Neural Recording and Simulation Tools to Address the Mesoscale Gap

摘要 我们设计了一种新的方法，在大脑中进行跨区域和深度的多尺度记录。这种工具因其方向性和可伸缩性传感而被称为圆盘，它是围绕引线主体的微电极阵列，旨在最大限度地实现“衬底屏蔽”现象。电-准静态模拟和活体数据表明，与微线和环形电极相比，有显著的改进，包括(I)信号幅度，(Ii)信噪比，(Iii)分类测试中的源分离。DISC测量立体声中的局部场势，并具有显著的放大作用，这在隔离中尺度源方面特别强大。推广这项技术的几个关键挑战是光刻制造方法的固有限制，以及我们仍然无法将局部场电位与详细的电路功能联系起来。为了应对这两个挑战，我们将开发一种基于喷雾打印的革命性微电子制造方法(目标1)，并开发能够预测特定电压输出的生物物理模型(目标2)。当与生物物理正演模型相结合时，盘的放大和方向性将是提高局域场势利用率的独特而有力的工具。硬件和软件工具的验证将使用慢性大鼠和猕猴听觉实验进行。在音频刺激期间，DISC将在听觉核心显示层状和网络范围的记录。我们将分析光盘记录区分最佳频率电路的能力，并将其与各种虚拟宏观电极进行比较，包括目前在sEEG中使用的环形电极。我们相信，这项多学科的工作将最终为神经科学和临床社区提供3种关键工具：(1)立体定向深度阵列，能够进行长期、低噪声的宽带记录，擅长高分辨率中尺度信息；(2)详细的多尺度正演模型(NetPyNE/BrainStorm管道)，产生特定于包括磁盘在内的几种设备类型的模拟电压读数；以及(3)高分辨率逆模型，它将源定位扩展到中尺度电压输入。软件开发将是开源的。

Abstract We have designed a novel approach to perform multi-scale recordings in the brain across regions and depths. This tool, referred to as DISC for its directional and scalable sensing, is an array of microelectrodes surrounding the lead body and designed to maximize the phenomenon of “substrate shielding”. Electro-quasistatic modeling and in vivo data demonstrate significant improvements over microwires and ring electrodes, including (i) signal amplitude, (ii) signal-to-noise ratio, and (iii) source separation in classification testing. DISC measures local field potentials in stereo and with significant amplification, which is especially powerful in isolating sources at the mesoscale. Several critical challenges for the propagation of this technology are the inherent limitations in photolithographic manufacturing methods, and our continuing inability to relate the local field potential with detailed circuit function. To address these two challenges, we will develop a revolutionary manufacturing method for microelectronics based on aerosol jet printing (Aim 1) and develop a biophysical model that can predict specific voltage outputs (Aim 2). The amplification and directionality of DISC when combined with biophysical forward models will be a unique and power tool to improve the utility of the local field potential. The validation of the hardware and software tools will be performed using chronic rat and macaque auditory experiments. DISC will demonstrate both laminar and network-wide recordings in the auditory core during audio stimulation. We will analyze the ability of DISC recordings to discriminate the best frequency circuits and contrast this with a variety of virtual macroelectrodes, including the ring electrode currently used in sEEG. We believe this multidisciplinary work will culminate in 3 critical tools being made available to the neuroscience and clinical communities: (1) a stereotactically-guided depth array capable of chronic, low-noise wideband recordings that excel at high-resolution mesoscale information; (2) a detailed, multi-scale forward model (NetPyNE/Brainstorm pipeline) that produces simulated voltage readings specific to several device types including DISC; and (3) a high-resolution inverse model, which will extend source localization to mesoscale voltage inputs. The software development will be open-source.