BRAIN Initiative: Exploratory Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (R61 Clinical Trial Not Allowed)

BRAIN Initiative: Exploratory Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (R61 Clinical Trial Not Allowed) is sponsored by National Institutes of Health (NIH). Encourages research using invasive neural recording and stimulating technologies to advance understanding of the human brain.

Expired RFA-DC-24-001: BRAIN Initiative: Exploratory Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (R61 Basic Experimental Studies with Humans Required) 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 on Deafness and Other Communication Disorders ( NIDCD ) National Eye Institute ( NEI ) 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 Drug Abuse ( NIDA ) National Institute of Mental Health ( NIMH ) National Institute of Neurological Disorders and National Center for Complementary and Integrative Health ( NCCIH ) All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers.

The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Behavioral and Social Sciences Research ( OBSSR ) Funding Opportunity Title BRAIN Initiative: Exploratory Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (R61 Basic Experimental Studies with Humans Required) R61 Phase 1 Exploratory/Developmental Grant 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. April 04, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025.

See Notice NOT-OD-24-084 October 10, 2023 - Notice of Change to Funding Opportunity Announcement, RFA-DC-24-001, BRAIN Initiative: Exploratory Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (R61 Basic Experimental Studies with Humans Required).

See Notice NOT-DC-24-004 NOT-OD-22-195 New NIH "FORMS-H" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2023 NOT-OD-22-189 Implementation Details for the NIH Data Management and Sharing Policy NOT-OD-22-198 Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023 NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available NOT-MH-19-010 Notice of Data Sharing Policy for the BRAIN Initiative Notice of Funding Opportunity (NOFO) Number Companion Funding Opportunity Research Project (Cooperative Agreements) See Section III.

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

173, 93. 865, 93. 286, 93.

213, 93. 242, 93. 853, 93.

866, 93. 279, 93. 867 Funding Opportunity Purpose Invasive surgical procedures offer the opportunity for unique intracranial interventions such as the ability to record and stimulate intracranially within precisely localized brain structures in humans.

Human studies using invasive technology are often constrained by a limited number of patients and available resources, and frequently the resulting datasets need to be aggregated across sites to achieve sufficient statistical power.

To overcome these fundamental barriers and to investigate high-impact questions in human neuroscience, this Notice of Funding Opportunity (NOFO) seeks applications to assemble integrated, multi-disciplinary teams that cross boundaries of interdisciplinary collaboration.

The research should be proposed as exploratory research and planning activities to establish feasibility, proof-of-principle and early-stage development that, if successful, would support, enable, and/or lay the groundwork for a potential, subsequent Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain, as described in the companion NOFO ( RFA-NS-22-041 ).

Projects should maximize opportunities to conduct innovative in vivo neuroscience research made available by direct access to the brain from invasive surgical procedures. Projects should employ approaches guided by specified theoretical constructs and by quantitative, mechanistic models where appropriate.

Recipients will join a consortium working group, coordinated by the NIH, to identify consensus standards of practice, including neuroethical considerations, to collect and provide data for ancillary studies, and to aggregate and standardize data for dissemination among the wider scientific community.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) August 22, 2023; August 21, 2024; August 20, 2025 Renewal / Resubmission / Revision (as allowed) 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 May 24, 2025 per NOT-OD-25-113 (Originally September 20, 2025) Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) 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. 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 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 recipients will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings and in other activities such as the annual PI meeting.

The data sharing expectations for BRAIN Initiative awards can be found at NOT-MH-19-010 . The BRAIN Initiative Research Opportunities in Humans Program The BRAIN Initiative seeks to understand the circuits and patterns of neural activity that give rise to mental experience and behavior, which will provide a foundation for understanding and treating various neurological, psychiatric, and behavioral disorders.

Dynamic activity of ensembles of neurons in spatially organized networks gives rise to the internal states we experience as sensations, perceptions, emotions, thoughts, and memories and to observable motor behavior.

The activity of these networks is the substrate of cognitive processes such as attention, intention, reasoning, and decision making; of emotional states of happiness, sadness, and fear; of sensation such as touch, pain, hearing, olfaction, taste, and vision; and to motor behaviors such as balance, and motor control.

Dysfunction of these large systems of neurons due to disease, injury, or developmental anomaly is the basis of neural and mental disorders. Investigative studies of neural circuits in human subjects offer unique opportunities for mechanistic understanding of complex capabilities especially advanced in humans.

While research using non-invasive imaging and stimulation methods is typically considered non-significant risk by Institutional Review Boards and does not require an Investigational Device Exemption (IDE) from the FDA, opportunities for research involving invasive, higher resolution stimulating/recording devices for human neuroscience research often have limited time windows.

