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

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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.