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，当对脊髓进行强直性刺激以增加腰骶运动回路的兴奋性时，完全胸中段脊髓横断的成年大鼠可以在一定范围的速度、负荷甚至方向上恢复完全负重行走。 此外，我们了解到，负荷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理学和运动训练干预进一步改善。 在目前BRP资助的前2.5年内，而不是最初提出的5年内，我们收集了足够的数据来证明人类腰骶脊髓具有类似的功能。 我们已经证明，一个运动完全性脊髓损伤的人可以恢复独立站立，辅助行走，甚至在硬膜外刺激存在下，经过几个月的测试不同的脊髓刺激模式和运动训练后，下肢的自愿控制的显着水平。 同样重要和令人印象深刻的是，该患者的膀胱控制、血压和体温调节，甚至性功能都得到了显著恢复（13a）。 这些有趣的结果迫使我们开始额外的努力来克服现在被认为是限制我们在临床上使用这种干预措施的进展的最关键因素。 根据我们的研究结果，很明显，我们可以开发选择性激活神经网络组合的能力，这些神经网络可以使患有功能性运动完全脊髓损伤的人类能够通过改进的技术站立并可能行走。 这些功能改善甚至更有可能使那些运动功能不全但活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，最初是为不同的目的设计的， 也就是说，疼痛管理 因此，我们要求提供资金，以便尽可能方便和谨慎地克服目前的技术限制，而不是生理限制。 更具体地说，大鼠的限制因素是缺乏大量电极的慢性植入技术，以及需要更清楚地了解这些硬膜外刺激阵列如何调节脊髓回路。 为了克服这些因素，我们需要1）开发一种设备，该设备将允许我们在具有必要的信号控制能力的大鼠中长期植入集成电极阵列和多路复用刺激设备，2）评估将指导我们更清楚地理解如何调节刺激参数以激活所需脊髓回路的假设，3）开发学习策略以自动优化给定患者站立、迈步或施加自主控制的刺激参数，以及4）开始探索在严重脊髓损伤后可以通过其重新获得自主控制的途径。 公共卫生相关性：现在似乎有可能开发一种技术，使运动完全性脊髓损伤后的人体姿势和运动功能恢复。 该技术包括刺激下脊髓的能力，其方式可以使完全截瘫的患者能够站立和行走。 该项目概述了为实现这一目标而必须开发的新认识的技术能力。

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.