Targeted intraspinal stimulation for restoration of limb movement following spina

描述(由申请人提供)：脊髓损伤(SCI)后肢体运动的恢复是通过电刺激周围神经和骨骼肌实现的。然而，这些刺激技术受到肌肉疲劳快速发作和有限自由度的限制，这些自由度可以使用现有技术独立控制。椎管内微刺激(ISMS)是一项新兴的技术，在克服电刺激相关的一些局限性方面显示出巨大的潜力。 技巧。具体地说，脊髓内刺激通过直接激活脊髓腹侧灰质内的运动神经元，成功地唤起了以前瘫痪的肢体的受控肢体运动。最先进的椎管内微刺激技术依赖于手动定位神经元群体和手动将刺激微电极插入脊髓。然而，神经解剖学的差异加上手术策略和技巧的差异可能会影响临床结果，并阻止交叉研究分析。这项建议的目标是开发一种靶向策略，用于在大型动物模型中识别与特定靶运动相关的运动神经元群体，并证明靶向脊髓内刺激可以引起受控的、可重复的和持续的肌肉收缩。除了唤起肢体运动外，本文提出的靶向和刺激策略将允许描述负责调节大型动物运动功能的脊髓网络。这反过来将允许优化刺激范例，以选择性和协调地招募耐疲劳的运动单位。此外，它将使这项技术更接近于人类使用的临床治疗系统。

DESCRIPTION (provided by applicant): Restoration of limb movement following spinal cord injury (SCI) has been achieved using electrical stimulation of peripheral nerves and skeletal muscles. However, these stimulation techniques are limited by a rapid onset of muscle fatigue and by limited degrees of freedom that can be independently controlled using existing technology. Intraspinal microstimulation (ISMS) is an emerging technology that has shown significant potential for overcoming some of the limitations associated with electrical stimulation techniques. Specifically, intraspinal stimulation has been successful in evoking controlled limb movements in previously paralyzed limbs by directly activating motor neurons within the ventral gray matter of the spinal cord. State-of-the-art intraspinal microstimulation techniques rely on manual targeting of neuron populations and manual insertion of stimulating microelectrodes into the spinal cord. However, variance in neuroanatomy combined with differences in surgical strategy and skill can compromise clinical outcomes and prevent cross-study analysis. The goals of this proposal are to develop a targeting strategy for identifying motor neuron populations associated with specific target movements in a large animal model and demonstrate that targeted intraspinal stimulation can evoke controlled, reproducible, and sustained muscle contractions. In addition to evoking limb movements, the targeting and stimulation strategies proposed herein will allow characterization of spinal networks responsible for mediating motor function in a large animal. This in turn will allow optimization of stimulation paradigms for selective and coordinated recruitment of fatigue-resistant motor units. Moreover, it will allow ths technology to move closer to a clinical therapeutic system for human use.