It is critical that applicants follow 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 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

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

The human brain is a highly complex organ, comprised of an intricate system of cells and circuits driven by multifaceted molecular interactions. Alterations in this elaborate biological system can give rise to neurological and psychiatric conditions that collectively account for the largest proportion of years lived with disability worldwide.

New technologies, advances in computing, and the rise of team science have led to parallel revolutions in human genetics and multiple fields of experimental biology, which are generating large, complex datasets. Large team science efforts, such as the Psychiatric Genetics Consortium (PGC) and the Autism Sequencing Consortium (ASC), have made significant progress in delineating the genetic architecture of mental disorders by identifying robust and reliable genetic associations across the allelic spectrum for several DSM disorders. In schizophrenia, early successes in gene discovery have highlighted the contribution of many individual loci of small effect, while in the case of autism spectrum disorders, most of the progress has focused on very rare or de novo coding mutations of large(r) effect.

The circuit-level understanding of behavioral traits has recently started to advance, driven by large-scale initiatives in connectomics and technology development (Human Connectome, http://www.humanconnectomeproject.org/, and BRAIN, https://www.braininitiative.nih.gov/). Innovative computational models have started to link brain network level data to specific phenotypic outcomes for disorders like autism and schizophrenia. Despite the advancements at each level of analysis, understanding the etiology of serious mental illness and its many manifestations, such as psychosis, remains elusive. Additionally, phenotypic heterogeneity and genetic pleiotropy are known phenomena in neuropsychiatric disorders that pose a major hurdle in understanding the underlying pathophysiology. To decode the biological underpinnings of psychopathology, we must tackle the hard problem of linking causal explanations of biological phenomenon across multiple levels of analysis from genetic factors to cells, circuits, networks, and behavioral (including cognitive and/or affective) phenotypes.

Currently, well-founded and informative probabilistic or causal models that cross levels of analysis are rare, as most cross-level analyses are correlative and insufficient with respect to understanding causality. Understanding how factors at each level of analysis work together to ultimately produce changes in behavioral, cognitive, and affective phenotypes will require innovative and paradigm-shifting approaches that can effectively integrate multi-level datasets into experimental paradigms and computational models to establish probabilistic and causal links across multiple levels of analysis.

In the convergent neuroscience (CN) framework, inter/transdisciplinary teams composed of members from the neurosciences and orthogonal fields (e.g., physics, engineering, astrophysics, mathematics, computer science, environmental sciences, etc.) will work together on the hard problems in neuropsychiatry. By breaking down intellectual silos, CN will capitalize on advances in neuropsychiatry (e.g., from BRAIN, Connectome, RDoC, etc.) and recent progress in complementary fields, such as applied mathematics or theoretical and computational sciences (e.g., dynamical systems theory, machine learning, estimation theory, hierarchical Bayesian inference). Exploring causal links across multiple levels of analysis through the CN framework will require innovation in computational methods and the integration of molecular- and genomic-level tools into circuit- and systems-level neuroscience. Novel convergent approaches will accelerate our understanding of neurobiological systems and processes that are relevant in health and disease, and may provide a path to identify novel avenues of inquiry to improve the diagnosis and treatment of neuropsychiatric disorders.

The overall objective of this FOA is to provide a mechanistic understanding of the key drivers of psychopathology, across disorders and throughout neurodevelopment, by establishing causal and/or probabilistic linkages across contiguous levels of analysis. The projects under this FOA will develop novel methods, theories, and approaches through a CN team framework, bringing together highly synergistic inter/transdisciplinary teams from multiple disciplines including neuroscience, data/computational science, physics, engineering, mathematics, and environmental sciences. Additionally, a goal of this program is to advance research in convergent neuroscience by creating a shared community framework of resources which may be used by the broader research community to further research, as such, successful team will have robust plan for sharing data and other resources. In order to move beyond cataloging statistical associations to defining causation, successful teams will utilize, combine, expand upon, or develop conceptual frameworks and theoretical approaches, and build explanatory computational models that connect contiguous levels of analysis. Such frameworks, theories, and computational explanatory models should be validated through experimental approaches to elucidate biological underpinnings of complex behavioral (including cognitive and affective) outcomes in psychopathology.

Applicants are strongly encouraged to link at least three contiguous levels of analysis and base their aims on findings from unbiased genetic or genomic studies (e.g., large-scale genome-wide association studies, rare de novo mutations and structural variations, and tissue-specific or cell-type specific transcriptional and epigenetic profiles).

