Brain Behavior Quantification and Synchronization (R61/R33 Clinical Trial Optional) (2024)

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Mental Health (NIMH)

National Eye Institute (NEI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Deafness and Other Communication Disorders (NIDCD)

National Institute on Drug Abuse (NIDA)

National Institute of Neurological Disorders andStroke (NINDS)

National Center for Complementary and Integrative Health (NCCIH)

Funding Opportunity Title

BRAIN Initiative: Brain Behavior Quantification and Synchronization (R61/R33 Clinical Trial Optional)

Activity Code

R61/R33 Exploratory/Developmental Phased Award

Announcement Type

Reissue of RFA-MH-23-335

Related Notices

  • April 4, 2024- Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084.
  • August 31, 2022- Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See NoticeNOT-OD-22-198.
  • August 5, 2022- Implementation Details for the NIH Data Management and Sharing Policy. See NoticeNOT-OD-22-189.

Funding Opportunity Number (FON)

RFA-MH-26-100

Companion Funding Opportunity

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.242, 93.853, 93.865, 93.273, 93.173, 93.279, 93.286, 93.866, 93.213, 93.867

Funding Opportunity Purpose

This Notice of Funding Opportunity (NOFO) supports the development and validation of next-generation tools, methods, and analytic approaches to precisely quantify behaviors and combine them with simultaneous recordings of brain activity in humans. Tools used for measuring and analyzing behavior should be multi-modal, with the appropriate accuracy, specificity, temporal resolution, and flexibility necessary for integration with existing tools used to measure and modulate the brain circuits that give rise to those behaviors.

This R61/R33 NOFO is intended to support biphasic applications for novel tools development (i.e., hardware/software) in the R61 phase, followed by the integration/synchronization of these novel tools with established methods for recording human brain activity in the R33 phase. Applications must propose one or more milestones, which clearly define the criteria for the success of the R61 project objectives. Transition to the R33 phase will depend on demonstration of milestone completion. Applications should be submitted by multi-disciplinary teams with expertise spanning behavior and behavioral measurement, neurobiology, social systems, computer/data systems, engineering, biostatistics, neuroethics, and artificial intelligence. Applicants pursuing brain-behavior quantification and synchronization tool development in non-human animals, or pursuing comparative animal studies including humans, are not responsive to this NOFO and should consider related Brain-Behavior Quantification and Synchronization (BBQS) opportunities listed on the BRAIN Initiative website, or reach out to the contacts (see Section VII: Agency Contacts) for guidance on relevant opportunities.

This Notice of Fuding Opportunity (NOFO) requires a Plan for Enhancing Diverse Perspectives (PEDP).

Key Dates

Posted Date

July 09, 2024

Open Date (Earliest Submission Date)

December 22, 2024

Letter of Intent Due Date(s)

30 days prior to the application due date.

Application Due DatesReview and Award Cycles
NewRenewal / Resubmission / Revision (as allowed)AIDS - New/Renewal/Resubmission/Revision, as allowedScientific Merit ReviewAdvisory Council ReviewEarliest Start Date
January 22, 2025 January 22, 2025Not ApplicableJuly 2025October 2025December 2025

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.

Expiration Date

January 23, 2025

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in theHow 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.
  4. Table of Contents

    Part 1. Overview Information

    Key Dates

    Part 2. Full Text of Announcement

    Section I. Notice of 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


Section I. Notice of Funding Opportunity Description

Background

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

As one of several federal agencies involved in the BRAIN Initiative, NIH's contributions to the BRAIN initiative were initially guided by "BRAIN 2025: A Scientific Vision," a strategic plan that detailed seven high-priority research areas. This plan was updated and enhanced in 2019 by: "The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures" and "The BRAIN Initiative and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society." This and other BRAIN Initiative Notices of Funding Opportunity (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.

The NIH BRAIN Initiative recognizes that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform hom*ogeneous teams. There are many benefits that flow from a diverse scientific workforce, including fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.

To support the best science, the NIH BRAIN Initiative encourages inclusivity in research. Examples of structures that promote diverse perspectives include but are not limited to:

  • Transdisciplinary research projects and collaborations among neuroscientists and researchers from fields such as computational biology, physics, engineering, mathematics, computer and data sciences, as well as bioethics.
  • Engagement from different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
  • Individual applications and partnerships that enhance geographic and regional heterogeneity.
  • Investigators and teams composed of researchers at different career stages.
  • Participation of individuals from diverse backgrounds, including groups traditionally underrepresented in the biomedical, behavioral, and clinical research workforce (see NOT-OD-20-031), such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
  • Project-based opportunities to enhance the research environment to benefit early- and mid-career investigators.

