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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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

BACKGROUND

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 and was updated and enhanced in 2019 to: "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 along with scientific collaboration. There are many benefits that flow from a scientific workforce with team participation including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, and enhancing public trust.

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, BRAIN consortia activities, and the BRAIN Initiative Biennial Conference. The data sharing expectations for BRAIN Initiative awards can be found at BRAIN Data Knowledge Resources.

The Integrated BRAIN Circuits Program (iBCP): An Overview

The iBCP aims to understand how the nervous system gives rise to mental experience and behavior. A multi-level understanding of central nervous system (CNS) function is essential for identifying critical circuits involved in health and disease, and for advancing our ability to monitor and modulate neural circuits for both basic and translational applications.

Despite rapid advances in molecular, cellular, systems, and computational neuroscience, achieving a comprehensive understanding of brain function remains hindered by persistent methodological, conceptual, and disciplinary barriers within and between different levels of analysis. Technically, for example, fully mapping and interpreting the activity patterns of heterogeneous cell types with sub-millisecond temporal resolution in behaving animals remains a challenge. Conceptually, insights into how cellular heterogeneity and connectivity relate to dynamic neural processes and computations that underpin behavior remain limited. Moreover, scientific progress often occurs in disciplinary silos, hampering integration across levels of analysis.

The BRAIN Initiative fosters cross-disciplinary collaboration, yet transdisciplinary integration that enables, for example, a comprehensive linking of cellular components to circuit function and behavior, remains a major hurdle. While molecular and cellular neuroscience offers detailed "parts lists" and targeted manipulation tools, the role of cellular heterogeneity in complex neural computations is not well understood. Conversely, systems neuroscience provides powerful methods for analyzing population-level dynamics but often lacks the cell-type specificity necessary for mechanistic insight.

The iBCP directly addresses this challenge by emphasizing the need for dynamic circuits- and systems-level investigations that incorporate emerging knowledge and data on circuit components, including cell types and connectivity. As this is a significant challenge in neuroscience, the BRAIN Initiative now seeks to support development of innovative conceptual and theoretical frameworks, and cutting-edge approaches, both experimental and computational, to understand brain function holistically, from its circuit components to behavior output.

Deliverables from this effort are expected to advance our ability to investigate and understand how the CNS encodes, processes, and transmits information across spatial (cell to brain region) and temporal (milliseconds to behavioral timescales) dimensions. These will also lead to mechanistic, biologically grounded explanations of CNS function, ultimately revealing how cellular-level interventions produce circuit- and behavior-level effects and offering new targets and insights for treating dysfunction.

Program Expectations

Teams of 3–6 PDs/PIs are expected to combine distinct areas of expertise ranging from molecular and cellular to circuits to systems neuroscience, with strong interactions between experimentalists and computational neuroscientists, to pursue a single Specific Aim of developing mechanistic explanations of how neural circuits give rise to behavior and/or defined CNS functions.

A mechanistic insight is defined as an explanation of how defined circuit components and their dynamic activity and/or interactions causally generate CNS function, yielding predictive and testable hypotheses. To achieve this, applications are expected to explicitly integrate the following three levels of analysis (see Section IV for details on how each of these levels is defined):

1. Behavior. Behavior represents the functional output of nervous system activity and provides the essential context for interpreting neural circuit function. Anchoring cellular and circuit-level measurements to a well-defined behavior or clearly defined physiological measures of behavior enables causal links between neural activity, computation, and function, which are critical for understanding both normal brain processes and dysfunction.
2. Circuits. Circuit analysis at the level of population activity during behaviors provides the bridge between cellular properties and behavioral outcomes. This level reveals how neural signals evolve over time, how information flows within and across circuits, and how these dynamics shape behavior.
3. Circuit components. Neural circuits are composed of heterogeneous cell types with distinct roles within networks and characterized by distinct molecular identities, connectivity patterns, morphology, and/or physiological properties. It remains a challenge to identify which and how these components are critical for specific computations or behaviors.

