Dissecting Behavioral and Neural Mechanisms of Hand Dexterity after Stroke for Effective Rehabilitation

剖析中风后手部灵活性的行为和神经机制，以实现有效康复

• 批准号: 10803644
• 负责人: Jing Xu
• 金额: $ 59.19万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-26 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10803644
• 关键词: 3-Dimensional; Behavior; Behavioral; Behavioral Mechanisms; Behavioral Paradigm; Biological Markers; Biomechanics; Clinical; Clinical assessments; Corticospinal Tracts; Data; Devices; Diffusion Magnetic Resonance Imaging; Disease; Fingers; Goals; H-Reflex; Hand; Hand Strength; Hand functions; Health; Human; Human Activities; Impairment; Individuation; Interneurons; Isometric Exercise; Kinetics; Knowledge; Maps; Measures; Mediating; Methods; Mission; Modeling; Movement; Neural Pathways; Neuroanatomy; Neurobiology; Paresis; Pathway interactions; Patients; Peripheral Nerve Stimulation; Play; Proxy; Public Health; Quality of life; Recovery; Reflex action; Rehabilitation therapy; Reporting; Research; Resolution; Role; Severities; Spinal; Stroke; Structure; Techniques; Testing; Therapeutic Intervention; Time; Training; Transcranial magnetic stimulation; United States National Institutes of Health; Upper Extremity; Vertebral column; Work; behavior measurement; chronic stroke; design; dexterity; disability; flexibility; grasp; hand dysfunction; hand rehabilitation; improved; indexing; innovation; kinematics; neural; neural circuit; neural model; neural stimulation; neuromechanism; neurophysiology; novel; optimal treatments; post stroke; predictive modeling; prognostic; reticulospinal tract; sensor; sound; strength training; stroke patient; stroke rehabilitation; stroke survivor; targeted treatment; therapeutically effective; therapy design; tractography

PROJECT SUMMARY Following a stroke, hand dexterity does not recover fully for most patients, significantly reducing quality of life. Optimal and effective assessment and therapies for achieving hand dexterity are currently lacking due, in part, to limited scientific knowledge of human hand dexterity in health and disease. Hand dexterity hinges on multiple essential behavioral components embedded in a highly interactive neural circuit. How the behavioral components interact and how they are supported by descending neural pathways are still unclear. The long- term goal of this research is to build a predictive model and identify key behavioral and neural principles for designing targeted therapies to facilitate the reacquisition of hand dexterity to improve quality of life. The current objective of this project is to investigate behavioral and neural mechanisms of hand dexterity and its impairment and recovery after stroke. The central hypothesis is that three essential components of hand function, finger individuation, precision grip, and power grip, largely rely on three distinct control variables, flexibility, coordination, and strength, and separable descending pathways: direct- and indirect-corticospinal tract (CST), and reticulospinal tract (RST). The rationale for this project is that directly comparing different components of dexterity using kinematics/kinetics at the same levels of granularity, combined with the most advanced measures of descending neural pathway structure and function holds promise in a new model of hand dexterity. Two specific aims are proposed to test the central hypothesis: 1) characterize effect of stroke on individuation, precision grip, and power grip; and 2) determine if stroke-related disruption in the structure and function of three descending neural pathways are associated with three behavioral components. Under Aim 1, chronic stroke patients and healthy controls’ Individuation and Precision Grip will be directly compared using isometric forces recorded in high resolution at all ten fingertips in 3D, and their interaction with Power Grip will be examined. Under Aim 2, high-resolution tractography using diffusion-weighted MRI will be obtained to assess structural integrity of the three descending pathways. Transcranial magnetic stimulation (TMS) paired with peripheral nerve stimulation will be used to assess functional involvement of the three pathways using short-, long-, and extra-long interval modulation of Hoffmann-reflex. Under Aim3, a model will be built to map severity of impairment in behavioral measures to neurophysiological markers derived from Aim 1&2 to test the hypothesis that stroke survivors’ direct-, indirect-CST and RST measures will be predictive of individuation, precision grip, and power grip behaviors, respectively. The proposal is innovative because it reconceptualizes dexterity by, for the first time, directly assessing essential components of dexterity behaviors and descending pathways with cutting-edge techniques and build a neural model from these findings. It is significant because findings from this project will guide the creation of sensitive clinical assessments and redefine therapeutic interventions for optimal hand rehabilitation after stroke to enhance patients’ quality of life.

项目摘要 中风后，大多数患者的手敏度无法完全恢复，从而大大降低了生活质量。 目前缺乏最佳有效的评估和实现手敏度的疗法 有限的科学知识对健康和疾病中的手动敏捷性。手敏感在 多个基本行为成分嵌入了高度交互式神经回路中。如何行为 尚不清楚成分相互作用以及如何通过下降神经途径支持它们。长期 这项研究的术语目标是建立一个预测模型，并确定关键的行为和神经原理 设计有针对性的疗法，以促进手工敏捷性以改善生活质量。这 该项目的当前目标是研究手敏感的行为和神经机制及 中风后的障碍和恢复。中心假设是手的三个基本组成部分 功能，手指个性化，精度握把和功率抓地力，很大程度上依赖于三个不同的控制变量， 灵活性，协调性和强度，以及可分离的下降途径：直接和间接脊髓中心 区域（CST）和网状脊髓道（RST）。该项目的理由是直接比较不同的 使用运动学/动力学在相同水平的粒度上使用灵巧性的组成部分，结合最多 降级神经通路结构和功能的高级测量在一个新模型中有望 手敏感。提出了两个具体目标来检验中心假设：1）卒中的效果表征 发明，精确抓地力和功率抓地力； 2）确定结构中的中风相关的破坏是否 三个下降神经途径的功能与三个行为成分相关。在下面 AIM 1，慢性中风患者和健康对照组的个性化和精度握把将直接比较 使用3D的所有十个指尖记录在高分辨率中记录的等距力，并与功率相互作用 将检查抓地力。在AIM 2下，将获得使用扩散加权MRI的高分辨率拖拉术 评估三个下降途径的结构完整性。经颅磁刺激（TMS） 与周围神经刺激配对，将用于评估三种途径的功能参与 使用Hoffmann-Reflex的短，长和长时间的间隔调制。在AIM3下，将建立一个模型 在行为测量中，损伤的严重程度对来自AIM 1和2的神经生理标记物进行测试 中风存活的直接，间接-CST和RST措施的假设将预测个性化， 精确抓地力和权力抓地力行为。该提议具有创新性，因为它重新概念化 敏捷性首次直接评估敏捷行为的基本组成部分和下降 具有尖端技术的途径，并通过这些发现建立神经模型。这很重要，因为 该项目的发现将指导创建敏感临床评估并重新定义治疗 中风后最佳手动康复的干预措施，以提高患者的生活质量。