The NIH also encourages businesses to participate in the BRAIN Initiative. It is possible for companies to submit applications directly to BRAIN Initiative program announcements or to collaborate with academic researchers in joint submissions. Small businesses should consider applying to one of the BRAIN Initiative small business NOFOs.

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

Brain Behavioral Quantification and Synchronization (BBQS) Funding Opportunities

The two BRAIN Initiative 2.0 reports ("The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures" and "The BRAIN Initiative and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society") highlight that a critical step forward is to study “the brain in action,” including efforts to develop “tools to analyze naturalistic (untrained) and trained behaviors” and “to assimilate and link brain recordings with behavior” (p. 34 of "The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures"). Matching the scientific rigor and precision of measurements of brain activity with equally precise, temporally dense measurements of the functional output of the brain, as expressed in a broad range of behaviors, will accelerate the discovery of brain-behavior relationships in both health and disease. Achieving a comprehensive understanding across these levels of analysis demands the same level of rigor, precision of measurement, and temporal resolution across all levels.

At present, tools for measuring behavior in humans and other species lack the necessary precision and resolution to fully capture behavioral dynamics synchronously with data from the environment with which the organism is interacting and which shapes the behavior under study.To address this gap, the BRAIN Initiative BBQS funding opportunities support 1) development of tools for simultaneous, multimodal measurement of behavior within complex, dynamic physical and/or social environments and align these data with simultaneously-recorded neural activity; and 2) development of novel conceptual and computational models that capture dynamic behavior-environment relationships across multiple timescales and that can integrate correlated neural activity into the model. Potential applicants and others interested are encouraged to visit the BRAIN Initiative website for information and guidance.

Research Objectives

Achieving higher-resolution quantification of complex behavior in more naturalistic environments in humans is especially crucial for understanding higher-order cognitive functions, whose associated brain activity may be readily available to train and control closed-loop neuromodulatory devices designed to treat complex behavioral disorders and interrupt maladaptive behaviors before they occur (such as self-harm, substance misuse, etc.). Long-term objectives of this research are 1) to advance understanding of how the brain gives rise to complex behaviors; 2) to answer questions related to brain-behavior associations; and 3) to enable the development of interventions (e.g., closed-loop methodologies) for complex neurobehavioral, neurodegenerative, neurodevelopmental or communication disorders.

This RFA focuses on the development of cutting-edge tools that can transition from lab-based settings to naturalistic or home-based environments. Tools may be developed to explore a broad spectrum of naturally occurring behavior, across multiple environments, in both health and disease states. Such tools should seek to innovate technological approaches (e.g., photonics, light detection and ranging [LiDAR]) to measure and integrate multiple behavioral dimensions (e.g., body kinetics, vocalizations) and capture responses to different acute and/or longer-lasting environmental challenges. Novel behavioral measurement tools and analytical approaches should be compatible for use in individuals across the lifespan, in NIH-designated U.S. health disparity populations, in diverse sociocultural settings, and in a range of disease states.

Research that is appropriate for this RFA includes (but is not limited to):

  • Development of hardware and/or software tools that advance novel methods to capture and quantify multiple dimensions of behavior in real time
  • Development of hardware and/or software tools to advance environmental sensing (e.g., Internet of Things [IoT]) and/or to improve integration of contextual measures with measures of behavior
  • Novel application and/or utilization of existing smart hardware technologies (e.g., phones, wearable technology) to capture dynamic behavior and/or to integrate behavioral and physiological measures at the same time scale
  • Development of less obtrusive, ambulatory devices that are wireless (e.g., no backpack), that have longer term and high storage capacity (e.g., memory or power consumption that allows for sampling across days as opposed to intermittently) to achieve a higher temporal resolution and/or usage across temporal scales (e.g., from milliseconds to days)
  • Development and validation of reliable tools that can passively obtain objective measures that accurately reflect or predict subjective or internal mental states
  • Development of novel approaches that integrate passive measures of behavior with subjective reports of individuals’ internal states (e.g., subjective mood or cognitive state using ecological momentary assessments [EMAs])
  • Development of novel approaches to integrate multiple data modalities and/or data streams (e.g., integration of peripheral biophysiological measures with complex behaviors)
  • Development of novel analytic tools and approaches (e.g., ML/AI methods) focused on behavioral quantification and/or novel conceptual or computational frameworks that incorporate integration/synchronization of multi-modal data streams

