Electrodes for selective stimulation of the lateral spinal cord to restore sensation after lower-limb amputation

项目摘要/摘要 设计和驱动方面的进步导致了假肢的戏剧性改进。然而，这些设备不能 提供感觉反馈，这会导致步态变慢，增加摔倒的风险。我们实验室的最新证据表明 刺激脊髓和背根的侧向结构可以有效地在远端肢体产生感觉。 在这些研究中，外侧SCS(LSCs)在截肢的手或脚的区域引起感觉，尽管其中许多 感觉也覆盖了残肢的更近端区域。为了在缺失的肢体上获得更多的焦点感觉 将需要开发具有更小触点、更紧密的触点间间距和更好的布置的电极 目前存在SCS电极。此外，由于外侧硬膜外间隙比外侧硬膜外间隙更窄和更弯曲 传统的SCS中线靶，这些新型的SCS电极必须比现有的SCS器件更薄、更灵活。 我们的长期目标是创造一种神经刺激系统，通过选择性刺激外侧神经来恢复感觉 脊髓中的结构。在本项目中，我们将描述灾难恢复如何响应LSC并优化 刺激这些结构的电极设计。通过结合大型动物神经生理学实验， 组织学分析和计算模型研究，我们将表征LSC的选择性和设计 电极最大限度地选择性和实现足部和脚踝的局部异常覆盖，同时避免对 潜伏在神经组织下面。为实现这些目标，我们将完成以下目标： 目的1：量化腰椎DR的功能组织和LSCs的选择性。 我们将通过记录诱发动作电位的逆行传播来测量猫LSCs的选择性。 后肢的神经。我们还将切除硬脑膜，使用钩电极重复这些实验，同时 选择性地刺激个体DR以表征其神经支配模式和体位排列。 目标2：开发包括DR在内的脊髓的解剖学精确计算模型，并使用该模型 模型作为设计LSCS电极的平台。 利用人类脊髓的高分辨率成像数据和显微外科测量，我们将建立一个 有限元与等效电路模型相结合模拟膝关节侧方结构的解剖和神经生理学 人类脊髓及其对LSCs的反应。我们将利用这个平台来设计电极触点的布局 LSCS设备和刺激配置和波形，以最大限度地提高个体DR的刺激选择性。 目的3：进行大型动物手术以优化LSCs电极基板的机械性能 避免神经损伤，保持电极放置的长期稳定性。 在猪身上，我们将长期植入具有多种不同机械衬底设计的LSCs电极，包括 改变装置的横截面和有助于装置插入和稳定的任何工具。我们会 进行组织学分析，以确定组织损伤的特征以及机械性能与组织之间的关系 受伤。

PROJECT SUMMARY/ABSTRACT Advances in design and actuation have led to dramatic improvements in prosthetic limbs. However, these devices cannot provide sensory feedback, which leads to slow gait and increased risk of falling. Recent evidence from our lab has shown that stimulation of lateral structures in the spinal cord and dorsal roots can effectively generate sensations in the distal limbs. In these studies, lateral SCS (LSCS) evoked sensations in regions of the amputated hands or feet, though many of these sensations also covered more proximal regions of the residual limb. To achieve more focal sensations in the missing limb will require development of electrodes with smaller contacts, tighter inter-contact spacing, and better arrangements than currently exist for SCS electrodes. Further, because the lateral epidural space is narrower and more curved than the traditional midline target of SCS, these novel SCS electrodes must be thinner and more flexible than existing SCS devices. Our long-term goal is to create a neurostimulation system to restore sensation by selectively stimulating lateral structures in the spinal cord. In this project, we will characterize how the DR respond to LSCS and optimize electrode design for stimulating these structures. Through a combination of large animal neurophysiology experiments, histological analyses, and computational modeling studies, we will characterize the selectivity of LSCS and design electrodes to maximize selectivity and achieve focal paresthetic coverage of the foot and ankle while avoiding injury to the underlying neural tissue. To achieve these goals, we will complete the following aims: Aim 1: Quantify functional organization of the lumbar DR and selectivity of LSCS. We will measure the selectivity of LSCS in cats by recording antidromic propagation of evoked action potentials in nerves throughout the hindlimb. We will also resect the dura and use hook electrodes to repeat these experiments while selectively stimulating individual DR to characterize their innervation patterns and somatotopic arrangement. Aim 2: Develop an anatomically-accurate computational model of the spinal cord, including the DR, and use that model as a platform to design LSCS electrodes. Utilizing high-resolution imaging data and microsurgical measurements of the human spinal cord, we will build a combined finite element and equivalent circuit model to simulate the anatomy and neurophysiology of lateral structures in the human spinal cord and their response to LSCS. We will use this platform to design the layout of electrode contacts on the LSCS device and stimulation configurations and waveforms to maximize selectivity of stimulation of individual DR. Aim 3: Perform large animal surgeries to optimize the mechanical properties of the LSCS electrode substrate to avoid neural damage and maintain chronic stability of electrode placement. In pigs, we will chronically implant LSCS electrodes with multiple different mechanical substrate designs, including varying the cross-section of the device and any tooling that may aide in insertion and stabilization of the device. We will perform histological analysis to characterize tissue damage and the relationship between mechanical properties and tissue injury.