These opportunities are mostly restricted to patients undergoing neurosurgical procedures or implantation for less than 30 days with devices such as ECoG/EEG grids and indwelling penetrating arrays. There are few stimulating/recording devices that are FDA market-approved for implantation for greater than 30 days.

These inherent challenges associated with research using invasive devices in the human nervous system therefore require a high degree of planning and interdisciplinary collaboration. Investigations within the human brain offer revolutionary, but challenging, opportunities for experimental investigation of how the human brain senses, perceives, remembers, plans, makes decisions, registers emotions, and activates movements.

Invasive surgical procedures offer the opportunity for unique intracranial interventions, such as the ability to record and stimulate neurons within precisely localized brain structures in humans. Human studies using invasive technology are often constrained by a limited number of patients and available resources, and frequently the resulting datasets need to be aggregated across sites to achieve sufficient statistical power.

To overcome these fundamental barriers and to investigate high-impact questions in human neuroscience, this NOFO seeks applications to assemble integrated, multi-disciplinary teams that cross boundaries of interdisciplinary collaboration.

The research should be proposed as exploratory research and planning activities to establish feasibility, proof-of-principle and early-stage development that, if successful, would support, enable, and/or lay the groundwork for a potential, subsequent Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain, as described in the companion NOFO ( RFA-NS-22-041 ).

Projects should maximize opportunities to conduct innovative in vivo neuroscience research made available by direct access to the brain from invasive surgical procedures. Applicants should propose prospective testing and validation of explicit or model-driven hypotheses.

Studies that offer deployment or development for high temporal resolution of behavioral quantification integrated with invasive recording of brain activity are encouraged. Of particular interest are approaches that would enable a transition to naturalistic environments outside of strict laboratory settings.

Projects should engage multidisciplinary teams consisting of clinicians, scientists, device engineers, data/computational scientists, regulatory specialists, and/or ethics specialists. Mentorship relationships that would facilitate acquisition or expansion of special research expertise for investigators in intracranial studies in humans are allowed.

Teams may be assembled within a single institution, but because of the likelihood of a limited number of patients at any single research center, integration of research teams across sites is strongly encouraged.

Recipients are expected to actively participate in a consortium working group, coordinated by the NIH, to identify consensus standards of practice, including neuroethical considerations, to collect and provide data for ancillary studies, and to aggregate and standardize data for dissemination among the wider scientific community.

We anticipate that implantable devices for most of these applications will rely on existing technology sufficiently advanced for an IRB non-significant risk designation, or an FDA IDE without needing significant additional pre-clinical testing on the device. We also anticipate that newly IDE-approved devices may become available over the course of these awards.

NIH BRAIN is supporting new device development and regulatory approval through other NIH BRAIN initiatives, including the availability of template Memoranda of Agreements (MOUs), Confidential Disclosure Agreements (CDAs) and Collaborative Research Agreements (CRAs) with various private and commercial device providers that may facilitate recipients to adopt novel technologies (see http://braininitiative. nih.

gov/ for up-to-date information and NIH Scientific/Research contacts). Where appropriate, applicants are encouraged to anticipate potential and alternative plans for adopting newly available technologies. The list below includes representative, but not exhaustive, examples of activities that could be considered responsive to this NOFO.

Utilize direct intracranial recording and/or stimulation. The use of clinical interventions such as tract transections. Propose statistically powered hypothesis testing.

Integrate non-invasive technologies to image and/or perturb the nervous system for use in conjunction with the invasive implants in order to cross spatial and temporal scales. Combine multi-modal techniques. Propose a combination of quantitative psychophysics and behavioral assays in combination with brain recording or stimulating that test mechanistic hypotheses.

Behavioral assays with time resolution comparable to neural recording assays are strongly encouraged. Utilize approved, chronic implants, (e.g., DBS implants; FDA-approved indwelling electrodes) to address mechanistic hypotheses about brain function, plasticity, etc. The list below includes representative, but not exhaustive, examples of topics that could be considered responsive to this NOFO.

Human research studies as mechanistic investigations. A mechanistic investigation is designed to understand a biological or behavioral process. Investigative studies for understanding the neurobiology of cognitive functions specifically advanced in humans.

Approaches to understanding network coding of sensory information. Paradigms to assess motor coding during complex behaviors. Approaches to understand neural circuitry associated with social behaviors.

