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)瘫痪肌肉的策略，以促进不完全脊髓损伤患者的恢复。拟议的工作受到三个重要事态发展的推动。首先，最近的基础科学和临床研究表明，损伤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，最近的进步为FNS系统产生了自适应控制器，提供了一种自动调整刺激参数以可靠地实现特定节奏运动的手段。第三，脊髓损伤的啮齿动物模型(完全性和不完全性损伤)正被广泛应用于分子、细胞和系统水平，以研究创伤损伤的影响并评估治疗干预的结果。利用FNS进行运动训练和药物干预的联合疗法可能是最有效的增强脊柱创伤后幸免的脊髓回路的重组(可塑性)的方法。FNS辅助运动的啮齿动物模型将有助于对包括FNS的治疗方案进行定量评估，并将提供表征FNS辅助运动对受损脊髓的神经解剖和神经生理学影响的能力。这项生物医学工程研究拨款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带有固定模式和自适应控制器的功能性神经肌肉刺激(FNS)。完整动物的运动学和肌电(EMG)模式将被检测，然后用于开发FNS辅助运动的刺激模式。一系列的任务将通过刺激脊髓化大鼠的后肢肌肉来完成。这些任务将在困难的情况下进行，从控制暂停的后肢运动到控制部分重量支持的脊髓化大鼠在跑步机运动过程中的后肢运动。每个动作将使用两种不同的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基础上，并有望提供更准确和更可重复的运动模式。该项目的成功完成将为FNS辅助的运动训练提供一种新的动物模型，并为评估运动行为提供量化方法。在未来的研究中，我们计划使用FNS辅助运动的不完全性脊髓损伤的啮齿动物模型来验证FNS辅助的运动训练促进不完全性脊髓损伤后运动恢复的假设。我们预计，自适应控制系统提供的改进性能可能会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.