Functional Role of Golgi tendon organ feedback in health and disease

项目摘要/摘要 本体感觉反馈在协调整个肢体的肌肉活动方面起着重要作用。 中风和脊髓损伤后反馈的中断会导致关节间不正常的协调。因此， 特定感觉回路的作用，如果已知并可用于治疗操作，就有很大的希望。 用于治疗一系列运动障碍。研究的重点是依赖于长度的反馈的作用 从肌梭(即伸展和H反射)，以及通过操作性条件反射将其用作治疗靶点。 关于高尔基体肌腱器官(GTO)的力依赖反馈知之甚少，但现有证据表明 提示力反馈可能提供另一种可能更有效的治疗选择 治疗协调障碍。GTO回路主要连接跨越不同关节的肌肉，这意味着 在整个肢体协调中起关键作用。此外，肌肉之间的力反馈的强度，甚至 符号，被认为是以依赖于任务的方式变化的，因此可能被瞄准以减少或 增加肌肉的运动输出。然而，目前研究GTO的方法是侵入性的，仅限于 取消猫的大脑，阻止研究它们在自然行为中的功能作用，或在 人类受试者。神经刺激被用来研究人类的肌肉间回路，但这种方法 无法选择性地激活GTO回路，许多神经无法获得刺激。我们建议 使用肌肉刺激引起的收缩，这是我们在猫身上验证的GTO的选择性刺激，以 非侵入性地研究人类肌肉间力反馈的强度。目标1将决定唯一的 坐位时GTO反馈对肌间抑制反馈的贡献 股神经和股四头肌刺激正在进行的比目鱼肌电和H反射。GTO反馈 将在中风和脊髓损伤患者与年龄匹配的对照组之间进行比较，以确定 下行控制改变对可能导致关节间异常协调的GTO反馈的影响 (目标2)。由于本体感觉反馈的任务依赖性调节对于适应变化的任务是必不可少的 根据需求，我们将比较坐姿和站姿时腿部肌肉之间的反馈(目标3)。这个 从这项提案中获得的新知识将是确定 对运动障碍进行反馈。候选人的长期目标是阐明其独特的职能作用 GTO反馈并使用神经调节技术治疗运动障碍 神经方面的情况。PI是一名物理治疗师，曾接受过使用生物力学工具进行评估的培训 去大脑猫的人体运动和本体感觉反馈回路的研究。K01培训计划将 通过对人体神经生理学方法、神经调节技术、临床试验的培训来准备PI 用于临床的动物模型中基础科学方法的翻译设计和指南 在人类身上的应用。

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.