The BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) aims to support innovative, early-stage research for developing novel technologies to record and modulate neural activity. Managed by the National Eye Institute (NEI) in collaboration with other NIH components, this initiative focuses on advancing cutting-edge tools that could significantly improve the ability to monitor and manipulate neural circuits at large scales and with precise resolution. The initiative seeks applications for technologies employing modalities such as acoustic, chemical, electrical, magnetic, optical, or genetic tools, with an emphasis on approaches compatible with studies in behaving animals or humans.

The primary goal is to accelerate the development of transformative technologies capable of enhancing spatial, temporal, and cell-type precision in neural recording and manipulation. Applications should propose new, untested ideas in the earliest stages of conceptualization, including theoretical models, simulations, or prototype validation. Projects may focus on improving recording scale, resolution, precision, or enabling non-invasive modulation of neural circuits. Applications are encouraged from diverse fields, including engineering, materials science, computational biology, and physics, with multidisciplinary and transdisciplinary collaborations highly recommended.

The program offers up to $400,000 in total direct costs over a maximum three-year period, with no more than $200,000 per year in direct costs. NIH anticipates funding approximately ten awards per fiscal year, with a total budget of $3-4 million annually. Eligible applicants include higher education institutions, non-profits, for-profit organizations, government entities, and foreign organizations. Foreign components of U.S.-based organizations are also eligible.

Proposals must include a Plan for Enhancing Diverse Perspectives (PEDP), outlining actionable strategies to promote inclusivity and diversity in the research team, study population, or institutional partnerships. The PEDP will be evaluated as part of the scientific and technical review process. Applications without a PEDP will be deemed incomplete and withdrawn from review.

Applications must be submitted electronically through NIH ASSIST, Grants.gov Workspace, or institutional system-to-system solutions. Proposals must adhere to NIH's Data Management and Sharing Plan policy, ensuring data transparency and availability through approved archives like DANDI or OpenNeuro. Researchers are also required to plan participation in annual investigator meetings to foster collaboration across BRAIN Initiative-funded projects.

Key deadlines include an application due date of June 17, 2025, with subsequent cycles in June 2026. Review and funding decisions will follow standard NIH peer review and council review processes, with earliest award start dates anticipated in April 2026. Prospective applicants are strongly encouraged to consult NIH program staff early in the proposal development process to ensure alignment with program goals and requirements. For more information, applicants can refer to NIH resources or contact designated program staff listed in the NOFO.