Tunneling microfiber electrode arrays for stable neural recording

描述(申请人提供)：该项目旨在开发一种微创电极阵列，用于长期记录大脑活动，具有单细胞分辨率。多电极阵列是实验神经科学中必不可少的工具，然而目前的阵列严重受限于大电极或僵硬电极与脆弱的大脑环境之间的不匹配。长期植入的电极会对大脑造成持续的损害，而积极的排斥过程最终会使神经信号沉默。长时间的慢性植入失败使学习的神经基础研究变得非常具有挑战性，并阻碍了人类患者长期稳定的脑机接口的实施。为了最大限度地减少电极损伤，必须减小植入物的尺寸，但由于单个纤维的弯曲，从最小的电极构建的多通道阵列不可能植入。建议的电极阵列解决了这一机械问题--实现了大通道数和亚细胞(5微米)单个电极尺寸的捆绑，通过相互支撑加强了每根光纤。然而，在植入过程中，纤维束分开，每一根纤维都沿着自己单独的路线进入大脑，保留了单一纤维的微创特性。 原型设计的慢性记录显示了稳定的信号，包括具有数月时间尺度的多单元记录，显示了神经放电模式的最小漂移。该项目旨在记录植入过程中电极如何与血管系统相互作用，它们在三个月的时间尺度上造成什么损害，以及这些因素如何与连续收集三个月的慢性记录的产量和稳定性相关。这些方法包括电极插入的体内成像，自由行为动物神经信号的慢性记录，以及植入附近神经元健康和局部免疫激活迹象的组织学分析。预期的结果是，在插入过程中，单个纤维沿着各自阻力最小的路径进入大脑，从而减少血管损伤。在慢性记录的时间尺度上，预期的结果是改善组织健康，并在靠近电极的地方稳定神经信号。这里提出的实验中的具体变化将为未来的设计提供参考，这些设计寻求扩大隧道光纤阵列中的通道数量，从而提供同时跟踪大型细胞集合的机会。该项目的近期应用将在小型动物研究中看到，在这些研究中，几乎不可能通过使用现有的大规模电极学习来跟踪神经元整体的放电模式。集中在这一可交付成果上的进展也可能转化为更稳定的大型生物体的记录，对人脑-机器接口具有潜在的直接好处。

DESCRIPTION (provided by applicant): This project seeks to develop a minimally invasive electrode array for long term recording of brain activity, with single cell resolution. Multielectrode arrays are an essential tool in experimental neuroscience, yet current arrays are severely limited by a mismatch between large or stiff electrodes and the fragile environment of the brain. Chronically implanted electrodes cause ongoing damage to the brain, and an active process of rejection eventually silences neural signals. Failure of chronic implants over long time-scales makes it very challenging to study the neural basis of learning, and prohibits the implementation of long term stable brain machine interfaces for human patients. To minimize electrode damage, the size of implants must be reduced, but multichannel arrays built from the smallest electrodes are impossible to implant due to buckling of the individual fibers. The proposed electrode array solves this mechanical problem - achieving large channel count and sub-cellular (5 micron) individual electrode size in an bundle that strengthens each fiber through mutual support. During implant, however, the bundle splays apart and each fiber follows its own separate course into the brain, preserving the minimally invasive properties of the single fibers. Chronic recordings from prototype designs reveal stable signals, including multiunit recordings with time-scales of months that show minimal drift in neural firing patterns. This project seeks t document how the electrodes interact with vasculature during implant, what damage they cause over three month time-scales, and how these factors relate to the yield and stability of chronic recordings gathered continuously for three months. The methods involve in-vivo imaging of electrode insertion, chronic recording of neural signals in freely behaving animals, and histological analysis of neuronal health and signs of local immune activation near the implant. The anticipated result is that during insertion, individual fibers travel along their own paths of least resistance into the brain, leading to reduced vascular damage. On the timescales of chronic recordings, the anticipated result is improved tissue health and stable neural signals in close proximity to the electrode. Specific variations in experiments proposed here will inform future designs that seek to scale up the number of channels in the tunneling fiber array, providing an opportunity to track large ensembles of cells simultaneously. The near term application of this project will be seen in small animal studies where it is virtually impossible t track the firing patterns of ensembles of neurons through learning with existing large-scale electrodes. Advances focussed on this deliverable are likely to also translate into more stable recordings in larger organisms, with potential direct benefits to human brain machine interfaces.