Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

The BRAIN Initiative

Since 2014, the Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative has aimed to accelerate the development and application of innovative neurotechnologies, enabling researchers to produce a new dynamic picture of the brain that reveals how individual cells and complex neural circuits interact in both time and space. It is expected that these advances will ultimately lead to new ways to treat and prevent brain disorders.

As one of several federal agencies involved in the BRAIN Initiative, NIH's contributions to the BRAIN Initiative were initially guided by "BRAIN 2025: A Scientific Vision," a strategic plan that detailed seven high-priority research areas. This plan was updated and enhanced in 2019 by: "The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures" and "The BRAIN Initiative and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society." This and other BRAIN Initiative Notices of Funding Opportunities (NOFOs) are based on this vision and issued with input from Advisory Councils of the 10 NIH Institutes and Centers supporting the BRAIN Initiative, as assisted by the NIH BRAIN Multi-Council Working Group  and Neuroethics Working Group.

The NIH BRAIN Initiative recognizes innovative ideas require creativity, scientific expertise, and experience. There are many benefits that flow from a scientific workforce with broad participation including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, and enhancing public trust. The NIH also encourages businesses to participate in the BRAIN Initiative. It is possible for companies to submit applications directly to BRAIN Initiative program announcements or to collaborate with academic researchers in joint submissions.

The BRAIN Initiative requires a high level of coordination and sharing between investigators. It is expected that BRAIN Initiative recipients will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings and in other activities such as the BRAIN Initiative Biennial Conference. The data sharing expectations for BRAIN Initiative awards can be found at NOT-MH-19-010.

BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS)

This announcement is a reissue of RFA-NS-22-049, from the following suite of BRAIN CONNECTS funding opportunities, to develop scalable technologies for brain-wide mapping of neural connectivity.  BRAIN CONNECTS is an anticipated 10-year program to develop the research capacity and technical capabilities to generate wiring diagrams that can span entire brains across multiple scales. The objective of the first five years is to develop these capabilities through innovation, iterative engineering, and optimization for the required throughput and capacity scale-up.

RFA-NS-22-047 UM1 Comprehensive Centers for Human and Non-Human Primate Brain

RFA-NS-22-048 UM1 Comprehensive Centers for Mouse Brain

RFA-NS-22-049 U01 Specialized Projects for Scalable Technologies

RFA-NS-24-028 U24 Data Coordinating Centers

Comprehensive Centers funded under RFA-NS-22-047 and RFA-NS-22-048 use the UM1 activity code for large-scale research activities with interdependent components.  Funded projects aim to establish full production pipelines, from sample collection through data integration, analysis, and dissemination, applied to sub-volumes that are sufficiently large to prove feasibility of whole-brain mapping, and chosen to test specific hypotheses relating circuit structure to function.  Specialized Projects (RFA-NS-22-049 and this re-issue) use the U01 activity code for cooperative agreements to develop current or emerging technologies for scalable mapping of brain connectivity. Data Coordinating Centers (RFA-NS-24-028) facilitate and organize the activities of the BRAIN CONNECTS Network.

Through these awards, the program will support:

• A portfolio of complementary approaches for data acquisition and reconstruction of brain connectivity, with metrics for comparing and choosing approaches
• Teams from a variety of disciplines including but not limited to neuroscience, engineering, computational and molecular biology, chemistry and physics, mathematics, computer and data sciences, and bioethics
• Engineering and innovation efforts aimed at scale-up to map entire brains with high throughput and precise fidelity
• Demonstration of lossless acquisition and accurate reconstruction, validated with ground truth data, across large distances required for whole-brain mapping
• Proof-of-concept datasets, representing large and unprecedented sub-volumes within the brain or spinal cord, aimed at understanding the wiring principles of specific circuits and their implications for neural function
• New approaches and toolsets for mining and integrating into the neuroscience knowledge base, including morphological, functional, and molecular data
• New infrastructure for the research community to discover cell types, circuit motifs, wiring principles and circuit elements, and to develop new computational and conceptual models based on these rich new sources of data