Circuit functions underlying the brain's ability to store information and to learn new behaviors (plasticity). New approaches designed to capture and assess information processing across brain regions during memory consolidation, memory retrieval, learning, spatial/relational processing, attention, or planning.

Assessment of distributed representations and information processing associated with advanced mental processes such as language, decision making, numerical cognition, reasoning, consciousness, and metacognition. Investigation of distributed circuits that contribute to the coordination of motivational states and reward behavior.

Empirical and analytical approaches to understand how behavioral states are emergent properties of the interaction of neurons, circuits, and networks.

Applications Not Responsive to this NOFO Studies that are not responsive to this NOFO and will not be reviewed include the following: Human research studies that include clinical trials designed to answer specific questions about safety, tolerability, efficacy, and/or effectiveness of pharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions (e.g., phase 1, phase II, phase II, or pivotal clinical trials).

Studies designed primarily to develop or improve disease/disorder therapeutics or devices. Studies for which the primary goal is to achieve regulatory approval of neurotechnology (see http://braininitiative. nih.

gov/ for other BRAIN NOFOs supporting this activity, and the NIH bioengineering grant program https://www. nibib. nih.

gov/research-funding/bioengineering-research-partnerships ) or the peripheral nervous system (see NIH SPARC http://commonfund. nih. gov/sparc/index ).

Imaging approaches not coupled with intra-cranial interventions, recording or stimulating. Implementing rehabilitation therapies. Definitive clinical trials of therapeutic devices, such as a traditional feasibility study and/or pivotal trial (see http://www.

fda. gov/downloads/MedicalDevices/DeviceRegulati%20onandGuidance/GuidanceDocuments/UCM279103. pdf2 for the definition of an early feasibility study, feasibility study, and pivotal trial).

Projects focused on augmentation of neural function in healthy individuals. Applications that do not include information on neuroethical considerations. Applications that lack the required one-page team management plan.

Prior Consultation with Scientific/Research Staff See Section VIII. Other Information for award authorities and regulations.

All applications submitted to this Notice of Funding Opportunity must propose basic science experimental studies involving humans, otherwise referred to in NOT-OD-18-212 as prospective basic science studies involving human participants, that fall within the NIH definition of a clinical trial and also meet the definition of basic research.

NIH defines basic research consistent with the definition of basic research in federal code, the systematic study directed toward greater knowledge or understanding of the fundamental aspects of phenomena and of observable facts without specific applications towards processes or products in mind. ( 32 CFR 272. 3 ).

NIH defines a clinical trial as "A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes." ( NOT-OD-15-015 ).

Types of studies that should submit under this NOFO include studies that prospectively assign human participants to conditions (i.e., experimentally manipulate independent variables) and that assess biomedical or behavioral outcomes in humans for the purpose of understanding the fundamental aspects of phenomena without specific application towards processes or products in mind.

For the purposes of this NOFO, specific application towards processes or products refers to the application of biomedical or behavioral products, procedures, or services intended to affect a health-related outcome of the individual or a group of individuals either by better understanding the mechanism of action of an intervention or a measurable improvement in health.

Basic experimental studies in which participants are prospectively assigned to experimental conditions and receive an intervention or experimental manipulation where the effect will be assessed for the purpose of understanding fundamental aspects of phenomena may submit under this NOFO. Section II.

Award Information Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Required: Basic Experimental Studies with Humans: Only accepting applications that propose clinical trial(s) that also meet the definition of basic research. 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 $6M total costs to fund approximately 5 awards per receipt date.

Application budgets may not exceed $700,000 (Direct Costs, exclusive of facilities and administrative costs for consortia) in any single year. The scope of the proposed project should determine the project period. The maximum project period is 3 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 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 Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

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 SF424 (R&R) Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement. 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 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 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 SF424 (R&R) 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. 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: [email protected] All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO. All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed. Applicants are required to include the following items: 1) Neuroethics considerations, and 2) Team management plan. 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.

In an "Other Attachment" of up to 3-pages entitled "Neuroethical considerations", applicants must describe and discuss in detail the process of informed consenting of research subjects 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, and other ethical issues specific to invasive human neuroscience research (e.g., compensation, informed consent, undue influence, therapeutic misconception and capacity, dual roles of clinician and investigator, etc).

The consent methodology should address how the possibility of coercion or undue influence, and therapeutic misconception, will be minimized. Please note that the Federal mandate for cooperative research at 45 CFR 46.

