Tunneling microfiber electrode arrays for stable neural recording

描述（由申请人提供）：本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的重要工具，但由于大电极或硬电极与脆弱的大脑环境不匹配，电流阵列受到严重限制。长期植入的电极会对大脑造成持续的损伤，而一个积极的排斥过程最终会使神经信号沉默。慢性植入物在长时间尺度上的失败使得研究学习的神经基础非常具有挑战性，并且阻碍了人类患者长期稳定的脑机接口的实现。为了尽量减少电极损伤，必须减小植入物的尺寸，但是由于单个纤维的屈曲，由最小电极构建的多通道阵列是不可能植入的。所提出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）的单个电极尺寸，通过相互支持加强了每根纤维。然而，在植入过程中，纤维束散开，每根纤维沿着自己的独立路线进入大脑，保留了单个纤维的最小侵入性。

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.