Objectives and Requirements for this Announcement

Applications to this announcement may address any aspect(s) of the production and analysis pipeline – from data collection, reconstruction, analysis, integration, dissemination, and interpretation of brain connectivity and associated data.  The proposed development must aim to enable faster, more precise, and more cost-effective generation and interpretation of brain-wide wiring diagrams.  Projects may develop and optimize current technologies or propose entirely new, disruptive, and potentially risky approaches. In all cases, the expectation is that technologies and approaches will be sufficiently scalable to enable brain-wide connectivity mapping in a subsequent five-year follow-on period, if not earlier.

Applications to this announcement are expected to complement existing BRAIN CONNECTS awards with distinct capabilities and competencies. Applicants are strongly encouraged to use NIH RePORTER to retrieve information on awards from each of aforementioned announcements.

The focus of the BRAIN CONNECTS Program is on human, NHP, and mouse brain.  For mouse, technologies must demonstrate feasibility of local and long-range cell-to-cell connectivity at the level of synaptic connections.  For human and NHP, technologies must demonstrate region-to-region connectivity at the level of axonal projections. Other species are permitted, if their use is well justified and the goal is to test and validate approaches that can be generalized across species.

The BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS) Network

Awards funded under this announcement will be integrated into the BRAIN CONNECTS Network for project coordination and program integration.  Throughout the funding period, all CONNECTS Network recipients will work cooperatively to further common goals and identify collaborative opportunities. The CONNECTS Network will develop and harmonize common data processing pipelines, integrate and disseminate data analytic tools and capabilities, initiate efforts towards a unified knowledge base for connectivity data from a variety of modalities, and organize and implement outreach and engagement to the wider research community and the general public.

Applications Not Responsive to this Announcement

Proposed research that is not responsive to this announcement and will not be reviewed includes the following:

• Projects not aimed at developing or improving technologies that can serve as components of scalable pipelines for brain-wide connectivity.
• Projects using approaches that will not be applicable to mammalian brain.
• Technologies not expected to support mapping of region-to-region connectivity at the level of axonal projections in human or NHP, or local and long-range cell-to-cell connectivity at the level of synaptic connections in mouse.

Applicants considering related technologies that may not meet requirements for this announcement should consider other BRAIN Initiative funding opportunities, and in particular the following:

RFA-MH-26-170, BRAIN Initiative: Development and Validation of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in the Brain (R01 Clinical Trial Not Allowed)

Prior Consultation with Scientific/Research Staff

Consultation with Scientific/Research Contact staff listed in Section VII is strongly recommended. If requested by the applicants, staff can advise whether the proposed project meets the goals of this NOFO and the mission of the BRAIN Initiative, and discuss responsiveness questions. Staff will not evaluate the technical and scientific merit of the proposed project; technical and scientific merit will be determined during peer review using the review criteria indicated in this NOFO. During the consultation phase, if the proposed project does not meet the programmatic needs of this NOFO, applicants will be strongly encouraged to consider other Funding Opportunities.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions - Includes all types

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized).

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

Applications Involving the NIH Intramural Research Program

The requests by NIH intramural scientists will be limited to the incremental costs required for participation.  As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs).  These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses.  Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program.  Intellectual property will be managed in accord with established policy of NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application.  The intramural scientist may submit a separate request for intramural funding as described above. Intramural scientist cannot be MPIs on extramural awards. 

Foreign Organizations/International Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16.8 Collaborative International Research Awards.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

BRAIN Initiative and CONNECTS Network In-person Meeting Costs:

• Applications may include allowable costs for participating in annual in-person BRAIN CONNECTS Network meetings.
• The budget should include funds necessary for travel for up to two key personnel to participate in the BRAIN Initiative Biennial Conference.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims:

In the Specific Aims section, explain how the project will contribute to scalable pipelines for brain connectivity and associated data, and how it will result in new or improved capabilities that can be scaled to whole brains.

