BRAIN Initiative: Investigative Human Neuroscience (U01 Clinical Trial Not Allowed)

BRAIN Initiative: Investigative Human Neuroscience (U01 Clinical Trial Not Allowed) is sponsored by National Institutes of Health (NIH). The NIH BRAIN Initiative funds innovative neuroscience research, including projects that advance understanding of language processing and its neural underpinnings, particularly those using invasive recording and stimulation procedures in humans.

Expired RFA-NS-19-001: BRAIN Initiative: Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (U01 Clinical Trial Required) This notice has expired. Check the NIH Guide for active opportunities and notices. Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Neurological Disorders and Stroke ( NINDS ) 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 Mental Health ( NIMH ) National Center for Complementary and Integrative Health ( NCCIH ) Office of Behavioral and Social Sciences Research ( OBSSR ) Office of Research on Women's Health ( ORWH ) Funding Opportunity Title BRAIN Initiative: Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (U01 Clinical Trial Required) U01 Research Project Cooperative Agreements May 24, 2022 - This RFA has been reissued as RFA-NS-22-041 July 20, 2021 - Notice of Intent to Publish a Funding Opportunity Announcement for BRAIN Initiative: Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (U01 Clinical Trial Required).

See Notice NOT-NS-21-064 . September 24, 2020 - Notice of Change to Key Dates for RFA-NS-19-001. See Notice NOT-NS-21-009 .

March 10, 2020 - Reminder: FORMS-F Grant Application Forms & Instructions Must be Used for Due Dates On or After May 25, 2020- New Grant Application Instructions Now Available. See Notice NOT-OD-20-077 . Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research.

See Notice Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128 . January 22, 2019 - Notice of Data Sharing Policy for the BRAIN Initiative.

See Notice NOT-MH-19-010 . November 26, 2018 - NIH & AHRQ Announce Upcoming Updates to Application Instructions and Review Criteria for Research Grant Applications. See Notice NOT-OD-18-228 .

Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity See Section III. 3. Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) 93. 853; 93. 867; 93.

866; 93. 273; 93. 286; 93.

865; 93. 173; 93. 279; 93.

242; 93. 213, 93. 313 Funding Opportunity Purpose Invasive surgical procedures provide the unique 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 resources available to implement complex experimental protocols and are rarely aggregated in a manner that addresses research questions with appropriate statistical power.

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

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

Awardees will join a consortium work 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) October 14, 2018; September 18, 2019; May 19, 2020; September 19, 2020, and September 29, 2021 November 14, 2018; October 18, 2019; June 19, 2020; October 19, 2020, and October 29, 2021 by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opport unity announcement are due on these dates.

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.

AIDS Application Due Date(s) Jan/Feb 2019; Jan/Feb 2020; Sept/Oct 2020; Jan/Feb 2021 and February 2021 May, 2019; May 2020; Jan 2021; May 2021 and May 2022 June, 2019; June 2020; Feb 2021; June 2021 and June 1, 2022 New Date October 30, 2021 per issuance of NOT-NS-21-009 .

(Original Expiration Date: October 20, 2020 ) 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 FOA or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced.

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

Part 1. Overview Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is a Presidential initiative aimed at revolutionizing our understanding of the human brain.

By accelerating the development and application of innovative technologies, researchers will be able to produce a new dynamic picture of the brain that, for the first time, will show how individual cells and complex neural circuits interact in both time and space. It is expected that the application of these new tools and technologies will ultimately lead to new ways to treat and prevent brain disorders.

NIH is one of several federal agencies involved in the BRAIN Initiative. Planning for the NIH component of the BRAIN initiative is guided by the long-term scientific plan, "BRAIN 2025: A Scientific Vision," which details seven high-priority research areas and calls for a sustained federal commitment of $4. 5 billion over 12 years.

This report can be found at http://braininitiative. nih. gov/ .

This FOA and other FOAs issued in Fiscal Year 2015 are based on careful consideration by the NIH of the recommendations of the BRAIN 2025 Report, and input from the NIH BRAIN Multi-Council Working Group ( http://braininitiative. nih. gov/MCWG-Roster.

pdf ), which held its first two meetings in 2014 and 2015 (see http://videocast. nih. gov/summary.

asp? file=18555&bhcp=1 and http://videocast. nih.

gov/Summary. asp? File=18880&bhcp=1 ) .