The approach is expected to be driven by innovative conceptual or theoretical frameworks, predictive models, and/or cutting-edge methodologies that unify these three levels of analysis, bridge experimental and computational components, and use BRAIN-developed tools or resources where appropriate. The scale, complexity, and impact of this effort should reflect the transformative nature of the BRAIN Initiative. A successful program will deliver both mechanistic insights and broadly useful solutions to the challenges of bridging these levels of analysis.

This NOFO welcomes the use of a wide range of species, from invertebrate to human studies, including comparative approaches and the use of new approach methodologies (NAMS), with the requirement that these are chosen based on their power to address the specific question at hand and to reveal generalizable and fundamental principles.

Cross-species approaches to investigate generalizability are welcome.  At least one species under study is expected to fully integrate all three levels of analysis (circuit components, dynamic circuit activity, and behavior). Other species may be included even if technical limitations prevent accessing all three levels.

Recipients are expected to actively participate in BRAIN Initiative consortium activities aimed at developing, harmonizing, and disseminating standards of practice that facilitate rigorous multi-level integration across cellular, circuit, and behavioral analyses.

Representative (not exhaustive) examples of integrative neuroscience research responsive to this NOFO:

Topics:

• Elucidating how heterogeneous CNS cell types contribute to the dynamic computations underlying behavior or functional output of the circuit (e.g., sensory, motor, cognition, social behavior, internal state, affective, brain-body physiology).
• Neural computations underlying distributed representation and information processing across brain regions during cognitive processes.
• Understanding how behavioral states are emergent properties of the interaction of neurons, circuits, and networks.
• Understanding the role of interactions between neuronal and non-neuronal cells in shaping neurocircuit function and behavior.
• Leveraging developmental processes to understand how cell type heterogeneity and circuit formation and organization contribute to function across life stages.
• Understanding the cellular basis of circuit reconfiguration or plasticity during learning, adaptation, or behavioral state transitions.
• Modeling flexible, goal-directed, or context-dependent behavior through frameworks that incorporate dynamic cellular contributions and network-level computation.

Approaches:

• Using comparative or evolutionary approaches to identify conserved circuit motifs or principles across species that inform general rules of CNS function.
• Using cellular and circuit analyses to generate computational models that are predictive of mechanisms of CNS function and behavior.
• Developing approaches that bridge across spatial (from single cells to networks) and temporal (from milliseconds to behavioral timescales) scales to understand dynamic neural computations that underlie behavior.
• Forming connection across levels of abstraction, by bringing mechanistic approaches, causal explanations, and biological constraints to the rich descriptive observations and/or normative models of brain function
• Developing generalizable analytic or modeling tools that can be applied across systems to facilitate integrative, multi-level analyses.
• Combining cutting-edge tools (e.g., multi-area imaging, electrophysiology, optogenetics, connectomics, single-cell omics) to relate cellular identity with circuit dynamics and behavior.
• Leveraging disease-related perturbations to provide mechanistic insights into normal CNS function and behavior.

Consultation with relevant Program Staff:

Potential applicants should consult with the NOFO contact about responsiveness to the NOFO priorities, single research aim, team composition, and anticipated scope very early in the planning stage and a minimum of 8 weeks prior to the application due date. Staff will not assess technical or scientific merit; this will be determined during peer review using the criteria in this NOFO.

Applications that exhibit any of the following characteristics will be considered non-responsive and withdrawn from consideration:

Primarily focuses on disease mechanisms, therapeutics, or treatments. Although disease-related perturbations may be employed to probe causality, such approaches are allowed only for elucidating fundamental mechanisms of CNS function. This NOFO does not support studies that are explicitly disease-focused; such proposals should be directed to the appropriate NIH IC.

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

Foreign Organizations/Foreign Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are 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 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.  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.

