It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) 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.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The BRAIN Initiative

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) InitiativeSM is aimed at revolutionizing our understanding of the human brain. By accelerating the development and application of innovative technologies, researchers will be able to produce a new dynamic picture of the brain that, for the first time, will show how individual cells and complex neural circuits interact in both time and space. It is expected that the application of these new tools and technologies will ultimately lead to new ways to treat, cure, and even prevent brain disorders.

NIH is one of several federal agencies involved in the BRAIN Initiative. Planning for the NIH component of the BRAIN initiative is guided by the long-term scientific plan, BRAIN 2025: A Scientific Vision, which details seven high-priority research areas and calls for a sustained federal commitment of $4.5 billion over 12 years. This report can be found at http://braininitiative.nih.gov/ . This FOA and other BRAIN Initiative FOAs are based on careful consideration by the NIH of the recommendations of the BRAIN 2025 Report, and input from the NIH BRAIN Multi-Council Working Group (MCWG, Roster). Information about meetings of the MCWG are available at https://videocast.nih.gov/.

In addition to the National BRAIN initiative, the NIH continues to have a substantial annual investment in neuroscience research. The Institutes and Centers contributing to the NIH BRAIN Initiative support those research efforts through investigator-initiated applications as well as through specific FOAs. Potential applicants to this FOA are strongly encouraged to contact Scientific/Program staff if they have any questions about the best FOA for their research.

To enable rapid progress in development of new technologies as well as in theory and data analysis, the BRAIN Initiative encourages collaborations between neurobiologists and scientists from statistics, physics, mathematics, engineering, and computer and information sciences; and NIH welcomes applications from investigators in these disciplines.

NIH encourages BRAIN Initiative applications from investigators that are underrepresented in the biomedical, behavioral, or clinical research workforce (see data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27 and the most recent report on Women, Minorities, and Persons with Disabilities in Science and Engineering). Such individuals include those from underrepresented racial and ethnic groups, those with disabilities, and those from disadvantaged backgrounds.

The BRAIN Initiative will require a high level of coordination and sharing between investigators, and this FOA will use a cooperative agreement to facilitate these activities. The details of the management of the cooperative agreements can be found in Section VI. It is expected that BRAIN Initiative awardees will cooperate and coordinate their activities after awards are made.

This FOA is related to the Recommendations in Section III. 2, 3, 4, 5 and 7 of the Final Report (http://www.nih.gov/science/brain/2025/index.htm) of the BRAIN working group. Specifically, this FOA solicits applications that will address the recommendations on Maps at Multiple Scales , "The Brain in Action", "Demonstrating Causality", "Identifying Fundamental Principles" and From BRAIN Initiative to the Brain (Section III Implementation: Goals, Deliverables, Timelines and Costs, Parts 2 3, 4, 5 and 7) of the Final Report.

Integrated Approaches Funding Opportunities

This FOA is one of a family of Integrated Approaches NIH BRAIN FOAs that range from small or exploratory, targeted brain circuits projects with specific research deliverables (R21, R01) to large, team-research projects with exploratory aims (U01) or with extensive and elaborated goals and a 5-10 year horizon of discovery (U19). In each case, the FOAs are guided by BRAIN 2025 A Scientific Vision: The Application of Integrated Technologies to Study Fundamental Questions in Neuroscience: Numerous long-standing problems in brain science will benefit dramatically from the integrated experimental approach made possible by the BRAIN Initiative.

Potential applicants are encouraged to visit the NIH BRAIN Initiative website for information and guidance https://www.braininitiative.nih.gov/funding/initiatives.htm.

All FOAs in this family of initiatives emphasize the use of cutting-edge methods of activation and recording to understand the behavior of circuits at cellular and sub-second levels of spatial and temporal resolution; that is, at the level of the functional units of circuits. All FOAs welcome basic research using human or non-human animal subjects. However, there is a specific FOA for neurobiology research involving research opportunities employing invasive neural recording (Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain). This family of initiatives also seeks advances in theory and/or analytics, and has a requirement of a data standards and management plan, as well as a data dissemination plan to facilitate use of the results by the research community.