Combining existing tools in a novel way (e.g., multimodal integration) to improve behavioral classification with advanced precision or temporal resolution is encouraged. The use of concomitant invasive and non-invasive approaches is encouraged. Modalities selected for measuring brain activity should have high enough spatial and temporal resolution appropriate for investigation of the specific circuit-level mechanisms of interest. Studies that include environmental sensing and those that enable studies across the lifespan, in populations and communities that experience disparities in health outcomes (see NIH-designated U.S. health disparity populations), in both health and disease states, are strongly encouraged. Studies that incorporate multidisciplinary teams that include behavioral scientists, neuroscientists, and computer/data science and engineering are strongly encouraged.

Quality assurance processes for data collection, annotation, open source/open sharing, and dissemination are required. Because the responsible collection, storage, and use of these data can raise potential ethical challenges, demonstration that these considerations have been incorporated into the application is required (see Other Attachments, Section IV). To facilitate the integration of these ethical considerations into the proposed research, the inclusion of an ethicist on the research team is also required.

Required components of R61/33:

This NOFO utilizes a biphasic, milestone-driven R61/R33 mechanism consisting of novel tool (i.e., hardware/software) and/or methodological development in the R61 phase, followed by the integration/synchronization of these novel tools with established methods for recording human brain activity in the R33 phase. The R33 phase may or may not contain an additional clinical trial component described below. Applications using only the R61 mechanism or only the R33 mechanism will be considered incomplete and will not be accepted under this NOFO. Applicants are strongly encouraged to consult with relevant agency staff when developing plans for an application (see Agency Contacts,Section VII). This early contact will provide an opportunity to clarify institute policies and guidelines and discuss whether the proposed project is consistent with program priorities.

The R61 Phase

The R61 phase focuses on supporting novel tool development (i.e., hardware/software) to enable or facilitate capture of quantifiable complex behavioral data, in real time, for subsequent integration with brain data. Proposed new tools should overcome current limitations by providing multi-modal data capture (e.g., movement, vocalization, or facial expressions in conjunction with biophysiological measures such as blood flow or heart rate); advancing less obstructive recording apparatus or increasing ease of monitoring; extending storage and telemetry capabilities to enable longer-term data collection with high temporal resolution in the ambulatory setting; incorporating environmental sensing (e.g., noise, temperature, distractions, odor); and/or developing innovative remote sensing/detector technologies, not currently used in neuroscience, that may provide new means to detect aspects of behavior not accessible with existing neurotechnology.

Milestones and Timeline

Delineation of milestones in the application for the R61 phase is a key requirement of this NOFO. Applications must provide a section entitled "Milestones," at the end of the R61 Research Strategy. This section must include a clear description of the R61 phase milestones that, if met, will justify proceeding to the R33 phase. A milestone is defined as a scheduled event in the project timeline that signifies completion of a major project stage/activity. Criteria for success of proposed tools and methodological approaches should be clearly outlined (prespecified) in the milestones and should be defined in terms of outcomes achieved (rather than tasks to be completed) to demonstrate initial validation of proposed tools and feasibility of their integration with neural recording. The milestones proposed in the application must be objective, quantifiable, rigorously defined, feasible (in terms of the study timeline and approach), and scientifically justified. Satisfactory completion of R61 milestones will be assessed administratively by agency staff to determine eligibility to transition to the R33 phase. After administrative review of the R61, it is possible that a project will not be recommended for transition to the R33 phase. Transition to the R33 phase will depend upon demonstration of milestone completion, feasibility of plans, and availability of funds.