The application is required to be submitted as a multiple PD/PI application, with 3–6 PDs/PIs who have complementary expertise. Visit the multiple PD/PI Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide, and the Grant Policy Statement on Multiple Principal Investigators. Minimum allowed efforts by the PDs/PIs are described in the R&R Budget instructions in Part 2. Section IV.2.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement 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 How to Apply - 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.

For this specific NOFO, the Research Strategy section is limited to 15 pages.

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 Budget

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

• Generally, each PDs/PIs should commit at least 2.4 person months (i.e., the equivalent of 20% effort on a full-year appointment, 26.67% on a 9-month appointment, or 40% on a 6-month appointment) throughout the duration of the award).  A dedicated Program Manager with at least 50% FTE is required. Applications with less than 3 or more than 6 PD/PIs and/or without a dedicated Program Manager with at least 50% FTE will be considered non-compliant.
• Allocate budget for costs associated with team coordination, integrative activities, travel across labs (particularly as it relates to co-mentoring activities), travel to the BRAIN Initiative Conference, participation in BRAIN consortium activities, and the sharing of key resources and data across team members. Applicants may request and justify data and resource sharing and management systems and/or the hiring of professional data science staff.
• Data sharing costs: Applicants may include costs associated with preparing and submitting data to a data archive (as outlined in this NIH BRAIN data sharing policy: https://www.nih.gov/brain/research/data-knowledge-resources
• Certain supporting functions such as equipment, animal research costs, and clinical research costs may be requested if well justified and unique to the institution(s) involved. Equipment that duplicates existing institutional or regional shared facilities available to investigators must be identified, and such duplication must be well justified. Do not request inflationary increases in the overall budget or any of the budget categories. Changes in budget should reflect changes in activities required by the science.

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 aim

• State only one Specific Aim that describes the mechanistic insights expected from the proposed project. Applications that include more than one Specific Aim will be considered noncompliant, as multiple independent aims can hinder true integration.
• Summarize anticipated deliverables and key innovations in research strategy and approach.
• Describe and justify the levels of analysis to be bridged (e.g., circuit components, circuit dynamics, and behavior) and choice of experimental system(s). Summarize how these levels will be explicitly connected through conceptual/theoretical frameworks and integrated experimental-computational strategies.
• Justify the team-based approach and explain how the project's scale, complexity, and impact align with the transformative goals of the BRAIN Initiative.

Research Strategy
Applications that fail to include the three components listed below and do not follow the page limits will be considered incomplete and non-compliant, respectively, and will be withdrawn.

1. Scientific Plan (up to 12 pages)
2. Benchmarks for Success and Timeline (up to 1 page)
3. Multi-Level Integration and Team Management Plan (up to 2 pages)

1. Scientific Plan (12-pages max)

Program Structure: This program should focus on a single aim composed of interdependent and tightly interconnected components. Provide a visual schematic summarizing the program's organization and illustrating how its key components interact and are fully integrated.

Significance: Describe the scientific problem and key anticipated deliverables, which must include: (1) a mechanistic, biologically grounded explanation of CNS function, and (2) broadly useful solutions to challenges in bridging levels of analysis. Mechanistic insights explain how defined circuit components and their dynamic activity and/or interactions causally generate neural circuit function and behavior, with predictive and testable implications.

Innovation: Describe how the project's scale, complexity, and impact align with the transformative nature of the BRAIN Initiative and warrant a team-based approach. Highlight key conceptual, theoretical, experimental, and/or computational innovations that enable multi-level integration.