Research Strategy:

In the Research Strategy section, detail how the project will contribute to scalable pipelines for brain connectivity and associated data, and how it will result in new or improved capabilities that can be scaled to whole brains. Applications may address any aspect(s) of data collection, analysis, and dissemination pipelines, from tissue processing to data acquisition, alignment, segmentation and annotation, error correction, analysis, integration into the larger neuroscience data environment, and dissemination to the research community. The proposed development must aim to enable faster, more precise, and more cost-effective generation, analysis, and interpretation of brain-wide wiring diagrams.

Describe how the chosen strategies will advance state-of-art technologies and address current gaps and challenges, and why the approaches offer advantages over alternative methods. For entirely new, disruptive, and potentially risky approaches, explain how success of the project will lead to quantitative and/or qualitative gains in brain mapping capabilities. If a new dataset will be generated or analyzed to validate the approach, explain the significance of the data and/or resulting analysis for understanding neural circuit structure and function, and indicate how availability of the proposed data or toolsets will contribute to novel research findings and/or new capabilities for the field. If producing or analyzing data from species other than mouse, NHP, or human, provide justification for the choice of species and explain how the approach can be generalized more broadly.

Funded awards will be integrated into the BRAIN CONNECTS Network, consisting of other Specialized Projects, Comprehensive Centers, and Data Coordinating Centers as a coordinated effort aimed at developing the capabilities to generate wiring diagrams spanning entire brains across multiple scales. Accordingly, proposals should include plans to ensure efficient coordination, communication, and decision support with the other entities of BRAIN CONNECTS Network.

Feasibility Metrics and Milestones: In a separate section of the Research Strategy, provide performance metrics that can be used to demonstrate feasibility of scaling to entire brains and/or comparison to other approaches. Include information on expectations of cost, time, and any ancillary requirements that would affect decisions on project continuation in a potential subsequent funding period. In addition, provide a project timeline and annual milestones using SMART criteria (Specific, Measurable, Attainable, Relevant, and Time-bound). Milestones should be delineated into aspirational but realistic goals vs. go/no-go criteria representing minimally acceptable progress for project success.

Letters of Support: Include as appropriate letters of support/agreement for any collaborative/cooperative arrangements, subcontracts, or consultants.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

 Other Plan(s): 

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed. 
• An updated listing of BRAIN Initiative archives is provided at the BRAIN Informatics website. Currently established archives that may be relevant to this funding opportunity include, but are not limited to:
  1. Distributed Archives for Neurophysiology Data Integration (DANDI; https://www.dandiarchive.org; R24MH117295) for cellular neurophysiology data;
  2. The Neuroscience Multi-omic Data Archive (NeMO; https://nemoarchive.org/about; R24MH114788) for data from -omics experiments;
  3. The Brain Image Library (BIL; https://www.brainimagelibrary.org; R24MH114793) for confocal microscopy data;
  4. Data Archive for the BRAIN Initiative (DABI; https://dabi.loni.usc.edu; R24MH114796) for data related to human invasive device research;
  5. OpenNeuro (https://openneuro.org; R24MH117179) for magnetic resonance imaging and other neuroimaging data; and
  6. Block and Object Storage Service (BossDB; https://bossdb.org; R24MH114785) for electron microscopy and x-ray microtomography data.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply - Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH's electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the  How to Apply – Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in the  How to Apply – Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed. 

