神经元形态和空间分布对刺激背根神经节选择性的影响

Juhi Farooqui, Ameya C Nanivadekar, Marco Capogrosso, Scott F Lempka, Lee E Fisher
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摘要

目的: 对于假肢使用者来说,来自缺失肢体的感觉反馈可以改善他们的功能、信心和幻肢痛。许多临床前研究都认为,通过穿透背根神经节(DRG)的微电极进行刺激是躯体感觉神经义肢的一种潜在方法。然而,要开发可应用于临床的神经假体设备,最好采用创伤较小的方法,如通过会神经大电极进行刺激。与穿透性电极相比,本研究通过研究神经外膜电极对刺激的选择性激活机制,探讨了使用此类电极提供局灶感觉反馈的可行性。为了评估神经元形态和空间排列等特性的作用,我们设计了三个模型,包括一个只包含轴突的模型(只包含轴突)、一个随机排列假双极神经元的模型(随机)和一个按照现实空间分布放置假双极神经元的模型(现实)。 主要结果: 我们的模型表明,在现实模型中,通过会神经电极刺激产生的激活反应通常是在邻近细胞体的轴突起始节段开始的,而穿透电极通常会在 T 型接头和轴突中引起反应。此外,与穿透电极相比,我们发现会神经电极的动态范围更广。这种差异似乎是由现实中 DRG 的空间组织和神经元形态决定的:我们证明,DRG 的解剖学特征使其有可能成为神经外膜刺激的有效目标,从而传递来自四肢的病灶感觉。具体来说,我们表明,由于 DRG 的神经解剖学排列,对 DRG 的神经外膜刺激具有高度选择性,这使其成为未来神经假体开发的一种有前途的方法。
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The effects of neuron morphology and spatial distribution on the selectivity of dorsal root ganglion stimulation.

Objective.For prosthesis users, sensory feedback that appears to come from the missing limb can improve function, confidence, and phantom limb pain. Numerous pre-clinical studies have considered stimulation via penetrating microelectrodes at the dorsal root ganglion (DRG) as a potential approach for somatosensory neuroprostheses. However, to develop clinically translatable neuroprosthetic devices, a less invasive approach, such as stimulation via epineural macroelectrodes, would be preferable. This work explores the feasibility of using such electrodes to deliver focal sensory feedback by examining the mechanisms of selective activation in response to stimulation via epineural electrodes compared with penetrating electrodes.Approach.We developed computational models of the DRG, representing the biophysical properties of the DRG and surrounding tissue to evaluate neural responses to stimulation via penetrating microelectrodes and epineural macroelectrodes. To assess the role of properties such as neuron morphology and spatial arrangement we designed three models, including one that contained only axons (axon only), one with pseudounipolar neurons arranged randomly (random), and one with pseudounipolar neurons placed according to a realistic spatial distribution (realistic).Main results.Our models demonstrate that activation in response to stimulation via epineural electrodes in a realistic model is commonly initiated in the axon initial segment adjacent to the cell body, whereas penetrating electrodes commonly elicit responses in t-junctions and axons. Moreover, we see a wider dynamic range for epineural electrodes compared with penetrating electrodes. This difference appears to be driven by the spatial organization and neuron morphology of the realistic DRG.Significance.We demonstrate that the anatomical features of the DRG make it a potentially effective target for epineural stimulation to deliver focal sensations from the limbs. Specifically, we show that epineural stimulation at the DRG can be highly selective thanks to the neuroanatomical arrangement of the DRG, making this a promising approach for future neuroprosthetic development.

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