Functional Role of Golgi tendon organ feedback in health and disease

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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.