Force Feedback Redistribution & Eccentric-Focused Rehab post-SCI

力反馈重新分配

• 批准号: 9905318
• 负责人: DENA R. HOWLAND
• 金额: --
• 依托单位: LOUISVILLE VA MEDICAL MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9905318
• 关键词: Address; Adult; Animal Model; Animals; Behavior; Bilateral; Characteristics; Chest; Chronic; Cicatrix; Data; Data Collection; Databases; Decerebrate State; Development; Disease; Distal; Dorsal; Experimental Designs; Extensor; Feedback; Felis catus; Gait; Goals; Golgi Tendon Organs; Health; Histology; Human; Injury; Joints; Knowledge; Laboratories; Lateral; Leg; Lesion; Limb structure; Link; Locomotion; Locomotor training; Maps; Mediating; Mission; Modeling; Motor; Motor Skills; Movement; Muscle; Normal Statistical Distribution; Pathway interactions; Performance; Phase; Physical Rehabilitation; Preparation; Procedures; Production; Productivity; Quality of life; Ramp; Recovery; Reflex action; Rehabilitation therapy; Research; Research Proposals; Specificity; Spinal; Spinal Cord; Spinal Cord Lesions; Spinal cord injury; Stains; System; Testing; Thoracic spinal cord structure; Time; Tissues; Training; Veterans; Walking; Weight; Work; base; care systems; design; evidence base; experimental study; force feedback; gait examination; gait rehabilitation; improved; injured; innovation; insight; kinematics; locomotor tasks; motor control; motor disorder; motor recovery; motor rehabilitation; nervous system disorder; novel; receptor; rehabilitation strategy; relating to nervous system; response; translational model; treadmill

Extensor muscles of the leg are actively involved in weight support and walking activities. These muscles are extensively linked by inhibitory, bidirectional, force dependent pathways that contribute to the successful execution of a range of functional behaviors, including locomotion. These reflex pathways are thought to arise from Golgi tendon organs and are believed to regulate limb stiffness and promote inter-joint coordination during movements. The relative magnitudes of these linkages in the two directions between any two muscles vary across control decerebrate animals when quiescent, but obey a predominantly proximal to distal gradient during stepping on a treadmill. This finding indicates that the strength and distribution of these reflex pathways are subject to modulation in a task-dependent manner. Our preliminary data suggest that thoracic spinal cord lateral hemisection immediately and persistently alters the normal distribution and a dominant distal-to- proximal inhibitory gradient emerges. Animals with this lesion do not exhibit clasp-knife inhibition, a phenomenon known to be mediated by receptors other than Golgi tendon organs and that results from bilateral injury to the dorsal half of the spinal cord. The change in the strength and distribution of force feedback that we have observed is correlated with diminished limb stiffness and poor weight acceptance during locomotor tasks – both of which are challenging problems seen in humans with spinal cord injuries. These findings provide new insight into potential mechanisms contributing to disruption of motor function following injury and identify a new, potential rehabilitation strategy. Our guiding hypothesis is that SCI-induced force-feedback dysregulation results in strong inhibition directed toward proximal muscles, contributes to inadequate limb stiffness during weight support phases of movement, and can be reversed using eccentric- focused training. The current application has evolved from collaborative work, using a large animal model, across two established laboratories, bringing together expertise in spinal cord injury, plasticity, force feedback and motor control. The proposed studies are divided into two sets of experiments. The first set will carefully characterize the impact of a low thoracic hemisection on gait kinematics during subphases where inhibitory force feedback is thought to be most active (Aim 1a). These phases typically are associated with coordinated eccentric activity and/or weight acceptance/support. Pre- and post-SCI data, across time, will be compared. In the same animals, a comprehensive picture of force-feedback organization following SCI will be developed during terminal decerebrate studies at two chronic time points (Aim 1b). Both standing and walking preparations, in combination with mechanographic approaches, will be used to test task-specificity of heterogenic force feedback responses in specific muscle combinations. In the second set of experiments, the basic experimental design is the same except that eccentric-focused training will be introduced at 2 wks post- SCI. This allows animals used in Aims 1a and 1b to serve as the controls for Aims 2a and 2b. Eccentric training will use different ‘downslope’ gait tasks to more strongly activate force feedback circuitry. Gait kinematics will be carefully assessed during select subphases to test for training effects during different flat and downslope tasks (Aim 2a) and decerebrate, mechanographic studies used to characterize training effects on force dependent organization at the level of specific muscle combinations. Histology will be completed in all animals to verify lesion characteristics. Data generated in the proposed work will be compared with an existing laboratory database containing force feedback findings from control decerebrate preparations, to reduce the number of animals used. Collectively, these studies will provide important information for evidence-based rehabilitation of motor skills by understanding the gait-associated impact of disrupting force feedback (Aim 1a), the extent of the disruption of this intralimb control system following SCI (Aim 1b), and the potential to alter this disruption at the voluntary gait (Aim 2a) and basic reflex levels (2b) using a physical training approach.