Levels of analysis include, but are not limited to:

• genomic (e.g., DNA variation, epigenomic, transcriptomic, etc.)
• molecular interactions and pathways (e.g., signaling pathways, neurotransmitter-receptor interactions, protein-protein interactions, etc.)
• single cell and small-scale multi-cellular function (micro-circuitry, etc.)
• cell population interactions across circuits (macro-circuitry, etc.)
• system-wide connections (neural networks, etc.)
• behavioral/cognitive/affective phenotypes relevant to mental health and mental illness

Specific Areas of Research Interest:

Examples of potential research topics include, but are not limited to:

• Biologically-based theoretical frameworks and computational models that would attempt to explain how cell-type specific epigenomic modifications interact with genetic variation, how these interactions lead to molecular perturbations, and how these perturbations then impact function across different circuits and cell types.
• Combinations of computational predictions with synthetic biology, emerging genetic techniques, and innovative engineering solutions to provide rapid and reliable assessments of the functional consequences of variation for psychiatric genetic signals (common and rare de novo mutations in coding and non-coding regions of the genome), by manipulating multiple genes at once in silico, and validating the model predictions using in vivo or in vitro (e.g., pluripotent stem cell-based) systems.
• Biologically realistic theoretical frameworks and computational models to explain how genetic perturbations (e.g., highly penetrant genetic risk factors) can alter synaptic-level activity to impact spatio-temporal oscillatory dynamics in patient populations. Such models should yield predictions whose neurobiological bases might be tested in suitable in vivo and in vitro model systems.
• Computational modeling using multi-modal, multi-dimensional data (e.g., clinical, neurocognitive, electrophysiological data, structural and functional connectivity, environmental) across developmental timeframes to link relevant genetic risk factors to development of circuit-level consequences and systems-level dysfunction, and finally to onset/remission of symptoms or clinical diagnosis (e.g., psychosis, Autism Spectrum Disorder, etc.).
• Exploration of the dynamic and synergistic cooperation of brain systems through examination of in vivo circuit-level function using electrophysiological data (e.g., high density EEG, ECOG, etc.) or imaging data from patient populations with and without known genetic mutations/lesions associated with disease risk, with accompanying theoretical frameworks and/or explanatory computational models that link these data with their putative underlying neurobiology.
• Theoretical and computational models integrating global transcriptional, epigenetic, and proteomic profiles (tissue specific or cell type data from human brain tissue) with other brain measures (electrophysiology, neuroimaging, etc.) to compare and/or integrate gene regulatory networks and functional connectivity measures.
• Development of machine-based learning algorithms incorporating time-dependent transcriptomic, epigenetic, proteomic and cellular phenotyping data to study systems-level modulations using in vivo or in vitro (e.g., pluripotent stem cell-based) preparations with risk variants for neuropsychiatric and neurodevelopmental diseases (e.g., those derived from patient populations carrying risk variants).
• Use of theoretical frameworks and computational approaches, such as artificial intelligence and/or machine learning, to integrate cell-type and or cell-population specific spatio-temporal datasets (e.g., molecular data, physiological data, genomic data, structural and functional connectivity data) and link the trajectory of changes across developmental time periods to understand the development of brain function and dysfunction associated with cognitive, behavioral, and affective domains.
• Cross-species comparisons (e.g., mouse to macaque to human) to develop theoretical frameworks and computational models of causal linkages across levels of analysis, taking into account structural, anatomical and functional homology, and evolutionary conservation.

Due to the transdisciplinary nature of the projects and the focus on collaboration, this FOA requires the applicants to assemble a diverse transdisciplinary team of investigators with expertise from fields such as physical, mathematical, and computational sciences, as well as neuroscience, neuropsychiatry, and other areas of the biological sciences. We require the multi-PD/PI mechanism to assemble the required transdisciplinary team. Successful applications MUST have at least one PD/PI with expertise in orthogonal sciences (e.g., data/computational science, physics, engineering, mathematics, environmental sciences) and one PD/PI with synergistic expertise in neuroscience/neuropsychiatry. Additional PD/PIs, key personnel, and collaborators should provide appropriate breadth and balance of physical sciences and neuroscience research expertise and complementary abilities organized around a scientific framework to address fundamental question(s) in neuropsychiatric research. New collaborations are especially encouraged to foster innovation.

