Optimization of Flexible Neural Probe Arrays for Multi-Region Recordings in Rodents and Nonhuman Primates

大脑倡议的一个核心目标是将神经活动与行为联系起来，这需要技术来获取随着时间的推移从不同大脑区域获得高质量的动态神经活动记录。为了实现这一核心目标，这项优化建议将解决技术开发中最紧迫的领域，以实现具有这种能力的聚合物微电极阵列的传播，并促进其与神经科学研究实践的整合。基于聚合物的神经接口可以在一年或更长时间内实现高质量的记录，这归因于与更坚硬的金属线和硅基神经接口相比，设备-组织接口具有更高的稳定性。另一个明显的优势是，同样的微制造技术可以用来生产批量的表面和穿透电极阵列，这些阵列具有微米和亚微米尺寸精度的精心控制的特征。微制聚合物探针已经在有限的设计中可用，其小腿长度为10 mm或更短，因此主要用于大鼠。这项技术需要扩展，以获得啮齿动物更深层次的大脑区域，以及更大动物的广泛大脑靶点，包括非人类灵长类动物，这是神经科学和临床前研究的重要模型。现有的设备设计，如以前为大鼠海马体开发的原型阵列，不能简单地放大或缩小，以扩大进入不同物种的大脑区域。相反，需要与用户合作进行仔细的设计，以满足空间和重量要求以及工作流程要求，以实现所需深度的精确放置。因此，这项建议涉及对先前开发的技术进行必要的优化，以实现一个设计库，使其能够在不同的动物模型中使用，并针对不同的大脑区域。另一个目标是开发适当的插入方法，以可靠地将电极放置在所需深度和目标区域。一旦被动记录阵列和匹配的手术插入方法在台面上被开发和优化，这些方法将在小鼠、大鼠和NHP中进行评估。总体而言，这项建议不仅涉及神经接口聚合物微电极阵列技术的优化，而且还涉及进一步的进展。这将使早期传播聚合物阵列系统，与早期采用者合作，大规模监测和操纵神经活动，并展示长期在多个物种获得的高质量记录，将吸引更多的用户。成功的演示将有助于我们实现可靠的慢性神经接口在不同神经组织和物种中广泛传播的长期目标。

A core goal of the BRAIN Initiative is to link neural activity to behavior which requires technology to acquire high-quality recordings of dynamic neural activity from different brain regions over time. To achieve this core goal, this optimization proposal will address the most pressing areas of technology development to enable the dissemination of polymer microelectrode arrays with such capability and promote their integration into neuroscience research practice. Polymer-based neural interfaces can achieve high-quality recordings over a year or more which is attributed to the greater stability of the device-tissue interface compared to more rigid metallic wire and silicon-based neural interfaces. Another distinct advantage is that the same microfabrication technology can be used to produce batches of surface and penetrating electrode arrays with carefully controlled features with micron and submicron dimensional precision. Microfabricated polymer probes are already available in limited designs having shank lengths of 10 mm or less and therefore predominantly used in rats. This technology needs to be extended for access to deeper brain regions in rodents and a wide range of brain targets in larger animals, including nonhuman primates, an important model in neuroscience and preclinical research. Existing device designs such as the prototype arrays previously developed for the rat hippocampus cannot simply be scale up or down to expand access to brain regions across different species. Instead, careful design is required in collaboration with users to meet space and weight requirements as well as workflow requirements to achieve precise placement at the desired depth. Therefore, this proposal tackles the necessary optimization of the previously developed technology to enable a library of designs that will enable their use in different animal models and to target different brain regions. Another goal is to develop the appropriate insertion methods for reliably placing electrodes at the desired depth and targeted region. Once the passive recording arrays and the matching surgical insertion methods are developed and optimized at the benchtop, these will be evaluated in mice, rats, and NHPs. Overall, this proposal not only addresses optimization but further advances in polymer microelectrode array technology for neural interfaces. This will enable early dissemination of polymer array systems for large-scale monitoring and manipulation of neural activity in collaboration with early adopters and demonstration of high-quality recordings obtained in multiple species over long periods that will attract additional users. Successful demonstration will facilitate our long-term goal of realizing the wide dissemination of reliable chronic neural interfaces across different neural tissues and species.