Reflex control of multi-joint mechanics following stroke

描述（由申请人提供）：申请人的长期研究目标是了解多关节运动的神经控制与人体运动系统的机械设计之间的相互依赖关系，并了解这些系统中任何一个的损伤如何损害正常的运动功能。这项特殊研究的重点是牵张反射对人类手臂力学调节的贡献，以及这种脊髓介导的调节在中风后如何改变。每年约有40万美国人首次中风，预计到2050年这一数字将超过100万。脑血管损伤如中风可导致多种运动相关疾病，包括肌无力、异常运动协同和痉挛。这些运动障碍中的许多被认为是由脊髓回路的行为变化引起的，脊髓回路的行为对运动行为有贡献;然而，很少有研究检查这些变化对整个肢体功能协调的影响。本研究旨在填补这一空白，通过使用肢体阻抗和牵张反射的贡献，这个阻抗的估计，以量化的变化，多关节手臂力学中风后的调节。具体目的是（1）检查保持手臂姿势的健全个体对全肢僵硬度调节的反射贡献，（2）量化中风后全肢僵硬度调节的变化和脊柱对该调节的贡献，以及（3）检查替扎尼定（一种有前途的恢复中风后运动功能的药物）改变多关节反射行为的可能机制。对于所有目标，将使用手臂肢体阻抗的估计来量化肢体力学，手臂肢体阻抗描述了肢体姿势的外部施加位移与响应中产生的力之间的动态关系。阻抗将在与正常运动功能相关的所有自由度（DOF）中进行量化，使用6 DOF机器人操纵器扰动手臂姿势，并使用6 DOF测力传感器测量与正常功能相关的所有DOF中的相应力。将在身体健全的个体和中风患者中进行测量。将进行一项小型补充动物研究，以研究替扎尼定作用的潜在机制。

DESCRIPTION (provided by applicant): The applicant's long-term research objectives are to understand the interdependent relationship between the neural control of multi-joint movements and the mechanical design of the human motor system, and to understand how injury to either of these systems compromises normal motor function. The focus of this particular study is on the stretch reflex contributions to the regulation of human arm mechanics, and how this spinally mediated regulation is altered following stroke. Approximately 400,000 Americans suffer their first stroke each year, and this number is expected to exceed 1,000,000 by the year 2050. Cerebral vascular injuries such as stroke can result in a variety of movement related disorders including muscular weakness, abnormal motor synergies and spasticity. Many of these motor disorders are thought to arise from changes in the behavior of spinal circuits contributing to motor behavior; however, few studies have examined the effect of these changes on the coordination of whole limb function. This study seeks to fill this void by using estimates of limb impedance and the stretch reflex contributions to this impedance to quantify changes in the regulation of multi-joint arm mechanics following stroke. The specific aims are (1) to examine the reflex contributions to whole limb stiffness regulation in able-bodied individuals maintaining arm posture, (2) to quantify the changes in whole limb stiffness regulation and the spinal contributions to this regulation following stroke, and (3) to examine the possible mechanisms by which tizanidine, a promising drug for restoring motor function following stroke, alters multi-joint reflex behavior. For all aims, limb mechanics will be quantified using estimates of arm limb impedance, which describes the dynamic relationship between externally imposed displacements of limb posture and the forces generated in response. Impedance will be quantified in all degrees of freedom (DOFs) relevant to normal motor function using a 6 DOF robotic manipulator to perturb arm posture and a 6DOF load cell to measure the corresponding forces in all DOF relevant to normal function. Measurements will be made in able-bodied individuals and in individuals who have suffered a stroke. A small, complementary animal study will be performed to investigate possible mechanisms underlying the actions of tizanidine.