We strongly encourage applications with a single, cohesive project, combining computational methods and experimental approaches that will demonstrably engage and incorporate scientists from the transdisciplinary team in meaningful ways. Critically, applicants should focus on a human trait or function relevant to psychopathology. Applicants should utilize new or existing data from human populations wherever possible (e.g., clinical phenotypes, genotypes, imaging, electrophysiology, etc.), but may also utilize new or existing data from animals, including non-human primates (e.g., macaques). We expect projects to contain a strong computational element to identify the pertinent properties at each level of analysis and to integrate datasets across levels in a manner that permits computational modeling and hypothesis testing across various levels of complexity. Critically, any computational methods should integrate multiple pieces of information at each level. Computational frameworks/theories/models should have a clearly defined purpose and role in the explanatory process across their chosen levels of analysis. Specification should encompass the degree to which the computational frameworks/theories/model will be biologically realistic, and include an explicit explanation of how mental (behavioral-level) or neurobiological (systems-level) processes will be mapped to their corresponding mathematical concepts, if applicable, and any limitations inherent in the model. Multiple computational frameworks/theories/models may be necessary to fully describe different traits or functions.

Conceptual frameworks, theoretical approaches and computational explanatory models developed under this FOA should be validated through experimental approaches to elucidate biological underpinnings of behavioral, cognitive, and affective outcomes in psychopathology. All applications should include explicit follow-up strategies to test and confirm the findings from the computational frameworks/theories/models and deploy novel strategies for iteratively improved frameworks/theories/model building, with a particular focus on causality. Iterative refinements may utilize input from in silico experiments and/or new or existing data from biological experiments, such as from in vitro systems well-suited to model or recapitulate complex cellular heterogeneity and interactions in the human brain (e.g., cell-based platforms derived from induced pluripotent stem cells), as well as from in situ or in vivo systems. Applicants are encouraged to adapt existing tools and measures, such as those from the BRAIN and RDoC initiatives. Development of new tools or measures should be used when necessary. Use of cutting edge technologies is also encouraged. Use of detailed, standardized, and validated phenotypic measurements for humans (e.g., PhenX Toolkit, NIH Toolbox, RDoC) is especially encouraged where available and appropriate.

We strongly encourage applicants to leverage existing data sets and to coordinate and collaborate with other national and international groups that may be generating relevant datasets wherever possible. We also strongly encourage applicants to utilize new or existing data from human populations wherever possible (e.g., clinical phenotypes, genotypes, imaging, electrophysiology, etc.). Applicants may also utilize new or existing data from animals, including non-human primates (e.g., macaques). Any use of animal data should be appropriate in the context of the human trait or function under investigation and applicants should provide justification that these data are able to represent or inform our understanding of the human trait or function in question. When using animal models, applicants are encouraged to ensure that the models are etiologically relevant, with the same genetic modification as human patients for construct validity. When directly addressing behavior, applicants are encouraged to include non-human primate and human data. Any new data collection should be appropriately justified. When considering the genomic level of analysis, we encourage applicants to leverage data from large-scale genomic studies in psychiatry and other related efforts (BRAIN Cell Census, Allen Brain Atlas, CommonMind, GENCODE, Roadmap Epigenomics Mapping Consortium, International Human Epigenome Consortium, Psychiatric Genomic Consortium, GTEx, ENCODE, PsychENCODE Consortium, Autism Sequencing Consortium, Bipolar Sequencing Consortium, etc.). A candidate gene approach is not encouraged unless resulting from unbiased studies and such plans include providing a broad functional context for their candidate(s) in their proposed studies. When considering the circuit-level of analysis, applicants are encouraged to examine the circuits that have been characterized most in terms of our understanding of the behaviors that they sub-serve, taking into account the underlying anatomy and structural and functional connectivity. Connection of at least three contiguous levels of analysis is strongly encouraged; however, applicants may connect only two levels with strong justification for projects that aim to connect multiscale models of genetic risk to complex circuit-level activity. Applicants may also take into account dynamic interactions between the nervous system and external (e.g., environmental) and internal (e.g., other organ systems, including the immune system) factors in the production of human behavioral dysfunction in their computational models. In particular, applicants should address how similar genetic insults can result in disparate phenotypes.

Applications proposing to model genetic- or molecular-level analyses directly correlated to behavioral/cognitive/affective phenotypes, without considering data from intervening levels, are not appropriate and will not be supported.

Applicants are strongly encouraged to carefully examine Section IV.2 for complete details on necessary application elements.

Applicants should develop milestones to ensure progress on the specific aims of the project. Milestones are goals that should include clear and objective criteria for success. Applicants are required to outline biannual milestones to provide clear indicators of a project s continued progress or developing difficulties. Milestones should cover the required elements of this application and may include, but are not limited to:

• computational frameworks/theories/model development progress, including testing and refining the computational models
• validation of the computational predictions through experimental approaches
• in silico experimental refinement
• feasibility tests of biological validation experiments
• datasets generated
• progress on data harmonization and integration
• projected throughput improvements
• computational tools generated
• number and schedule of in-person meetings
• cross-training opportunities

The milestones should be unambiguous, quantifiable, and scientifically justified to allow NIMH staff to assess progress. Final milestones may be negotiated at the time of the award, where appropriate. The milestones will be used to evaluate the application not only in peer review, but also in consideration of the awarded project for funding of non-competing award years.

