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: 10318158
• 负责人: Eric CLAUDE Leuthardt
• 金额: $ 53.1万
• 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 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10318158
• 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.

在用脑机接口（BCI）康复慢性运动障碍中风幸存者时， 在理解大脑如何随着损伤而变化以及BCI如何参与这些方面存在根本性的差距。 动力学以诱导功能恢复。目前的障碍是缺乏一个灵长类动物模型，可以测试 慢性卒中的BCI策略。大多数动物模型采用灰质病变，而大多数动物模型采用脑灰质病变。 临床上显著的中风涉及更深的白色物质。该项目的长期目标是恢复 通过协同患者的BCI康复策略与其特定的中风诱导的运动功能， 病理生理学这项提案的总体目标是建立一个非人灵长类动物中风模型， 将检查微血管皮质脊髓束（CST）损伤后的生理学变化，并测试 神经假体干预对慢性环境中功能恢复的影响。核心假设 BCI驱动的CST损伤的运动康复将是有效的， 未受影响的半球与本体感受反馈配对。这项研究的基本原理是， 动物模型和积累的科学见解将创造一种机制驱动的方法， 中风的解决方案在强有力的初步证据的指导下，我们将用 以下三个具体目标：1）创建皮层电极以实现大脑的多模态测量 在CST微血管病变之前和之后，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和行为表现，以及3）恢复 脑机接口康复治疗慢性脊髓束损伤猕猴的运动功能在第一个目标下，我们将 创建一个双半球，MRI不可见，微皮层电图（µECoG）植入物，可以测量 病灶同侧和病灶对侧运动皮质的皮质生理学， 磁共振成像。在第二个目标中，该植入物，沿着一种新的方法， 对内囊后肢的立体定向损伤，将使我们能够连接微尺度皮质 电生理学与更大规模的功能成像，因为大脑的变化，从中央侮辱。下 第三个目标，将使用来自对侧病灶的信号源使慢性麻痹的猴子康复。 半球这个项目是创新的，因为它是一个实质性的偏离现状， 未受影响的半球和双半球的相互作用可以在BCI介导的康复中发挥作用。 拟议的研究将是有意义的，因为知识将建立一个关键的桥梁， 功能，电生理学和功能成像，这将大大提高如何表征 皮质动力学受到白色物质中风的干扰， 专门为你量身定制的神经修复手术最终，这将为小说的发展提供信息 治疗中风的方法