A Rodent Model for Locomotor Training with FNS

这项工作的长期目标是开发使用功能性神经肌肉刺激（FNS）的瘫痪肌肉的策略，以促进不完全脊髓损伤患者的恢复。 拟议的工作是由三个重要的事态发展推动的。 首先，最近的基础科学和临床研究表明，受损脊髓的功能恢复程度取决于脊髓神经输入的活动模式。 其次，最近的进展已经产生了用于FNS系统的自适应控制器，其提供了自动调节刺激参数以可靠地实现指定的节律运动的手段。 第三，啮齿动物模型的脊髓损伤（完全和不完全的病变）被广泛用于在分子，细胞和系统水平上研究创伤性损伤的影响，并评估治疗干预的结果。利用FNS和药物干预的运动训练的组合疗法可能是最有效的，以增强脊柱创伤后保留的脊髓回路的重组（可塑性）。 FNS辅助运动的啮齿动物模型将有助于定量评价包括FNS的治疗方案，并将提供表征FNS辅助运动对受损脊髓的神经解剖学和神经生理学的影响的能力。 这项生物医学工程研究资助提案将开发一种运动训练的啮齿动物模型，该模型利用跑步机行走和功能性神经肌肉刺激（FNS），并采用固定模式和自适应控制器。将检查完整动物的运动学和肌电图（EMG）模式，然后用于开发FNS辅助运动的刺激模式。 将使用脊髓化大鼠后肢肌肉的FNS刺激执行一系列任务。这些任务将进展困难，从控制悬挂后肢运动到控制后肢运动在跑步机运动在脊髓化大鼠与部分重量支持。 每种运动将使用两种不同的FNS控制策略：固定模式或开环刺激模式和自适应刺激控制系统。自适应刺激控制系统将建立在我们以前的工作，预计将提供更准确，更可重复的运动模式。该项目的成功完成将为FNS辅助运动训练提供一种新的动物模型，并为评估运动行为提供定量方法。在未来的研究中，我们计划使用FNS辅助运动的不完全脊髓损伤的啮齿动物模型来测试FNS辅助运动训练增强不完全脊髓损伤后运动恢复的假设。 我们预计，由自适应控制系统提供的改进的性能可以增强该技术的治疗效果。 这种运动训练也可以与药物干预，组织移植和神经修复疗法相结合，以确定运动训练是否可以增强这些疗法的有效性。

The long-term goal of this work is to develop strategies for using functional neuromuscular stimulation (FNS) of paralyzed muscles to enhance the recovery of individuals with incomplete spinal cord injury. The proposed work is motivated by three important developments. First, recent basic science and clinical studies have demonstrated that the degree of functional recovery of the injured spinal cord depends on the activity patterns of neural inputs to the spinal cord. Second, recent advances have produced adaptive controllers for FNS systems that provide a means of automatically adjusting stimulation parameters to reliably achieve specified rhythmic movements. Third, rodent models of spinal cord injury (complete and incomplete lesions) are extensively being used at the molecular, cellular, and systems level to investigate the effects of traumatic injury and to assess the results of therapeutic intervention. A combination therapy that utilizes locomotor training with FNS and pharmacological intervention is likely to be the most effective in enhancing the reorganization (plasticity) of the spinal circuitry that is spared after spinal trauma. A rodent model for FNS-assisted locomotion would facilitate quantitative evaluation of therapeutic regimens that include FNS and would provide the ability to characterize effects of FNS-assisted locomotion on the neuroanatomy and neurophysiology of the injured spinal cord. This biomedical engineering research grant proposal will develop a rodent model of locomotor training that utilizes treadmill walking and functional neuromuscular stimulation (FNS) with fixed-pattern and adaptive controllers. Kinematic and electromyogram (EMG) patterns of intact animals will be examined and then used to develop stimulation patterns for FNS-assisted movement. A series of tasks will be performed using FNS stimulation of hindlimb muscles in spinalized rats. These tasks will progress in difficulty from controlling suspended hindlimb movements to controlling hindlimb movements during treadmill locomotion in spinalized rats with partial weight support. Two different FNS control strategies will be used for each movement: a fixed-pattern, or open-loop, stimulation pattern and an adaptive stimulation control system. The adaptive stimulation control system will build upon our previous work and is expected to provide movement patterns that are more accurate and more repeatable. Successful completion of the proposed project will result in a novel animal model for FNS-assisted locomotor training and provide quantitative methods for evaluating locomotor behavior. In future studies, we plan to use a rodent model of incomplete spinal cord injury with FNS-assisted locomotion to test the hypothesis that FNS-assisted locomotor training enhances motor recovery after incomplete spinal cord injury. We anticipate that the improved performance provided by the adaptive control system may enhance the therapeutic effects of the technique. This locomotor training could also be combined with pharmacological intervention, tissue transplant, and neural repair therapies to determine if locomotor training can enhance the effectiveness of these therapies.