The BRAIN Initiative: New Technologies and Novel Approaches for Recording and Modulation in the Nervous System (R01 Clinical Trial Not Allowed) is a funding opportunity issued by the National Institutes of Health (NIH), involving multiple participating institutes such as NINDS, NEI, NIA, NIAAA, NICHD, NIDCD, NIDA, NIMH, NCCIH, and NIBIB. This opportunity seeks to support early-stage, high-risk projects focused on the development and proof-of-concept testing of transformative technologies for recording and modulating neural activity at cellular or circuit resolution. The initiative aligns with updated agency priorities and the broader goals of the BRAIN Initiative, which aims to advance neurotechnologies and revolutionize neuroscience research.

The purpose of this NOFO is to encourage the development of innovative technologies that will significantly reduce barriers to conducting neurobiological experiments and enable deeper understanding of central nervous system (CNS) function. The funded projects should aim to record or modulate neural activity using any modality—optical, electrical, magnetic, acoustic, or molecular—and be compatible with in vivo experiments in behaving animals. The focus is on demonstrating technological capabilities, rather than generating biological insights. Projects that focus solely on non-invasive imaging or are not applicable to CNS research are not eligible under this announcement.

Eligible applicants include a broad range of organizations such as higher education institutions, non-profits, for-profit entities, local and state governments, tribal organizations, and foreign organizations. Applicants must complete registrations in multiple systems, including SAM, eRA Commons, and Grants.gov, to be eligible to apply. Individual principal investigators must also have eRA Commons accounts. There is no cost-sharing requirement, and organizations may submit multiple scientifically distinct applications.

Applications must follow specific instructions outlined in the Research (R) Application Guide, and proposals that deviate from these instructions may be rejected. A letter of intent is encouraged but not mandatory. Submissions must include comprehensive details such as current state-of-the-art comparisons, rigorous resource and data-sharing plans, and clear rationales justifying technological development. Budget details should also include funding for key personnel to attend annual BRAIN investigator meetings.

Proposals will be evaluated based on three main factors: the importance of the research, the rigor and feasibility of the proposed approach, and the expertise and resources available to the team. Reviewers will assess whether the proposed technology represents a significant improvement over current methods, addresses major barriers in neuroscience research, and offers the potential for substantial impact. The maximum project duration is three years, and while the budget is not capped, it must align with the project’s scope.

Applications are due on June 2, 2025, and January 20, 2026, with respective review cycles concluding in April 2026 and December 2026. The earliest project start dates are April 2026 and December 2026. A one-page post-submission update is allowed, and applications must demonstrate compliance with NIH policies on data sharing, human subjects protection, and use of vertebrate animals where applicable.