BRAIN Initiative: Optimization of Instrumentation and Device Technologies for Recording and Modulation in the Nervous System (U01 Clinical Trials Not Allowed)

BRAIN Initiative: Optimization of Instrumentation and Device Technologies for Recording and Modulation in the Nervous System (U01 Clinical Trials Not Allowed) is sponsored by National Institutes of Health (NIH). Supports applications to optimize instrumentation and device technologies for recording and modulation of neural cells and circuits, aiming to advance understanding of dynamic signaling in the central nervous system.

Expired RFA-NS-25-017: BRAIN Initiative: Optimization of Instrumentation and Device Technologies for Recording and Modulation in the Nervous System (U01 Clinical Trials Not Allowed) This notice has expired. For NIH, in limited situations, applications may be accepted on a case-by-case basis for a short period after expiration to accommodate NIH late or continuous submission policies .

Contact the eRA Service Desk for any submission issues. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Neurological Disorders and National Eye Institute ( NEI ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) 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 Mental Health ( NIMH ) National Center for Complementary and Integrative Health ( NCCIH ) National Institute of Biomedical Imaging and Bioengineering ( NIBIB ), October 21, 2024 - Participation added ( NOT-EB-24-016 ) Funding Opportunity Title BRAIN Initiative: Optimization of Instrumentation and Device Technologies for Recording and Modulation in the Nervous System (U01 Clinical Trials Not Allowed) U01 Research Project – Cooperative Agreements February 13, 2026 - Notice of Change to Key Dates for RFA-NS-25-017 and RFA-NS-25-018: BRAIN Initiative Technologies for Recording and Modulation in the Nervous System.

See Notice NOT-NS-26-005 . March 31, 2025 - This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission.

October 21, 2024 - Notice of NIBIB Participation in RFA-NS-25-017: "BRAIN Initiative: Optimization of Instrumentation and Device Technologies for Recording and Modulation in the Nervous System (U01 Clinical Trials Not Allowed)". See Notice NOT-EB-24-016 . 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 Notice NOT-OD-22-198 .

August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Section III.

3. Additional Information on Eligibility . Assistance Listing Number(s) 93.

853, 93. 273, 93. 242, 93.

866, 93. 213, 93. 867, 93.

173, 93. 865, 93. 279, 93.

286 Funding Opportunity Purpose This Notice of Funding Opportunity (NOFO) seeks applications to optimize instrumentation and device technologies for recording and modulation of neural cells and circuits, to address major challenges and to enable transformative understanding of dynamic signaling in the central nervous system.

It is expected that the proposed technologies and approaches have previously demonstrated their transformative potential through initial proof-of-concept testing, and are ready for accelerated refinement through iterative engineering and end-user feedback, appropriate for a path towards sustainable dissemination and user-friendly incorporation into routine neuroscience research.

Applications may propose development of instrumentation hardware and/or devices and associated software. Approaches may utilize any modality such as optical, electrical, magnetic, or acoustic recording/manipulation, to target neuronal electrical signals or other forms of neural activity, including intracellular signaling and engagement of non-neuronal cells in circuit function.

This NOFO is a re-issue of RFA-NS-21-027 , but unlike the previous NOFO the focus is narrowed to technologies associated with recording/manipulation instrumentation and devices, and excludes projects primarily focused on development of molecular reagents.

Potential applicants primarily optimizing molecular constructs should consider RFA-MH-22-245 (or its reissue), BRAIN Initiative: Engineering and optimization of molecular technologies for functional dissection of neural circuits (UM1 Clinical Trial Not Allowed).

For projects at an earlier stage of development of molecular reagents, potential applicants should consider the companion FOA (RFA-NS-25-018 ) or alternative BRAIN Initiative announcements including RFA-MH-21-175 and RFA-EY-21-001 (or their reissus).

For this and the companion NOFO, the aim of the proposed technologies should be to reduce major barriers to conducting neurobiological experiments, including considerations of cost and ease of access, and to enable new discoveries for understanding neural circuit function.

Technologies should address major challenges associated with recording and modulating CNS activity, at cellular or circuit resolution, and should contribute to an overall ecosystem of technologies spanning multiple spatial and temporal scales in any region throughout the CNS.

The approaches should be compatible with experiments in behaving animals, with an expectation that they will be validated with in vivo experiments during the course of the project. Proposed validation experiments must focus on demonstrating the capabilities and potential impact of the technology, rather than advancing the state of biological knowledge as the primary project goal.

Applications are encouraged to integrate multiple approaches, and where appropriate, to leverage a variety of domains of expertise from biological, chemical, and physical sciences, engineering, computational modeling, and statistical analysis.