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

This NOFO will accept a one-page update with preliminary data as post-submission materials. The deadline for submitting all post-submission materials, including preliminary data, will be 30 days before the study section meeting. All other materials listed in NOT-OD-19-083 as acceptable post-submission materials will continue to be accepted if submitted 30 days before the study section meeting.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

This NOFO supports Specialized Projects to develop current or emerging technologies to generate comprehensive atlases of brain connectivity. Applications may address any aspect(s) of collection, analysis, and dissemination pipelines, from tissue processing to acquisition, alignment, segmentation and annotation, error correction, analysis, integration into the larger neuroscience environment, and dissemination to the research community. The proposed development must aim to enable faster, more precise, and more cost-effective generation and interpretation of brain-wide wiring diagrams. Further development and optimization of current technologies, or entirely new, disruptive, and potentially risky approaches are encouraged, if success of the project will lead to quantitative and/or qualitative gains in brain mapping capabilities. If a new dataset will be generated or analyzed to validate the approach, the significance of the data and/or resulting analysis for understanding neural circuit structure and function must be justified. If using species other than mouse, NHP, or human, justification must be provided for the choice of species and for the broader generalizability of the approach.

Funded projects will be integrated into the BRAIN CONNECTS Network, consisting of other Specialized Projects from this NOFO, and Comprehensive Centers from the companion announcements, as a coordinated effort aimed at developing the capabilities to generate wiring diagrams that can span entire brains across multiple scales.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by CSR, in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

As part of the scientific peer review, allapplications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Requests for reconsideration of initial peer review will not be accepted for applications submitted in response to this NOFO. 

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant's federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant's integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 "Federal awarding agency review of risk posed by applicants." This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient's business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.

Applicants and recipients are strongly encouraged to refer to the NIH Director's Statement of Priorities, entitled "Advancing NIH's Mission Through a Unified Strategy." 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

• ongoing and consistent access to HHS owned or operated information or operational technology systems; and
• receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Cybersecurity plans and procedures must at minimum include the following:

• Develop cybersecurity plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data:
  • Identify:
    • Develop an inventory of all assets and accounts with access to HHS owned and operated information or operational technology systems or which obtain PII or PHI for the purposes of the award.
  • Protect:
    • Limit access to HHS owned and operated systems to only those in need of access to complete reward activities.
    • Require all staff to complete annual cybersecurity and privacy awareness training. Visit 405(d): Knowledge on Demand (hhs.gov) to obtain free trainings, if needed.
    • Enable multifactor authentication for all employees, subrecipients, and third-party entities to access HHS owned and operated information or operational technology systems.
    • Regularly backup sensitive data and test backups.
  • Detect:
    • Install anti-virus or anti-malware software on all devices, servers, and accounts used to connect to HHS owned and operated systems.
  • Respond:
    • Develop an incident response plan. See Incident-Response-Plan-Basics_508c.pdf (cisa.gov) to learn about developing incident response plans.
    • Have cybersecurity incident reporting procedures that ensure the relevant HHS awarding agencies are notified of a cybersecurity incident within 48 hours of discovery. A cybersecurity incident is defined as an unplanned interruption to a technology service or reduction in the quality of a technology service, or an occurrence that actually or potentially jeopardizes the confidentiality, integrity, or availability of an information system or the information the system processes, stores, or transmits.
  • Recover:
    • Investigate incidents and plug any security gaps identified. 

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings.  Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate; racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety.  If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

For applications involving substance abuse, the application must not support harm reduction. Please see Updated Funding Guidance for Recipients on Supplies and Services.

As of October 1, 2025, HHS has adopted 2 CFR Part 200, with some modifications included in 2 CFR Part 300. These regulations replace those in 45 CFR Part 75. However, for NIH, under the Consolidated Appropriations Act for FY 2026, (P.L. 119-75, Division B, Title II, Sec. 224), the provisions relating to indirect costs in 45 CFR 75 continue to apply to NIH awards. Consistent with the statute, NIH will not apply updated thresholds outlined within 2 CFR Part 200, at this time.