Objectives

The broad goal of the BRAIN Initiative is to understand the circuits and patterns of neural activity that give rise to mental experience and behavior, which will provide a foundation for understanding and treating diverse neurological, psychiatric, and behavioral disorders. It is the dynamic activity of massively interconnected ensembles of neurons in specially organized networks that give rise to the internal states we experience as sensations, perceptions, emotions, thoughts, memories, and movements. The activity of these networks is the substrate of cognitive processes such as attention, intention, emotions, and rational processes such as reasoning and decision making. Ultimately, these covert, internal activities are translated into patterns of neural activation that lead to overt behaviors, from simple reflexes to highly coordinated movements such as reaching and walking, to more complex behaviors such as navigating the environment and foraging, or speech and language. Dysfunction of these large systems of neurons due to disease, injury or developmental anomaly are the basis of neural and mental disorders. The mission of the NIH BRAIN initiative is to understand how large scale neural systems contribute to cognitive and neurological function in both health and disease.

We can seek to understand circuits of the brain by systematically controlling stimuli and measuring the resulting behaviors, while actively recording and manipulating the dynamic patterns of neural activity. We now have transformational technologies that allow us to record large, interrelated ensembles of neurons on an unprecedented scale during active behaviors. For example, it is now possible to study the collective neural activities of entire sensory-motor circuits. By clever manipulation of environments and contingencies, we can devise behavioral tasks that engage memories, decision making, and selective attention, while documenting and manipulating the functional relationships within the neural circuits that subtend the behaviors.

Increasingly, sophisticated approaches are required for data acquisition, analysis, interpretation, and dissemination. These demanding requirements often involve expertise not typically associated with traditional neurobiological experiments and training, such as expertise in computer and information science, hardware and software engineering, statistics, machine learning, and computational methods. As new, large-scale, systems approaches become routine, it will be essential to develop testable theories of how information originating from millions of neurons in diverse and widespread brain regions can be integrated to produce a wide range of motor, sensory and cognitive behaviors, and how this information evolves dynamically to adapt, refine and learn.

The purpose of this FOA is to provide resources for integration of experimental, analytic, and theoretical capabilities for large-scale analysis of neural systems and circuits within the context, and during the simultaneous measurement of complex behavior. We seek applications to build teams of experts for exploratory studies that integrate theory and modeling with new and emerging methods for recording and manipulating neural circuits across multiple brain regions, to elucidate a specific behavioral or neural system in terms of dynamic circuit activity. Novel and innovative approaches to theory and analysis are expected.

Successful exploratory studies should lead to subsequent, competing applications for support of multicomponent, team-research projects consistent with the BRAIN Initiative's goal to understand the circuits of the brain, measure the fluctuating patterns of electrical and chemical activity flowing within those circuits, and understand how their interplay creates our advanced cognitive and behavioral capabilities. Applications to this FOA should propose teams of investigators that seek to cross boundaries of interdisciplinary collaboration by bridging fields and linking theory and data analysis to experimental design. Innovative approaches to cross-cutting questions in neuroscience are expected. Applicants are required to develop or adopt a quantitative modeling framework, which incorporate theories about causal mechanisms of circuit functions, to drive experiments and build testable hypotheses.

The list below includes representative, but not exhaustive, examples of topics that could be considered responsive to this FOA.

