Functional Role of Golgi tendon organ feedback in health and disease

高尔基腱器官反馈在健康和疾病中的功能作用

• 批准号: 10476993
• 负责人: Mark A Lyle
• 金额: $ 12.91万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-19 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10476993
• 关键词: Acute; Age; Animal Model; Ataxia; Axon; Basic Science; Behavior; Biomechanics; Clinical; Clinical Trials Design; Data; Disease; Equilibrium; Evaluation; Fatigue; Feedback; Felis catus; Foundations; Future; Goals; Golgi Tendon Organs; H-Reflex; Health; Human; Impairment; Injury; Intervention; Joints; K-Series Research Career Programs; Knowledge; Length; Limb structure; Link; Lower Extremity; Mechanics; Methods; Motion; Motor; Motor output; Movement; Muscle; Muscle Fatigue; Muscle Spindles; Nerve; Nervous system structure; Neurologic; Operant Conditioning; Participant; Pathway interactions; Persons; Posture; Recurrence; Rehabilitation Outcome; Research; Research Training; Role; Sensory; Soleus Muscle; Source; Spasm; Spinal; Spinal Injuries; Spinal cord injury; Stimulus; Stroke; Techniques; Testing; Therapeutic; Time; Training; Translating; Walking; clinical application; design; fall injury; femoral nerve; force feedback; human subject; improved; innovation; motor behavior; motor impairment; neuropathology; neurophysiology; neuroregulation; new therapeutic target; physical therapist; post stroke; prevent; quadriceps muscle; sensory feedback; spasticity; stretch reflex; synergism; therapeutic target; therapeutically effective; tool

Project Summary/Abstract Proprioceptive feedback is known to have a role in coordinating muscle activity throughout the limb. Disruption in feedback after stroke and spinal cord injury contributes to abnormal interjoint coordination. Thus, the role of specific sensory circuits, if known and accessible for therapeutic manipulation, holds great promise for treating a range of motor impairments. Research has focused on the role of length dependent feedback from muscle spindles (i.e. stretch & H-reflex), and its use as a therapeutic target through operant conditioning. Less is known about force dependent feedback from Golgi tendon organs (GTOs), but current evidence suggests force feedback could provide an additional and potentially more effective therapeutic option for treating coordination impairments. GTO circuits primarily link muscles spanning different joints implying a critical role in whole limb coordination. Moreover, the strength of force feedback between muscles, and even sign, is believed to vary in a task-dependent way and as such could potentially be targeted to reduce or increase motor output of muscles. However, current approaches to study GTOs are invasive and restricted to decerebrate cats, preventing studies examining their functional role during natural behaviors, or evaluation in human subjects. Nerve stimulation is used to study intermuscular circuitry in humans, but this approach is unable to selectively activate GTO circuits and many nerves are not accessible for stimulation. We propose to use muscle stimulation evoked contractions, a selective stimulus for GTOs that we have validated in the cat, to noninvasively study the strength of intermuscular force feedback in humans. Aim 1 will determine the unique contribution of GTO feedback to intermuscular inhibitory feedback while sitting by comparing the influence of femoral nerve and quadriceps muscle stimulation onto ongoing soleus EMG and the H-reflex. GTO feedback will be compared between persons with stroke and spinal cord injury with age-matched controls to identify effects of altered descending control on GTO feedback that may contribute to abnormal interjoint coordination (Aim 2). Since task-dependent modulation of proprioceptive feedback is essential for adapting to changing task demands, GTO feedback between lower limb muscles will be compared while sitting and standing (Aim 3). The new knowledge from this proposal will be a first step toward identifying the functional role and contribution of GTO feedback to motor impairments. The candidate’s long-term goal is to elucidate the unique functional role of GTO feedback and use neuromodulation techniques to treat movement impairments in people with neurologic conditions. The PI is a physical therapist with prior training using biomechanical tools to evaluate human motion and studying proprioceptive feedback circuits in the decerebrate cat. The K01 training plan will prepare the PI with training in human neurophysiological methods, neuromodulatory techniques, clinical trial design and guidance on translating basic science methods developed in an animal model for clinical applications in humans.

项目概要/摘要 众所周知，本体感觉反馈在协调整个肢体的肌肉活动方面发挥着作用。 中风和脊髓损伤后的反馈中断会导致关节间协调异常。 如果特定的感觉回路的作用已知且可用于治疗操作，则具有巨大的前景 用于治疗一系列运动障碍的研究重点是长度依赖反馈的作用。 来自肌梭（即拉伸和 H 反射）的作用，以及通过操作性调节将其用作治疗目标。 关于高尔基腱器官 (GTO) 的力依赖性反馈知之甚少，但目前的证据 表明力反馈可以为以下疾病提供额外且可能更有效的治疗选择 治疗协调障碍的 GTO 回路主要连接跨越不同关节的肌肉，这意味着 而且，肌肉之间的力反馈的强弱，甚至对整个肢体的协调性都起着至关重要的作用。 符号，被认为以依赖于任务的方式变化，因此可能有针对性地减少或 然而，目前研究 GTO 的方法是侵入性的，并且仅限于 去大脑猫，阻止研究检查它们在自然行为中的功能作用，或评估 神经刺激用于研究人类的肌间回路，但这种方法是不可行的。 无法选择性激活 GTO 回路，并且许多神经无法接受刺激。 使用肌肉刺激诱发收缩，这是我们在猫身上验证过的 GTO 选择性刺激， 无创地研究人类肌肉间力反馈的强度将确定独特的。 通过比较坐姿时 GTO 反馈对肌间抑制反馈的影响 股神经和股四头肌刺激持续比目鱼肌肌电图和 GTO 反射。 将中风和脊髓损伤患者与年龄匹配的对照组进行比较，以确定 下降控制改变对 GTO 反馈的影响可能导致关节间协调异常 （目标 2）由于本体感觉反馈的任务依赖性调节对于适应不断变化的任务至关重要。 根据要求，将比较坐着和站立时下肢肌肉之间的 GTO 反馈（目标 3）。 该提案中的新知识将是确定职能作用和贡献的第一步 GTO 对运动障碍的反馈是候选人的长期目标是阐明其独特的功能作用。 GTO 反馈并使用神经调节技术来治疗患有 GTO 的人的运动障碍 PI 是一名物理治疗师，接受过使用生物力学工具进行评估的培训。 K01 训练计划将研究人体运动并研究去大脑猫的本体感觉反馈回路。 通过人类神经生理学方法、神经调节技术、临床试验方面的培训来准备 PI 将动物模型中开发的基础科学方法转化为临床的设计和指导 在人类中的应用。