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.

项目摘要/摘要 众所周知，本体感受反馈在整个肢体的协调肌肉活动中起作用。 中风后反馈和脊髓损伤的干扰会导致异常的间交配。那， 特定的感觉电路的作用，即使可以进行热操作，可以访问 用于治疗一系列运动障碍。研究重点是依赖长度的反馈的作用 从肌肉纺锤体（即拉伸和H反射）及其通过操作条件用作治疗靶标。 关于高尔基肌腱器官（GTO）的依赖力的反馈的知之甚少，但目前的证据 建议力反馈可以为 治疗协调障碍。 GTO电路主要连接肌肉，跨越不同关节的肌肉，这意味着 在整个肢体协调中的关键作用。此外，肌肉之间的力量反馈的强度，甚至 符号被认为以任务依赖的方式变化，因此有可能针对减少或 增加肌肉的运动输出。但是，当前研究GTO的方法是侵入性的，并且仅限于 脑猫，阻止研究研究其在自然行为中的功能作用或评估 人类主题。神经刺激用于研究人类的肌间电路，但这种方法是 无法选择性激活GTO电路，并且无法访问许多神经以进行刺激。我们建议 使用肌肉刺激诱发收缩，这是我们在猫中验证的GTO的选择性刺激 非侵入性研究人类肌间反馈的强度。 AIM 1将决定独特 GTO反馈对肌间抑制反馈的贡献，同时通过比较 股神经和股四头肌的肌肉刺激在持续的比目鱼EMG和H反射上。 GTO反馈 将在中风和脊髓损伤的人与年龄匹配的对照中进行比较以识别 降降控制对GTO反馈的影响可能导致异常交互配位的影响 （目标2）。由于任务依赖于本体感受反馈的调制对于适应更改任务至关重要 需求，将在坐着和站立时比较下肢肌肉之间的GTO反馈（AIM 3）。 该提案的新知识将是确定功能作用和贡献的第一步 GTO对运动障碍的反馈。候选人的长期目标是阐明独特的功能角色 GTO反馈并使用神经调节技术来治疗患有患者的运动障碍 神经系统条件。 PI是一名物理治疗师 人类运动和研究脑猫中的本体感受反馈电路。 K01培训计划将 通过人类神经生理方法，神经调节技术，临床试验的培训准备PI 在临床动物模型中开发的基础科学方法的设计和指南 在人类中的应用。