• Innovative approaches to understand network coding of sensory information, at multiple stages of processing, in response to diverse naturalistic inputs and perceptual contexts.
• Innovative approaches and new paradigms for identifying and understanding nocioception and pain in the context of circuit mechanisms of the central nervous system
• New paradigms to assess motor coding during complex behaviors or freely-moving subjects.
• Novel approaches to understand neural circuitry associated with diverse social behaviors.
• Large-scale, dynamic changes in functional circuit connectivity underlying the brain's ability to store information and to learn new behaviors.
• Distributed circuits that contribute to the coordination of motivational states and reward behavior.
• New approaches to capture and assess information processing across brain regions during memory consolidation, memory retrieval, spatial/relational processing, attention, or planning.
• Large-scale approaches to assess distributed representations and the information processing underlying advanced mental processes such as decision making, numerical cognition, reasoning, and metacognition.
• Empirical and analytical approaches to understand how behavioral states are emergent properties of the interaction of neurons, circuits, and networks.
• Research to advance principles of circuit function and neural systems in the central nervous system that regulate homeostasis, including biorhythms, and the balance of temperature, respiratory, energy and metabolic functions.

Applications must apply NIH standards of experimental and publication rigor (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-011.html), should strive to promote ethnic, racial, gender and career stage diversity of the research teams, and must comply with NIH policy on reporting disaggregated sex-based data and other consideration of sex as a biological variable as elaborated in NOT-OD-15-102, NOT-OD-15-103 and NOT-OD-16-031. The NIH BRAIN Initiative will not accept applications under this announcement that include clinical trials (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html).

Applicants are strongly encouraged to consult the Scientific/Research Contact listed below to discuss the alignment of their proposed work with the goals of this FOA, and the BRAIN Initiative Program.

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

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

Higher Education Institutions

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

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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)

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)
• 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 Institutions) are not 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 allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) 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.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 DUNS number and 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.

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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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. 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 NOT-OD-11-101).
• Additional Eligibility Information: Applications submitted in response to this solicitation may not duplicate or be substantially similar to other applications concurrently under consideration by other programs or study sections including the inter-agency program, Collaborative Research in Computational Neuroscience (CRCNS). Duplicate or substantially similar applications will not be reviewed.

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Dr. James Gnadt, PhD
6001 Executive Blvd
North Bethesda, MD
NSC 2230
Telephone: 301-496-9964
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: This FOA supports exploratory collaborative studies to develop experimental capabilities and theoretical frameworks to prepare for a future multi-component research effort, focused on understanding a specific behavioral or neural system in terms of circuit dynamics.

All applications should include the following points, which should be incorporated within the page limits of the Research Strategy:

• Statement of the neurobiological questions to be addressed. Applications should propose to elucidate the contributions of dynamic circuit activity to a specific behavioral or neural system. Applications should identify fundamental principles about circuit dynamics and functional connectivity for understanding the biological basis of neural processes through application of new methods, and theoretical and data analysis tools. This FOA welcomes basic research using human or non-human animal subjects; applications for the study of specific disease mechanisms, or specific disease therapeutics and treatments will be considered nonresponsive to this BRAIN Initiative FOA. Studies for the investigation of specific diseases and disorders should be directed to the appropriate NIH Institutes. Studies of human neuroscience that utilize invasive neural recording will not be accepted under this FOA. Invasive studies of human neuroscience should consider the BRAIN Initiative FOAs for Research Opportunities in Humans (see https://www.braininitiative.nih.gov/).
• Justification of the team of experts to address the multiple components of approach. Applications should propose teams of investigators that seek to cross boundaries of interdisciplinary collaboration by bridging fields and linking theory and data analysis to experimental design. Projects should engage research teams that integrate across diverse approaches for observation, experimental perturbation, and theoretical modeling of circuits and neural dynamics. Teams should leverage appropriate multi-disciplinary expertise to develop new principles and methods for data acquisition, analysis and interpretation.
• Detailed description of the theories and models that frame explicit empirical questions, and discussion of the analytical tools for interpretation of results. The purpose of this FOA is to promote the integration of experimental, analytic, and theoretical capabilities for large-scale analysis of neural systems and circuits.
• Studies are required to develop or use a quantitative theoretical framework for building testable hypotheses (i.e., model-driven empirical design). Mechanistic tests of cause-and-effect are expected, such as testing whether modifying electrophysiological patterns during behavior can alter the observed behavior.
• Development or use of innovative algorithmic approaches for dynamic tracking of function in continuous data and real-time signal processing is encouraged, as are methods for interactive data exploration and dimensionality reduction in high-dimensional data sets.
• Analytical methods and experimental approaches to link neural processes across multiple scales of structure and time (spanning the requirement of cellular recording resolution) are encouraged (e.g., channels, to cell compartments/structures, to spike rates/timing, to LFPs/oscillations, to circuits/networks/ensembles, to brain states).
• Description of large-scale recording/manipulation methods that will be employed or developed to approach the questions as a functional system. Projects should describe how they will employ and/or develop new and emerging capabilities for large scale recording and manipulation of neural activity of specific circuits or systems, ideally across multiple brain regions.
• 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 species-appropriate considerations.
• A cellular resolution of recording circuit activity is expected in order to address mechanistic understanding of circuit functions. The resolution of mechanistic manipulation of circuits is relaxed from that of single cells to that of cell type/location specificity (e.g., compatible with 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).
• Explanation of the experimental strategies to investigate mechanisms within the circuits studied. Applicants should demonstrate how new and unprecedented experimental capabilities can be used to transform general understanding of neural information processing within the context of specific systems or circuits.
• Description of tractable goals or milestones for the project, which will serve as a basis for a subsequent application in a competition for large-scale, multicomponent projects.

