BRAIN Initiative: Non-Invasive Neuromodulation - New Tools and Techniques for Spatiotemporal Precision (R01)

BRAIN Initiative: Non-Invasive Neuromodulation - New Tools and Techniques for Spatiotemporal Precision (R01) is sponsored by National Institutes of Health (NIH). This opportunity supports mission-aligned projects and measurable outcomes.

Expired RFA-MH-17-240: BRAIN Initiative: Non-Invasive Neuromodulation - New Tools and Techniques for Spatiotemporal Precision (R01) This notice has expired. 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 ) of Participating Organizations National Institute of Mental Health ( NIMH ) National Eye Institute ( NEI ) National Institute on Aging ( NIA ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) National Institute of Biomedical Imaging and Bioengineering ( NIBIB ) Eunice Kennedy Shriver National Institute of Child Health and Human National Institute on Deafness and Other Communication Disorders ( NIDCD ) National Institute on Drug Abuse ( NIDA ) National Institute of Neurological Disorders and Stroke ( NINDS ) National Center for Complementary and Integrative Health ( NCCIH ) Funding Opportunity Title BRAIN Initiative: Non-Invasive Neuromodulation - New Tools and Techniques for Spatiotemporal Precision R01 Research Project Grant June 27, 2019 - This RFA has been reissued as RFA-MH-20-310 .

May 10, 2017 - New NIH "FORMS-E" Grant Application Forms and Instructions Coming for Due Dates On or After January 25, 2018. See NOT-OD-17-062 . September 16, 2016 - Notice to Extend RFA-MH-17-240 .

See Notice NOT-MH-16-024 . Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity RFA-MH-17-245 ; R01 Research Project Grant Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) 93.

242, 93. 867, 93. 866, 93.

273, 93. 286, 93. 865, 93.

173, Funding Opportunity Purpose This Funding Opportunity Announcement (FOA) solicits grant applications in two related but distinct areas. The first area is in the development and testing of novel tools and methods of neuromodulation that go beyond the existing variations on magnetic or electrical stimulation, and that represent more than an incremental advance over existing approaches.

The second distinct area that this FOA seeks to encourage is the optimization of existing electrical and magnetic stimulation methods. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) New Dates per issuance of NOT-MH-16-024 November 23, 2016 and October 13, 2017 by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

No late applications will be accepted for this Funding Opportunity Announcement. 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) New Dates March 2017 and March 2018 per issuance of NOT-MH-16-024 New Dates May 2017 and May 2018 per issuance of NOT-MH-16-024 New Dates September 2017 and September 2018 per issuance of NOT-MH-16-024 New Date October 14, 2017 per issuance of NOT-MH-16-024 .

(Original Expiration Date: November 24, 2016 ) It is critical that applicants follow the instructions in the Research Instructions for the SF424 (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced.

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

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

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

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

Agency Contacts Section VIII. Other Information Full Text of Announcement Section I. Funding Opportunity Description The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is aimed at revolutionizing our understanding of the human brain.

By accelerating the development and application of innovative technologies, researchers will be able to produce a new dynamic picture of the brain that, for the first time, will show how individual cells and complex neural circuits interact in both time and space. It is expected that the application of these new tools and technologies will ultimately lead to new ways to treat 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 FOA and other FOAs issued in Fiscal Year 2017 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. Videocasts of the NIH BRAIN Multi-council Working Group are available at http://www. braininitiative.

nih. gov/about/mcwg. htm .

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

NIH encourages BRAIN Initiative applications from investigators that are underrepresented in the biomedical, behavioral, or clinical research workforce (see data at http://www. nsf. gov/statistics/showpub.

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

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

nih. gov/funding/index. htm ).

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. The BRAIN Initiative will require a high level of coordination and sharing between investigators.

While this FOA does not use 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 This FOA is related to the Recommendations in Sections III. 4 and III. 6 of the Final Report ( http://www.

nih. gov/science/brain/2025/index. htm ) of the BRAIN working group.

Specifically, this FOA solicits applications that will address the recommendations on "Demonstrating Causality" and "Advancing Human Neuroscience" in Section III.

Non-invasive neuromodulation devices are rapidly becoming one of the tools considered for the treatment and diagnosis of brain disorders and could become an alternative or an adjunct to neurological, neuropsychopharmacological, rehabilitative, or cognitive behavioral therapies. Non-invasive devices can be defined as those that do not require surgery and do not penetrate the brain parenchyma.