Approach:

• Describe how the three required levels of analysis will be directly bridged, and how relationships across these levels will be uncovered. Justify the choice of experimental paradigms at each level and the choice of experimental and model systems, including NAMS (e.g., in silico methods), explaining how these are most appropriate to address the specific question and to reveal generalizable, fundamental principles.  Explain the conceptual/theoretical frameworks, predictive models, and/or methodologies enabling this integration, emphasizing how experimental and computational components will interact to connect these levels.
  1. Behavior. This refers to the functional (i.e. physiological or behavioral) output of the circuit or system in the intact animal. The selected behavior, or behaviorally relevant physiological correlate, should be experimentally tractable and, depending on the limits of the experimental system, amenable to causal manipulation and analysis, allowing for meaningful integration with cellular and dynamic circuit-level data. It is expected that the in vivo neural activity and cell types are characterized within the context of this behavior of an organism or the physiological correlate of a well-defined percept or behavior.
  2. Circuits. Projects must include in vivo CNS recordings of neural population activity at cellular resolution, with sub-second temporal precision, acquired during the expression of the behavior. These data should capture the dynamic interactions among neurons and circuits in real time within a behaviorally relevant context.
     • Scale of recording should be sufficient to account for the dynamic activity of the circuit or distributed ensemble of neurons under study, or to validate a specific, model-predicted outcome. This will be evaluated using model system-appropriate considerations.
     • Cellular and sub-second temporal resolution of recording circuit activity (e.g., electrophysiology, calcium imaging, voltage imaging) is expected in order to address mechanistic understanding of circuit functions. The required resolution for mechanistic manipulation of circuits need not be limited to single-cell precision but may extend to cell type– or location-specific interventions (e.g., focal TMS, micro-stimulation, micro-injection, and optogenetic/DREADD/etc. manipulation, including by non-germ cell induction such as viral vectors in non-transgenic species).
  3. Circuit components. Teams must define and justify what the appropriate "building blocks" of the circuits under study. Relevant "cell types" can be operationally defined through appropriate modalities, capturing their heterogeneity through molecular, physiological, anatomical, functional, and/or connectivity data at a scale sufficient to inform circuit function.
• If applicable, highlight the use of BRAIN-developed tools, technologies, and resources such as atlases.
• Balance risk, reward, and feasibility: The iBCP program will assume inherent risk consistent with innovative, transformative research. While bold approaches are encouraged, applicants must address feasibility through risk mitigation strategies, alternative approaches, and evidence supporting a strong likelihood of success. Feasibility can be presented in a holistic way, presenting several ways by which the team manages the risk, possibly through collaborations, contingencies, premise, preliminary data, and description of alternative approaches and pitfalls.
• Justify the team composition. Describe how expertise spanning molecular/cellular through systems neuroscience will be synthesized to develop new scientific principles and approaches to multi-level integration, linking theory, modeling, and/or data analysis with experimental design.
• Neuroethics: Address neuroethical considerations relevant to this project, as appropriate (e.g., NOT-MH-22-010: NIMH Priorities on Research Using Genetically Modified Nonhuman Primates). Studies that include human subjects must include relevant neuroethical considerations, such as consent of patients recruited into studies with possibility for risk beyond therapeutic standards of care without the expectation of personal therapeutic benefit. Additional risks should be identified and justified as minor and manageable. The consent methodology needs to address how the possibility of coercion or undue influence, and therapeutic misconception, will be minimized.

2. Benchmarks for Success and Timeline (1-page max)

This section is critical for assessing feasibility of the integrative strategy, degree of scientific and team integration, and likelihood of achieving mechanistic insight across levels of analysis within the award period. It will serve as a framework for NIH BRAIN Initiative oversight and progress monitoring.

A. Provide a project timeline in a visual format (e.g., Gantt chart, milestone map, or other infographic) that includes:

• Key scientific benchmarks toward integrated, mechanistic understanding across circuit components, circuit dynamics, and behavior;
• Integrative team activities essential for multi-level synthesis (e.g., project launch meetings, experimental–computational interactions, co-mentorship activities, lab exchanges, annual team meetings, and data integration milestones);
• Estimated start and end dates, responsible contributors, and benchmarks for success for each major activity.

If using an External Advisory Committee, describe its operations and role in providing advice and perspectives. Avoid identifying or contacting potential members prior to review.

Applicants should plan for an annual check-in with NIH BRAIN staff, either virtual or in person. Teams should also plan on joining active BRAIN consortia or leading a new one focused on discussing challenges and effective practices for multi-level integration.

