CAREER: Scalable, Penetrating Multimodal Neural Interfaces for Adaptive Closed-Loop Neuromodulation

在美国，焦虑症是最普遍的神经精神疾病，被定义为一种精神和神经系统的疾病，然而对这些疾病的标准治疗未能显示出疾病患病率或严重程度的显著降低。一个主要的挑战是，焦虑症是由被称为神经回路的高度相互关联的大脑区域群的中断发展而来的，而缺乏描述这些神经回路的适当技术。这个CAREER项目将开发和利用神经接口技术来表征受焦虑症影响的神经回路。最终，这项工作将增加对强调焦虑相关行为的神经机制的理解，并可能导致新的治疗选择。本提案的研究目标与教育和推广计划相结合，以提高神经工程的知名度和培训。具体而言，该计划包括以下活动：建立神经工程研究中心；为妇女和代表性不足的少数群体提供体验式学习和指导机会；互动和远程学习外展活动；对研究生和本科生进行多学科培训。现有治疗神经精神疾病（如焦虑）的方法存在缺陷，这凸显出迫切需要更好地了解受影响神经回路中的功能相互作用。这个CAREER项目的目标是开发一种变革性的多模态神经接口制造工艺和设计，为建立焦虑相关行为的神经回路机制铺平道路。现有的多模态神经接口通常利用人工组装技术，这些技术实际上是不可扩展的，并且无法到达大脑皮层表层以外的区域。这些缺点将通过两个重点加以解决。工程重点将开发微制造和微组装工艺的神经接口设计，可以很容易地优化不同的应用。开发这些工艺的优点包括更高的器件良率，更低的制造器件变化，以及高通道数的设计可扩展性。这项工作在整体设计上也与最先进的设计不同，它利用了高度生物相容性的材料，可以轻松地与制造管道集成，并适用于多模式功能。在生物焦点下，深层穿透神经接口将用于研究避近选择信息如何在相关神经回路中表示和传递，并实施电神经调节范式来建立焦虑相关行为异常变化背后的因果回路机制。通过这项工作获得的知识将为开发可扩展的多模态神经接口提供一种全新的策略，并为任何神经系统疾病的神经回路水平表征奠定基础-最终导致新的神经调节干预。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

In the United States, anxiety disorders are the most prevalent neuropsychiatric illness, defined as an illness of the mind and nervous system, yet standard treatments for these disorders have failed to show a significant reduction in the prevalence or severity of illness. A major challenge is that anxiety disorders develop from disruptions in highly interconnected groups of brain areas, which are referred to as neural circuits, and the appropriate technologies to characterize these neural circuits are lacking. This CAREER project will develop and leverage a neural interface technology to characterize neural circuits impacted by anxiety disorders. Ultimately the work will increase understanding of neural mechanisms underscoring anxiety-related behavior and potentially lead to new treatment options. The research objectives in this proposal are integrated with an educational and outreach plan to increase visibility and training in neuroengineering. Specifically, the plan includes the following activities: establishing a neuroengineering research concentration; experiential learning and mentoring opportunities for women and underrepresented minorities; interactive and remote learning outreach activities; and multidisciplinary training for graduate and undergraduate students. The shortcomings of existing therapies for neuropsychiatric illnesses, such as anxiety, highlight the urgent need to better understand functional interactions in the affected neural circuits. The goal of this CAREER project is to develop a transformative multimodal neural interface fabrication process and design that will pave the way for establishing neural circuit mechanisms of anxiety-related behavior. Existing multimodal neural interfaces typically leverage manual assembly techniques that are not practically scalable and fail to reach brain areas beyond the superficial cortex. These shortcomings will be addressed by two foci. The Engineering Focus will develop microfabrication and microassembly processes for a neural interface design that can be easily optimized to different applications. The advantages of developing these processes include greater device yield, lower variation in fabricated devices, and design scalability to high channel counts. This work also distinguishes itself from the state-of-the-art in its holistic design that leverages a highly biocompatible material that easily integrates with the fabrication pipeline and is appropriate for multimodal functionality. Under the Biological Focus, the deep penetrating neural interface will be used to examine how approach-avoidance choice information is represented and communicated across relevant neural circuitry and implement an electrical neuromodulation paradigm to establish causal circuit mechanisms underlying aberrant changes in anxiety-related behavior. The knowledge gained through this work will provide a fundamentally new strategy to develop scalable multimodal neural interfaces and lay the foundation for neural circuit-level characterizations of any neurological condition – ultimately leading to new neuromodulatory interventions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.