Other specific requirements and considerations:

• Applications should describe how they incorporate rich information on cell types and circuit connectivity to inform assessments of neural activity patterns.
• Studies of dynamic neural activity should be performed in conjunction with sophisticated analysis of complex, ethologically relevant behaviors. When simple circuits are employed, it should be made clear how they are ideal for revealing general principles about the circuit basis of the specific behavior of interest. Studies of complex behaviors, including behavioral assays of freely-moving animals up to objective measures of cognitive/perceptual processes, are encouraged.
• Projects should have a plan for innovative approaches to large-scale data analysis, visualization, storage and dissemination, to maximally leverage the value of newly acquired data for broad communities of researchers.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Applicants are welcome to consider editing this example data sharing plan, https://grants.nih.gov/grants/sharing_example_data_sharing_plan.doc to include the sharing of all the tool deliverables from this FOA (e.g. theories, models, methods, software, etc.).

Awards made under this FOA will encourage that data be shared using appropriate standards in an appropriate repository. For example, the NIH BRAIN Initiative will be supporting candidate activities and repositories through 3 BRAIN Informatics FOAs (RFA-MH-17-255, RFA-MH-17-256, and RFA-MH-17-257). Project-specific details will be established at the time of award. Budgets should include sufficient resources to prepare and disseminate data.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. 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

Part I. Overview Information 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 Policy on Late Application Submission.

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 SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

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.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) 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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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 Component of the SF424(R&R) Application Package. 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 FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) 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.

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

This FOA supports exploratory collaborative studies to develop experimental capabilities and theoretical frameworks to prepare for a future large-scale, multi-component research effort, focused on understanding a specific behavioral or neural system in terms of circuit dynamics.

Because projects are expected to be early-stage and potentially high-risk, preliminary data on feasibility are not required. However, a sound rationale should be provided as to why the approach is tractable and the research team are the most appropriate, and likely to generate an exceptionally high impact if successful. Although reviewers will consider feasibility, they will not penalize unavoidable risks that are intrinsic to new and innovative approaches.

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.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Does the project seek to identify fundamental principles or produce conceptual foundations about circuit dynamics and functional connectivity consistent with the goals of this FOA and the BRAIN Initiative? Does the project justify how its development of experimental capabilities and quantitative, theoretical frameworks will prepare for a future competition for multi-component, team-research awards?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Does the team seek to cross boundaries of interdisciplinary collaboration by bridging fields and linking theory and data analysis to experimental design?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Does the project offer novelty and innovation appropriate for/commensurate with the goals of the BRAIN Initiative? Innovative approaches to cross-cutting questions in neuroscience are expected.

