图预测了整个队列的临床结果(P=0.034),但该模型对交叉验证不稳健。总的来说,结果表明刺激部位的结构连接可能对介导症状改善很重要,并且 tic 改善涉及的网络可能因手术靶点而异。这些网络提供了对潜在机制的重要见解,并可用于指导导联放置和刺激参数选择,以及细化抽动秽语综合征的神经调节治疗靶点。
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