Recording/Stimulation of Stepping in Spinal Cord L1-l2

描述（由申请人提供）：脊髓损伤影响超过230，000人，人均费用在487，150美元至2，185，667美元之间。脊髓L1-L2区域内的神经元间网络本质上能够协调运动所需的多个功能性肌肉群的激活。通过利用脊髓内的脊柱内微刺激进入这个网络，可以实现简单、自然和适应性强的运动控制。为了确定激活的关键区域和时间，我们将在步进过程中同时记录L1-L2区域内一系列位点的细胞外活性，以创建时空群体图。神经元系综记录的最新进展使得在体内观察神经元网络的空间和时间特性成为可能。我们将记录从L1-L2区域的脊髓运动过程中使用高密度多电极阵列，并将相关的时空分布与肌电图（EMG）数据，录像，和踝关节位置/力的测量。将通过刺激中脑运动区研究急性去脑大鼠的运动，并在跑步机上长期植入多电极阵列进行记录和刺激的大鼠中研究运动。使用主成分分析和独立成分分析，我们将描述整体神经活动的特征，并识别与步进周期或步进速率的特定阶段高度相关的神经元。然后，我们将使用定向相干性来确定这些集合的动态相互依赖性，以确定哪些站点是适当的目标。将通过电刺激脊髓横断大鼠中植入的多电极来探索这些序列的有效性。为此，正在开发一种能够输出空间和时间模式化刺激的96通道多电极刺激系统。这些研究的结果可能导致开发用于激活人类腰椎回路的模型，并且可以与跑步机训练、药物干预、功能性神经刺激策略和其他神经修复疗法结合使用，用于恢复运动。

DESCRIPTION (provided by applicant): Spinal cord injury affects upwards of 230,000 people and can cost between $487,150 and $2,185,667 per person. Interneuronal networks within the L1-L2 region of the spinal cord are intrinsically capable of coordinating the activation of multiple functional muscle groups as is required in locomotion. By tapping into this network using intraspinal microstimulation within the spinal cord, simple, natural, and adaptable control of locomotion may be achievable. In order to identify the key regions and timing of activation, we will simultaneously record the extracellular activity at an array of sites within the L1-L2 region during stepping to create a spatiotemporal population map. Recent advances in neuronal ensemble recording make it possible to look at the spatial and temporal properties of neuronal networks in vivo. We will record from the L1-L2 region of the spinal cord using high-density-multielectrode arrays during locomotion, and will correlate the spatiotemporal profile with electromyographic (EMG) data, videography, and ankle position/force measurements. Locomotion will be studied in acute decerebrate rats by stimulation of the mesencephalic Iocmotor region and in rats that have been chronically implanted with a multielectrode array for recording and stimulation on a treadmill. Using principal component analysis and independent component analysis, we will characterize the overall neural activity and identify neurons that are highly correlated with specific phases of the step cycle or rate of stepping. Then we will determine the dynamic interdependence of these sets using directed coherence to determine which sites are appropriate targets. The efficacy of these sequences will be explored by electrically stimulating the implanted multielectrodes in spinal transected rats. To do this, a 96- channel multielectrode stimulation system capable of outputting a spatially and temporally patterned stimulus is being developed. The results of these studies could lead towards the development of models for activation of the lumbar circuits in humans and could be used in combination with treadmill training, pharmacological intervention, functional nerve stimulation strategies, and other neural repair therapies, for the restoration of locomotion.