Functional Role of Golgi tendon organ feedback in health and disease

项目总结/摘要 已知本体感受反馈在协调整个肢体的肌肉活动中具有作用。 中风和脊髓损伤后反馈中断导致关节间协调异常。因此，在本发明中， 特定感觉回路的作用，如果已知并可用于治疗操作，则具有很大的希望 用于治疗一系列运动障碍研究集中在长度依赖反馈的作用 从肌梭（即拉伸和H-反射），及其作为一个治疗目标，通过操作性条件反射的使用。 关于高尔基体腱器官（GTO）的力依赖反馈知之甚少，但目前的证据表明， 力反馈可以提供额外的和潜在的更有效的治疗选择， 治疗协调障碍GTO电路主要连接跨越不同关节的肌肉， 在整个肢体协调中起着关键作用。此外，肌肉之间的力反馈的强度，甚至 符号，被认为是在一个任务依赖的方式变化，因此可能有针对性地减少或 增加肌肉运动输出。然而，目前研究GTO的方法是侵入性的，并且仅限于 去脑猫，阻止研究检查其在自然行为中的功能作用，或评估 人类实验对象神经刺激被用于研究人类的肌间回路，但这种方法是可行的。 不能选择性地激活GTO电路，并且许多神经不能用于刺激。我们建议 使用肌肉刺激诱发的收缩，一种我们在猫身上验证的GTO选择性刺激， 非侵入性地研究人类肌肉间力反馈的强度。目标1将确定唯一的 GTO反馈对肌间抑制反馈的贡献，而坐在比较的影响， 股神经和股四头肌刺激持续比目鱼肌肌电图和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 下降控制改变对GTO反馈的影响，可能导致关节间协调异常 (Aim 2）。由于本体感受反馈的任务依赖性调制对于适应变化的任务是必不可少的 根据需求，将比较坐着和站立时下肢肌肉之间的GTO反馈（目标3）。的 从这一建议中获得的新知识将是确定以下职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作用 GTO反馈，并使用神经调节技术来治疗患有 神经系统疾病PI是一名物理治疗师，之前接受过使用生物力学工具评估 人类运动和研究本体感觉反馈回路在去大脑猫。K 01训练计划将 通过人体神经生理学方法、神经调节技术、临床试验等方面的培训，准备PI 设计和指导将动物模型中开发的基础科学方法转化为临床 应用于人类。

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.