The following special terms of the award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 2 CFR 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH's purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility reside with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibilities as described below:

• Define the details for the project within the guidelines of this NOFO. Oversee and perform the scientific activities and administratively manage the project.
• Accept close coordination, cooperation, and participation of NIH program staff consistent with the goals of the BRAIN CONNECTS Network.
• Serve as a member of the BRAIN CONNECTS Network Steering Committee (described below) and participate in BRAIN CONNECTS Network activities, including periodic meetings to report project progress, develop shared metrics and standards, and identify opportunities for collaboration and coordinate publication of research results.
• Accept and implement the common guidelines and procedures approved by the Steering Committee and NIH. Agree to project modifications consistent with the shared goals of the BRAIN CONNECTS Network, as agreed upon by the BRAIN CONNECTS Steering Committee, with concurrence from NIH program staff.
• Share data and resources according to data release and resource sharing policies developed for and by this project as appropriate and consistent with achieving the goals of the program.
• Fully disclose algorithms and software source code to the other members of the Network for the purpose of scientific evaluation.
• Maintain confidentiality of information obtained from other members of the Network.
• Submit data for quality assessment and/or validation in a manner specified by the Steering Committee and/or NIH Program staff to ensure scientific rigor.
• Adhere to NIH policies regarding intellectual property and other NIH policies that might be established during the course of this activity.
• Coordinate and collaborate with other U.S. and international groups that may be generating complementary datasets.
• Recipients(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• A Program Officer will be named in the award notice and will be responsible for normal scientific and programmatic stewardship and guidance for the overall project. The Program Officer will be responsible for milestone negotiations and reporting, to ensure that benchmarks are being achieved and project goals are met, and for monitoring the agreed data and resource sharing plans.
• A group of NIH extramural program staff from the ICs contributing to the NIH BRAIN Initiative will form a Project Team for this award. The Project Team will review annual progress reports and other documents from this and other BRAIN CONNECTS awards and will assist the Program Officer in the evaluation of progress and coordination of Network activities.
• One or more extramural NIH program staff member(s) will be assigned as Project Coordinator(s), and will provide technical assistance, advice, coordination, and other program actions supporting the Program Officer and award recipients during the conduct of research activities, which may be above and beyond the levels normally required for program stewardship of grants. The same person may serve as the Project Coordinator for multiple awards under this and other BRAIN CONNECTS NOFOs.

Areas of Joint Responsibility include:

• Mutual agreement on project milestones, timelines, and performance criteria.  In some cases, creation of an external project advisory committee will be warranted, to provide expert input and feedback on strategic priorities and decisions critical for project success.  Committee membership will be determined by mutual agreement between the PD(s)/PI(s) and NIH program staff.

BRAIN CONNECTS Network Steering Committee

The CONNECTS Network Steering Committee will consist of the PD(s)/PI(s) of awards of this and other BRAIN CONNECTS NOFOs (as listed in Section 1). It will plan and design activities, review and discuss progress, and establish priorities and policies for the BRAIN CONNECTS Network. PD(s)/PI(s) will have one vote for each project. All NIH staff combined will share one vote in support of the project. The frequency of meetings will be determined jointly with NIH program staff. Recipient members of the Steering Committee will be required to accept and implement policies and common guidelines approved by the Steering Committee.

The CONNECTS Network Steering Committee will:

• Coordinate and improve connectivity data production, for example by reporting progress, disseminating best practices, and collectively evaluating new procedures, resources, and technologies.
• Assess feasibility metrics for establishing scalability, benchmarking performance, and comparing approaches.
• Facilitate the development of uniform procedures and policies, for example for data standards, quality measures and assessment, nomenclature and annotation conventions for data depositions, and so forth.
• Establish working groups as needed to address particular issues and interests. Working groups will include representatives from the BRAIN CONNECTS investigators, NIH program staff, and possibly outside experts by mutual agreement. Working groups may be formed to: 1) develop and implement data production and analysis standards; 2) address data submission, management, and analysis issues; 3) develop quality standards and methods for quality control and assurance; and 4) develop and benchmark shared informatics tools. In these cases, common policies, uniform practices (as needed), and data exchange will be critical to the success of the effort and will enable harmonization and eliminate duplication/overlap.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed. 

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk - Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

The Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative
National Institute of Neurological Disorders and Stroke
Email: BRAIN-CONNECTS-Inquiries@nih.gov

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.