Intraspinal microstimulation for restoring limb movement

椎管内微刺激恢复肢体运动

• 批准号: 7572955
• 负责人: VIVIAN K. MUSHAHWAR
• 金额: $ 24.82万
• 依托单位: UNIVERSITY OF ALBERTA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7572955
• 关键词: Address; Adult; Affect; Animals; Axon; Cells; Clinical; Coupled; Development; Dimensions; Effectiveness; Electric Stimulation; Environment; FOS gene; Felis catus; Fiber; Flexor; Future; Generations; Goals; Hair; Horns; Human; Human Volunteers; Image; Imaging Techniques; Implant; Individual; Injury; Kinetics; Label; Laboratories; Lead; Leg; Limb structure; Location; Locomotion; Lower Extremity; Magnetic Resonance Imaging; Measures; Methods; Modification; Motor; Movement; Neurons; Outcome; Paralysed; Pattern; Peripheral Nerves; Physiological; Procedures; Rehabilitation therapy; Resolution; Safety; Sensory; Site; Spinal Cord; Spinal cord injury; Stimulus; Structure; System; Techniques; Testing; Time; Tissues; Ventral Horn of the Spinal Cord; Walking; Weight; Weight-Bearing state; analog; base; design; extracellular; implantation; improved; in vivo; intraspinal microstimulation; kinematics; limb movement; nervous system disorder; neural circuit; research study; spinal cord regeneration

DESCRIPTION (provided by applicant): The overall goal of this project is to develop the use of intraspinal microstimulation (ISMS) for restoring lower extremity function after spinal cord injury (SCI). Intraspinal microstimulation is a new neuroprosthetic approach which entails implanting a few ultra fine wires, smaller than the human hair, in the spinal cord and delivering electrical stimuli through these wires to generate functional limb movements. All wires are implanted in a small region of the cord (only ~3 cm long) known to contain the neural circuits involved in controlling leg movements. Previous experiments demonstrated the effectiveness of ISMS in restoring standing and stepping after complete SCI in adult cats. Stimulation through some microwires (less than 0.3 mA) generated powerful leg contractions capable of carrying the weight of the hind quarters in animals with SCI, while ISMS through other wires generated upward, forward and backward movements of the legs. By coordinating ISMS through wires generating these movements weight-bearing and kinematically stable in-place stepping of the legs was achieved. The aims of the present project are to advance the technical development of this miniature implant, obtain a better understanding of how ISMS interacts with the nerve cells in the spinal cord, and design "smart" methods of controlling the stimulation paradigms to produce walking movements outside the lab environment. The effect of microwire implantation on spinal cord tissue will also be examined to determine the safety of this technique. Intraspinal microstimulation is expected to eliminate several of the difficulties associated with conventional peripheral nerve electrical stimulation systems used for augmenting limb movements in paralyzed individuals. If found to be safe and capable of generating walking movements reliably, the results from this project could lead to the first ISMS trials in human volunteers with SCI. Experiments will be conducted in adult cats. Arrays of microwires will be constructed for implantation in the lumbosacral cord using a standardized insertion technique. Dimensions of the cord will be obtained from high-resolution in vivo magnetic resonance imaging (MRI) scans to guide the fabrication of the arrays for each animal, and to track their location over time. The extent to which ISMS activates fibers-in-passage in the ventral horn of the spinal cord will be determined using extracellular recordings of local field potentials from single cells throughout the lumbosacral enlargement during ISMS, and activity-dependent immunohistochemical c-fos labeling techniques. The best control paradigms for restoring robust over-ground walking will be investigated in animals with complete SCI and a neuromorphic chip incorporating these control paradigms will be developed and tested. Electromyographic, kinematic and kinetic measures will be used to evaluate the ISMS-induced locomotor patterns in the paralyzed hind limbs.

描述（由申请人提供）： 本项目的总体目标是开发脊髓内微刺激（ISMS）在脊髓损伤（SCI）后恢复下肢功能的应用。椎管内微刺激是一种新的神经假体方法，它需要在脊髓中植入一些比人类头发还小的超细电线，并通过这些电线传递电刺激以产生功能性肢体运动。所有的金属丝都被植入脊髓的一个小区域（只有3厘米长），已知该区域包含控制腿部运动的神经回路。先前的实验证明了ISMS在成年猫完全SCI后恢复站立和行走的有效性。通过一些微导线（小于0.3 mA）的刺激产生了强大的腿部收缩，能够承载SCI动物的后躯重量，而通过其他导线的ISMS产生了腿部的向上，向前和向后运动。通过协调ISMS通过电线产生这些运动的承重和运动学稳定的腿的地方步进实现。本项目的目的是推进这种微型植入物的技术发展，更好地了解ISMS如何与脊髓中的神经细胞相互作用，并设计控制刺激范例的“智能”方法，以在实验室环境外产生行走运动。还将检查微导丝植入对脊髓组织的影响，以确定该技术的安全性。脊柱内微刺激有望消除与用于增强瘫痪个体的肢体运动的常规外周神经电刺激系统相关的若干困难。如果发现它是安全的，并且能够可靠地产生行走运动，该项目的结果可能会导致第一次在SCI志愿者中进行ISMS试验。实验将在成年猫中进行。将使用标准化插入技术构建微导丝阵列以植入腰骶髓。脊髓的尺寸将从高分辨率体内磁共振成像（MRI）扫描中获得，以指导每只动物的阵列制造，并随时间跟踪它们的位置。将使用ISMS期间整个腰骶膨大的单个细胞的局部场电位的细胞外记录和活性依赖性免疫组织化学c-fos标记技术来确定ISMS激活脊髓腹角中的纤维通道的程度。最好的控制模式，恢复强大的地上行走将在动物与完整的SCI和神经形态芯片，将开发和测试这些控制模式。将使用肌电图、运动学和动力学测量来评价瘫痪后肢中ISMS诱导的运动模式。