BRAIN Initiative: Exploratory Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (R61 Basic Experimental Studies with Humans Required) | RFA DC 24 001

FAQs: NIH BRAIN Initiative R61 - Exploratory Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (RFA-DC-24-001)

What is this funding opportunity?

This is a National Institutes of Health (NIH) BRAIN Initiative discretionary grant opportunity titled "Exploratory Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain." It uses the R61 mechanism and is identified by Funding Opportunity Number (FON) RFA-DC-24-001.

What is the main goal of the program?

The program supports early-stage, high-impact human neuroscience projects that leverage rare access to the living human brain during clinically necessary invasive procedures. The goal is to use intracranial recording and stimulation in precisely localized brain structures to answer fundamental questions about how the human brain works, while building the cross-site coordination needed to make findings meaningful despite small per-site sample sizes.

Why does the opportunity emphasize multi-site coordination and consortia?

Individual clinical sites often have too few eligible participants and too many logistical constraints to run large, statistically powered invasive human neuroscience experiments on their own. This FOA is designed to push teams to organize across sites and disciplines so data can be aggregated, methods aligned, and conclusions strengthened even when each site contributes a limited number of participants.

What does the R61 mechanism imply about the stage and structure of the work?

An R61 award is exploratory and milestone-driven, focused on feasibility and proof-of-principle rather than a fully mature, large-scale program at the outset. Applicants are expected to propose planning and early development activities that show a credible path toward later, more definitive studies.

How is this R61 intended to connect to later funding?

The R61 is positioned as an on-ramp to later, larger efforts under the companion funding opportunity described as "Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain" (RFA-NS-22-041). Successful exploratory efforts under this R61 are intended to set teams up for that subsequent, more definitive research stage.

What kinds of challenges is the R61 project expected to de-risk?

The opportunity is aimed at de-risking the hardest parts of doing invasive human neuroscience, including harmonizing protocols across hospitals, validating that an experimental paradigm can run in clinical environments (such as the operating room or epilepsy monitoring unit), establishing data quality and reproducibility, and demonstrating the ability to recruit, coordinate, and analyze in a way that supports later statistical power.

What kinds of technologies or methods are central to the opportunity?

The FOA centers on invasive human neuroscience using intracranial recording and stimulation. It highlights the unique ability to record neural activity with high temporal and spatial resolution and to perturb neural circuits with stimulation to test causal hypotheses.

Is the program focused on descriptive data collection, or hypothesis-driven work?

The FOA encourages approaches that go beyond descriptive signal collection. It emphasizes studies guided by clear theoretical constructs and, where appropriate, quantitative mechanistic models that link recordings and stimulation to interpretable accounts of computation, circuit dynamics, or behavior.

What does "Basic Experimental Studies with Humans Required" mean in practice (based on this description)?

Based on the description provided, the program is explicitly supporting human neuroscience studies that occur in the context of clinically necessary invasive procedures, using invasive neural recording and/or stimulation in living human brain tissue and circuits. The work is expected to be experimental and focused on fundamental brain function questions, while fitting within clinical workflows and constraints.

What settings are contemplated for conducting the research?

The FOA specifically references executing paradigms in settings such as the operating room and the epilepsy monitoring unit, reflecting the time-limited and clinically constrained nature of invasive human research opportunities.

What types of teams are expected to be competitive?

Competitive projects are expected to involve diverse, integrated, multidisciplinary teams that bridge clinicians and researchers. The description specifically mentions collaborations among neurosurgeons, epileptologists or functional neurosurgery teams, cognitive neuroscientists, biomedical engineers, computational modelers, statisticians, and neuroethicists, along with strong infrastructure for data management.

What is meant by "precisely localized brain structures" in this opportunity?

The program emphasizes the scientific value of intracranial approaches that allow recording and stimulation in specific, localized brain structures. This localization supports stronger inference about where and how neural activity relates to behavior and how stimulation-based perturbations test causal hypotheses.

How should applicants handle variability across patients, devices, and sites?

The FOA signals that strong applications will include careful experimental design and analysis planning tailored to clinical workflows, with strategies to handle variability across patients, devices, and sites. This includes well-justified tasks, stimulation parameters, and analysis plans that remain interpretable under real-world constraints.

What are awardees expected to do as part of the NIH-coordinated working group?

A defining feature is participation in a working group coordinated by NIH to develop consensus standards of practice. This includes practical standards such as consistent metadata, electrode localization practices, stimulation reporting, and quality control, along with explicit attention to neuroethical considerations.

What data sharing or dataset expectations are described?

Awardees are expected to collect and provide data that can support ancillary studies and to help aggregate and standardize datasets for dissemination to the broader scientific community. The program is building an interoperable ecosystem where datasets and methods can be reused and compared across projects.

Why is neuroethics explicitly emphasized?

The FOA highlights neuroethical considerations because the research occurs in the context of medical care and involves direct intervention in the human brain. The working group standards are expected to address these issues alongside technical and methodological standards.

Who is eligible to apply?

Eligibility is broad for U.S.-based organizations and includes state, county, and local governments; special districts; independent school districts; public and private institutions of higher education; federally recognized Native American tribal governments; tribal organizations other than federally recognized governments; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations other than small businesses; and small businesses. Additional eligible categories called out include Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, faith-based or community-based organizations, Hispanic-serving institutions, HBCUs, tribally controlled colleges and universities, regional organizations, eligible federal agencies, and U.S. territories or possessions.

Are foreign institutions or non-U.S. entities eligible to apply?

No. The description states that non-U.S. (non-domestic) entities and foreign institutions are not eligible to apply, and non-domestic components of U.S. organizations are not eligible.

Are any international elements allowed at all?

Yes, but with limits. The description states that "foreign components" as defined in the NIH Grants Policy Statement are allowed. That means a U.S. applicant may include well-justified foreign elements within the project under NIH policy, even though a foreign organization cannot be the applicant.

What is the application due date listed in the provided information?

The original application closing date provided is 2025-09-19.

Is there an award ceiling or expected number of awards stated here?

No. The provided text explicitly notes that it does not specify an award ceiling or the expected number of awards. Applicants would need to consult the full FOA for budget structure, project period details, and milestone or go/no-go requirements typical of R61 awards.

Which agency is offering this grant and under what broader initiative?

The grant is offered by the National Institutes of Health (NIH) under the NIH BRAIN Initiative.

What CFDA numbers are associated with this opportunity, and what do they imply about scope?

The opportunity lists CFDA numbers 93.173, 93.213, 93.242, 93.279, 93.286, 93.853, 93.865, 93.866, and 93.867. In the provided description, this is presented as a signal that the scientific scope can span several neuroscience-relevant domains.

What kinds of outputs is this program trying to create beyond individual project results?

Beyond any single experiment, the program aims to build coordinated infrastructure: aligned protocols across sites, shared standards of practice, interoperable datasets, and reusable methods. The expectation is that this scaffolding will enable scalable human intracranial research and accelerate future discovery and reuse by the broader community.

What should an applicant emphasize to align with the program intent (based on this summary)?

Based on the summary, alignment would likely include: a clear plan for cross-site coordination; milestone-driven feasibility work; strong clinical workflow integration; rigorous data quality and reproducibility practices; model-informed hypotheses and analysis; a multidisciplinary team that includes both clinical and quantitative expertise; attention to neuroethical issues; and a concrete plan to standardize and share data in ways that support aggregation and ancillary studies.