The R33 Phase

The R33 phase focuses on integration of tools developed in the R61 phase with approaches to measure brain activity in humans. Work in this phase should seek to synchronize behavioral and neural data collection and measure both behavioral and neural data with a high degree of temporal resolution. The R33 phase is clinical trial optional and may also incorporate a neuromodulation/neurostimulation component. R33 applications that do not contain a clinical trial component should strive to advance brain-behavioral quantification systems to accelerate discovery of how underlying neural activity gives rise to complex cognition and behaviors. R33 applications that include a clinical trial component should strive to facilitate development of next-generation closed-loop systems by modulating brain activity and consequent behavior through incorporation of a neurostimulation component. Proposed clinical trials should be appropriately mechanistic in order to address questions related to how the brain gives rise to specific behaviors or components of cognition. Proposed clinical trials must be mechanistic or Basic Experimental Studies involving Humans (BESH) studies that meet the NIH definition of a clinical trial. Proposed clinical trials that aim to develop a therapeutic intervention for a specific disorder are outside the scope of this NOFO.

Applications Not Responsive to the NOFO

Studies that are not responsive to this NOFO and will not be reviewed include the following:

  • Incomplete applications using only the R61 mechanism or only the R33 mechanism
  • Applications that do not pre-specify objective criteria for success of proposed novel tools in the R61 milestones
  • Applications that do not include a timeline for proposed work
  • Studies involving technology development (e.g., in the R61 phase) that do not involve human testing (e.g., in the R33 phase)
  • Studies only using non-human animals
  • Studies in R33 phase that do not propose simultaneously recording of brain and behavioral data
  • Applications that do notboth consider the potential ethical challenges of proposed work and include an ethicist
  • R33 clinical trial proposals that aim to develop a therapeutic intervention for a specific indication or disorder, such as a traditional feasibility clinical trial and/or a pivotal clinical trial
  • Applications that do not include a PEDP submitted as Other Project Information as an attachment

The NIMH has published updated policies and guidance for investigators regarding human research protection and clinical research data and safety monitoring (NOT-MH-19-027). The application’s PHS Human Subjects and Clinical Trials Information, including the Data and Safety Monitoring Plan, should reflect the policies and guidance in this notice. Plans for the protection of research participants and data and safety monitoring will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations.

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

Plan for Enhancing Diverse Perspectives (PEDP)

The NIH recognizes that teams comprised of investigators with diverse perspectives working together and capitalizing on innovative ideas and distinct viewpoints outperform hom*ogeneous teams. There are many benefits that flow from a scientific workforce rich with diverse perspectives, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.

To support the best science, the NIH encourages inclusivity in research guided by the consideration of diverse perspectives. Broadly, diverse perspectives can include but are not limited to the educational background and scientific expertise of the people who perform the research; the populations who participate as human subjects in research studies; and the places where research is done.

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation. Assessment of applications containing a PEDP are based on the scientific and technical merit of the proposed project. Consistent with federal law, the race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status) of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

The PEDP will be submitted as Other Project Information as an attachment (see Section IV). Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance materials.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

Funding Instrument

Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

New
Resubmission
Revision

TheOER Glossaryand the How to Apply - Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIMH and partner components intend to commit an estimated total of $10 million to fund 8-10 awards in FY2026.

Award Budget

Application budgets are not limited but need to reflect the actual needs of the proposed project.

Award Project Period

The proposed project period for the R61 must not exceed 4 years.

The proposed project period for the R33 must not exceed 2 years.

The total duration of the R61 and R33 may not exceed 5 years.

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

Eligible Organizations

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)

Local Governments

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

Federal Governments

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

Other

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

Foreign Organizations

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

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

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

Required Registrations

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.
    • 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.
    • 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 theirGrants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

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. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support.See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement 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 (seeNIH 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 theHow to Apply - Application Guideexcept where instructed in this notice of funding opportunity to do otherwise. 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.

Letter of Intent

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:

Email: nimhpeerreview@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

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.

Other Attachments:

Applicants are required to include the following items: 1) Neuroethics considerations and 2) Plan for Enhancing Diverse Perspectives (PEDP). These items must be uploaded as separate attachments in pdf format with filenames that correspond to the individual items. Applications lacking these required items will be deemed incomplete and will not be reviewed.