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Does the project use cutting-edge methods of activation and recording to understand behavior or a neural system in terms of a mechanistic understanding of specific circuits at cellular and sub-second levels of spatial and temporal resolution? Is the scale of recording 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 should be evaluated using species-appropriate considerations.

Does the project justify how the selected model species offer the best conditions for revealing general principles about the circuit basis of the specific behavior or neural system of interest?

Does this project link theory and data analysis to experimental design and will it produce predictive models (quantitative or conceptual) as deliverables?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

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.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

Not Applicable

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.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NINDS, 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:

• 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.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

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 FOA. 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.

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.

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.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. 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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of 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 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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 awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH 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 resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• PDs/PIs will determine and coordinate the research approaches and procedures, conduct experiments, and analyze and interpret research data generated under this award.
• PDs/PIs will endeavor to meet or exceed the timeline stated in their application.
• PDs/PIs will agree to participate as a voting member in a Steering Group composed of other BRAIN Initiative awardees, and NIH staff.
• PDs/PIs will share resources and data in a consistent manner to be developed by the Steering Group.
• PDs/PIs will ensure that results are published in a timely manner.
• PDs/PIs will submit data for quality assessment and/or validation in any manner specified by the Steering Group or the NIH Project Scientist.
• PDs/PIs will submit periodic progress reports as agreed by the Steering Group.
• PDs/PIs will accept and implement any other common guidelines and procedures approved by the Steering Group.
• PDs/PIs will attend Steering Group meetings. It is likely that there will be one in-person meeting per year and that other meetings will be by telephone or using internet assisted meeting software.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government 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 assigned to this award. The Program Officer will be responsible for normal scientific and programmatic stewardship and guidance.
• A group of NIH program staff from the ICs contributing to the NIH BRAIN Initiative will form a Project Team for this award.
• The Project Team will be led by the Program Officer(s) for these BRAIN Initiative awards.
• The Project Team will review annual progress reports and other documents from the awardees and will advise the Program Officer about their view of the progress being made by the awardee as well as about progress being made by others in the field.
• One extramural NIH program staff member will be assigned as the Project Scientist for this award. The same person may serve as the Project Scientist for multiple BRAIN Initiative awards
• The Project Scientist will also be a member of the Project Team.
• The Project Scientist will interact scientifically with the PDs/PIs of the cooperative agreement and other named key personnel as a partner in the research.
• The Program Officer(s), the Project Scientist(s), and one member of the Project Team will be members of the Steering Group.
• The purpose of the Steering Group is to transfer information between BRAIN Initiative awardees in order to achieve the goals outlined in the BRAIN Initiative Working Group Interim Report.
• It is expected that most of the decisions on the activities of the Steering Group will be reached by consensus. If a vote is needed, each awardee will have one vote, and the Project Scientist(s) will each have a vote. The number of NIH votes will be less than the number of awardee votes. When a vote is required, at least 60% of the votes will be required for approval.
• The Project Scientist interacts scientifically with the Steering Group and may assist in research planning, may present experimental findings from the group from published sources or from relevant contract projects, may participate in the design of experiments agreed to by the group, may participate in the analysis of results, and may help ensure that duplication is avoided.
• The Project Officer may attend Steering Group meetings as a non-voting participant.
• In all cases, the role of NIH staff will be to assist and facilitate, but not to direct activities.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

None; all responsibilities are divided between awardees and NIH staff as described above.

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 awardee. This special dispute resolution procedure does not alter the awardee'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.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

James Gnadt, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email: [email protected]

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: [email protected]

Tijuanna E. DeCoster, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: [email protected]

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 45 CFR Part 75.