Functional analysis of an LGN-based visual prosthesis

我们正在开发一种可以恢复盲人视力的视觉假体。找到一种治疗失明的方法 重要的是，预计到2030年，每28名45岁以上的人中就有1人受到影响(约3.5%的 人口)，包括100,000多名退伍军人。此外，失明与更高水平的 抑郁症、肥胖症、糖尿病和意外跌倒，据估计，三分之二的盲人是 失业了。潜在的治疗方法正在开发中，包括药物、遗传、干细胞、 光遗传和假体方法，但几乎都是针对视网膜的，因此对大型 部分盲人人口。这包括战场上的士兵，带着双侧创伤的战斗归来 眼睛受伤，以及其他有类似痛苦的普通人群成员。它还包括那些拥有 青光眼、老年性黄斑变性和糖尿病视网膜病变--三大最常见的致盲原因 在老年退伍军人(和普通人群)中。丘脑外侧膝状核(LGN)是一个 有吸引力的假体植入地点，因为它超越了与大多数原因相关的疾病/创伤 因此，一种有效的设备将为大部分盲人人口提供治疗。在……里面 此外，LGN在空间上比视网膜更具扩张性，因此允许更多的刺激 位置和更高的敏锐度。同时，LGN神经元使用的神经信号模式要少得多 抽象比视觉皮质的抽象，从而允许更直接的编码方案(比 皮质假体所需的部分)。虽然开发一种高计数、多通道的 可以安全地植入大脑深层结构的设备，我们的同事最近开发出了这样一种 设备和大量的努力正在推进这项技术。然而，人们对如何做到这一点知之甚少 用假体有效地刺激LGN，这种缺乏理解将阻碍向 临床设备。在这里，我们提出了4个目标，重点是学习如何有效地驱动LGN神经元 假肢。我们的初步测试表明，来自LGN的刺激确实可以驱动下行视觉 此外，初级视觉皮质(V1)也被激活(次级于LGN的激活)。 因此，我们的目标将集中在确定如何最有效地激活LGN，我们将探索 同样的条件，最大限度地激活LGN也会产生强大的视觉皮质激活。作为以下内容的一部分 在这项研究中，我们还将探索LGN中不同类型的细胞是否对电有不同的敏感性 刺激，就像在中枢神经系统的许多其他区域一样。这将非常有用，因为不同层的 LGN由不同的细胞类型组成，了解如何以最佳方式激活每种细胞可能会导致更好的 结果。最后，我们将评估用于慢性植入的植入器的性能稳定性。 我们认为，这里提出的全面评价将提供一个基础，以便 系统地推进未来的临床前和临床研究。

We are developing a visual prosthesis that can restore vision to the blind. Finding a treatment for blindness is significant as it is projected to impact 1 in 28 individuals over the age of 45 by the year 2030 (~3.5% of the population), including over 100,000 Veterans. Further, blindness is associated with increased levels of depression, obesity, diabetes, and accidental falls, and estimates suggest two-thirds of the blind are unemployed. Potential treatments are under development, including pharmaceutical, genetic, stem cell, optogenetic and prosthetic approaches, but almost all target the retina and thus offer little hope to a large portion of the blind population. This includes battlefield soldiers, returning from combat with bilateral traumatic eye injury, and other members of the general population with similar afflictions. It also includes those with glaucoma, age-related macular degeneration, and diabetic retinopathy, the 3 most common cause of blindness in aging Veterans (and the general population). The lateral geniculate nucleus (LGN) of the thalamus is an attractive site for implantation of a prosthesis as it is beyond the disease/trauma associated with most causes of blindness and thus a working device would offer a treatment to large portions of the blind population. In addition, the LGN is more spatially expansive than the retina and thus allows for a larger number of stimulation sites and higher acuity. At the same time, the neural signaling patterns used by LGN neurons are much less abstract than those of the visual cortex, thereby allowing for more straightforward encoding schemes (than those required by cortical prostheses). While it has been challenging to develop a high-count, multi-channel device that can safely be implanted into a deep brain structure, our colleagues have recently developed such a device and much effort is underway to advance this technology. However, little is known about how to effectively stimulate the LGN with a prosthesis and this lack of understanding will impede progress towards a clinical device. Here, we propose 4 Aims focused on learning how to effectively drive LGN neurons with a prosthesis. Our initial testing shows that stimulation from of the LGN can indeed drive downstream visual circuits and further, that primary visual cortex (V1) is activated as well (secondary to the activation of the LGN). Thus, our Aims will focus on determining how to most effectively activate the LGN and we will explore whether the same conditions that maximize LGN activation also produce robust activation of visual cortex. As part of this investigation, we will also explore whether individual cell types in LGN have different sensitivities to electric stimulation as is the case in many other regions of the CNS. This will be quite useful as the different layers of LGN are comprised of different cell types and understanding how to optimally activate each may lead to better outcomes. Finally, we will evaluate the stability of performance for implanted devices for chronic implantation. We believe that the comprehensive evaluation proposed here will provide a foundation from which to systematically advance future pre-clinical and clinical studies.