During the course of the funding period, technologies will improve and the rate of progress and scope of the research may change. It is expected that the PDs/PIs, in consultation with NIMH program staff, will make necessary adjustments to accommodate the changing research environment, to remain focused on appropriate goals, to maintain excellent coordination among team members, and to incorporate new technological advances.

Convergence Neuroscience Network for Psychiatry (CNN-Psych) Steering Committee

All awards supported under this FOA and the companion collaborative U01 FOA (PAR-17-176) will be governed by the Convergence Neuroscience Network for Psychiatry (CNN-Psych) Steering Committee. Through the CNN-PSYCH Steering Committee, members are encouraged to leverage the Convergence Neuroscience framework to address causally or probabilistically linking contiguous levels of analysis in an explanatory model of psychopathology. The CNN-Psych Steering Committee members will 1) share ideas, approaches, technologies, and methods, 2) identify synergies across projects, 3) coordinate across projects for data standardization and validation, 4) facilitate immediate data and resource sharing among the CNN-Psych members, 5) coordinate CNN-Psych activities, such as meetings. U01 applicants applying for future submission dates under this FOA and the companion collaborative U01 FOA (PAR-17-176) will also be governed by the CNN-Psych Steering Committee and are expected to align their research with the overall CNN-Psych research priorities.

Applicants are strongly encouraged to consult the appropriate Scientific/Research Contacts, listed in Section VII, to discuss the structure of the collaborations, and research topics of interest for alignment of their proposed work with the Program objectives and the CNN-Psych research priorities. NIMH encourages and expects both large and small research projects for this FOA.

Protection of Human Subjects: Applications with data collection plans that involve multiple respondent groups (e.g., clients/patients, therapists/providers, supervisors, administrators) should address provisions for human subject protections and consenting procedures for all participant groups accordingly. 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’s Protection of Human Subjects section and data and safety monitoring plans should reflect the policies and guidance in this notice. Plans for the protection of research subjects and data and safety monitoring will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations.

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

NIH grants policies as described in the NIH 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:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign 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 to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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.

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.

Multiple PDs/PIs (MPI) are required.

Due to the transdisciplinary nature of the projects and the focus on collaboration and expertise sharing, this FOA requires the applicants to comprise a diverse transdisciplinary team of investigators with expertise from fields such as physical, mathematical, and computational sciences, as well as neuroscience, neuropsychiatry, and other areas of the biological sciences. Successful MPI applications MUST have at least one PD/PI with expertise in orthogonal sciences (e.g., data/computational science, physics, engineering, mathematics, environmental sciences) and one PD/PI with synergistic expertise in neuroscience/neuropsychiatry.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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).

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.

It is critical that applicants follow the Research (R) Instructions in 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 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:

Geetha Senthil, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-402-0754
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

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.

All instructions in the SF424 (R&R) Application Guide must be followed. Teams localized within close geographical proximity (intra-institutional or inter-institutional) are strongly preferred to allow for frequent in-person interaction. Applications with Key Personnel from distant locations will need to demonstrate that the integrated efforts can be successful without this co- localization.

All instructions in the SF424 (R&R) Application Guide must be followed.

Facilities and Other Resources:

Applications must describe the facilities and resources available. Applicants should especially focus on the unique resources at their institution and any sub-contracts which lend themselves to the completion of a convergent project.

Other Attachments: The following items should be included as other attachments.

1. Project Management Plan

Applications must provide a Project Management Plan submitted as a single pdf attachment, with the title Project Management that includes the following information:

Provide a plan detailing the measures that will be taken to ensure cross-disciplinary communication and integration across the team (i.e. the collaborating laboratories) and addressing the division of labor across the team. The plan must provide a detailed description of how different elements of the project would operate in a synergistic and integrated manner. To be cross-disciplinary, projects proposed by the applicants should be a single integrated effort, incorporating methodologies and tools which span neuroscience/neuropsychiatry and the "orthogonal" fields represented (i.e., combine physical/computational and biological knowledge and tools). Teams must carefully address how their individual laboratory's contributions converge on a project that spans the relevant disciplines.

