ACTIVITY DEPENDENT PLASTICITY AFTER HUMAN SPINAL CORD INJURY

人类脊髓损伤(SCI)后恢复行走的前景令人沮丧。康复的预后主要基于可检测到的自主腿功能，这为脊髓损伤后步行的康复策略提供了指导。这种方法是基于人类运动神经控制的传统层次模型中的假设，该模型将大脑指定为主要控制器，将脊髓指定为脊椎上信号和反射路径的管道。我们实验室和其他实验室的最新结果提出了一个运动神经控制的综合模型，将脊髓分配为一个重要的运动神经控制器，将感觉和脊髓上的信号整合在一起，产生有效的运动输出。在这个提案中，我们通过理解感官和 在每项特定任务训练前后，人类脊髓在行走和站立运动任务中对脊髓上的信号进行处理。我们的理论是，当一组预期的运动学和运动学模式出现时，人类脊髓的神经回路在功能上被组织起来，以产生特定的传出模式。我们假设，这种神经回路可以适应一组特定运动学和动力学模式的重复呈现，以可预测的方式调节传出输出。我们进一步假设，在不完全脊髓损伤后，棘上和感觉信号都可以被人类脊髓整合，以产生与重复站立或步进训练相关的特定运动输出。我们 将研究临床完全脊髓损伤后的个体，以了解人类脊髓在处理感觉信号中的作用。我们将研究临床上不完全脊髓损伤的个体，以评估脊柱上和感觉信号在重复站立或台阶训练后产生功能输出的整合潜力。我们将检测这些脊髓损伤受试者在双侧和单侧踏步以及在重复踏步或站立训练后在跑步机上使用体重支持进行功能任务时的肌电活动、运动学和动力学。这些研究将展示正在PPG的动物模型中研究的依赖使用的可塑性的各个方面。确定在步进过程中促进运动输出的特定感觉线索，并评估重复的特定任务训练是否可以诱导 脊髓损伤后脊髓和脊髓上中枢的活动依赖性可塑性导致功能改善，这将对神经损伤后恢复行走的新的康复策略具有重要意义。此外，结合不断涌现的有前途的神经再生方法，优化功能恢复的训练策略也将是极其重要的。

The prospects for recovery of walking after human spinal cord injury (SCI) are dismal after a severe injury. The prognosis for recovery is primarily based on detectable voluntary leg function and this directs the rehabilitative strategy for walking after SCI. This approach is based on assumptions from the conventional hierarchal model of the neural control of locomotion in humans that designates the brain as the primary controller and the spinal cord as a conduit for supraspinal signals and reflex pathways. Recent results from our laboratory and others suggest an integrative model of the neural control of locomotion, allocating the spinal cord as an important neural controller of locomotion that integrates sensory and supraspinal signals to generate effective locomotor output. In this proposal we test this model by understanding sensory and supraspinal signal processing by the human spinal cord during the motor tasks of stepping and standing before and after each task specific training. We theorize that the neural circuitry of the human spinal cord is functionally organized to generate a particular efferent pattern when an expected set of kinematic and kinetic patterns are presented. We hypothesize that this neuralcircuitry can adapt to the repetitive presentation of a specific set of kinematic and kinetic patterns to modulate the efferent output in a predictable manner. We further hypothesize that after incomplete SCI both supraspinal and sensory signals can be integrated by the human spinal cord to generate a specific motor output that is related to repetitive stand or step training. We will study individuals following clinically complete SCI to understand the role of the human spinal cord in processing sensory signals. We will study individuals with clinically incomplete SCI to assess the integrative potential of supraspinal and sensory signals to generate functional output after repetitive stand or step training. We will examine the electromyographic activity, kinematics and kinetics of the lower limbs of these SCI subjects during bilateral and unilateral stepping and during functional tasks using body weight support on a treadmill after repetitive step or stand training. These studies will demonstrate aspects of use-dependent plasticity that are being studied in the animal models of this PPG. Identifying the specific sensory cues that facilitate motor output during stepping; and assessing whether repetitive task specific training can induce activity-dependent plasticity of spinal and supraspinal centers to result in functional improvements after spinal cord injury will have significant implications for new rehabilitative strategies for the recovery of walking after neurologic injury. Further, optimizing training strategies for functional recovery will also be extremely important in combination with promising neural regeneration approaches that are continuously emerging.