These devices include, but are not limited to, those used for focused ultrasound stimulation, magnetic seizure therapy, electroconvulsive therapy, static magnets, transcranial alternating current stimulation, transcranial direct current stimulation, and transcranial magnetic stimulation.

Applications involving devices that require surgery or penetrate the brain parenchyma will be deemed nonresponsive and will not be A related FOA ( RFA-MH-17-245 ) in the area of non-invasive technology seeks applications focused on understanding how neural activity is modified in response to an exogenously applied stimulus using existing devices. This FOA solicits grant applications in two related but distinct areas.

The first area is in the development and testing of novel tools and methods of neuromodulation that go beyond the existing variations on magnetic or electrical stimulation. These novel approaches/tools must be clearly beyond incremental advances over existing approaches. The rationale for this objective is that existing magnetic and electrical stimulation methods have limited spatial and temporal precision.

To overcome these obstacles and move beyond incremental advances in the field, collaborations between physicists, engineers, neuroscientists, and clinicians are encouraged.

The fresh perspective of such integrative teams would enable the development and testing of novel approaches that leverage other types of energy in a way that can lead to novel tools for scientific discovery and for therapeutic brain stimulation with high spatial and temporal resolution.

This type of application may be in the initial stages and may therefore still be in the animal testing phase; however, the proposed tools and methods must be adaptable for use in humans.. In recognition of the fact that these methods might be in early stages of development, work with human volunteers can, but does not need to, be included.

The second, distinct, area that this FOA seeks to encourage is the significant improvement of existing electrical and magnetic stimulation methods. The related FOA ( RFA-MH-17-245 ) in the area of non-invasive technology seeks applications focused on understanding how neural activity is modified in response to an exogenously applied stimulus using existing devices.

This second area of this FOA is aimed at improving existing devices rather than elucidating their mechanism of action.

Applications should propose technology improvements and testing methods in areas such as: (1) substantial improvement of the focality and depth of penetration of the stimulus, (2) prevention of extraneous stimulation (e.g. auditory clicking, scalp sensation, stimulation of non-target brain regions), (3) integration with endogenous rhythmic activity and advancing closed-loop stimulation capabilities, (4) use in natural ambulatory settings such as home or community settings, and (5) improved sham and control conditions.

These five topics are discussed below in greater detail. They are not meant to be an exhaustive list, but provide examples of the types of improvements that are needed in this field. The first type of improvement is related to improving the focality and depth of the stimulation signal.

The issue of focality is compounded for deep brain areas where existing non-invasive devices and protocols do not adequately provide both depth of penetration and target resolution. Advances toward noninvasive devices that allow deep and focal stimulation of the brain are strongly desired. Devices that could specifically stimulate more than one site are welcome.

A second type of improvement involves the elimination of unintended extraneous stimulation. Current noninvasive techniques generally stimulate large regions of the brain. This is due both to the lack of focality of the stimulation signal as well as extraneous mechanical effects associated with device operation that independently stimulate auditory and somatosensory systems, thereby confounding experimental protocols.

These extraneous effects can be a significant confound in trying to deliver A third type of improvement entails enhanced control of the temporal component of the delivered stimulation dose. Such temporal control can apply both to the stimulation signal itself as well as the interaction of the stimulation with dynamic brain processes.

Applications could focus on developing closed-loop devices that are sensitive and responsive to dynamic neural activity recorded from the brain, but this is not a requirement.

Improvements that enable an exploration of the frequency of the stimulation, the duration, number, or shape of pulses that are delivered during the stimulation, or the shape of the pulse of the delivered stimulation would allow the research community to understand how those parameters affect A fourth area would be modifying devices for use in more natural settings.

For example, devices that could be used outside the clinic, that allow long term stimulation, that are informed by endogenous oscillations, or are personalized to individual anatomy and physiology could all be significant improvements to existing technologies. A fifth area entails creating a common standard for sham and control conditions for non-invasive neuromodulation.

As mentioned above, this FOA uses two paths to foster development of new neuromodulation tools and techniques: development of wholly novel brain stimulation methods that do not involve the existing electrical or magnetic stimulation methods, and optimization of existing technologies. The higher risk inherent in the former is balanced overall by the parallel emphasis on improving existing methods in the second area.