In addition to the National BRAIN initiative, the NIH continues to have a substantial annual investment in neuroscience research. The Institutes and Centers contributing to the NIH BRAIN Initiative ( http://braininitiative. nih.

gov/ ) support those research efforts through investigator-initiated applications as well as through specific FOAs. Potential applicants to this FOA are strongly encouraged to contact Scientific/Program staff if they have any questions about the best FOA for their research.

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

This RFA encourages applications from diverse teams of investigators, including team members that are underrepresented in the biomedical, behavioral, or clinical research workforce (see data at http://www. nsf. gov/statistics/showpub.

cfm? TopID=2&SubID=27 and the most recent report on Women, Minorities, and Persons with Disabilities in Science and Engineering). Such individuals include those from underrepresented racial and ethnic groups, those with disabilities, and those from disadvantaged backgrounds.

To achieve the goals of the program, the BRAIN Initiative will require a high level of coordination and sharing between investigators. By involvement as a cooperative agreement mechanism, 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.

This RFA is related to the Recommendations in Section III. 6 of the Final Report ( http://www. nih.

gov/science/brain/2025/index. htm ) of the BRAIN working group. Specifically, this RFA solicits applications that will address the recommendations on "ADVANCING HUMAN NEUROSCIENCE" (Section III Implementation: Goals, Deliverables, Timelines and Costs, Part 6) of the Final Report.

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 diverse neurological, psychiatric, and behavioral disorders.

Dynamic activity of ensembles of neurons in specially 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, motor control.

Dysfunction of these large systems of neurons due to disease, injury, or developmental anomaly is the basis of neural and mental disorders. Furthermore, 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 greater 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, thinks, perceives, remembers, plans, registers emotions, activates movements, and makes decisions.

Invasive surgical procedures provide the unique ability to record and stimulate neurons within precisely localized brain structures in humans. However, human studies using invasive technology are often constrained by a limited number of patients and resources available to implement complex experimental protocols and are rarely aggregated in a manner that addresses research questions with appropriate statistical power.

Therefore, this RFA seeks applications to assemble diverse, integrated, multi-disciplinary teams that cross boundaries of interdisciplinary collaboration to overcome these fundamental barriers and to investigate high-impact questions in human neuroscience. Projects 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 is encouraged, especially those that would transition to use in naturalistic environments outside of strict laboratory settings.

Projects should engage diverse, multidisciplinary teams consisting of clinicians, scientists, device engineers, data/computational scientists, regulatory specialists, and/or ethics specialists. 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.

Awardees are expected to actively participate in a consortium work 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.

In the interest of iterative models of discovery, support for complementary animal studies are allowed if they validate or inform these empirical studies of human physiology. Applicants are expected to employ approaches guided by specified theoretical constructs, and are encouraged to employ quantitative, mechanistic models where appropriate.

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 awardees to adopt novel technologies to fit their needs (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. Furthermore, use of the cooperative agreement mechanism will allow awardees to negotiate the incorporation of new technologies by working through NIH Program staff in collaboration with technology providers.

The list below includes representative, but not exhaustive, examples of activities that could be considered responsive to this RFA . Applications may: 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. offer a combination of quantitative psychophysics and behavioral assays in combination with brain recording or stimulating that tests mechanistic hypotheses.

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 RFA. Human research studies as mechanistic investigations.

A mechanistic investigation is designed to understand a biological or behavioral process, or the mechanism of action of an intervention. Investigative studies for understanding the neurobiology of cognitive functions specially 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 diverse social behaviors. Changes in circuit functions underlying the brain's ability to store information and to learn new behaviors (plasticity).

New approaches to capture and assess information processing across brain regions during memory consolidation, memory retrieval, spatial/relational processing, attention, or planning. Assessment of distributed representations and information processing underlying 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.

The following are non-responsive for this program: 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 FOAs supporting this activity, and the NIH bioengineering grant program http://www. ninds. nih.

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

gov/sparc/index ). Imaging approaches not coupled with intra-cranial 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. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Cooperative Agreement: A support 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 FOA.

Application Types Allowed The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Required: Only accepting applications that propose clinical trial(s) 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 $8M to fund 5 awards per receipt date.

Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period. The maximum project period is 5 years.

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

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

Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted.

Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission. Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number.

After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application. System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually.

