The BRAIN Initiative: Optimization of Instrumentation and Device Technologies for Recording and Modulation in the Nervous System (U01 Clinical Trials Not Allowed), issued by the National Institutes of Health (NIH), seeks to support the development and refinement of advanced technologies aimed at recording and manipulating neural activity. The initiative is part of a broader effort under the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, which since 2014 has prioritized the acceleration of novel neurotechnologies to understand the functioning brain and ultimately inform treatments for brain disorders. This specific Notice of Funding Opportunity (NOFO) focuses on the optimization stage of technology development, where tools have already demonstrated transformative potential and are ready for iterative engineering enhancements and validation in real-world neuroscience experiments.

The overarching objective of this NOFO is to support projects that improve the ability to record and modulate neural cell and circuit activity using innovative devices and instrumentation. Eligible technologies include those based on optical, electrical, magnetic, or acoustic modalities, and may target various forms of neural signaling, including intracellular events and non-neuronal cell contributions. The technologies must be compatible with in vivo experiments in behaving animals and must emphasize validation of technical capabilities over biological discovery. The goal is to overcome existing experimental barriers, reduce costs, and enable more accessible neuroscience research. Projects focused primarily on molecular technologies are excluded from this FOA and are directed instead to alternative BRAIN NOFOs.

Applications may address one or more of three specific goals: development of new network recording capabilities, tools for circuit manipulation, and technologies linking neural activity to behavior. The types of approaches encouraged include imaging systems, advanced electrode platforms, and miniaturized recording devices, all tailored for high-resolution, large-scale, and long-duration experiments. Technologies must be evaluated against current state-of-the-art methods and include milestones and metrics for performance assessment. Applicants should demonstrate a clear strategy for end-user engagement, iterative development, and a credible pathway to broad adoption and sustainable manufacturing.

Applicants must adhere strictly to NIH application guidelines, including submission through the ASSIST system, Grants.gov Workspace, or institutional S2S solutions. A letter of intent is encouraged and should be submitted at least 60 days before the application due date. Key application dates include due dates of June 2, 2025, and January 20, 2026. Projects may span up to four years, with budgets reflecting the true costs of the proposed work. The anticipated total program funding is $10 million annually, supporting approximately 15–20 awards.

The application review will focus on the significance and innovation of the proposed work, the rigor and feasibility of the research plan, and the expertise and environment of the project team. Special attention will be given to how well the technology addresses gaps in current capabilities, how performance metrics are defined and measured, and the extent of end-user feedback integration. Applications will undergo peer review followed by advisory council review, and decisions will consider scientific merit, availability of funds, and program relevance.

Important contacts for this opportunity include scientific, peer review, and grants management staff at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), with contact emails and phone numbers provided in the NOFO. This opportunity falls under the cooperative agreement mechanism, which entails substantial programmatic involvement by NIH staff throughout the project period. Compliance with NIH data sharing and ethical standards is mandatory, and all applicants must maintain active SAM, eRA Commons, and Grants.gov registrations.