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

项目总结 中风后，大多数患者的手部灵活性不能完全恢复，显著降低了生活质量。 目前缺乏实现手部灵巧性的最佳和有效的评估和治疗， 对人类手部在健康和疾病方面的灵巧性的科学知识有限。手的灵巧性取决于 嵌入高度交互的神经回路中的多个基本行为组件。行为如何 组件之间的相互作用以及它们是如何由下行神经通路支持的仍不清楚。长的- 这项研究的长期目标是建立预测模型，并确定关键的行为和神经原理 设计有针对性的治疗方法，以促进手部灵活性的重新获得，以提高生活质量。这个 该项目目前的目标是研究手灵巧性的行为和神经机制以及它的 中风后的损伤和恢复。中心假设是手的三个基本成分 功能、手指个性化、精确抓握和力量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、力量和可分离的下行通路：直接和间接皮质脊髓 和网状脊髓束(RST)。这个项目的基本原理是直接比较不同的 在相同的粒度级别上使用运动学/动力学的灵活性组件，结合大多数 神经通路结构和功能下行的先进措施有望在一种新的模型中实现 手的灵巧度。提出了两个具体的目标来检验中心假设：1)表征中风的效果 关于个性化、精确握力和力量握力；以及2)确定结构中与中风相关的破坏 三条下行神经通路的功能与三种行为成分有关。在……下面 目的1.直接比较慢性卒中患者和健康对照组的个体化和精确化握力 在3D中使用以高分辨率记录的所有十个指尖的等角力，以及它们与Power的相互作用 将检查抓地力。在目标2下，将获得使用扩散加权磁共振成像的高分辨率纤维束成像 以评估三条下行通道的结构完整性。经颅磁刺激(TMS) 配对外周神经刺激将用于评估三个通路的功能受累 使用霍夫曼反射的短、长和超长间隔调制。在Aim3下，将构建一个模型来 将行为测量中的损害严重程度映射到源自目标1和2的神经生理标记物以进行测试 假设中风幸存者的直接、间接CST和RST测量将预测个体化， 精度夹点和增强夹点行为。这项提议具有创新性，因为它重新构思了概念。 通过第一次直接评估灵巧行为的基本组成部分和下降 并根据这些发现建立一个神经模型。这一点意义重大，因为 该项目的发现将指导创建敏感的临床评估并重新定义治疗 中风后最佳手部康复的干预措施，以提高患者的生活质量。

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.