CRCNS: Role of sensory feedback in locomotor recovery after spinal cord injury

CRCNS：感觉反馈在脊髓损伤后运动恢复中的作用

• 批准号: 8055677
• 负责人: Michel A Lemay
• 金额: $ 35.43万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-20 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8055677
• 关键词: Ankle; Biomechanics; Biomedical Engineering; Body Weight; Characteristics; Collaborations; Cutaneous; Educational process of instructing; Experimental Models; Feedback; Felis catus; Hindlimb; Hip region structure; Individual; Institutes; Institution; Knowledge; Location; Locomotion; Locomotor Recovery; Medicine; Modality; Modeling; Motion; Motor; Muscle; Neuromechanics; Neurosciences; Pattern; Physiology; Play; Postdoctoral Fellow; Recovery; Rehabilitation therapy; Research Personnel; Role; Sensory; Simulate; Spinal; Spinal cord injury; Structure; Students; Synapses; Technology; Testing; Training; Transplantation; Universities; Weight; Work; central pattern generator; college; foot; models and simulation; multidisciplinary; neural model; neurophysiology; neuroregulation; neurotrophic factor; programs; research study; sensory feedback; Ankle; Biomechanics; Biomedical Engineering; Body Weight; Characteristics; Collaborations; Cutaneous; Educational process of instructing; Experimental Models; Feedback; Felis catus; Hindlimb; Hip region structure; Individual; Institutes; Institution; Knowledge; Location; Locomotion; Locomotor Recovery; Medicine; Modality; Modeling; Motion; Motor; Muscle; Neuromechanics; Neurosciences; Pattern; Physiology; Play; Postdoctoral Fellow; Recovery; Rehabilitation therapy; Research Personnel; Role; Sensory; Simulate; Spinal; Spinal cord injury; Structure; Students; Synapses; Technology; Testing; Training; Transplantation; Universities; Weight; Work; central pattern generator; college; foot; models and simulation; multidisciplinary; neural model; neurophysiology; neuroregulation; neurotrophic factor; programs; research study; sensory feedback

DESCRIPTION (provided by applicant): Afferent feedback plays a critical role in the control of locomotion and in the recovery afforded by body-weight supported treadmill training or graft of neurotrophin producing cellular transplants after spinal cord injury (SCI). Yet our knowledge of the structure of the locomotor circuitry is limited and the roles of the modality and/or origin of the afferent feedback in recovery have been for the most part unexplored. We propose to integrate a neural model of the locomotor circuitry developed at Drexel University College of Medicine with a biomechanical hindlimb model developed at Georgia Institute of Technology, and to use this integrated model to study the roles of afferent feedback in the control of locomotion under normal conditions and in the absence of sensory feedback. We will demonstrate using the integrated model that in the intact cat the control of locomotion is dependent on afferent feedback from the hip muscles for the initiation of swing while afferent feedback from the ankle extensors and/or cutaneous input from the foot pad are critical to the control of stance. We hypothesize that in the cat with spinal cord injury, training or neurotrophin producing transplants enhance the synaptic strengths of the sensory feedback and that these increases allow the circuitry to produce a stable locomotor pattern in the absence of supraspinal control. The model developed will allow us to investigate this hypothesis and make predictions about the motor pattern deficits obtained when certain sensory modalities are removed after spinal cord injury. Experiments with partially deafferented or re-innervated muscles will allow us to test these predictions and further refine the model. The proposed multidisciplinary project is a collaboration between investigators at Drexel University College of Medicine and Georgia Institute of Technology. Experiments are planned at both locations to identify model parameters and verify the model's predictions. The experimental and modeling work will provide new and important information about the roles of sensory feedback in locomotor recovery after SCI. The intellectual merit of this proposal has several components. First, a comprehensive neuromechanical model of spinal locomotion will be developed that includes the cat hindlimb, motion-dependent proprioceptive feedback, and central pattern generator (CPG). Second, model parameters including feedback weights, modality, and connectivity patterns within CPG will be identified by matching simulated normal and spinal locomotion characteristics with those recorded experimentally. Third, several hypotheses about the role of sensory feedback in locomotion post-SCI will be tested using model simulations and experiments. The results of the model will increase our understanding of the spinal locomotor circuitry and may guide rehabilitation training efforts in individuals with spinal cord injury. The proposal will have broader impacts on the interdepartmental Neuroengineering program at Drexel University, the Neuroscience program at The College of Medicine, and the Applied Physiology and Biomedical Engineering programs at Georgia Institute of Technology by supporting students and a postdoctoral fellow from the programs and providing them with the opportunity to truly integrate computational and experimental neurophysiological concepts acquired in the educational programs. We also expect the models developed in the project to be used in classes taught by Drs. Lemay and Prilutsky on the neural control and biomechanics of locomotion at their respective institutions.

描述（由申请人提供）：传入反馈在控制运动以及由体重支撑的跑步机训练或神经营养蛋白的移植物所提供的恢复中起着至关重要的作用，从而在脊髓损伤后产生细胞移植（SCI）。然而，我们对运动电路结构的了解是有限的，并且传入反馈在恢复中的形式和/或起源的作用在大多数情况下都没有探索。我们建议将Drexel大学医学院运动电路的神经模型与佐治亚理工学院开发的生物力学后肢模型开发的神经模型，并使用这种综合模型来研究传入反馈在正常条件下和缺乏感官反馈的情况下控制机车的作用。我们将使用集成模型证明，在完整的CAT中，运动的控制取决于髋部肌肉的传入反馈以启动挥杆，而脚踝伸肌的传入反馈和/或脚垫的皮肤输入的传入反馈至关重要。我们假设在患有脊髓损伤的猫中，训练或神经营养蛋白产生移植可以增强感觉反馈的突触强度，并且这些增加使电路在没有上脊柱上的情况下产生稳定的运动模式。开发的模型将使我们能够研究这一假设，并在脊髓损伤后去除某些感觉方式时获得的运动模式缺陷。进行部分脱离或重新发射肌肉的实验将使我们能够测试这些预测并进一步完善模型。拟议的多学科项目是德雷克塞尔大学医学院与佐治亚理工学院研究人员之间的合作。在两个位置都计划实验以识别模型参数并验证模型的预测。实验和建模工作将提供有关SCI后感觉反馈在运动恢复中的作用的新的重要信息。该提案的智力优点具有多个组成部分。首先，将开发一个综合的脊柱运动神经力学模型，其中包括猫后肢，运动依赖性的前置反馈和中央模式发生器（CPG）。其次，将通过将模拟的正常和脊柱运动特性与实验记录的模拟正常和脊柱运动特性匹配，包括CPG中的反馈权重，模式和连接模式在内的模型参数。第三，将使用模型仿真和实验测试有关感觉反馈在SCI运动后的作用的一些假设。该模型的结果将增加我们对脊柱运动电路的理解，并可能指导脊髓损伤患者的康复训练工作。该提案将对Drexel大学的部门间神经工程计划，医学院的神经科学计划以及Georgia技术研究所的应用生理学和生物医学工程计划，通过为学生提供支持，并与他们提供真正的调查概念的机会，并为他们提供真正的计算概念的机会，从而实验性地进行概念。我们还希望项目中开发的模型将用于DRS教授的课程。 Lemay和Prilutsky对各自机构的神经机制的神经控制和生物力学。