Open Date (Earliest Submission Date) Dates in bold and italics reflect changes per NOT-NS-26-005 New Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed Scientific Merit Review Advisory Council Review Earliest Start Date June 02, 2025 Not Applicable Not Applicable November 2025 January 2026 April 2026 January 20, 2026 Not Applicable Not Applicable July 2026 October 2026 December 2026 June 15, 2026 Not Applicable Not Applicable November 2026 January 2027 April 2027 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. New Date June 16, 2026 per issuance of NOT-NS-26-005 .

(Original Expiration Date: January 21, 2026 ) Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information 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 Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description 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. The NIH BRAIN Initiative recognizes that teams working together and capitalizing on innovative ideas and distinct technical domains enhance research opportunities and outcomes.

This includes encouraging cross-disciplinary 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.

Prior Consultation with Scientific/Research Staff Consultation with Scientific/Research Contact staff listed in Section VII is strongly recommended, preferably well before the Letter of Intent due date . If requested, NIH staff can advise whether the proposed project meets the NOFO goals and the mission of the BRAIN Initiative, and discuss potential responsiveness questions (see “Applications Not Responsive to this NOFO” below).

Staff will not evaluate the technical and scientific merit of the proposal, which will be determined during peer review using the criteria indicated in Section V. During the consultation phase, potentially more suitable NOFOs will be recommended for proposals that might not fully align with the goals and requirements of the FOA or the mission of the BRAIN Initiative.

NOFO Overview and Requirements This NOFO is related to the recommendations in section III of the BRAIN 2025 Report, with the goal to ‘produce a dynamic picture of the functioning brain by developing and applying improved methods for large-scale monitoring of neural activity'.

Towards this end, the report calls for accelerated development of new and improved technologies for recording and manipulating neural activity at the level of cells and circuits. These new technologies and approaches will provide unprecedented opportunities for exploring how the nervous system encodes, processes, utilizes, stores, and retrieves vast quantities of information.

A better understanding of this dynamic neural activity will enable researchers to seek new ways to diagnose, treat, and prevent brain disorders.

This NOFO is part of a suite of RFAs representing different stages of technology development spanning early proof-of-concept and technology validation through optimization and dissemination, as well as studies aimed at understanding the biological and biophysical mechanisms of neural signals and their modulation (for more information, see https://braininitiative. nih. gov/brain-programs/technology-development ).

This NOFO seeks applications to optimize instrumentation and device technologies for recording and modulation of neural cells and circuits, to address major challenges and to enable transformative understanding of dynamic signaling in the central nervous system.

It is expected that the proposed technologies and approaches have previously demonstrated their transformative potential through initial proof-of-concept testing, and are ready for accelerated refinement through iterative engineering and end-user feedback, appropriate for a path towards sustainable dissemination and user-friendly incorporation into routine neuroscience research.

Applications may propose development of instrumentation hardware and/or devices and associated software. Approaches may utilize any modality such as optical, electrical, magnetic, or acoustic recording/manipulation, to target neuronal electrical signals or other forms of neural activity, including intracellular signaling and engagement of non-neuronal cells in circuit function.

This NOFO is a re-issue of RFA-NS-21-027 , which included support for molecular constructs for recording and manipulating neural activity. However, with this re-issue projects primarily focused on molecular technologies are not supported by this NOFO.

Investigators proposing molecular approaches are encouraged to consider the following alternative NOFOs (or their reissue), which is specifically targeted to molecular technologies that are ready for iterative engineering, optimization, and benchmark testing: RFA-MH-22-245 BRAIN Initiative: Engineering and optimization of molecular technologies for functional dissection of neural circuits (UM1 Clinical Trial Not Allowed) Projects at an earlier stage of development can consider the following more general NOFOs (or their reissue), which do allow projects primarily focused on development of molecular technologies: RFA-MH-21-175 BRAIN Initiative: Development and Validation of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in the Brain (R01 Clinical Trial Not Allowed) RFA-EY-21-001 BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) (Clinical Trial Not Allowed) RFA-NS-25-018 (companion to this FOA) BRAIN Initiative: New Technologies and Novel Approaches for Recording and Modulation in the Nervous System (R01 Clinical Trial Not Allowed) For this and the companion NOFO, the aim of the proposed technologies should be to reduce major barriers to conducting neurobiological experiments, including considerations of cost and ease of access, and to enable new discoveries for understanding neural circuit function.

Technologies should address major challenges associated with recording and modulating CNS activity, at cellular or circuit resolution, and should contribute to an overall ecosystem of technologies spanning multiple spatial and temporal scales in any region throughout the CNS.

Precise cellular or circuit targeting may be attained via experimental design features such as genetic manipulation, in combination with the spatial resolution capabilities of the proposed technology.

