Neuroprosthesis development utilizing afferent neural activity recorded with non-

描述(由申请人提供)： 这项工作的目标是在背根神经节(DRG)水平上开发一种实用的、非穿透性的躯体感觉神经接口，用于感觉反馈。背根神经节是记录躯体感觉神经信号的理想位置，这些信号传递身体状态信息，如来自肢体的触觉和本体感觉反馈。这些信号可以用作闭环功能电刺激(FES)应用中的控制信号，在FES应用中，肢体的位置被解码并用于调节FES系统以适应疲劳或负荷增加或平稳地执行复杂的多关节运动。内部神经接口传感器，如这些可能是最小的突出，并容易与植入的神经假体集成，而不需要大量的传感器或定期佩戴和校准，外部传感器所做的。我们的实验室已经展示了通过插入腰部DRG的穿透性微电极从初级传入神经活动的记录中高精度解码肢体位置的能力，并将这些信号作为反馈应用于对下肢的闭环FES控制。然而，来自这些穿透电极的长期记录的有效性尚未确定，而在人体中使用穿透电极进行记录是具有挑战性的。我们假设，从背根节表面的记录可能足以提取有关肢体位置的详细信息，并可能为临床评估提供一条更实用的途径。与其他神经结构不同，细胞体紧密地堆积在DRG会阴下，使其成为不使用穿透电极从单个细胞获得活动的理想候选者。此外，由于组织反应降低，这种表面方法在长期记录中可能比穿透电极具有更高的效率。最近，我们在动物实验中证明，使用非穿透电极从背根节表面进行记录，可以产生神经信号，可以用来预测肢体的状态。我们将评估这项研究计划中的两个具体目标。目的1：在动物实验中，我们将评估L6和L7背根神经节上非穿透电极神经记录的能力，以提供FES控制的下肢步进运动的功能闭环控制。这项研究将通过表明是否可以记录足够范围的神经活动来获得对肢体功能运动的反馈来确定这种方法的实用性。目的2：在术中人体实验中，我们将评估放置在暴露的背根节表面的非穿透电极记录神经活动的能力，以预测对小腿施加机械和振动刺激的能力。这项研究将首次获得人类DRG的记录，并证明我们能够破译人类DRG的活动。这项拟议工作的成功将是发展基于这种非穿透性DRG方法的闭环神经假体的重要进展，并将推动未来使用优化电极延长动物和人类记录时间的研究。 公共卫生相关性： 这项研究的目的是研究一种方法，从大型感觉神经的表面记录它们进入下背部脊髓的位置。这些神经提供有关腿部位置的信息。我们计划利用这些信息帮助脊髓损伤和其他疾病患者以自然的方式移动他们的腿。

DESCRIPTION (provided by applicant): The goal of this work is the development of a practical, non-penetrating somatosensory neural interface at the level of the dorsal root ganglia (DRG), for use as sensory feedback. The DRG is an ideal location to record somatosensory neural signals which convey body-state information such as tactile and proprioceptive feedback from the limbs. These signals can be used as control signals in closed loop functional electrical stimulation (FES) applications in which the position of a limb is decoded and used to regulate the FES system to adapt to fatigue or the addition of a load or to perform complex, multi-joint movements smoothly. Internal neural interface sensors, such as these may be minimally obtrusive and integrate easily with implanted neuroprostheses while not requiring the large number of sensors or regular donning and calibration that external sensors do. Our lab has shown the ability to decode limb position with high accuracy from recordings of primary afferent neural activity with penetrating microelectrodes inserted in lumbar DRG, and has applied these signals as feedback within closed-loop FES control of the lower limb. However, the efficacy of long-term recordings from these penetrating electrodes has yet to be established, and recordings with penetrating electrodes in humans are challenging to obtain. We hypothesize that recordings from the surface of the DRG may be sufficient for extracting detailed information about limb position and may provide a more practical route for clinical evaluations. Unlike other neural structures, cell bodies are packed closely under the DRG perineum, making it an ideal candidate for obtaining activity from individual cells without using penetrating electrodes. Also, this surface approach may have a higher efficacy in long-term recordings, due to a reduced tissue response, than penetrating electrodes. Recently we showed that recordings from the surface of the DRG, with non-penetrating electrodes, can yield neural signals that can be used to predict the state of the limb, in animal studies. We will evaluate two specific aims in the research planned in this study. Aim 1: In animal experiments, we will evaluate the ability of neural recordings from non-penetrating electrodes on the L6 and L7 DRG to provide functional closed loop control of FES controlled lower limb stepping movements. This study will establish the utility of this approach, by indicating whether a sufficient range of neural activity can be recorded from, to obtain feedback towards functional limb movements. Aim 2: In intraoperative human experiments, we will evaluate the ability of non-penetrating electrodes placed on the surface of exposed DRG to record neural activity that predicts mechanical and vibratory stimulation applied to the lower leg. This study will obtain the first recordings from DRG in humans and demonstrate that we are able to decode human DRG activity. Success in this proposed work will be an important advance towards development of closed-loop neuroprostheses based on this non-penetrating DRG approach and will drive future studies on extended duration animal and human recordings using optimized electrodes. PUBLIC HEALTH RELEVANCE: The goal of this research is to study a method to record from the surface of large sensory nerves where they enter the spinal cord in the lower back. These nerves provide information on the position of the legs. We plan to use this information to help people with spinal cord injuries and other disorders move their legs in a natural manner.