The following types of studies are not responsive to this FOA and will not be reviewed: Studies with devices that require surgery or penetrate the brain Projects without a description of how the methods would be scaled Projects that propose to explore the use of non-invasive devices Studies directed toward inducing maladaptive behaviors Applicants may want to make use of some of the ideas that have been made available as part of the NIH BRAIN Initiative Public Private Partnership program ( http://braininitiative.

nih. gov/BRAIN_PPP/ ). VIII.

Other Information for award authorities and regulations. Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on Funds Available and Anticipated Number of Awards Issuing IC and partner components intend to commit an estimated total of $3 million to fund approximately 5 awards. 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 4 years. Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: o Hispanic-serving Institutions o Historically Black Colleges and Universities (HBCUs) o Tribally Controlled Colleges and Universities (TCCUs) o Alaska Native and Native Hawaiian Serving Institutions o Asian American Native American Pacific Islander Serving Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions 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 Eligible Agencies of the Federal Government - including the NIH 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) Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

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

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 must have an active DUNS number and SAM registration in order to complete the 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 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 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 A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission 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 ). Section IV. Application and Submission Information 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 Instructions for the SF424 (R&R) Application Guide , including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise.

Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant 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 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 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 All instructions in the SF424 (R&R) Application Guide SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Current State-of-the-Art Statement: Applicants must describe the significance of their proposed devices/techniques by comparing them to the current state-of-the-art and will propose metrics to measure the success of their new tools or techniques.

Investigators must describe how their new device/technique will be a significant improvement on existing technologies, that is likely to be adopted by the research community. Any proposed work in animals must include a description of how the methods would be scaled up for use in humans.

In recognition of the fact that these methods might be in early stages of development, work with human volunteers can, but does not need to, be included. of Human Subjects: The NIMH has published updated policies and guidance for investigators regarding human research protection and clinical research data and safety monitoring ( NOT-MH-15-025 ). The application \ should reflect the policies and guidance in this notice.

Safety Monitoring Plan: The NIMH has published updated policies and guidance for investigators regarding human research protection and clinical research data and safety monitoring (NOT-MH-15-025). The application should reflect the policies and guidance in this notice.

Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. The NIMH has published a guide notice in reference to data sharing in clinical research (including NOT-MH-15-012 ).

Data sharing plans should reflect the guidance in this notice. The specific infrastructure for such data sharing will be established prior to award. One purpose of this data sharing is to establish standards related to describing noninvasive experiments for the research community.

A second purpose is to prevent duplication of effort in order to move the field Do not use the Appendix to circumvent page limits.

Follow all instructions for the Appendix as described in the SF424 (R&R) Application PHS Inclusion Enrollment Report When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement , and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM) See Part 1. Section III.

1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and 4. Submission Dates and Times Part I. Overview Information contains information about Key Dates and times.

Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies).

Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for grants administration. NIH and Grants. gov systems check the application against many of the application instructions upon submission.

Errors must be corrected and a changed/corrected application must be submitted to Grants. gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applications that miss the due date and time are subjected to the NIH Policy on Late Application are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission. Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide. 5.

Intergovernmental Review This initiative is not subject to intergovernmental All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement . Pre-award costs are allowable only as described in the NIH Grants Requirements and Information Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.

Paper applications will not be accepted. Applicants must complete all required registrations before the application due date. Section III.

Eligibility Information contains information about registration. For assistance with your electronic application or for more information on the electronic submission Electronically . If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must for Applicants Experiencing System Issues .

For assistance with application submission, contact the Application Submission Contacts in Section VII . All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package . Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

See Section III of this FOA for information on registration requirements. The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors. Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations , NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIMH Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application. Applications Involving the NIH Intramural Research Program The requests by NIH intramural scientists will be limited to the incremental costs required for participation.

As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs).

These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits. If selected, appropriate funding will be provided by the NIH Intramural Program.

NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA.

Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application.

The intramural scientist may submit a separate request for intramural funding as described above. Post Submission Materials Applicants are required to follow our Post Submission Application Materials policy. Section V.

Application Review Information Only the review criteria described below will be considered in the review process.

As part of the NIH mission , all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each.

An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field. Does the project address an important problem or a critical barrier to progress in the field?

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

Will the proposed device/technique be a significant improvement on existing technologies? Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators those in the early stages of independent careers, do they have appropriate experience and training?

If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

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

Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Do the specific goals of the application include defining the current state of the science/technology as a benchmark against which the proposed research will be measured?

Do the applicants provide an assessment of how their application will advance the field beyond the current state-of-the-art? Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed?

Are potential