Relating spontaneous activity to electrical stimulation properties of primate retinal ganglion cells

将自发活动与灵长类视网膜神经节细胞的电刺激特性相关

• 批准号: 10456725
• 负责人: Sasidhar Madugula
• 金额: $ 4.04万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456725
• 关键词: Accommodation phosphene; Acquired Blindness; Address; Advanced Development; Algorithms; Anterior; Axon; Blindness; Brain; Bypass; Cells; Characteristics; Clinical; Custom; Data; Devices; Electric Stimulation; Electrodes; Electrophysiology (science); FDA approved; Future; Goals; Human; Image; Implant; Location; Macaca; Methods; Modeling; Neuraxis; Neurons; Non-linear Models; Operative Surgical Procedures; Outcome Study; Patients; Pattern; Peripheral; Photoreceptors; Population; Preparation; Primates; Problem Solving; Process; Property; Prosthesis; Prosthesis Design; Research; Resolution; Retina; Retinal Ganglion Cells; Specificity; Stimulus; Surface; System; Techniques; Testing; Time; Tissues; Training; United States; Vision; Visual Perception; Work; blind; brain machine interface; cell type; density; design; electric field; electrical property; experimental study; extracellular; ganglion cell; improved; multi-electrode arrays; neuronal cell body; photoreceptor degeneration; predicting response; predictive modeling; receptive field; relating to nervous system; response; retina implantation; retinal prosthesis; spatiotemporal; visual information

Project Summary / Abstract The most promising treatment option for photoreceptor degeneration, which is the leading cause of blindness in the United States, are retinal prostheses that are surgically implanted on the anterior retina in order to gain electrical access to the retinal ganglion cells (RGCs), bypassing the damaged photoreceptor cell layer. Despite there being a few FDA approved epiretinal prostheses on the market, the high density of RGCs at the surface of the retina makes it difficult to deliver current from electrodes with enough precision to recapitulate the natural patterns of ganglion cell activity, and thus useful visual perception for blind patients. This is due to coarse electrical stimulation that evokes unwanted activity in cells and axons at the epiretinal surface, especially in the central retina where cells are the densest. The goal of this research is to use information from the natural RGC activity recorded on the multi-electrode array in order to guide precise, spatially targeted electrical stimulation. Careful application of the properties of electric fields propagating in tissue to calibrate stimulation currents will allow epiretinal implants to produce meaningful visual perception in blind patients. The relationship between the recorded signature of a given RGC’s activity on the array—its ​Electrical Image (EI)—and its sensitivity to single or multi-electrode stimulation—its ​Electrical Receptive Field (ERF)—will be determined. First, experiments will be conducted in peripheral primate retina to collect data on RGC activation characteristics in response to delivering current from each of the ~500 electrodes on the array. Next, we will extend this model to experimental data collected on the smaller, densely-packed RGCs in the central Raphe region of the retina. Despite dense electrode spacing, arrays are limited in their ability to deliver precisely targeted stimulation by the distance between electrodes. This can be addressed by weakly stimulating with multiple neighboring electrodes at the time same, pushing the strength of stimulation current at the intersection of the multiple generated electric fields over the threshold required for target RGC activation. We will stimulate with combinations of two to seven neighboring hexagonally arranged electrodes to collect RGC ERFs in the peripheral and central retina. An cascading linear-nonlinear model, popular for modeling neuronal spiking, will be fit with EIs as input to predict ERFs across the array. A thorough understanding of the EI-ERF relation in the retina will enable the closed-loop, precise, spatially localized stimulation necessary for designing a high-fidelity epiretinal device, and uncover general principles applicable elsewhere in the central nervous system.

项目摘要 /摘要 光感受器变性的最有前途的治疗选择，这是失明的主要原因 在美国，是视网膜假体，这些假体被手术植入前视网膜以获取 绕过受损的感光细胞层的视网膜神经节细胞（RGC）的电气通道。尽管 市场上有几个FDA批准的首脑假体，地面RGC的高密度 视网膜的中心很难从电子中以足够的精度传递电流以概括自然 神经节细胞活性的模式，因此对盲人患者有用的视觉感知。这是由于粗糙的 电刺激引起了赛后表面的细胞和轴突不良活性，尤其是在 中央视网膜，其中细胞是最密集的。这项研究的目的是使用自然RGC中的信息 为了指导精确的，空间靶向的电刺激，记录在多电极阵列上的活性。 仔细应用在组织中传播的电场的性能来校准刺激电流 允许盲肠内腹中首上，在盲人患者中产生有意义的视觉感知。 给定RGC在阵列上活动的记录签名之间的关系 - 电图像 （EI） - 对单电极模拟的敏感性 - 它的电气接收场（ERF） - 决定。首先，将在周围灵长类动物视网膜中进行实验，以收集有关RGC激活的数据 响应从阵列上约500个电子中的每个电子中传递电流的特征。接下来，我们会的 将此模型扩展到中央raphe中较小的，不填充的RGC的实验数据 视网膜区域。尽管密集的电极间距，但阵列的精确输送能力仍有限制 通过电子之间的距离进行靶向刺激。这可以通过微弱刺激来解决 当时的多个相邻电子，在交叉路口推动刺激电流的强度 在目标RGC激活所需的阈值上的多个生成的电场。我们将刺激 结合两到七个相邻的六角形排列的电极，以收集RGC ERF 外围和中央视网膜。级联的线性非线性模型，用于建模神经元尖峰，将 与EIS一起拟合，以预测整个数组的ERF。对EI-ERF关系的透彻理解 视网膜将实现设计高保真性所需的闭环，精确的空间局部刺激 映内装置，并发现适用于中枢神经系统其他地方的一般原则。