114 requires a single IRB and the National Institutes of Health (NIH) Policy on the Use of a Single Institutional Review Board of Record for Multi-Site Research establishes the expectation that all sites participating in multi-site studies involving non-exempt human subjects research funded by the National Institutes of Health (NIH) will use a single Institutional Review Board (sIRB) to conduct the ethical review required by the Department of Health and Human Services regulations for the Protection of Human Subjects at 45 CFR Part 46 ( NOT-OD-16-094 ).

Long-Term Plan for Patients: Applicants must describe a plan for the care of patients at the end of the study and after the study period, if appropriate.

These plans may vary from project to project, but examples might include 1) explant of indwelling devices once the approved study period is complete, 2) surgical removal of batteries and capping the exposed metals from leads/IS-1 connectors, 3) manufacturer-supported device maintenance for patients responding to therapy, 4) manufacturer support for filing of compassionate use exemptions for device maintenance, etc. An "Other Attachment" of up to 1-page entitled team management plan must be included.

NIH strongly encourages applicants to form multidisciplinary teams that consist of clinicians, scientists, device engineers, mathematicians, statisticians, data scientists, regulatory specialists and/or ethics specialists, as appropriate. This multidisciplinary team should be able to address the details of the plans and experiments, and to execute the research strategy.

An organizational structure that clearly defines the team structure and relationships among the various components should be described in the team management plan and illustrated in an organizational chart. This plan should also describe the governance and organizational structure of the leadership team, including communication plans, processes for making decisions on scientific direction, and procedures for resolving conflicts.

For publications, policies to address the ordering and recognition of authors, and decisions about what material to publish, consistent with the interests of commercial partners (where applicable), should be presented. The team management plan should establish a Scientific Steering Group that consists of representatives from each of the partnering organizations and meets regularly to discuss project status, problems, and directions.

Those individuals identified in the team management plan, who together would have the intellectual and leadership responsibilities, would likely be members of the Scientific Steering Group. Plans for enhancing the abilities and opportunities for investigators to work across disciplinary boundaries should also be included. SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed.

Applications to this NOFO should assemble integrated, multi-disciplinary teams of clinicians, scientists, device engineers, mathematicians, statisticians, data scientists, regulatory specialists and/or ethics specialists, as appropriate, to propose innovative research plans within the context of the unique research opportunities offered by these clinical procedures.

These teams may be assembled within a single university or medical center, or may comprise integrated teams across multiple institutions to aggregate these limited opportunities to address high-impact neuroscience questions. All instructions in the SF424 (R&R) Application Guide must be followed. Research Budget: To be successful, programs of this level of complexity are expected to require significant effort from all PDs/PIs involved.

All PDs/PIs must commit at least 2. 4 person months (i.e., the equivalent of 20% effort on a full-year appointment, 26. 67% on a 9-month appointment, or 40% on a 6-month appointment) throughout the duration of the award.

Certain supporting functions such as equipment, animal research costs, and clinical research costs may be requested if well justified and unique to the institution(s) involved. Within the research budget, equipment, including data sharing and management systems, can be included if well justified.

Equipment that duplicates existing institutional or regional shared facilities that are available to investigators must be identified and the proposed duplication should be well justified. Do not request inflationary increases in the overall budget or any of the budget categories. Changes in budget should reflect changes in activities required by the science.

All instructions in the SF424 (R&R) Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Applications to this NOFO must propose to investigate fundamental questions in human neuroscience.

Harmonization of research subjects recruitment and methods (including collection, curation, and analysis) across multiple sites should be well planned and described as appropriate and consistent with achieving the goals of the program. While fundamental basic research often generates insights relevant to disorders of the nervous system, this NOFO is not intended to generate research that is explicitly disease-related.

All applications are required to include the following points, which must be incorporated within the page limits of the Research Strategy: Description of how the proposed R61 application will enable the research goals of future Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain.

Specifically, the application must describe how the aims and approach of the proposed R61 will establish feasibility, validity or other technically qualifying results that, if successful, would support, enable, and/or lay the groundwork for the future companion U01.

Statement of the neurobiological, neurological or mental health questions to be addressed, including justification of the theoretical and conceptual framework and models that drives the research design and questions, and discussion of the analytical methods for interpreting the results.

Justification of why these studies are best engaged in humans (vs. nonhuman species) and why the specified cohort of human patients is best for the questions posed. Description of how studies in the brain tissues potentially affected by the disease or disorder can adequately address the research questions and mechanisms posed, including comparison to complementary studies in animals if appropriate and feasible.

Justification of recording/manipulation methods and parameters that will be employed or developed to approach the questions as a functional system, and how the invasive intervention and/or the implantation of foreign (device) materials may confound the interpretation of