Computational Modeling of Deep Brain Stimulation of the Ventral Striatum

该项目将从麦金太尔实验室转移一种计算建模技术“StimVision”， 凯斯西储大学到马萨诸塞州的脑深部电刺激（DBS）小组 医院（MGH）。DBS目前用于治疗严重的强迫症（OCD）， 腹侧内囊/腹侧纹状体（VC/VS）的高频电刺激。VC/VS是一个 复杂的大脑区域，包含投射到多个额叶皮质区域的白色物质束。是 我们不知道哪种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并激活这种电不规则 组织.这导致临床效果非常不一致（约50%的患者反应不佳或根本没有反应） 这种侵入性的昂贵手术StimVision旨在模拟这些电场，但 不适合或部署在该特定应用中。作为BRAIN倡议努力的一部分， 为了在实验室之间转移方法，McIntyre小组将使StimVision适应VC/VS建模 并训练MGH团队使用它。然后，我们将部署它作为我们正在进行的分析的一部分， 神经生理学和行为学数据。我们希望表明，使用 这些先进的建模技术阐明了已知行为效应的神经机制， 通过补偿异质VC/VS解剖结构。 我们的目标是实现技术转让，并证明MGH成功地“吸收”了 方法，以便我们可以独立地使用它们。我们通过两个途径来解决这个问题 目标。目标1代表病例组对StimVision用户界面和算法的变更 与MGH的成像和分析工作流程兼容。这包括改进 电模型，可能需要适当捕捉VC/VS的影响，并结合新的 最初由MGH/Brigham合作者开发的纤维束成像算法。目标2然后转移初始 和修订版本的StimVision MGH，并证明其成功地用于数据分析。 我们将重新分析两个MGH数据集，一个关于轻躁狂（一种主要的DBS副作用），另一个关于抑郁症（一种主要的DBS副作用）。 关于在心理物理任务期间DBS操纵的行为影响。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皮层回路， 影响，并进一步假设这将主要涉及前扣带。这个目标 然而，目的并不一定是证明这些假设。它是技术转让的示范， 这是该脑部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.