Spinal Epidural Electrode Array To Facilitate Standing and Stepping After SCI

描述（由申请人提供）：在我们BRP的前5年期间，我们有两个主要目标：1)确定我们是否可以通过硬膜外刺激神经调节脊髓腰骶回路来改善下肢的运动功能；2)开始开发和改进与电极阵列和慢性植入式刺激装置相关的技术，以最大限度地发挥神经调节潜力。这些新技术有可能微调硬膜外刺激参数，以帮助理解硬膜外刺激的一些潜在机制。，研究硬膜外刺激、药物调节的协同作用，并研究可能影响完全瘫痪后运动功能恢复水平的活动依赖干预。我们已经证明，当脊髓受到紧张性刺激以增加腰骶运动回路的兴奋性时，一个完整的胸椎中段脊髓横断的成年大鼠可以在一定的速度、负荷甚至方向上恢复完全的负重行走。此外，我们了解到负重感觉信息可以作为这些复杂运动任务的控制器，并且通过硬膜外刺激、药物和运动训练干预的组合可以进一步改善这些任务的表现。我们已经证明，四名患有完全性脊髓损伤的患者在硬膜外刺激下可以恢复独立站立，辅助行走，甚至在很大程度上可以自主控制下肢，其中一名患者在没有刺激的情况下甚至可以控制一些意志。膀胱控制、血压、体温调节，甚至性功能都得到了改善。因此，我们目前面临的挑战是发展选择性激活神经网络组合的能力，通过改进所需的技术，使这种干预在临床和使用慢性硬膜外电极植入的完全运动瘫痪患者的家中可用。具体来说，我们将进一步

DESCRIPTION (provided by applicant): In the first 5-year period of our BRP we had two major objectives: 1) to determine whether we could improve motor function of the lower limbs by neuromodulating the spinal lumbosacral circuitry with epidural stimulation and 2) to begin to develop and improve the technologies associated with electrode arrays and chronic implantable stimulation devices to maximize the neuromodulatory potential. These new technologies have the potential to fine tune the epidural stimulation parameters, to help in understanding some of the underlying mechanisms of epidural stimulation., to examine synergistic effects of epidural stimulation, pharmacological modulation, and examine activity-dependent interventions that might affect the level of recovery of motor function after complete paralysis. We have demonstrated that an adult rat with a complete, mid-thoracic spinal cord transection can regain full weight-bearing stepping over a range of speeds, loads, and even directions when the spinal cord is stimulated tonically to increase the excitability of the lumbosacral locomotor circuitry. Furthermore, we learned that load-bearing sensory information can serve as the controller of these complex motor tasks and that the performance of these tasks can be improved even further with combinations of epidural stimulation, pharmacological, and motor training interventions. We have shown that four humans with a motor complete spinal injury have regained independent standing, assisted stepping, and even a significant level of voluntary control of the lower limbs in the presence of epidural stimulation, with one subject now even having some volitional control without stimulation. Improvement in bladder control, blood pressure, temperature regulation, and even sexual function has been realized. Thus, our present challenge is to develop the capability to selectively activate combinations of neural networks that can enable standing, and probably stepping, by improving the technologies needed to make this intervention available in the clinic and in the home of individuals with complete motor paralysis using a chronic epidural electrode implant. Specifically, we will further improve the electrode array stimulation technology needed for fine-tune control in rats and humans and transform the present hardwired technology for rats to a wireless capability to stimulate and record evoked potentials along the brain-spinal cord-muscle axis in the rat. To advance the clinical potential, we will continue to develop, refine and validate our machine-learning strategies which automatically optimize stimulation parameters for standing, stepping, and voluntary control. We will develop an improved interface between the devices implanted in our present subjects and the control devices for defining the specific stimulation parameters needed for a given subject to perform a motor task in the clinic or at home.