Supplementary Material for: Stimulation Sweet Spot in Subthalamic Deep Brain Stimulation – Myth or Reality? A Critical Review of Literature

Introduction: While deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been extensively used for more than 20 years in Parkinson’s disease (PD), the optimal area of stimulation to relieve motor symptoms remains elusive. Objective: We aimed at localizing the sweet spot within the subthalamic region by performing a systematic review of the literature. Method: PubMed database was searched for published studies exploring optimal stimulation location for STN DBS in PD, published between 2000 and 2019. A standardized assessment procedure based on methodological features was applied to select high-quality publications. Studies conducted more than 3 months after the DBS procedure, employing lateralized scores and/or stimulation condition, and reporting the volume of tissue activated or the position of the stimulating contact within the subthalamic region were considered in the final analysis. Results: Out of 439 references, 24 were finally retained, including 21 studies based on contact location and 3 studies based on volume of tissue activated (VTA). Most studies (all VTA-based studies and 13 of the 21 contact-based studies) suggest the superior-lateral STN and the adjacent white matter as the optimal sites for stimulation. Remaining contact-based studies were either inconclusive (5/21), favoured the caudal zona incerta (1/21), or suggested a better outcome of STN stimulation than adjacent white matter stimulation (2/21). Conclusion: Using a standardized methodological approach, our review supports the presence of a sweet spot located within the supero-lateral STN and extending to the adjacent white matter.

引言：尽管丘脑底核（subthalamic nucleus, STN）脑深部电刺激术（deep brain stimulation, DBS）在帕金森病（Parkinson’s disease, PD）中已被广泛应用逾20年，但用于缓解运动症状的最优刺激区域仍未明确。
研究目的：本研究旨在通过对现有文献开展系统综述，定位丘脑底核区域内的最优刺激位点（sweet spot）。
方法：检索PubMed数据库，筛选2000年至2019年间发表的、针对帕金森病患者丘脑底核脑深部电刺激术最优刺激位点的相关研究。采用基于方法学特征的标准化评估流程遴选高质量文献。最终纳入分析的研究需满足以下条件：于脑深部电刺激术完成3个月后实施、采用偏侧化评分和/或刺激条件进行评估、并报告激活组织体积（volume of tissue activated, VTA）或刺激触点在丘脑底核区域内的位置。
结果：在439篇参考文献中，最终纳入24项研究，其中21项基于刺激触点位置展开分析，3项基于激活组织体积（VTA）。多数研究（所有基于VTA的研究以及21项基于触点位置研究中的13项）提示，丘脑底核上外侧区域及其邻近白质为最优刺激位点。其余基于触点位置的研究中，5项结论无明确指向、1项支持尾侧未定带作为最优靶点，另有2项提示丘脑底核刺激的效果优于邻近白质刺激。
结论：通过采用标准化的方法学流程，本系统综述证实丘脑底核上外侧区域存在最优刺激位点，且该位点可延伸至其邻近白质。