BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS): Specialized Projects for Scalable Technologies (U01 Clinical Trial Not Allowed) | RFA NS 27 015

FAQs: BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS) - Specialized Projects for Scalable Technologies (U01 Clinical Trial Not Allowed) (RFA-NS-27-015)

What is this funding opportunity?

This opportunity is the NIH BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS): Specialized Projects for Scalable Technologies, offered as a U01 cooperative agreement (Clinical Trial Not Allowed) under NOFO RFA-NS-27-015. It supports technology development to enable comprehensive brain connectivity mapping across multiple spatial scales.

What is the main goal of the program?

The main goal is to push brain connectivity mapping into a new era of scale, speed, and usability by developing transformative technologies that make it practical to generate and interpret comprehensive brain “wiring diagrams.” The intent is to accelerate understanding of how neural circuits drive brain function and behavior and to lay groundwork for future circuit-based strategies to prevent and treat major brain disorders.

How does this NOFO fit into the larger BRAIN CONNECTS Program?

This NOFO sits within the broader BRAIN CONNECTS Program, which is designed to establish the scientific and technical foundation needed for future circuit-based strategies addressing major brain disorders. Rather than supporting a single narrow biological study, this opportunity emphasizes enabling capabilities that help the field produce reliable, brain-wide connectivity atlases and interpret them effectively.

Is the focus on answering a specific neuroscience question or on building tools?

The emphasis is on enabling capabilities: tools, methods, and end-to-end pipelines that make connectivity atlas generation and interpretation practical, scalable, reproducible, and broadly usable. The expectation is not a single experiment or a narrow biological question, but technology development that reduces key bottlenecks for the field.

What does "Connectivity across Scales" mean in this context?

It refers to technologies that can scale to whole brains and work across multiple spatial levels, ranging from fine microcircuit details to long-range, brain-wide pathways. Projects are expected to develop, improve, and validate methods that function across these different scales.

What types of organisms are prioritized?

The NOFO highlights humans, non-human primates (NHP), and mice as priority organisms due to translational relevance and their central role in modern neuroscience. These species are especially aligned with the program’s goals of building connectivity atlases that can inform brain function and disorders.

Can applicants propose work in other species besides human, NHP, and mouse?

Yes. Other species may be proposed if there is strong justification and the project clearly tests or validates approaches that can generalize across species. The NOFO notes that some innovations may be developed more quickly in certain systems before being adapted to human or primate tissue and data.

What kinds of projects are in scope for "Specialized Projects for Scalable Technologies"?

Projects should develop, improve, and validate scalable technologies for whole-brain connectivity mapping and interpretation. The scope includes both experimental and computational components, as long as the work advances scalable atlas-generation and atlas-interpretation capabilities across scales.

Which parts of the connectivity workflow can a project address?

Applications may address any part of the end-to-end workflow, including: data collection methods; tissue processing and labeling strategies; imaging and recording innovations; reconstruction techniques; computational analysis; multimodal integration; quality control; standardization; dissemination platforms; and interpretive frameworks that help scientists and clinicians use connectivity information effectively.

Does the NOFO emphasize data pipelines and interpretation, or only imaging and tracing?

It explicitly emphasizes that connectivity atlases depend on end-to-end pipelines that turn raw measurements into usable maps. The opportunity is not limited to generating images or tracing neurons; it also supports computational ecosystems, quality control, standardization, and interpretive approaches that make connectivity data usable and meaningful.

What outcomes or impacts are expected from funded projects?

Funded projects are expected to credibly improve the speed, precision, and cost-effectiveness of generating and interpreting brain-wide wiring diagrams. Projects should demonstrate a realistic path to scaling and address bottlenecks that limit atlas production, reproducibility, or downstream usability.

Are incremental improvements acceptable, or is major innovation expected?

The NOFO stresses credible paths to scaling and reducing major bottlenecks, suggesting that proposals should go beyond small incremental improvements. The overall aim is transformative, cutting-edge technology development that materially advances practical, comprehensive connectivity mapping.

What does it mean that this is a U01 cooperative agreement?

A U01 cooperative agreement implies substantial NIH program involvement and a coordinated, networked approach rather than a fully independent, investigator-initiated award. Awardees should expect collaboration and alignment with program goals and network-wide practices.

Will awardees operate as part of a network?

Yes. Funded projects will be integrated into the BRAIN CONNECTS Network, which includes projects supported under this and earlier BRAIN CONNECTS announcements. The intent is to build interoperable, coordinated capabilities rather than isolated systems.

What kinds of coordination expectations might come with joining the BRAIN CONNECTS Network?

The NOFO indicates awardees will likely be expected to align with shared milestones, common data and metadata practices, interoperability goals, and collaborative planning. The goal is that methods, standards, and deliverables work together across projects.

What does "Clinical Trial Not Allowed" mean for this opportunity?

It means the proposed work must not include clinical trial activities as NIH defines them. Projects must remain within non-trial research boundaries and should focus on technology development and atlas-building rather than testing interventions or prospectively assigning participants to conditions to measure health-related outcomes.

Can projects involve human data or human tissues?

Yes, but only in ways consistent with the “Clinical Trial Not Allowed” designation. Applicants using human data or tissues must ensure the design remains non-clinical-trial research and fits the NOFO’s technology and atlas-building intent.

Who is eligible to apply?

Eligibility is broad and includes public and private institutions of higher education, nonprofit and for-profit organizations, small businesses, and various units of government (including state, county, city/township, and special districts), as well as eligible tribal entities and public housing authorities/Indian housing authorities.

Are non-U.S. organizations allowed to apply?

Yes. The NOFO states that non-U.S. organizations (foreign organizations) may apply directly, and non-U.S. components of U.S. organizations are allowed.

Are "foreign components" allowed under this opportunity?

No. The NOFO specifies that “foreign components,” as defined in the NIH Grants Policy Statement, are not allowed. Applicants planning international collaborations need to structure roles, performance sites, and budgets to comply with this restriction.

How should applicants think about international collaborations given the restrictions?

The NOFO makes a distinction between foreign organizations being able to apply and “foreign components” not being allowed. This means applicants need to be careful in how they define performance sites and project roles and in how they structure budgets, to align with NIH policy and the NOFO’s constraints.

Which agency is issuing this opportunity and what funding category does it fall under?

The opportunity is issued by the National Institutes of Health (NIH) under the broader health funding category, using the cooperative agreement mechanism (U01) within the NIH BRAIN Initiative framework.

What is the application closing date mentioned in the opportunity description?

The original closing date listed is 2027-10-04, reflecting a long application window typical for major NIH initiatives that anticipate complex, multi-year technology development efforts.

Are there specific assistance listing (CFDA) numbers associated with this NOFO?

Yes. The NOFO is associated with multiple assistance listing numbers: 93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.372, 93.853, 93.865, 93.866, and 93.867.

Why are multiple assistance listing numbers included?

The multiple assistance listing numbers reflect participation across NIH institutes and BRAIN Initiative components that intersect with neuroscience, brain disorders, and technology development.

What makes a proposal competitive based on the description provided?

Competitive proposals will typically make a strong case that the approach is genuinely enabling and demonstrably scalable, that it helps accelerate the creation and interpretation of comprehensive connectivity atlases, and that it is compatible with network-wide goals for interoperability, data integration, and dissemination. Strong proposals also directly address current bottlenecks in atlas production, reproducibility, and usability.

Does the program prioritize dissemination and standardization?

Yes. The NOFO explicitly includes standardization, quality control, dissemination platforms, and interoperability goals as part of the broader workflow it seeks to advance, reflecting a strong emphasis on making outputs broadly usable across the network and the field.