Inducing Neural Plasticity after Spinal Cord Injury to Recover Impaired Voluntary Movement

项目摘要/摘要 脊髓损伤(SCI)通常是一种丧失行为能力的神经损伤，最常见的原因是创伤性打击 脊椎，破坏在大脑和脊髓之间传递感觉和运动信号的轴突，以及在 转身，身体的其余部分。然而，脊髓挫伤后，至少上面和上面的一些神经纤维 下面的病变保持完好。最近，我们实验室和其他实验室推出了新的神经假体 试图通过利用脑-机器-脊髓接口(BMSI)恢复功能的方法。这些 基于设备的系统使用活动依赖刺激(ADS)，它区分完整的神经活动 运动皮质作为刺激脊髓损伤下方运动神经元的信号。我们的长期目标是 本研究旨在恢复脊髓损伤后受损的肢体运动功能。可行性 在脊髓损伤后使用ADS作为一种促进功能恢复的策略得到了积极结果的支持 本实验室证明了ADS在恢复创伤性脑损伤后熟练运动功能方面的作用。 因此，这一系列研究的主要假设是，ADS将导致增强运动恢复 脊髓损伤后的步行能力。拟议的项目将通过以下方式确定最佳的神经生理条件 哪些ADS可以促进大脑皮层和脊髓运动神经元之间的沟通。 该项目将解决三个具体目标：1)确定脊髓挫伤对脊柱的影响 大鼠运动神经元活动、皮质脊髓偶联和传导时间2)决定最佳的棘波刺激 使用ADS范例增加下行运动通路中突触有效性的延迟， 麻醉的大鼠脊髓损伤模型，以及3)确定棘波触发的ISM是否导致运动改善 脊髓损伤大鼠模型的表现。我们将使用急性和慢性神经学来测试这些目标 麻醉和清醒状态下的记录和刺激技术，表现为健康和脊髓损伤的啮齿动物。这个 该项目意义重大，因为如果实现，这种方法可能会增加伴随而来的身体和职业 治疗和功能能力的改善。最终，患者可能会恢复应有的自主活动 以提高皮质脊髓纤维的突触效率。

PROJECT SUMMARY/ABSTRACT Spinal cord injury (SCI) is often an incapacitating neural injury most commonly caused by a traumatic blow to the spine, damaging the axons that carry sensory and motor signals between the brain and spinal cord, and in turn, the rest of the body. However, after a contusion to the spinal cord, at least some neuronal fibers above and below the lesion remain intact. Recently, our laboratory and others have introduced new neuroprosthetic approaches in an attempt to restore function by utilizing brain-machine-spinal cord interfaces (BMSIs). These device-based systems use activity-dependent stimulation (ADS) which discriminates neural activity in the intact motor cortex to use as signals to stimulate motor neurons below the spinal cord lesion. Our long-term goal for this research is restoration of impaired motor function in the lower limbs following spinal cord injury. The feasibility of using ADS as a strategy to enhance recovery of function after SCI is supported by the positive results seen in this laboratory demonstrating the effect of ADS in restoring skilled motor function after traumatic brain injury. Thus, the overarching hypothesis of this line of research is that ADS will result in enhanced motor recovery in ambulatory ability after SCI. The proposed project will determine the optimal neurophysiological conditions by which ADS can facilitate enhanced communication between the cerebral cortex and spinal cord motor neurons. The project will address three specific aims: 1) Determine the effects of a contusive spinal cord injury on spinal motor neuron activity, corticospinal coupling, and conduction time in rats 2) determine the optimal spike-stimulus delay for increasing synaptic efficacy in descending motor pathways using an ADS paradigm in an acute, anesthetized rat model of SCI, and 3) determine whether spike-triggered ISMS results in improved motor performance in an ambulatory rat model of SCI. We will test these aims using acute and chronic neurologic recording and stimulating techniques in both anesthetized and awake, behaving healthy and SCI rodents. The project is significant because, if realized, this approach may augment concomitant physical and occupational therapy and result in improved functional abilities. Ultimately, patients may could regain voluntary movement due to increased synaptic efficacy in corticospinal fibers.