B. Outputs: Summarize anticipated key deliverables with specific examples and success metrics, organized into these categories, as applicable: Discovery, Dissemination, Impact on team members and the next generation of neuroscientists, Health

Multi-Level Integration and Team Management Plan (2-pages max)

Overall, this section should summarize how the project will integrate the three required levels of analysis, the included disciplines (e.g., molecular/cellular to systems neuroscience, experimental, theoretical, and computational), and key personnel across different scientific backgrounds and career stages, at the level of both scientific strategy and team structure. Under the following sub-headings, describe the unifying activities and defined shared goals, outcomes, or benchmarks that will serve as conceptual, technical, and organizational bridging mechanisms. This section may cross-reference relevant components of the Research Strategy.

A. Scientific Integration
Summarize the conceptual and/or theoretical frameworks that unify the three required levels of analysis (circuit components, circuit dynamics, and behavior). Describe how these frameworks will connect different disciplines, labs, and key personnel. Detailed descriptions should be provided in the "Scientific Plan" section of the Research Strategy.

B. Technical Integration 

• Summarize the experimental, computational, and analytical approaches used to integrate data and methods across the required levels of analysis and across laboratories. Detailed descriptions should be provided in the "Scientific Plan" section of the Research Strategy.
• Cross-team data management, sharing, and integration: Describe how data across the three levels of analysis will be shared, analyzed, and integrated across the team, including strategies to address challenges associated with multimodal data integration. Explain how multimodal data will be jointly analyzed to support mechanistic and predictive understanding. This section may cross-reference relevant components of the Research Strategy. This effort must be properly resourced through inclusion of professional data science staff and data/resource sharing and management systems. This plan and its costs are distinct from the Data Management and Sharing Plan, which focuses on sharing data with the public.
• Resource sharing and allocation across the team: Describe how resources that are key to achieving the project aim will be shared, prioritized, and allocated across team members. This plan and its costs are distinct from the Resource Sharing Plan, which focuses on sharing resources with the public.

C. Team Management Plan
Applicants are encouraged to consult resources to aid in developing effective team-based programs (see e.g., the NCI Collaboration and Team Science Field Guide and literature on the Science of Team Science), and/or participate in team-science related training.

Team Structure: While the Multiple PD/PI Leadership Plan addresses PI leadership, this section should describe the overall team management structure, inclusive of all key personnel. Refer to the MPI Leadership Plan as needed and avoid duplicating information. Address team composition, resources, policies, and specific roles and responsibilities of all key personnel and organizations in fulfilling the scientific and integration goals of this project. Describe how major decisions will be made or conflicts resolved. The structure must ensure balanced participation, avoiding undue authority by any single individual in setting priorities, allocating resources, or recognizing contributions. Strong leadership is expected, but decision-making should reflect collective expertise and project goals.

Team Integration: Because transdisciplinary integration requires intentional effort, applicants must describe roles and activities that accelerate the transition from parallel disciplines to an integrated team, including:

• Program Manager (required): A dedicated Program Manager with at least 50% FTE is required.Summarize how this individual's qualifications and bandwidth are appropriate for the project scale and subject matter to: (1) coordinate administrative and scientific activities of the program, (2) establish communication activities and infrastructure (in-person and virtual) (3) monitor progress towards success metrics and serve as liaison between the investigative team and NIH BRAIN staff for annual oversight and evaluation, (4) monitor and coordinate learning and career development of early-career team members.
• Co-mentorship (required): Co-mentorship is required to bridge expertise across laboratories and prepare the next generation for transdisciplinary research. Describe activities enabling early-career scientists to be immersed in the lexicons, perspectives, and methodologies of multiple disciplines (e.g., cross-lab training, joint supervision, transdisciplinary seminars, collaborative problem-solving). Applications missing this component will be considered incomplete. 
• Knowledge transfer and communication: Describe how knowledge and progress will be shared across disciplines and career stages, including frequency, formats, infrastructure, and the Program Manager's role. Examples may include:
  • Team building and communication: Launch and onboarding activities, shared virtual collaboration spaces, regular project meetings, team retreats, and informal/ formal gatherings.
  • Promoting cross-disciplinary understanding from molecular/cellular to systems neuroscience, between experimentalists and computational neuroscientists: Expert speaker series, laboratory visits, tutorials, workshops, participation in NIH BRAIN consortia and conferences, and other educational or experiential learning activities.
• Credit attribution: Describe how scientific contributions will be documented and fairly attributed, with particular attention to transparency and fairness for early-career researchers. 