Neuroethics Considerations

In an "Other Attachment" of up to three pages entitled "Neuroethics Considerations," applications must include detailed description and discussion of the process of informed consenting of research participants who can expect no direct benefit from engaging in the investigative research proposed, considerations of FDA-defined conditions of non-significant risk/significant risk beyond established standards of clinical care, ethical and practical considerations of invasive device maintenance and ultimate removal (if applicable), how research teams will engage the communities contributing to and affected by the proposed research (e.g., inclusion of a community advisory board, incorporation of perspectives from patient-advocates), the specific role and integration of the neuroethicist within the study team, and any other ethical considerations specific to the proposed human neuroscience research (e.g. compensation, informed consent, undue influence, therapeutic misconception and capacity, dual roles of clinician and investigator,consideration of the cultural and social contexts from which study participants are drawn, etc). The consent methodology needs to address how the possibility of coercion or undue influence, and potential therapeutic misconception, will be minimized.

Plan for Enhancing Diverse Perspectives (PEDP)

  • In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of actionable strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity.
  • Applicants should align their proposed strategies for PEDP with the research strategy section, providing a holistic and integrated view of how enhancing diverse perspectives and inclusivity are buoyed throughout the application.
  • The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.
  • The PEDP may be no more than 2 pages in length and should include:
    • Actionable strategies using defined approaches for the inclusion of diverse perspectives in the project;
    • Description of how the PEDP will advance the scientific and technical merit of the proposed project;
    • Anticipated timeline of proposed PEDP activities;
    • Evaluation methods for assessing the progress and success of PEDP activities.

Examples of items that advance inclusivity in research and may be appropriate for a PEDP can include, but are not limited to:

  • Partnerships with different types of institutions and organizations (e.g., research-intensive; undergraduate-focused; HBCUs; emerging research institutions; community-based organizations).
  • Project frameworks that enable communities and researchers to work collaboratively as equal partners in all phases of the research process.
  • Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as human subjects in clinical trials, including those from underrepresented backgrounds.
  • Description of planned partnerships that may enhance geographic and regional diversity.
  • Outreach and recruiting activities intended to diversify the pool of applicants for research training programs, such as outreach to prospective applicants from groups underrepresented in the biomedical sciences, for example, individuals from underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
  • Plans to utilize the project infrastructure (i.e., research and structure) to enhance the research environment and support career-advancing opportunities for junior, early- and mid-career researchers.
  • Transdisciplinary research projects and collaborations among researchers from fields beyond the biological sciences, such as physics, engineering, mathematics, computational biology, computer and data sciences, as well as bioethics.

Examples of items that are not appropriate in a PEDP include, but are not limited to:

  • Selection or hiring of personnel for a research team based on their race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status).
  • A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status).

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see PEDP guidance materials.

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.

PEDP implementation costs:

Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7): https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm.

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 theHow to Apply - Application Guide must be followed, with the following additional instructions:

Research Strategy

Significance

  • Describe how the project will advance technological, methodological, or computational approaches to characterize brain-behavior relationships and/or integrate behavior with environmental sensing or biophysiological measures.
  • Describe how the project will advance understanding of how the brain gives rise to human behavior, cognition, or changes in internal states; and/or advance mechanistic understanding of brain-behavior relationships.

Investigators

  • Describe the combined expertise of the research team as a whole in terms of its ability to support and advance the critical elements of the research.
  • Provide a detailed explanation of how the combined team expertise is multidisciplinary, spanning behavioral science, computer/data science, ethics, and/or engineering.

Innovation

  • Describe how the project will incorporate novel approaches or advance existing approaches to quantifying behavior, cognition, or changes in internal states.
  • Provide description of the novel methods or approaches used to integrate complex behaviors with neural data and/or biophysiological measure or information from the environment.
  • Describe any relevant computational or conceptual frameworks used to integrate/synchronize these multi-modal data streams.

Approach

  • Describe how the methods will utilize neural recording modalities with high temporal and spatial resolution appropriate for investigation of the specific circuit-level mechanisms of interest.

Provide a description of the R61 and R33 phases as follows:

The R61 Phase

  • R61 applications can either utilize existing tools in novel ways or develop completely novel tools for human use. In either case, describe how proposed tools will enable or facilitate capture of quantifiable complex behavioral data, in real time, for subsequent integration with brain data. Describe how proposed new tools should overcome current limitations, by providing multi-modal data capture (e.g., movement, vocalization, or facial expressions in conjunction with biophysiological measures such as blood flow or heart rate); by advancing less obstructive recording apparatus or increasing ease of monitoring; by extending storage and telemetry capabilities to enable longer-term data collection with high temporal resolution in the ambulatory setting; by incorporating environmental sensing (e.g., noise, temperature, distractions, odor); and/or by developing innovative remote sensing/detector technologies, not currently used in neuroscience, that may provide new means to detect aspects of behavior not accessible with existing neurotechnology.

