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Computational Modeling of Deep Brain Stimulation of the Ventral Striatum

腹侧纹状体深部脑刺激的计算模型

基本信息

批准号：
9203462
负责人：
DARIN D DOUGHERTY
金额：
$ 18.25万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-22 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9203462
关键词：
Accounting Adverse effects Affect Algorithms Americas Anatomy Anterior BRAIN initiative Behavioral Brain Brain region Caring Clinical Clinical Research Clinical Trials Cognition Cognitive Complex Computer Simulation Computer software Conflict (Psychology)Custom Data Data Analyses Data Set Deep Brain Stimulation Dissection Dorsal Electric Stimulation Electrodes Event-Related Potentials Fiber Frequencies General Hospitals Goals Habits Human Image Image Analysis Impairment Implant Institution Internal Capsule Intervention Label Laboratories Learning Life Maps Massachusetts Mental disorders Methods Modeling Movement Disorders Neurosciences Nucleus Accumbens Obsessive-Compulsive Disorder Outcome Patients Performance Prefrontal Cortex Procedures Protocols documentation Psychophysics Reaction Time Research Research Domain Criteria Rewards Services Site Source Structure Techniques Technology Technology Transfer Testing Tissues Training Treatment Efficacy Universities Ventral Striatum Work brain tissue clinical effect cohort computer science design electric field executive function hypomania improved insight neuromechanism neurotechnology next generation novel programs response software development success theories tool treatment-resistant depression uptake white matter

项目摘要

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.

该项目将转移来自 McIntyre 实验室的计算建模技术“StimVision” 凯斯西储大学到马萨诸塞州总医院深部脑刺激 (DBS) 小组医院（麻省总医院）。 DBS 目前用于治疗严重强迫症 (OCD) 腹侧内囊/腹侧纹状体（VC/VS）的高频电刺激。 VC/VS 是包含投射到多个额叶皮层区域的白质束的复杂大脑区域。这是不了解哪些 VC/VS 纤维对 DBS 对 OCD 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不规则的电组织。这导致临床效果非常不一致（大约 50% 的患者反应不佳或根本没有反应）对于这种侵入性且昂贵的手术。 StimVision 旨在模拟这些电场，但尚未适应或部署在此特定应用程序中。作为 BRAIN Initiative 努力的一部分实验室之间转移方法，McIntyre 团队将采用 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持续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。我们希望表明使用这些先进的建模技术阐明了已知行为效应背后的神经机制，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展示 MGH 成功“吸收”了方法，使我们可以在未来独立使用它们。我们通过两个方法来解决这个问题目标。目标 1 代表案例组对 StimVision 用户界面和算法的更改与 MGH 的成像和分析工作流程兼容。这包括对以下方面的改进正确捕获 VC/VS 效应并结合新颖的电气模型可能是必要的纤维束成像算法最初由 MGH/Brigham 合作者开发。目标 2 然后转移初始以及 StimVision 到 MGH 的修订版本，并展示了它们在数据分析中的成功应用。我们将重新分析两个 MGH 数据集，一个涉及轻躁狂（DBS 的主要副作用），另一个涉及轻度躁狂（DBS 的主要副作用）关于在心理物理任务期间 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功能的皮层回路效应，并进一步假设这将主要涉及前扣带回。此举的目标然而，目的不一定是证明这些假设。这是技术转移的示范，此 BRAIN RFA 的核心成功标准。