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.

• 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. 
• Consistent with authorities under the 21st Century Cures Act, all applications to BRAIN Initiative NOFOs must include a Data Management and Sharing Plan. All BRAIN-funded studies must comply with the BRAIN data sharing requirements. Please refer to the BRAIN Initiative requirements for additional information.

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.

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.

7. Other Submission Requirements and Information

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

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:

A successful iBCP is expected to deliver two key outcomes: (1) mechanistic insights and (2) broadly useful solutions to the challenges of bridging these levels of analysis. Applications are expected to assume a level of risk intrinsic to innovative approaches and transformative goals associated with the BRAIN initiative. This program supports a single Specific Aim composed of interdependent and tightly interconnected components. Strong and explicit integration is required across the three levels of analysis described below, across participating disciplines, and between experimental and computational components.

• Behavior. Refers to the functional output of the circuit or system in the intact organism. The selected behavior, or a behaviorally relevant physiological correlate, must be experimentally tractable and, within the constraints of the model system, amenable to causal manipulation and quantitative analysis.
• Circuits. Refers to dynamic circuit activity measured through in vivo CNS recordings of neural population activity with cellular and sub-second temporal resolution (e.g., electrophysiology, calcium imaging, voltage imaging), acquired during the expression of the relevant behavior or functional state.
• Circuit components. Refers to building blocks of the circuits under study. Relevant cell types may be operationally defined using appropriate molecular, anatomical, physiological, functional, and/or connectivity criteria, with sufficient resolution to capture heterogeneity necessary to inform circuit function.

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 review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

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

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 policy and procedures, 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.

Applications 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 National Institute of Neurological Disorders and Stroke. 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.

For applications involving funding Medication-Assisted Treatment (MAT) or medications for opioid use disorder (MOUD), this funding should be used to provide comprehensive treatment and recovery support services rather than medication-only models for opioid use disorder. Services should include medications, where clinically indicated, in conjunction with psychosocial and other treatment and recovery support services. Funding can also be used to support individualized tapering and discontinuation of medications when clinically indicated. Please see Updated Funding Guidance for Recipients on  MAT/MOUD.

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.

In administering programs under this and all funding announcements, NIH prioritizes: 

• Research involving rigorous scientific methods, including for studies related to children and adolescents, where NIH is committed to approaches that reflect the highest standards of clinical care and child safety. 
• Biological and physiological integrity: Recognizing the relevance of biological sex to health outcomes, NIH encourages applicants to account for sex-based health factors in program design, data collection, and service delivery where scientifically appropriate.
• NIH will implement these priorities consistent with applicable laws, regulations, court orders, and all required administrative procedures. Applicants are encouraged to describe how their proposed programs align with these priorities in their project narratives. Funded activities must advance NIH's vision of protecting and improving the health and well-being of Americans. The particular focus is on those who are medically vulnerable, or live in areas with limited access to care. NIH's duty is to serve wisely, effectively, and with measurable results that justify every taxpayer dollar invested. 

Not Applicable

3. Data Management and Sharing

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. 

Follow all instructions described in Section IV.2, "Other Plans," related to the BRAIN Data Sharing requirements.

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.

Not Applicable.

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 NIH BRAIN Initiative
National Institute of Neurological Disorders and Stroke (NINDS) 
Email: BRAINCircuits@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.