Milestones and timeline

  • Delineation of milestones in the application for the R61 phase is a key requirement of this NOFO, and applications must provide a section entitled “Milestones,” at the end of the R61 Research Strategy. Include a clear description of the R61 phase milestones that, if met, will justify proceeding to the R33 phase. A milestone is defined as a scheduled event in the project timeline that signifies completion of a major project stage/activity. Clearly outline prespecified criteria for success of proposed tools and methodological approaches in the milestones, which should be defined in terms of outcomes to be achieved (rather than tasks to be completed) to demonstrate initial validation of proposed tools and feasibility of their integration with neural recording. Propose milestones that are objective, quantifiable, rigorously defined, feasible (in terms of the study timeline and approach), and scientifically justified.
  • Provide a study timeline that is commensurate with the scope of the proposed work (i.e., applications that leverage extant technology should be shorter projects). Specify work to be performed in the R61 phase, which has a flexible duration of 1-4 years (i.e., work described in the R61 timeline should not exceed 4 years). Specify the duration of work to be performed in the R33 phase, limited to the number of years necessary to demonstrate feasibility of simultaneously recording cognition/behavior and brain activity in humans (up to 2 years may be requested for the R33 phase in the study timeline).

The R33 Phase

  • Describe how the R33 phase integrates tools developed in the R61 phase with approaches to measure brain activity in humans. Work in this phase should seek to synchronize behavioral and neural data collection and measure both behavioral and neural data with a high degree of temporal resolution.
  • The R33 phase is clinical trial optional and may also incorporate a neuromodulation/neurostimulation component. R33 applications that do not contain a clinical trial component should describe how the project advances brain-behavioral quantification systems to accelerate discovery of how underlying neural activity gives rise to complex cognition and behaviors.
  • R33 applications that include a clinical trial component should describe how the project facilitates development of next-generation closed-loop systems by modulating brain activity and consequent behavior through incorporation of a neurostimulation component. Proposed clinical trials should be appropriately mechanistic in order to address questions related to how the brain gives rise to specific behaviors or components of cognition. Descriptions of clinical trials should be consistent withmechanistic or Basic Experimental Studies involving Humans (BESH) studies that meet the NIH definition of a clinical trial, as proposed clinical trials that aim to develop a therapeutic intervention for a specific disorder are outside the scope of this NOFO.

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

Resource Sharing Plans should include the following:

  • A summary of resources to be shared
  • A description of the standard(s) that will be used to describe the resource(s)
  • Archive(s) that will house the resource(s)
  • A proposed timeline for submitting resource(s) to the archive and sharing them with the research and medical communities, if appropriate.
  • An overarching objective of this NOFO is to develop novel tools and approaches to quantify and integrate complex behaviors and neural activity in humans. For any hardware/software tool development that constitutes a unique resource (e.g., code), a plan for quality assurance and annotation, open source/open sharing of developed resources, and dissemination should be described in the Resource Sharing Plan.

Other Plan(s):

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

  • All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

The following modifications also apply:

The BRAIN Initiative requires a high level of coordination and sharing between investigators. It is expected that BRAIN Initiative awardees will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings and in other activities such as the annual PI meeting. The data sharing expectations for BRAIN Initiative awards can be found atNOT-MH-19-010.

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-definedclinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

Foreign Organizations

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

NIMH expects investigators for this funding announcement to collect Common Data Elements (CDEs) for mental health human subjects research. Unless NIMH stipulates otherwise during the negotiation of the terms and conditions of a grant award, this Notice applies to all grant applications involving human research participants. The necessary funds for collecting and submitting these CDE data from all research participants to theNIMH Data Archive (NDA)should be included in the requested budget. A cost estimator (https://nda.nih.gov/ndarpublicweb/Documents/NDA_Data_Submission_Costs.xlsx) is available to facilitate the calculation of these costs. NIMH may seek further information regarding CDEs prior to award. Additional information about CDEs can be found at theNIMH webpage on Data Management and Sharing for Applicants and Awardees.

6. Funding Restrictions

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

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.