The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants. gov registration.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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 his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement. 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. This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.

A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101 ) Additional Eligibility Information: Applications submitted in response to this solicitation may not duplicate or be substantially similar to other applications concurrently under consideration by other programs or study sections including the inter-agency programs such as Collaborative Research in Computational Neuroscience (CRCNS), EArly-concept Grants for Exploratory Research (EAGER) or Next Generation Networks For Neuroscience (NeuroNex).

Duplicate or substantially similar applications will be returned without review. Section IV. Application and Submission Information 1.

Requesting an Application Package Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 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 funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications .

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. By the date listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed activity Name(s), address(es), and telephone number(s) of the PD(s)/PI(s) Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent to: 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 FOA.

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: Team Management Plan and Clinical Protocol Synopsis. These items must be uploaded as separate attachments in pdf format with filenames that correspond to the individual items (Team Management Plan, and Clinical Protocol Synopsis). Applications lacking these required items will be deemed incomplete and will not be reviewed.

Team Management Plan: The team management plan must not exceed one page; applications that exceed this limit will be withdrawn. NIH strongly encourages applicants to form diverse, 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, to execute the research strategy, and to dedicate resources and personnel to participate in and contribute to consortia activities, which include coordinating data science and analysis within and across BRAIN teams, integrating data into the BRAIN data archives, and identifying consensus standards of practice.

An organizational structure that clearly defines the team structure and relationships among the various components must 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, without repeating information from the Multiple PD/PI Plan if submitted, and the research project, 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.

Clinical Protocol Synopsis: The clinical protocol synopsis must not exceed six pages; applications that exceed this limit will be withdrawn. The clinical protocol synopsis must include the following information: Compliance with HIPAA and informed consent must be explicitly described.

A list of participant eligibility criteria How recruitment and retention plans will accommodate access to the appropriate brain areas of recording, including a discussion of the availability of participants for the proposed study and the ability of enrollment sites to recruit and retain the proposed number of participants, including women and minority participants.

Participant recruitment and retention plans, including a discussion of the availability of participants for the proposed study and the ability of enrollment sites to recruit and retain the proposed number of participants meeting the eligibility criteria, including women and minority participants. Data supporting recruitment and retention estimates must be provided.

A description of all assessments including clinical, laboratory, physiological, behavioral, patient-centered, or other outcomes addressing the primary and secondary research questions.

Discussion of the potential biases in the study and how they will be addressed Statistical Methods: Discussion of sample size and power calculations where hypothesis testing is explicit, study outcome measures, plans for interim and final analyses, methods of bias control, and methods for handling missing data. Examples of the critical elements of a well-designed clinical study are summarized on the NINDS website. http://www.

ninds. nih. gov/funding/transparency_in_reporting_guidance.

pdf . Data Management and Quality Control: Details of efficient data management and methods for monitoring quality, methods for monitoring the quality and consistency of intervention administration, and methods for ensuring participant confidentiality. Applicants are expected to incorporate data elements from the NINDS Common Data Elements (CDE) Project in their data collection forms (see http://www.

commondataelements. ninds. nih.

gov ) Discussion of the challenges expected in implementing the studies and how these might be overcome SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed.

Applications to this RFA should assemble diverse, 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. 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: Research Strategy: Harmonization of 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.

The aims of this application must investigate fundamental questions in human neuroscience. While fundamental basic research often generates insights relevant to disorders of the nervous system, this RFA is not intended to generate research that is explicitly disease-therapeutic.

All applications are required to include the following points, which must be incorporated within the page limits of the Research Strategy: Statement of the neurobiological, neurological or mental health questions to be addressed, including the theoretical and conceptual framework that drives the research design and questions, and discussion of the analytical methods for interpreting the results.

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.

Description of recording/manipulation methods 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 results. If complementary animal studies are proposed, then anticipated, non-human, experimental components must be adequately described and justified.

Where the adoption of newly developing technology pending FDA-approved is anticipated, reasonable description as an alternative methodology (to the extent that details are available), along with potential advantages and pitfalls, is required. Description of a timeline for completion of tractable research goals, strategic goals, and key stages of progress for the project, especially in terms of participant accrual.

Description of resources and personnel dedicated to active participation in a consortium work 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.

Neuroethical considerations: Applications must include this section that describes and discusses in detail the process of