NSF/FDA SIR: Robust, Reliable, and Trustworthy Regulatory Science Tool for Stroke Recovery Assessment using Hybrid Brain-Muscle Functional Coupling Analysis

中风是与年龄相关的运动障碍的主要原因，并且在年轻人群中变得越来越普遍。脑卒中后运动康复技术的发展处于历史最高水平。其中许多技术都声称可以加速恢复。然而，对运动能力的主观和粗略的评估产生了关于康复设备的不一致的建议。有必要开发一种强大的、可靠的、可获得的脑卒中后恢复生物标志物。这种生物标志物可以作为一种监管科学工具（RST），改善美国食品和药物管理局（FDA）对康复设备应用的审查过程。考虑到中枢神经系统和外周神经系统区域之间的定向信息交换，本建议的重点是设计和验证一个鲁棒性和高保真的恢复标记。目前还没有批准的RST用于评估卒中后运动恢复康复装置的疗效。这项研究是纽约大学和FDA之间的合作，代表了临床、工程和监管部门的独特共同努力。该项目将包括研讨会和本科生研究，以促进STEM教育，重点是吸引来自代表性不足群体的学生。该项目的中心目标是实现一种无创生物标志物，揭示神经通信的方向性（传入和传出）、非线性和复杂模式，实现“神经生理放大镜”，客观量化脑卒中后患者解剖、激活和通路之间相互作用的退化。该项目将根据从中风患者康复中获得的数据，分析所提议的生物标志物的可靠性和有效性，目标是开发有史以来第一个以中风为重点的康复RST。为此，该项目(1)提出了与运动表现和活动能力相关的传入和传出神经通路调节的机制观点，(2)量化了卒中后感觉运动加工中涉及的皮质源及其与肌肉运动单元的连接，(3)建立了预测卒中患者运动表现和活动能力的皮质肌肉生物标志物。(4)除了使用独立数据集进行验证分析外，还进行了受试者之间和受试者内部的信度分析。该项目还将促进FDA对下一代脑机接口的监管科学。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Stroke is the leading cause of age-related motor disabilities and is becoming more prevalent in younger populations. The development of post-stroke motor rehabilitation technologies is at an all-time high. Many of these technologies claim to accelerate recovery. However, subjective and coarse evaluation of motor capacities have generated inconsistent recommendations regarding rehabilitation devices. There is a need for the development of a robust, reliable, and accessible biomarker for post-stroke recovery. Such a biomarker could be used as a regulatory science tool (RST) that improves the Food and Drug Administration (FDA) review process for rehabilitation device applications. This proposal focuses on the design and validation of a robust and high-fidelity marker of recovery, considering the directional information exchange between regions of the central and peripheral nervous systems. There is currently no approved RST for assessing the efficacy of rehabilitative devices for post-stroke motor recovery. This research is a collaboration between New York University and the FDA, and represents a unique joint effort from the clinical, engineering, and regulatory sectors. The project will include seminars and undergraduate research to promote STEM education with a focus on engaging students from underrepresented groups.The central goal of this project is to implement a noninvasive biomarker that demystifies the directional (afferent and efferent), nonlinear, and complex patterns of neural communication, realizing a “neurophysiological magnifier” that objectively quantifies degradation in the interaction between anatomy, activation, and pathway in post-stroke patients. The project will analyze the reliability and efficacy of the proposed biomarker based on data acquired from recovering stroke patients with the goal of developing the first-ever stroke-focused rehabilitation RST. For this, the project (1) proposes a mechanistic view of the modulations of afferent and efferent neural pathways in correlation with motor performance and mobility, (2) quantifies the cortical sources involved in sensorimotor processing after stroke and their connectivity to the motor units in muscles, (3) establishes corticomuscular biomarkers that predict motor performance and mobility for stroke patients, and (4) performs inter-and intra-subject reliability analyses in addition to validation analyses using independent datasets. This project will also promote FDA regulatory science on next-generation brain-machine interfaces.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.