  • Applications must include a Neuroethics Considerations attachment as Other Project Information. Applications that fail to include Neuroethics Considerations will be considered incomplete and will be withdrawn.

Mandatory Disclosure

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.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

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).

As part of the overall impact score, reviewers should consider and indicate how the Plan to Enhance Diverse Perspectives affects the scientific merit of the project.

Scored Review Criteria

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 the prior research that serves as the key support for the proposed project rigorous? 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?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Specific to this NOFO:

  • How well will the proposed R61 project advance technological, methodological, or computational approaches to characterize brain-behavior relationships and/or integrate behavior with environmental sensing or biophysiological measures?
  • How well will the proposed R33 project advance understanding of how the brain gives rise to human behavior, cognition, or changes in internal states; and/or advance mechanistic understanding of brain-behavior relationships?


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?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific to this NOFO:

  • To what extent does the proposed research include a multi-disciplinary team of researchers including complimentary expertise in neuroscience, behavioral science, computer/data science and/or engineering?


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?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Specific to this NOFO:

  • How well does the proposed project advance approaches to quantifying behavior, cognition, or changes in internal states?
  • How well does the proposed project incorporate novel approaches to integrate complex behaviors with neural data and/or biophysiological measure or information from the environment?
  • To what extent does the proposed project advance computational or conceptual frameworks to integrate/synchronize neural and behavioral data and/or information from the environment?


Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific to this NOFO:

  • To what extent are the milestones defining criteria for success of the R61 feasible and reasonable?
  • To what extent is the study timeline feasible and commensurate with the scope of the work?
  • In the R33, how viable is the plan to synchronize behavioral, neural, and/or peripheral or environmental measures?
  • How appropriate are the neuroethical considerations of the proposed work?
  • To what extent are the elements of the Resource Sharing Plan appropriate and well-described?


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?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Specific to this NOFO:

  • How well-suited is the environment to developing novel tools and approaches to collecting and integrating simultaneous behavioral and neural measures in humans?

Additional Review Criteria

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.


Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?


For research that involves human subjects but does not involve one of the 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 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 individuals of all ages (including children and older adults) 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 three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals 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.


For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.


Not Applicable


For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations

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.


Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.


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 Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.


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.

2. Review and Selection Process

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

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

Please note that the reviewers will not consider race, ethnicity, age, or gender (including gender identity, sexual orientation or transgender status) of a researcher, award participant, or trainee, even in part, in providing critques, scores, or funding recommendations. NIH will not consider such factors in making funding decisions.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in theNIH 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 theeRA 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 theNIH 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 inSection 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 theNIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, seeAward Process.

The NIMH has published policies and guidance for investigators regarding human research protection, data and safety monitoring, Independent Safety Monitors and Data and Safety Monitoring Boards, reportable events, and participant recruitment monitoring (NOT-MH-19-027). The application’s PHS Human Subjects and Clinical Trials Information should reflect the manner in which these policies will be implemented for each study record. These plans will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations. The NIMH will expect clinical trials to be conducted in accordance with these policies including, but not limited to: timely registration to ClinicalTrials.gov, submission of review determinations from the clinical trial’s data and safety monitoring entity (at least annually), timely submission of reportable events as prescribed, and establishment of recruitment milestones and progress reporting.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all 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.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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.
  • If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by theHHS Office for Civil Rights website.
    • HHS recognizes that NIH 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 NOFO.

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

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. NIH may terminate awards under certain circ*mstances. See2 CFR Part 200.340 Termination andNIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit theResearch 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.

  • Recipients will provide updates at least annually on implementation of the PEDP.

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

Section VII. Agency Contacts

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

Application Submission Contacts

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

Finding Help Online:https://www.era.nih.gov/need-help(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:GrantsInfo@nih.gov(preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support(Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email:support@grants.gov

Scientific/Research Contact(s)

Lizzy Ankudowich, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-480-8187
Email: lizzy.ankudowich@nih.gov

Peer Review Contact(s)

Nicholas Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email:nick.gaiano@nih.gov

Financial/Grants Management Contact(s)

Christine Clarkson
National Institute of Mental Health (NIMH)
Telephone:301-402-5756
Email: christine.clarkson@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.

Authority and Regulations

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.

Brain Behavior Quantification and Synchronization (R61/R33 Clinical Trial Optional) (2024)
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