Computational Modeling of Deep Brain Stimulation of the Ventral Striatum

该项目将把麦金太尔实验室的计算建模技术StimVision转移到 凯斯西部储备大学到马萨诸塞州综合医院的脑深部刺激(DBS)小组 医院(MGH)。DBS目前用于治疗严重强迫症(OCD)，通过 高频电刺激腹侧内囊/腹侧纹状体(VC/VS)。VC/VS是一个 复杂的脑区，包含向多个额叶皮质区域投射的白质束。它是 不知道哪些VC/VS纤维对DBS治疗强迫症的临床效果最重要，部分原因是我们知道 不知道刺激器的电场如何传播通过并激活这个不规则的电 组织。这导致了非常不一致的临床效果(大约50%的患者反应很差或根本没有反应) 为这一侵入性且昂贵的手术。StimVision旨在对这些电场进行建模，但它已经 未适应或部署在此特定应用程序中。作为大脑倡议努力的一部分 在实验室之间转移方法，McIntyre小组将采用StimVision进行VC/VS建模 并对MGH团队进行使用培训。然后，我们将部署它作为我们正在进行的分析的一部分 我们现有患者队列中的神经生理学和行为数据。我们希望展示使用 这些先进的建模技术阐明了潜在的已知行为效应的神经机制， 通过补偿不同的VC/VS结构。 我们的目标是实现这一技术转让，并证明MGH成功地“吸收”了 方法，这样我们就可以在将来独立使用它们。我们通过两个途径来解决这个问题 目标。目标1代表案例组对StimVision的用户界面和算法的更改 与MGH的成像和分析工作流程兼容。这包括对 正确捕获VC/VS效果和整合新技术可能需要的电气模型 跟踪算法最初是由MGH/Brigham的合作者开发的。然后，AIM 2将初始 以及StimVision到MGH的修订版，并演示了它们在数据分析中的成功使用。 我们将重新分析两个MGH数据集，一个是关于低躁狂(DBS的一个主要副作用)，另一个是 关于心理物理任务中DBS操作的行为影响。在这两种情况下，我们 假设使用StimVision建模将进一步阐明支撑这些的大脑皮层回路 影响，并进一步假设这将主要牵涉到前扣带回。这样做的目的是 然而，目的并不一定是要证明这些假设。它是技术转让的示范， 这个大脑RFA的核心成功标准。

This project will transfer a computational modeling technology, "StimVision", from the McIntyre Lab at Case Western Reserve University to the deep brain stimulation (DBS) group at Massachusetts General Hospital (MGH). DBS is currently used to treat severe obsessive-compulsive disorder (OCD) through high-frequency electrical stimulation of the ventral internal capsule/ventral striatum (VC/VS). VC/VS is a complex brain region containing white matter tracts projecting to multiple frontal cortical regions. It is not understood which VC/VS fibers matter most to DBS' clinical effects on OCD, in part because we do not know how the stimulator's electrical field propagates through and activates this electrically irregular tissue. This leads to very inconsistent clinical effects (about 50% of patients respond poorly or not at all) for this invasive and expensive procedure. StimVision is designed to model those electric fields, but has not been adapted to or deployed in this specific application. As part of the BRAIN Initiative's efforts to transfer methods between laboratories, the McIntyre group will adapt StimVision for VC/VS modeling and train the MGH team in its use. We will then deploy it as part of our ongoing analysis of neurophysiologic and behavioral data in our existing patient cohort. We expect to show that the use of these advanced modeling techniques clarifies neural mechanisms underlying known behavioral effects, by compensating for heterogeneous VC/VS anatomy. Our Objective is to achieve that technology transfer and demonstrate MGH's successful "uptake" of the methods to the point that we can use them independently going forward. We approach this through two Aims. Aim 1 represents the Case group's alterations to the user interface and algorithms of StimVision to be compatible with MGH's imaging and analysis workflows. This includes improvements to the electrical models that may be necessary for properly capturing VC/VS effects and incorporating novel tractography algorithms originally developed by MGH/Brigham collaborators. Aim 2 then transfers initial and revised versions of StimVision to MGH and demonstrates their successful use for data analysis. We will re-analyze two MGH datasets, one concerning hypomania (a major DBS side effect) and one concerning behavioral effects from DBS manipulation during a psychophysical task. In both cases, we hypothesize that use of StimVision modeling will further clarify the cortical circuits underpinning these effects, and further hypothesize that this will primarily implicate the anterior cingulate. The goal of this Aim, however, is not necessarily to prove these hypotheses. It is demonstration of technology transfer, the core success criterion of this BRAIN RFA.