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，大多数患者的手灵活性不能完全恢复，显著降低了生活质量。 目前缺乏用于实现手灵活性的最佳和有效的评估和治疗，部分原因是， 人类手部灵活性在健康和疾病方面的科学知识有限。手的灵活性取决于 多个基本的行为组件嵌入在高度交互的神经回路中。行为是如何 这些成分相互作用，以及它们如何受到下行神经通路的支持，目前仍不清楚。很长的- 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则， 设计有针对性的治疗方法，以帮助重新获得手的灵活性，提高生活质量。的 本研究的目的是探讨手灵活性的行为和神经机制， 中风后的损伤和恢复。核心假设是手的三个基本组成部分 功能、手指个性化、精确抓握和有力抓握，在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 脊髓束（CST）和网状脊髓束（CST）。这个项目的基本原理是，直接比较不同的 灵活性的组成部分，使用运动学/动力学在相同的粒度水平，结合最 在一个新的模型中，先进的神经通路结构和功能下降的措施有希望， 手的灵活性。提出了两个具体目标来检验中心假设：1）表征中风的影响 个性化，精确的抓地力，和权力的抓地力;和2）确定是否中风相关的破坏结构 三个下行神经通路的功能与三个行为成分相关。下 目的1、直接比较慢性脑卒中患者和健康对照者的个体化和精确抓握能力 在3D中使用高分辨率记录的所有十个指尖的等距力，以及它们与功率的相互作用， 将检查抓地力。在目标2下，将获得使用弥散加权MRI的高分辨率纤维束成像 来评估三条下行通路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个通路的功能参与 使用霍夫曼反射的短、长和超长间隔调制。在目标3下，将建立一个模型， 将行为测量中的损伤严重程度映射到源自目标1和2的神经生理学标记物，以测试 假设中风幸存者的直接、间接CST和CST测量将预测个体化， 精确抓握和强力抓握行为。该提案具有创新性，因为它重新定义了 第一次直接评估灵巧行为的基本组成部分， 用尖端技术研究神经通路，并根据这些发现建立神经模型。这很重要，因为 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 干预中风后的最佳手部康复，以提高患者的生活质量。