A Brain Centered Neuroengineering Approach for Motor Recovery after Stroke: Combined rTMS and BCI Training

PI：bin HeProposal number：1264782概述：拟议项目的长期目标是开发一种新的基于大脑的神经工程方法，以显著改善中风后的运动恢复。中风是一种突发性和破坏性的疾病，由脑血管闭塞引起。2008年美国中风的估计成本为343亿美元。这种疾病的慢性性质对卫生保健系统的疾病负担造成了持久的影响，并可能导致数十年的工资损失，影响到患者及其家人。在中风的表现中，对患者生活质量的功能影响最大的是那些导致运动障碍的表现。该项目试图通过结合脑机接口(BCI)和重复经颅磁刺激(RTMS)的新的神经工程方法，开发一种基于大脑的中风后运动恢复策略，而不是基于运动功能的策略。中心假设是，与传统的护理标准物理治疗相比，接受补充rTMS和BCI训练的受试者将随着时间的推移在手运动能力方面显示出更大的功能改善，并恢复正常的运动连接模式。将开发新的工程方法来实现拟议的目标。目的1.评价脑机接口训练对脑卒中后运动功能恢复过程的影响。这一目标的工作假设是，接受BCI培训的受试者比只接受标准护理治疗的对照组受试者表现出更大的运动改善。目的2.研究rTMS以抑制性方式应用于对侧大脑半球，并与随后的脑机接口训练相结合。这一目标的假设是，与只接受BCI训练的受试者和只接受标准护理治疗的对照组受试者相比，接受这种联合方法的受试者在运动功能方面表现出更大的改善。目的3.通过EEG/fMRI神经成像和有效连接性分析，探讨卒中后运动恢复的神经相关性。这一目标将允许客观和定量地评估运动恢复遵循BCI和BCI/rTMS方案，以及临床运动功能评估。智力优势：建议的项目代表了一种新的神经工程学方法，通过整合神经接口和调制来改善中风后的运动恢复。这些拟议的目标将导致新的神经工程技术的发展，并更好地理解与神经可塑性和运动功能相关的机制。特别是，这项研究将开发一种新的基于虚拟现实的中风患者脑机接口，新的方法来分析rTMS后脑电的时空分布，以及新的方法来多模式识别中风后运动恢复的神经关联，而不是仅仅依赖运动输出。更广泛的影响：a)社会：拟议的研究解决了神经工程中的一个重要问题，将基本的脑-机接口研究转化为潜在的临床应用，帮助了许多中风患者。B)加强研究和教育基础设施：拟议的项目是明尼苏达大学神经工程倡议的组成部分。拟议的项目将为研究生以及明尼苏达大学的本科生和当地高中生提供独特的跨学科培训机会。将特别注意招收少数民族和女性学生加入该项目。C)知识传播：研究结果将通过学术出版物广泛传播，并向科学界和公众传播。

PI: Bin HeProposal number: 1264782Overview: The long-term goal of the proposed project is to develop a novel brain-based neuroengineering approach to substantially improve motor recovery after stroke. Stroke is a sudden and devastating disease that arises from the occlusion of the cerebral vasculature. The estimated cost of stroke in the U.S. in 2008 is 34.3 billion dollars. The chronic nature of the disease creates a lasting impact in terms of disease burden on the health care system, and can result in decades of lost wages affecting both patients and their families. Among the manifestations of stroke with the highest functional impact on patient quality of life are those resulting in motor impairment. The project seeks to develop a brain-based strategy for motor recovery after stroke, rather than motor function based, by means of a novel neuroengineering approach combining brain-computer interface (BCI) and repetitive transcranial magnetic stimulation (rTMS). The central hypothesis is that, in comparison to traditional standard-of-care physical therapy, subjects receiving supplementary rTMS and BCI training will show greater functional improvement in hand motor ability over time as well as recovery of normal motor connectivity patterns. Novel engineering methods will be developed to accomplish the proposed goal. Aim 1. To evaluate the effects of BCI training on the process of motor recovery after stroke. The working hypothesis for this aim is that subjects receiving BCI training will demonstrate greater motor improvements than control subjects receiving standard-of-care therapy only. Aim 2. To investigate combined rTMS, applied in an inhibitory fashion to the contralesional hemisphere, with subsequent BCI training. The hypothesis for this aim is that subjects receiving this combined approach will show greater improvements in motor function than both subjects receiving BCI training alone and control subjects receiving standard-of-care therapy only. Aim 3. To investigate the neural correlates of motor recovery after stroke by performing EEG/fMRI neuroimaging and effective connectivity analysis. This aim will allow for objectively and quantitatively assessing motor recovery following BCI and BCI/rTMS protocols in addition to clinical motor function assessment. Intellectual Merits: The proposed project represents a novel neuroengineering approach to improve motor recovery after stroke by integrating neural interfacing and modulation. These proposed aims will lead to development of novel neuroengineering techniques and a better understanding of mechanisms associated with neural plasticity and motor functions. In particular, the proposed research will develop a novel virtual reality based BCI for stroke patients, novel methods for analyzing EEG spatio-temporal distributions following rTMS, and novel methods for multimodal identification of the neural correlates of motor recovery after stroke, rather than relying on motor output alone. Broader Impacts: a) Societal: The proposed research addresses a significant problem in neuroengineering to translate basic BCI research to potential clinical applications, aiding numerous patients with stroke. b) Enhancement of infrastructure for research and education: The proposed project is an integral part of the neural engineering initiative at the University of Minnesota. The proposed project will provide unique opportunities for interdisciplinary training of graduate students, as well as undergraduate students at the University of Minnesota and local high school students. Special attention will be paid to recruiting minority and female students into the project. c) Knowledge dissemination: The findings will be disseminated widely via scholarly publications, and to the scientific community and public.