Organic Closed-loop Electrochemical Array for Neurodevelopment (OCEAN)

项目总结/摘要 理解大脑回路的动态活动如何允许皮层功能出现的一个主要障碍是在大脑成熟过程中获得和操纵这种活动的能力不足。神经调质和神经活动模式在介导这种成熟中密切相关。迫切需要开发技术来获取和操纵来自小的、脆弱的、不成熟的大脑的神经生理信号，并解决这一知识缺口。我们的长期目标是确定发育中大脑中认知功能和神经精神障碍的神经相关性。在这里，我们通过追求该项目的总体目标来实现这一目标：建立一个完全可植入的闭环神经接口设备，该设备可以检测神经生理信号，并在小鼠幼崽生长和发育时响应地传递神经化学物质。我们的中心假设是，集成导电聚合物电极，适形离子电路和有机离子泵将能够创建用于神经发育的有机闭环电化学阵列（OCEAN），这将有助于我们阐明发育中大脑的神经活动和神经化学的协调。该假设得到了初步数据的支持，这些数据表明使用i）适形的高密度表面皮层电图阵列（NeuroGrids）来记录发育中啮齿动物的皮层网络; ii）适形的、生物相容的离子电路，其能够处理神经生理信号; iii）用于传输此类信号的高导电性、可拉伸的柔性材料; iv）有机离子泵，其以毫秒级的精度调制大脑信号。拟议研究的基本原理是，这些材料和设备的集成将使我们能够解决实质性的障碍，基本上排除慢性，高时空监测和操纵的神经网络在体内发育过程中。具体目标包括：（i）建立用于高时空分辨率电生理监测的可扩展、适形和生物相容的集成组件;（ii）建立用于高时空分辨率神经化学调制的可扩展、适形和生物相容的集成组件;（iii）集成神经生理记录和神经化学递送以执行概念验证闭环调制。在我们看来，拟议的研究是创新的，因为它在所有阶段都使用了有机电子方法-信号采集，处理/检测，数据传输，设备供电和神经化学物质输送，以首次创建一个完全可植入的响应神经接口设备，该设备与自然行为啮齿动物的体内使用兼容。这项工作预计将具有重要意义，因为它将为在与大脑成熟和复杂大脑功能出现相关的时期与神经网络进行交互奠定基础。它将对以前无法实现的实验范式的发展产生积极影响，并更广泛地促进安全，长期，微创生物电子设备的设计改进。

PROJECT SUMMARY/ABSTRACT A major obstacle to understanding how the dynamic activity of brain circuits permits the emergence of cortical function is the insufficient capability to acquire and manipulate this activity across the course of brain maturation. Neuromodulators and neural activity patterns are intimately linked in mediating this maturation. There is an urgent need to develop technology to acquire and manipulate neurophysiological signals from small, fragile, immature brains and address this gap in knowledge. Our long-term goal is to causally determine neural correlates of cognitive functions and neuropsychiatric disorders in the developing brain. Here, we step toward this goal by pursuing the overall objective of this project: to establish a fully implantable closed-loop neural interface device that can detect neurophysiologic signals and responsively deliver neurochemicals in mouse pups as they grow and develop. Our central hypothesis is that integrating conducting polymer electrodes, conformable ionic circuits, and organic ion pumps will enable the creation of an Organic Closed-loop Electrochemical Array for Neurodevelopment (OCEAN) that will help us elucidate the coordination of neural activity and neurochemistry in the developing brain. This hypothesis is supported by preliminary data demonstrating the use of i) conformable high-density surface electrocorticography arrays (NeuroGrids) to record from cortical networks in developing rodents; ii) conformable, biocompatible ionic circuits capable of processing neurophysiological signals; iii) highly conductive, stretchable, flexible materials for transmission of such signals; iv) organic ion pumps to modulate brain signals with millisecond precision. The rationale for the proposed research is that integration of these materials and devices will enable us to address the substantial barriers that essentially preclude chronic, high spatiotemporal monitoring and manipulation of neural networks in vivo during development. The specific aims include: (i) establish expandable, conformable, and biocompatible integrated components for high spatiotemporal resolution electrophysiologic monitoring; (ii) establish expandable, conformable, and biocompatible integrated components for high spatiotemporal resolution neurochemical modulation; (iii) integrate neurophysiologic recording and neurochemical delivery to perform proof-of-concept closed-loop modulation. The proposed research is innovative, in our opinion, because it uses organic electronic approaches at all stages – signal acquisition, processing/detection, data transmission, device powering, and neurochemical delivery to create for the first time a fully implantable responsive neural interface device compatible with in vivo use in naturally behaving rodents across development. This work is expected to be significant because it will provide the groundwork for interacting with neural networks across periods associated with brain maturation and the emergence of complex brain functions. It will have a positive impact on the development of previous unattainable experimental paradigms and contribute more broadly to improvement in the design of safe, long-term, minimally invasive bioelectronic devices.