Development of a Micro-ECoG Neuroprosthesis for Motor Rehabilitation in a Chronic Corticospinal Stroke Injury

开发用于慢性皮质脊髓中风损伤运动康复的微型 ECoG 神经假体

• 批准号: 10065528
• 负责人: Eric CLAUDE Leuthardt
• 金额: $ 56.34万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10065528
• 关键词: Acute; Affect; Anatomy; Animal Model; Behavioral; Brain; Chronic; Clinical; Corticospinal Tracts; Coupled; Data; Development; Devices; Electrodes; Electrophysiology (science); Feedback; Foundations; Frequencies; Functional Imaging; Functional disorder; Goals; Hand; Human; Impairment; Implant; Industry; Injury; Intention; Internal Capsule; Intervention; Knowledge; Lesion; Limb structure; Link; Macaca; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Methods; Mission; Modeling; Monkeys; Motor; Motor Cortex; Movement; National Institute of Neurological Disorders and Stroke; Orthotic Devices; Outcome; Paresis; Patients; Performance; Pharmacology; Physiology; Play; Primates; Public Health; Quality of life; Recovery; Recovery of Function; Rehabilitation therapy; Research; Robotics; Role; Signal Transduction; Site; Source; Stroke; Technology; Testing; Therapeutic; Translations; Universities; Washington; Work; behavioral impairment; brain computer interface; chronic stroke; clinically significant; functional gain; functional restoration; gray matter; haptic feedback; hemiparesis; improved; injured; innovation; insight; motor deficit; motor impairment; motor recovery; motor rehabilitation; multimodality; nervous system disorder; neuroprosthesis; nonhuman primate; novel; pilot trial; pre-clinical; recruit; rehabilitation strategy; restoration; stroke model; stroke patient; stroke survivor; stroke therapy; tool; white matter; white matter injury

In rehabilitating chronic motor-impaired stroke survivors with a brain computer interface (BCI), there is a fundamental gap in understanding how the brain changes with injury and in how a BCI can engage these dynamics to induce a functional recovery. The current barrier is the absence of a primate model that can test a BCI strategy in chronic stroke. The majority of animal models employ gray matter lesions, while the majority of clinically significant strokes involve the deeper white matter. The long-term goal of this project is to restore motor function by synergizing the patient's BCI rehabilitative strategy with their specific stroke-induced pathophysiology. The overall objective of this proposal is to create a nonhuman primate model for stroke that will examine the evolving physiology following a microvascular corticospinal tract (CST) lesion and test the impact of a neuroprosthetic intervention for functional restoration in the chronic setting. The central hypothesis is that BCI-driven motor rehabilitation for a CST injury will be effective when the control signals from the unaffected hemisphere are paired with proprioceptive feedback. The rationale for this research is that the animal model and the accrued scientific insights will create a mechanism-driven approach to neuroprosthetic solutions for stroke. Guided by strong preliminary evidence, we will test the central hypothesis with the following three specific aims: 1) Create a cortical electrode to enable multimodal measurements of the brain before and after a microvascular lesion to the CST, 2) Define acute and chronic alterations in cortical physiology and behavioral performance associated with a microvascular lesion to the CST, and 3) Restore motor function in macaque monkey with chronic CST injury using BCI rehabilitation. Under the first aim we will create a bihemispheric, MRI-invisible, micro-electrocorticographic (µECoG) implant that can measure the cortical physiology of ipsilesional and contralesional motor cortex and enable functional and anatomical magnetic resonance imaging. In the second aim, this implant, along with a new method for creating a stereotactic lesion to the posterior limb of the internal capsule, will enable us to link the micro-scale cortical electrophysiology with larger scale functional imaging as the brain changes from the central insult. Under the third aim, the chronically paretic monkeys will be rehabilitated using signal sources from the contralesional hemisphere. This project is innovative because it is a substantial departure from the status quo by expanding the role the unaffected hemisphere and bihemispheric interactions can play in BCI-mediated rehabilitation. The proposed research will be significant because the knowledge will create a critical bridge between motor function, electrophysiology, and functional imaging, which will vastly improve the characterization of how the cortical dynamics are perturbed with a white matter stroke and subsequently how these changes can be targeted for a tailored neuroprosthetic intervention. Ultimately, this will inform the development of novel treatments for stroke patients in the U.S.

在使用大脑计算机界面（BCI）恢复慢性运动障碍的中风存活时，有一个 了解大脑如何随伤害以及BCI如何参与这些的根本差距 诱导功能恢复的动力学。当前的障碍是缺乏可以测试A的私人模型 慢性中风的BCI策略。大多数动物模型员工灰质病变，而大多数 临床上重要的中风涉及更深的白质。该项目的长期目标是恢复 通过使患者的BCI康复策略协同其特定的中风引起的运动功能 病理生理学。该提案的总体目的是创建一种非人类的私人模型，以供行程 将检查微血管皮质脊髓束（CST）病变后不断发展的生理学 神经假体干预对慢性环境中功能恢复的影响。中心假设 当来自CST受伤的BCI驱动的电动机康复是否会在控制信号中有效 未受影响的半球与本体感受反馈配对。这项研究的理由是 动物模型和累积的科学见解将创建一种机制驱动的神经假体方法 中风解决方案。在强有力的初步证据的指导下，我们将测试中心假设 以下三个具体目的：1）创建一个皮层电极以实现大脑的多模式测量 微血管病变前后CST，2）定义皮质中的急性和慢性改变 与CST的微血管病变相关的生理学和行为表现，3）还原 使用BCI康复的慢性CST损伤，在猕猴中的运动功能。在第一个目标下，我们将 创建一个可以测量的双性化，可视MRI可视，微型皮质学（µECOG）植入物 ipsiles和对比运动皮质的皮质生理学，并启用功能和解剖学 磁共振成像。在第二个目标中，该植入物以及一种创建一个新方法 立体定向病变与内胶囊的后肢，将使我们能够将微尺度皮质联系起来 随着大脑从中央侮辱变化，具有较大规模的功能成像的电生理学。在 第三目的，使用对比度的信号源将慢性毛猴进行康复 半球。该项目具有创新性，因为它通过扩展是与现状的实质性不同 在BCI介导的康复中，未受影响的半球和Bihemisphere相互作用的作用可以起到作用。 拟议的研究将是重要的，因为知识将在电动机之间产生关键的桥梁 功能，电生理学和功能成像，这将大大提高如何表征 皮质动力学与白质中风一起干扰，随后如何变化 针对量身定制的神经假体干预措施。最终，这将为小说的发展提供信息 美国中风患者的治疗