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，并在年轻人群中变得越来越普遍。中风后运动康复技术的发展处于历史最高水平。其中许多技术声称可以加速复苏。然而，主观和粗略的运动能力评估产生了关于康复装置的不一致建议。有必要开发一种用于卒中后恢复的强大、可靠和可获得的生物标志物。这样的生物标记物可以用作一种监管科学工具(RST)，改善食品和药物管理局(FDA)对康复设备应用的审查过程。这项建议侧重于设计和验证一个健壮和高保真的恢复标志，考虑到中枢和周围神经系统区域之间的定向信息交换。目前还没有批准的RST来评估康复装置对中风后运动恢复的疗效。这项研究是纽约大学和FDA之间的合作，代表了临床、工程和监管部门独特的联合努力。该项目将包括研讨会和本科生研究，以促进STEM教育，重点是吸引代表不足的群体的学生。该项目的中心目标是实施一种非侵入性生物标记物，揭开神经沟通的方向性(传入和传出)、非线性和复杂模式的神秘面纱，实现一个客观量化中风后患者解剖、激活和通路之间相互作用中的退化的“神经生理学放大镜”。该项目将基于从中风患者康复中获得的数据来分析拟议的生物标记物的可靠性和有效性，目标是开发首个专注于中风的康复RST。为此，该项目(1)提出了传入和传出神经通路的调制与运动能力和灵活性相关的机械论观点，(2)量化了中风后感觉运动处理所涉及的皮质来源及其与肌肉中运动单位的连接，(3)建立了预测中风患者运动能力和灵活性的大脑肌生物标志物，以及(4)除了使用独立的数据集进行验证分析外，还进行了受试者间和受试者内的可靠性分析。该项目还将促进FDA在下一代脑机接口方面的监管科学。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.