Spinal Epidural Electrode Array to Facilitate Standing and Stepping After SCI

描述（由申请人提供）：我们已经证明，当脊髓受到强直刺激以增加腰骶运动回路的兴奋性时，一只完整的胸中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，并且这些任务的表现可以通过药物和运动训练干预进一步改善。在目前BRP资助的前2.5年，而不是最初提出的5年，我们已经收集了足够的数据来证明人类腰骶脊髓具有类似的能力。我们已经证明，经过几个月不同的脊髓刺激模式和运动训练的测试，运动完全性脊髓损伤患者可以在硬膜外刺激下恢复独立站立、辅助行走，甚至可以在很大程度上自主控制下肢。同样重要和令人印象深刻的是，患者膀胱控制、血压和体温调节，甚至性功能的显著恢复（13a）。这些有趣的结果迫使我们开始额外的努力，以克服现在被认为是限制我们将这种干预措施应用于临床的最关键因素。基于我们的研究结果，很明显，我们可以开发有选择性地激活神经网络组合的能力，通过改进的技术，可以使功能性运动性完全性脊髓损伤的人站立和行走。这些功能的改善更有可能使那些运动功能不全，但行动能力严重受损的人受益。我们目前的成就是利用30年前的技术实现的，最初的设计是为了不同的目的，

DESCRIPTION (provided by applicant): 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 pharmacological and motor training interventions. Within the first 2.5 years of the present BRP Grant, not within the five years as initially proposed, we have gathered sufficient data to demonstrate that the human lumbosacral spinal cord has similar capabilities. We have shown that an individual with a motor complete spinal cord injury can regain independent standing, assisted stepping, and even a significant level of voluntary control of the lower limbs in the presence of epidural stimulation after months of testing different spinal cord stimulation patterns and motor training. Just as important and as impressive is the recovery of significant levels of bladder control, blood pressure, and temperature regulation, and even sexual function in this patient (13a). These intriguing results compel us to begin additional efforts to overcome what are now recognized as the most critical factors limiting our progress toward making this intervention available in the clinic. Based on our results, it is clear that we can develop the capability to selectively activae combinations of neural networks that can enable standing and probably stepping with improved technology in humans with a functionally motor complete spinal cord injury. These functional improvements are even more likely to benefit those individuals that are functionally motor incomplete, but have severely impaired mobility. Our present accomplishments have been realized using technology that is three decades old and initially designed for a different purpose, i.e., pain management. Thus we are requesting funds to overcome the present technical, not physiological, limitations as expediently and as carefully as possible. More specifically, the rat limiting factors are the lack of technology for chronic implants for a high number of electrodes and the need for a more clear understanding of how these epidural stimulation arrays can modulate the spinal circuitries. To overcome these factors we need to 1) develop a device that will allow us to chronically implant an integrated electrode array and multiplexed stimulation device in rats with the necessary signal control capabilities, 2) evaluate hypotheses that will guide us to more clearly understand how to modulate the stimulation parameters to activate the desired spinal circuits, 3) develop a learning strategy to automatically optimize the stimulation parameters for a given patient to stand, step, or exert voluntary control, and 4) begin to explore the pathways through which voluntary control can be regained after a severe spinal cord injury. PUBLIC HEALTH RELEVANCE: It now seems possible to develop a technology that will enable the recovery of postural and locomotor function in humans after a motor complete spinal cord injury. This technology includes the capability to stimulate the lower spinal cord in a manner that can enable a patient with complete paraplegia to stand and to step. This project outlines the newly recognized technical capabilities that must be developed to accomplish this goal.