Applicants proposing non-invasive neuroimaging technologies (fMRI, PET, etc.) that are not expected to achieve cellular/circuit resolution (see “Applications Not Responsive to this NOFO” below) should consider the following BRAIN Initiative NOFO (or its reissue): RFA-EB-22-001 , BRAIN Initiative: Transformative Brain Non-invasive Imaging Technology Development (UG3/UH3 Clinical Trial Not Allowed).

The approaches should be compatible with experiments in behaving animals, with an expectation that they will be validated with in vivo experiments during the course of the project. Proposed validation experiments must focus on demonstrating the capabilities and potential impact of the technology, rather than advancing the state of biological knowledge as the primary project goal.

Applicants interested in applying new technologies to understand circuit function, rather than developing technologies, should consult the following website for a listing of relevant BRAIN NOFOs: https://braininitiative. nih. gov/brain-programs/understanding-circuits .

Applications are encouraged to integrate multiple approaches, and where appropriate, to leverage a variety of domains of expertise from biological, chemical, and physical sciences, engineering, computational modeling, and statistical analysis. Applications are expected to address any or all the following three general goals for the FOA: 1.

Develop New Network Recording Capabilities Recording dynamic neural activity from complete neural networks, over long periods, in any area of the brain is a challenging but essential goal. Advances in the exploration and development of new technologies for neuronal and non-neuronal cell recording, including methods based on electrodes, microelectronics/microchips, imaging, and nanoscience are encouraged. 2.

Develop Tools for Circuit Manipulation The ability to activate and inhibit specific populations of neurons is key to understanding functional circuits. It will advance the scope of knowledge from observation of neural phenomena to a mechanistic understanding of neural causation.

A new generation of hardware and software for instrumentation and devices for optogenetics, pharmacogenetics, biochemical, electromagnetic and/or acoustic modulation needs to be developed for use in animals, and potentially translated to humans, to enable the immense potential of circuit manipulation. 3.

Link Neural Activity to Behavior The goal of this FOA is to produce technologies with potential to elucidate central nervous system function in the context of complex behaviors. Proposed technologies should be compatible with experiments in behaving animals, with an expectation of in vivo validation during the course of the project.

Novel approaches to link neural activity to specific behaviors, including computational and statistical tools, are encouraged.

Applicants proposing technologies primarily focused on methods to quantify and interpret behavior should consider the following BRAIN Initiative NOFOs (or their reissue): RFA-MH-22-240 BRAIN Initiative: Brain Behavior Quantification and Synchronization (R61/R33 Clinical Trial Optional) RFA-DA-23-030 BRAIN Initiative: Brain-Behavior Quantification and Synchronization – Transformative and Integrative Models of Behavior at the Organismal Level (R34 Clinical Trial Not Allowed) The following types of approaches are encouraged.

Each bullet includes representative, but not exhaustive, examples. Note that unlike the previous issuance of this FOA ( RFA-NS-21-027 ) and unlike the current companion FOA ( RFA-NS-25-018) , the focus of this FOA is on optimization of technologies associated with instrumentation and devices for recording and manipulating neural activity.

Potential applicants primarily focused on development of molecular constructs should consider alternative BRAIN Initiative announcements listed above.

Imaging Instrumentation for Recording and/or Modulation of Neural Activity with Cellular or Circuit Resolution In Vivo Optical imaging instrumentation with major increases in large-scale sampling capabilities, including frame rates sufficient to capture millisecond-scale signaling events, across full volumes of neural tissue rather than single focal planes New imaging modalities for less-invasive or non-invasive cellular-resolution imaging at tissue depths that are currently unavailable, such as structured imaging or adaptive strategies using spatial light modulation and/or wavefront sensing, photoacoustic wavefront shaping, backscattering and deconvolution strategies, or signal relay approaches Methods for simultaneous imaging of cellular resolution neuronal activity from multiple brain regions, or for large-scale sampling/manipulation of cellular activity with simultaneous whole-brain activity measurements Development of Electrodes for Recording and/or Circuit Modulation In Vivo Transformative technologies for simultaneous high-density recording and manipulation of neural activity from multiple brain regions (cortical, sub-cortical, deep-brain) in freely behaving animals Adaptable multi-functional platforms to enable new combinations of capabilities sufficient for large-scale recordings in vivo (e.g., combinations of electrical recordings, optical modulation, chemical sensing, and/or fluid delivery) Innovative new electrode concepts, delivery methods or biocompatible materials to dramatically reduce the invasiveness of acute or chronic electrode recordings Innovative methods to solve the impediments to effective day-to-day stability of single-unit recordings New in vivo electrical capabilities, such as chronic multi-unit intracellular recording, or high-density three-dimensional arrays across multiple spatial planes Strategies for integrating in vivo electrical recordings with other recording technologies, such as optical imaging and stimulation or high-field MRI Techniques and Approaches for Recording/Manipulating CNS Activity during Behaviors New or improved miniaturized devices for head-mounted recording of neuronal and non-neuronal activity at cellular-resolution in freely behaving animals Innovative approaches for head-fixed recording or manipulation of neuronal and non-neuronal activity at cellular resolution, for ethologically robust behavioral analysis Innovative methods to transform neural signals into control signals In combination with concurrent development of large-scale technology for recording/manipulation, computational and statistical tools to analyze and model neural circuit activity underlying behavior and/or to affect systems of behavior Applications Not Responsive to this NOFO The following types of studies are non-responsive to this RFA and will not be reviewed: Projects primarily focused on development and optimization of molecular tools for recording or manipulating neural activity.

