BRAIN Initiative: Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (R01 Clinical Trial Not Allowed) | RFA NS 28 010

Opportunity Information: Apply for RFA NS 28 010

The NIH BRAIN Initiative funding opportunity RFA-NS-28-010, titled "Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (R01 Clinical Trial Not Allowed)," supports high-impact, mechanistic neuroscience research that uses rare clinical access to the living human brain to answer fundamental questions about how brain activity produces experience and behavior. The central goal is to move beyond descriptive human neuroscience and toward studies that can explain, in a cause-and-effect way, how the moment-to-moment activity of single neurons and coordinated neural populations, organized within specific brain circuits and networks, gives rise to sensations and perceptions, emotions, thoughts, memories, and measurable motor and social behaviors. The program is oriented toward work that is transformative by the end of the award period, meaning applications should propose ambitious but well-justified projects capable of producing clear conceptual advances rather than incremental findings.

A key feature of this opportunity is that it expects investigators to leverage invasive opportunities that occur in the context of human neurosurgical care. Typical examples include intracranial recordings (such as electrocorticography, stereo-EEG, microelectrode recordings, or related approaches) and direct brain stimulation performed for clinical reasons, where research can be embedded ethically and safely around those procedures. The intent is to capitalize on direct access to neural signals and causal perturbations that are not possible with noninvasive tools alone. Successful applications will generally be designed around rigorous experimental logic, careful control of confounds, and strong alignment between the questions being asked and what invasive access uniquely allows you to measure or manipulate.

Methodologically, the program emphasizes mechanistic approaches guided by explicit theoretical constructs and/or quantitative, mechanistic models. In practice, that means proposals should not simply collect large datasets from intracranial electrodes, but should be driven by hypotheses and analysis plans that can adjudicate between competing models of brain function, explain how neural dynamics implement computations, or clarify how information is represented and transformed across brain networks. Reviewers are likely to look for tight coupling between experimental design, analytic strategy, and the mechanistic claim being made, as well as evidence that the team can execute complex human intracranial research reliably and ethically.

The NOFO also encourages integrating complementary experimental models or systems to strengthen interpretation and connect insights across species and biological scales. For instance, applicants might pair human intracranial studies with animal models, ex vivo tissue work, computational modeling, or other platforms that provide techniques or validation steps that are impractical in humans. The point of this integration is not to dilute the human focus, but to use additional models to clarify mechanisms, test generality, or access circuit-level or cellular details that can make the human findings more explanatory and not just correlational.

Awards are made as cooperative agreements, which usually implies substantial NIH involvement during the project, such as coordination, milestone awareness, and structured collaboration expectations. Funded investigators will participate in an NIH-coordinated consortium working group focused on identifying consensus standards of practice, including neuroethical considerations. The consortium structure is also intended to support data sharing and broader scientific value: investigators will be expected to collect and provide data that can support ancillary studies, and to help aggregate and standardize datasets for dissemination to the wider community. In other words, awardees are not only running individual projects; they are also contributing to a coordinated effort to establish shared practices and reusable resources in invasive human neuroscience.

In terms of scope and administrative details, the opportunity is discretionary and run by the National Institutes of Health, with activity in the health research domain and multiple CFDA listings (including 93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.372, 93.853, 93.865, 93.866, 93.867). The expected number of awards is five, and the original closing date listed is February 8, 2029. The eligible applicant pool is broad and includes state, county, and local governments; special district governments; independent school districts; public and private institutions of higher education; federally recognized tribal governments and certain tribal organizations; public housing authorities/Indian housing authorities; nonprofits (both 501(c)(3) and non-501(c)(3), other than institutions of higher education); for-profit organizations other than small businesses; small businesses; and other eligible entities as described in the NOFO. Despite the title referencing an R01 mechanism, the funding instrument type listed is a cooperative agreement, so applicants should pay attention to the NOFO-specific instructions and expectations that come with that structure.

The opportunity is explicitly "Clinical Trial Not Allowed," which signals that applications should not propose studies that meet NIH’s definition of a clinical trial (for example, prospective assignment to an intervention with the primary intent to evaluate health-related biomedical or behavioral outcomes). Because intracranial stimulation can resemble an intervention, applicants typically need to be careful in framing and study design so the work remains mechanistic and does not cross into clinical trial territory as defined by NIH policy. This usually means the research is aimed at understanding neural mechanisms rather than testing a therapeutic effect, and that any stimulation or recording is aligned with clinical context and appropriate human subjects protections.

International eligibility and collaboration rules are strict. Non-U.S. entities (foreign organizations) cannot apply, and non-U.S. components of U.S. organizations are also not eligible to apply. However, foreign components as defined in the NIH Grants Policy Statement may be allowed, which generally refers to discrete elements of a project that occur outside the U.S. under certain conditions and approvals. At the same time, NIH policy described in the notice states that NIH will no longer issue awards to domestic or foreign entities that involve foreign subawards or subcontracts, unless the application is submitted under a NOFO specifically designated for funded international collaborations. As a result, any application to this NOFO that includes foreign subawards/subcontracts will be considered noncompliant and will not be reviewed for funding. This does not prohibit unfunded international scientific collaboration, nor does it prohibit paying foreign consultants, nor purchasing unique equipment or supplies from foreign vendors; the key restriction is on monetary international collaborations structured as subawards or subcontracts.

Taken together, this NOFO is designed for teams positioned to conduct sophisticated, ethically grounded invasive human neuroscience during neurosurgical care, with research questions that require direct access to neural recordings and/or causal perturbations. Competitive projects will be mechanistically ambitious, grounded in theory or quantitative models, methodologically rigorous, and built to generate results that change understanding of how human brain dynamics produce cognition, emotion, perception, and behavior, while also contributing to shared standards and broadly usable datasets through an NIH-coordinated consortium.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "BRAIN Initiative: Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (R01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.372, 93.853, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2026-09-30.
• Applicants must submit their applications by 2029-02-08.
• The number of recipients for this funding is limited to 5 candidate(s).
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA NS 28 010

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