腿的伸肌积极参与体重支撑和步行活动。这些肌肉是 通过抑制性，双向，力依赖性途径的广泛联系，有助于成功 执行一系列功能行为，包括运动。这些反射途径被认为是出现的 来自高尔基肌腱器官，据信可以调节肢体刚度，并促进关节间协调 动作。这些连接在任何两个肌肉变化之间的两个方向上的相对震动 静止时遍布控制脑杂交动物，但主要遵守远端的远端梯度 在踏上跑步机期间。这一发现表明这些反射途径的强度和分布 以任务依赖的方式受到调制。我们的初步数据表明胸椎 立即并持续改变正态分布，远端到远端到 - 近端抑制梯度出现。患有这种病变的动物不存在扣刀抑制，一个 现象已知是由高尔基肌腱器官以外的接收器介导的，这是双侧的 脊髓的背侧一半受伤。力量反馈的强度和分布的变化 我们观察到的与运动过程中的肢体刚度降低和重量接受程度相关 任务 - 两者都是脊髓损伤的人类看到的挑战问题。这些发现 对潜在机制提供新的见解，这些机制导致受伤后运动功能的破坏和 确定一种新的潜在康复策略。我们的指导假设是Sci诱导的力量反馈 失调导致针对近端肌肉的强抑制作用，导致不足 体重支撑运动期间的肢体刚度，可以使用偏心 专注的培训。当前的应用程序是从合作工作中演变而来的，使用大型动物模型， 在两个既定实验室中 和电动机控制。拟议的研究分为两组实验。第一组将仔细 表征抑制性抑制作用期间低胸腔半分钟对步态运动学的影响 力量反馈被认为是最活跃的（AIM 1A）。这些阶段通常与协调 偏心活动和/或体重接受/支持。将比较SCI前和SCI后数据。在 同一动物将开发SCI之后的力量反馈组织的全面图片 在两个慢性时间点的末端解脑研究中（AIM 1B）。站立和行走 准备工作，结合机械方法，将用于测试任务特异性 特定肌肉组合中的异质力反馈反应。在第二组实验中， 基本的实验设计是相同的 科学。这允许在目标1a和1b中使用的动物作为目标2A和2B的控制。偏心 培训将使用不同的“下坡”步态任务来更强烈地激活力反馈电路。步态 运动学将在选定的小节期间仔细评估，以测试不同平面期间的训练效果 下坡任务（AIM 2A）和杂交杂交，机械学研究用于表征训练的影响 在特定肌肉组合级别上依赖力的组织。组织学将全部完成 动物以验证病变特征。将拟议工作中产生的数据与现有的 实验室数据库，其中包含来自控制脑部制剂的力反馈发现，以减少 使用的动物数量。总的来说，这些研究将为基于循证的重要信息提供重要信息 通过了解破坏力反馈的步态相关影响（AIM 1A），对运动技能的康复（AIM 1A）， SCI之后（AIM 1B）的这种内部控制系统的破坏程度（AIM 1B），以及改变这一点的潜力 使用体育锻炼方法的自愿步态（AIM 2A）和基本反射水平（2B）的破坏。