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

BRAIN计划的一个核心目标是将神经活动与行为联系起来，这需要技术来获取不同大脑区域动态神经活动随时间的高质量记录。为了实现这一核心目标，本优化方案将解决技术发展中最紧迫的领域，使具有这种能力的聚合物微电极阵列得以传播，并促进其融入神经科学研究实践。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，这归因于与更刚性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，同样的微加工技术可以用于生产具有微米和亚微米尺寸精度的精心控制特征的表面和穿透电极阵列。微加工聚合物探针已经在有限的设计中可用，其柄长度为10毫米或更短，因此主要用于大鼠。这项技术需要扩展到啮齿类动物的更深的大脑区域，以及大型动物的更广泛的大脑目标，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，如先前为大鼠海马体开发的原型阵列，不能简单地按比例放大或缩小，以扩大对不同物种大脑区域的访问。相反，需要与用户合作进行精心设计，以满足空间和重量要求以及工作流程要求，以实现在所需深度的精确放置。因此，该提案解决了先前开发的技术的必要优化，以实现设计库，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。另一个目标是开发合适的插入方法，将电极可靠地放置在所需的深度和目标区域。一旦被动式记录阵列和匹配的手术插入方法在台上被开发和优化，这些将在小鼠，大鼠和NHPs中进行评估。总的来说，该建议不仅解决了优化问题，而且进一步推进了神经接口的聚合物微电极阵列技术。这将使聚合物阵列系统能够早期传播，与早期采用者合作，用于大规模监测和操纵神经活动，并展示长期在多个物种中获得的高质量记录，这将吸引更多的用户。成功的演示将有助于我们实现在不同神经组织和物种之间广泛传播可靠的慢性神经接口的长期目标。

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.