Structure and function of the fingers tendinous apparatus

描述(由申请者提供)：我们的长期目标是系统地揭示肌腱力学、脊髓和大脑如何相互作用以产生能够和病理的手指功能。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在研究大脑功能之前研究脊髓神经生理学和神经力学。我们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本身是否足以解释FST等长指尖力量的关键特征，而无需在线脊髓上调制；以及(Ii)了解肉毒毒素(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抑制机制的理论，在我们看来，这是对我们对系统理解的有力考验。也就是说，我们将通过一个由微处理器和马达组成的自主神经机电系统来控制身体手指的肌腱，以应对神经系统面临的非常严峻的挑战。该系统实现了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：研究对照受试者单关节和全指快速等长作业以及BTX前、后患者的H反射和操作特点。(对接受肌腱转移和肌腱长度改变的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，启动身体手指的肌腱，以(I)找到可行的张力来复制这种表现，以及(Ii)量化健壮性 肌腱张力的错误。目的2：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通性和动力学。对照文献中的数据进行验证。单肌假说：肌肉功能(如张力、伸展反射)来自神经元背景活动和通路增益的特定组合。测试生理上可行的干扰和BTX如何导致或减轻病理行为(例如，痉挛和阵挛)。目的3：实施假想的跨肌肉神经连通性和动力学，以再现对照组受试者以及患者BTX前后的H反射和快速等长任务的执行。通过驱动身体食指的肌腱来复制目标1中测量的行为，将确定临床上可站立的破坏如何导致病理行为，以及BTX(以及初步的肌腱转移和肌腱长度变化)可以在多大程度上缓解这些病理行为。A)单关节假说：单关节功能(例如，快速时变力矩)来自背景活动和跨越一对拮抗肌的运动神经元池的路径增益。测试单关节任务中单关节痉挛、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量任务自然产生于所有手指肌肉之间生理上站得住脚的相互作用。测试整个指尖力量任务中全指痉挛、阵挛、异常姿势和缺陷的出现和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.