Reflex control of multi-joint mechanics following stroke

申请人的长期研究目标是了解多关节运动的神经控制和人体运动系统的机械设计之间的相互依存关系，并了解这两个系统的损伤如何损害正常的运动功能。这项特殊研究的重点是伸展反射对人类手臂力学调节的贡献，以及这种脊椎调节在中风后是如何改变的。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，可导致各种与运动相关的疾病，包括肌肉无力、异常运动协同和痉挛。这些运动障碍中的许多被认为是由促进运动行为的脊髓回路行为的变化引起的；然而，很少有研究检验这些变化对整个肢体功能协调的影响。这项研究试图通过使用肢体阻抗的估计和伸展反射对该阻抗的贡献来填补这一空白，以量化中风后多关节手臂力学调节的变化。其具体目的是(1)研究保持手臂姿势的健全个体的反射对整个肢体僵硬调节的贡献，(2)量化中风后整个肢体僵硬调节的变化和脊髓对这种调节的贡献，以及(3)研究有望恢复中风后运动功能的替扎尼定改变多关节反射行为的可能机制。对于所有的目标，肢体力学将使用手臂肢体阻抗的估计来量化，该估计描述了肢体姿势的外部施加的位移和响应产生的力之间的动态关系。与正常运动功能相关的所有自由度(DOF)的阻抗将被量化，使用6自由度机器人机械手来扰动手臂姿势，并使用6自由度称重传感器来测量与正常功能相关的所有自由度中的相应力。将对身体健全的人和中风患者进行测量。将进行一项小型、互补性的动物研究，以调查替扎尼定可能的作用机制。

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.