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.

项目概要 中风后，大多数患者的手部灵活性无法完全恢复，从而显着降低生活质量。 目前缺乏实现手部灵活性的最佳且有效的评估和疗法，部分原因是： 关于人类手部灵活性的科学知识有限，手部灵活性取决于健康和疾病。 嵌入高度交互的神经回路中的多个基本行为组件。 各成分相互作用以及它们如何受到下行神经通路的支持仍不清楚。 这项研究的长期目标是建立一个预测模型并确定关键的行为和神经原理 设计靶向疗法以促进手部灵活性的重新获得，从而提高生活质量。 该项目当前的目标是研究手部灵活性及其影响的行为和神经机制 中风后的损伤和恢复的中心假设是手的三个基本组成部分。 功能、手指个性化、精确握持和力量握持，很大程度上依赖于三个不同的控制变量， 灵活性、协调性和力量，以及可分离的下行通路：直接和间接皮质脊髓 束（CST）和网状脊髓束（RST） 该项目的基本原理是直接比较不同的。 使用相同粒度级别的运动学/动力学的灵活性组成部分，并结合最 下行神经通路结构和功能的先进测量有望在新模型中得到应用 提出了两个具体目标来检验中心假设：1）表征中风的效果。 个性化、精确握力和力量握力；以及 2) 确定结构中是否存在与中风相关的破坏 三个下行神经通路的功能与三个行为成分相关。 目标1，直接比较慢性中风患者和健康对照的个体化和精确握力 使用在 3D 中以高分辨率记录的所有十个指尖的等距力，以及它们与 Power 的相互作用 在目标 2 下，将检查握力，使用弥散加权 MRI 获得高分辨率纤维束成像。 评估三个下行通路的结构完整性。 与周围神经刺激相结合将用于评估三个通路的功能参与 在 Aim3 下，将使用霍夫曼反射的短、长和超长间隔调制建立一个模型。 将行为测量中的损伤严重程度映射到源自目标 1 和 2 的神经生理学标记以进行测试 假设中风幸存者的直接、间接 CST 和 RST 测量将预测个体化， 该提案具有创新性，因为它重新概念化了。 首次直接评估灵巧行为的基本组成部分并下降 利用尖端技术研究通路并根据这些发现建立神经模型是很重要的。 该项目的研究结果将指导敏感临床评估的创建并重新定义治疗 中风后最佳手部康复干预措施，以提高患者的生活质量。