Pathway-Specific Targeting in Subcallosal Cingulate Deep Brain Stimulation for Depression

项目摘要 抑郁症是世界范围内残疾的主要原因，对于1- 2%的治疗抵抗性个体， 一种慢性的、持续的过程，胼胝体下扣带回（SCC）脑深部电刺激（DBS）是一种不断发展的 实验策略不同临床中心对SCC DBS的治疗反应差异很大， 需要客观的标准来帮助减轻未来临床试验中的可变结果。Connectomic DBS 建模是使SCC DBS的管理标准化和简化的一种途径。的 R 01 MH 102238前5年的开创性工作为DBS研究的新时代奠定了基础， 识别用于前瞻性手术计划的“连接组靶向”。我们新颖的个性化方法 精准医疗已经大大改善了SCC DBS的长期结局，但这种模式- 在其关键的行业赞助的试验中，没有基于的策略，该试验的结果不理想。 尽管如此，多个小组继续开发SCC DBS。临床试验在Mt。西奈半岛（UH 3 NS 103550）是 结合神经影像学和电生理学来优化DBS治疗抑郁症，这项提议增强了 努力，同时利用与其主题相关的独特临床数据集。我们的假设是 小镊子和扣带束是SCC DBS最可能的治疗靶点。整体 因此，该提议的目的是用计算的严格性来测试连接组学假设， 电生理验证第一个目标是开发一个标准的生物物理连接体， 用于基于连接组学假设在从头受试者中定制和优化参数。结果 这一目标将是在标准临床工作流程中处理连接组DBS策略的基础 大规模应用SCC DBS技术。第二个目标将完善SCC DBS生物物理 连接体使用高密度脑电图收集每月作为一个标准的研究协议的一部分，在山。西奈半岛，以及 然后，我们将使用连接模型来描绘特定的生物电头皮签名激活镊子 小的和至少一个扣带束。第三个目标将从理论上评估最佳方向和电流- SCC DBS在两个用例中的转向策略，即能量优化和孤立/局灶性目标激活。的 该提案的成果将是一套经过验证的计算工具，可用于近实时参数 定制和优化SCC DBS。个性化、可部署的基于模型的精确策略 DBS是重要的，因为它们有现实的机会来简化参数选择的过程， 有助于在未来的SCC DBS研究中使器械程控更加客观，变量更少。

Project Summary Depression is the leading cause of disability worldwide, and for the 1-2 % of treatment-resistant individuals with a chronic, unremitting course, subcallosal cingulate (SCC) deep brain stimulation (DBS) is an evolving experimental strategy. Treatment responses to SCC DBS are highly variable across different clinical centers, and objective standards are needed to help mitigate variable outcomes in future clinical trials. Connectomic DBS modeling is one avenue that holds promise for standardizing and simplifying the administration of SCC DBS. The pioneering work of the first 5 years of R01 MH102238 set the stage for a new era in DBS research, with the initial identification of “connectomic targeting” for prospective surgical planning. Our novel approach to individualized precision medicine has resulted in substantial improvements to SCC DBS' long-term outcomes, but this model- based strategy was not available in its pivotal industry-sponsored trial, which suffered from suboptimal outcomes. Nonetheless, multiple groups continue to develop SCC DBS. The clinical trial at Mt. Sinai (UH3 NS103550) is combining neuroimaging and electrophysiology to optimize DBS for depression, and this proposal augments that effort, while leveraging the unique clinical datasets associated with its subjects. Our working hypothesis is that forceps minor and the cingulum bundle are the most probable therapeutic targets of SCC DBS. The overall objective of this proposal is therefore to test that connectomic hypothesis with computational rigor and electrophysiological validation. The first aim will develop a standard biophysical connectome that can be used for customization and optimization of parameters in de novo subjects based on connectomic hypotheses. Results from this aim will be fundamental for processing connectomic DBS strategies within standard clinical workflows and applying SCC DBS technology on a larger scale. The second aim will refine the SCC DBS biophysical connectome using high-density EEG collected monthly as part of a standard research protocol at Mt. Sinai, and then we will use the connectomic model to delineate specific bioelectric scalp signatures for activation of forceps minor and at least one cingulum bundle. The third aim will evaluate theoretically optimal directional and current- steering strategies for SCC DBS in two use cases, energy-optimization and isolated/focal target activation. The proposal's outcome will be a validated set of computational tools that can be used for near real-time parameter customization and optimization in SCC DBS. Individualized, deployable model-based strategies for precision DBS are significant because they have a realistic opportunity to simplify the process of parameter selection and help make device programming more objective, and less variable, in future studies of SCC DBS.