Structure and function of the fingers tendinous apparatus

描述（由申请人提供）：我们的长期目标是系统地揭示肌肉肌腱力学，脊髓和大脑如何相互作用，以产生能够和病理手指功能。先前的资助揭示了手指功能和功能障碍的许多必要的神经机械相互作用。这迫使并使我们能够研究脊髓神经生理学和神经力学，作为解决大脑功能之前的一步。我们的科学家和外科医生团队的近期目标是（i）测试已知的体感反馈和脊髓神经元间回路在多大程度上足以单独解释FST等长指尖力的关键特征，而无需在线脊髓上调制;以及（ii）了解肉毒杆菌毒素（BTX）注射如何减少偏瘫CP和iSCI患者的痉挛和肌张力障碍与该回路的相互作用。我们将使用综合分析和物理实现来测试脊髓反射和兴奋性反射机制的理论，我们认为这是对我们对系统理解的有力测试。也就是说，我们将面对神经系统所面临的挑战，通过控制尸体手指的肌腱，用一个由微处理器和电机组成的自主神经机电系统，实现健康受试者和患者已知的运动和体感脊髓回路和肌肉特性。目的1：表征对照受试者和患者在BTX前后的H反射和单关节和全指快速等长任务的表现。（对接受肌腱转移和肌肉肌腱长度变化的CP患者进行的探索性测试将在研究的后期阶段验证其他生理过程和模型组件。然后，驱动尸体手指的肌腱以（i）找到可行的张力来复制该性能，以及（ii）量化鲁棒性， 肌腱张力误差。目标二：真实的实时实现单个传入肌肉的脊髓神经元、肌肉本体感受器和肌纤维的已知连接和动力学。与文献中的数据进行比较。单肌肉假说：肌肉功能（例如，张力、牵张反射）从神经元背景活动和通路增益的特定组合中自然出现。测试生理上可行的破坏和BTX如何导致或减轻病理行为（例如，痉挛和阵挛）。目标3：实施跨肌肉的假设的神经连接和动力学，以再现在对照受试者中以及在患者中的BTX前和后看到的H反射和快速等长任务的表现。通过驱动尸体食指的肌腱来复制目标1中测量的行为，将确定临床上可行的中断如何导致病理行为，以及BTX（以及初步的肌腱转移和肌肉肌腱长度变化）可以减轻这些病理的程度。a）单关节假设：单关节功能（例如，快速时变扭矩）从背景活动和穿过一对拮抗肌的运动神经元池的通路增益中自然出现。在单关节任务中测试单关节痉挛、阵挛、不稳定和缺陷的出现和BTX缓解。B）全指假说：目标1中记录的快速时变指尖力任务自然地出现在所有手指肌肉之间的生理上可行的相互作用。测试整个手指痉挛、阵挛、异常姿势和整个指尖力量任务中的缺陷的出现和BTX缓解。

DESCRIPTION (provided by applicant): Our long-term goal is to reveal systematically how the musculotendon mechanics, spinal cord and brain interact to produce able and pathologic finger function. The prior grant revealed many necessary neuromechanical interactions for finger function and dysfunction. This compels and enables us to study spinal neurophysiology and neuromechanics as a step before tackling brain function. The immediate goals of our team of scientists and surgeons are to (i) test the extent to which the known somatosensory feedback and spinal interneuronal circuitry is sufficient, on its own, to account for critical features of fst isometric fingertip forces without requiring on-line supraspinal modulation; and (ii) understand how botulinum toxin (BTX) injections to reduce spasticity and dystonia in hemiplegic CP and iSCI interact with that circuitry. We will test theories of spinal reflexive and excitation-inhibiton mechanisms using synthetic analysis and physical implementation, which in our view is a strong test of our understanding of a system. That is, we will confront the very challenge the nervous system faces by controlling the tendons of cadaveric fingers with an autonomous neuromechatronic system of microprocessors and motors that implements the known motor and somatosensory spinal circuitry and muscle properties of healthy subjects and patients. Aim 1: Characterize H-reflex and performance of Single Joint and Whole Finger fast isometric tasks in control subjects, and pre-&post-BTX in patients. (Exploratory test on CP patients undergoing tendon transfers and musculotendon length changes will validate other physiological processes and model components in the later phases of the research.) Then, actuate tendons of cadaveric fingers to (i) find feasible tensions to replicate that performance and (ii) quantify robustness to errors in tendon tensions. Aim 2: Implement in real time the known connectivity and dynamics of spinal neurons, muscle proprioceptors and muscle fibers of a single afferented muscle. Validate against data in the literature. Single Muscle Hypothesis: Muscle function (e.g., tone, stretch reflex) emerges naturally from specific combinations of neuronal background activity and pathway gains. Test how physiologically tenable disruptions and BTX lead to, or mitigate, pathologic behavior (e.g., spasticity and clonus). Aim 3: Implement the hypothesized neural connectivity and dynamics across muscles to reproduce the H- reflex and performance of fast isometric tasks seen in control subjects, and pre-&post-BTX in patients. Replicating the behavior measured in Aim 1 by driving tendons of cadaveric index fingers will identify how clinically tenable disruptions lead to pathologic behavior, and the extent to which BTX (and preliminarily tendon transfers and musculotendon length changes) can mitigate those pathologies. a) Single Joint Hypothesis: Single-joint function (e.g., fast time-varying torques) emerges naturally from background activity and pathway gains across motoneuron pools of a pair of antagonist muscles. Test the emergence and BTX mitigation of single joint spasticity, clonus, instability, and deficits in single joint tasks. b) Whole Finger Hypothesis: The fast time-varying fingertip force tasks recorded in Aim 1 emerge naturally from physiologically tenable interactions across all finger muscles. Test the emergence and BTX mitigation of whole-finger spasticity, clonus, abnormal postures, and deficits in whole fingertip force tasks.