Projects with this focus should consider the BRAIN Initiative NOFOs indicated above. Research that does not seek to develop novel technologies intended to reduce barriers to conducting neurobiological experiments.

Projects primarily focused on investigating biological mechanisms, understanding of diseases, or evaluation of therapeutic outcomes, rather than development of technologies and demonstrating their capabilities and potential impact. Studies focused on technologies that are primarily appropriate for the peripheral nervous system rather than the CNS.

Technologies that are not compatible with experiments in behaving animals, or that are focused on development of theoretical models without experimental validation. Projects primarily focused on noninvasive neuroimaging (fMRI, PET, etc.) or other technologies not aimed at recording and modulating CNS activity at cellular or circuit resolution, consistent with requirements stated above. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI. 2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO. Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards Issuing IC and partner components intend to commit an estimated total of $10,000,000 per year to fund 15-20 awards. Application budgets are not limited but need to reflect the actual needs of the proposed project.

The maximum project period is 4 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 Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) 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 including the NIH Intramural Program U.S. Territory or Possession 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 Non-domestic (non-U.S.) Entities (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.

Applicant organizations must complete and maintain the following registrations as described in the How to Apply-Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible.

Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2. 3. 9.

2 Electronically Submitted Applications . 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 their Grants.

gov registration; 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.

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. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. 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. 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.

All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply-Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply-Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. The budget should include funds necessary for travel for up to two key personnel to participate in a BRAIN investigator meeting, lasting not more than two days and including up to two overnight stays, for each year of the project.

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. All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: This NOFO is for the optimization of existing or emerging technologies and approaches for recording and modulation of neural cells and circuits.

Accordingly, applications are expected to have already demonstrated basic proof-of-concept for the technology via publications or preliminary data. Proposals must specify how design requirements will be solicited from end users and incorporated into the approach. Clear, quantifiable performance metrics encompassing the end-use experience should be detailed.

It is anticipated that many projects will begin with a limited roll-out to select end users to provide iterative feedback and further refinement in the context of conducting use case experiments. The costs of these experiments may be included in the budget if they contribute to the successful development of the technology. Where appropriate, the experiments should include metric-driven comparisons to current best practices.

Applications should provide a strategy or credible path for transitioning the technology to routine neuroscience practice, and advancing towards reliable, sustainable manufacturing suitable for broad dissemination. Applications must focus on technology development rather than experimental or biological aims.

Projects are expected to engage in iterative development in the context of specific experiments, but these experiments should be formulated to validate the technology and demonstrate its capabilities and potential impact, rather than advancing the state of biological knowledge.

All applications must include sections covering the following: Current State-of-the-Art: Applications must specifically define the current state of technology as a benchmark against which their proposed new technology or improvements will be measured. A clear statement of the specific barriers to scientific experiments addressed by the new technology must be included.

If a tool is truly first-in-class, comparisons may be done against a nearest-neighbor technology. Milestones and Timeline: Applications must propose annual milestones that represent verifiable go/no-go criteria for continued funding. Final milestones will be negotiated with NIH Program Staff at the start of the funded award, and as detailed in Section VI.

2 (Cooperative Agreement Terms and Conditions of Award) annual milestone progress will be evaluated by program staff for determination of continued funding. A timeline must be included that proposes indicators of progress at critical junctures. These should be tailored to the unique scope of each project and should provide sufficient information for concrete evaluation of achievements and crucial steps during the course of the project.

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

The following modifications also apply: Resource sharing plans should include the following: A summary of the resources that will 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 A potential plan for technology transfer and/or patent capabilities of the resource(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. Consistent with authorities under the 21st Century Cures Act, all applications to BRAIN Initiative NOFOs must include a Data Sharing Plan.

The plan should include a summary of the data that will be shared, a description of the standard(s) that will be used to describe the data, the archive(s) that will house the data, and the proposed timelines for submitting data to the archive and for sharing data with the research community. The data sharing expectations for BRAIN Initiative awards have been published as an official NIH Notice and can be found at NOT-MH-19-010 .

A current listing of BRAIN Initiative archives can be found at https://braininitiative. nih. gov/brain-programs/informatics .

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