Applications should describe the following:

• How procedures will be integrated across different laboratories and elements within a project. Plans should address reliability and quality control.
• How the overall managerial and administrative responsibilities will be divided in a team (i.e., which laboratory will coordinate various parts of the project and which will be responsible for overall coordination).
• What procedures will be used to assure sharing of resources across laboratories in the team, as well as reliability and quality control of data and resources, as appropriate and consistent with achieving the goals of the program.
• How close collaboration, coordination, and effective communication will be maintained among laboratories in the team through regular meetings (in person/teleconference). This plan should include frequency and types of contact between participating researchers, and documenting and disseminating group meeting proceedings.
• The plans for project data coordination, including standards and integration, and plans for ensuring comprehensive transparency of data reporting/sharing across sites as appropriate and consistent with achieving the goals of the program.
• The plans for ensuring experimental rigor and control of bias (e.g., with sample size estimation, data handling), as appropriate.
• The plans for completion of the research project should a key member leave the Group, including plans to replace the PD/PI, if needed.
• The plans for providing education and regular cross-training opportunities for early career scientists and trainees, as well as for broadening the training of established investigators.

2. Milestones and Timeline Plan

Applications must provide a Milestones and Timeline Plan submitted as a single pdf attachment, with the title Milestones and Timeline that includes the following information:

Describe a timeline (Gantt chart) for completion of project aims, including unambiguous, quantifiable, and scientifically justified biannual milestones covering the required elements of this application, to provide clear indicators of a project’s continued progress or developing difficulties. Milestones descriptions may include, but are not limited to:

• computational frameworks/theories/model development progress, including testing and refining the computational models
• validation of the computational predictions through experimental approaches
• in silico experimental refinement
• feasibility tests of biological validation experiments
• datasets generated
• progress on data harmonization and integration
• projected throughput improvements
• computational tools generated
• number and schedule of in-person meetings
• cross-training opportunities

3. Data and Samples Plan

Applications must provide a Data and Samples Plan submitted as a single pdf attachment, with the title Data and Samples Plan that includes the following information:

Provide a detailed description of any available data and/or samples that will be leveraged for this project, including amounts, quality, type, location, procedure for acquiring, etc.

All instructions in the SF424 (R&R) Application Guide must be followed.

Additional PD/PIs, key personnel, and collaborators should provide appropriate breadth and balance of physical sciences and neuroscience research expertise and complementary abilities organized around a scientific framework to address fundamental question(s) in neuropsychiatric research.

All instructions in the SF424 (R&R) Application Guide must be followed.

A minimum effort of 3 person months is required for each individual serving as PD/PI or multiple PD/PI(s).

All instructions in the SF424 (R&R) Application Guide must be followed.

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

Provide plans that clearly describe which neuropsychiatric problem your team plans to investigate and how the proposed physical sciences perspective or approach could bring novel insight to neurobiology and neuropsychiatric disorders. Indicate how this project will advance the CN framework and utilize physical sciences, engineering, and/or other relevant knowledge in the most rigorous and reproducible manner possible to develop novel strategies for establishing causal linkage across levels of analysis. Specify how this project will innovatively address current scientific or technical barriers to causally linking levels of analysis.

Describe how the project will link contiguous levels of analysis and provide sufficient scientific justification for the chosen approach (i.e., which levels they are connecting and why they are causally contiguous) in the context of one or more phenotypes or traits related to neuropsychiatric disorders which the project intends to investigate. Describe how the project will connect at least three contiguous levels of analysis. If planning to connect only two levels, provide strong justification that the proposed connection is of particular scientific value and of such depth as to make the addition of a third level unrealistic for the time period of the award (e.g., multiscale models of genetic risk connected to complex circuit-level activity).

If examining the genetic level, indicate plans to employ genomic findings in psychiatry based on large-scale unbiased genome-wide assessments. If a candidate gene approach is indicated, document the unbiased studies which provided the basis for this approach and present plans to plans to provide a broad functional context for the proposed candidate(s). When considering the circuit-level of analysis, describe the extent to which the circuits that will be examined have been characterized in terms of our understanding of the behaviors that they sub-serve, taking into account the underlying anatomy and structural and functional connectivity. Describe any plans to take into account dynamic interactions between the nervous system and external (e.g., environmental) and internal (e.g., other organ systems including immune system) factors in the production of human behavioral dysfunction in their computational models. In particular, describe any plans to address how similar genetic insults can result in disparate phenotypes.

Detail how the project will be a cohesive and integrated across all elements to combine computational methods and experimental approaches and how the project will demonstrably engage and incorporate scientists from the transdisciplinary team in meaningful ways.

Computational Model Development

Applicants should:

• Describe how they will build and/or develop their causal and/or probabilistic frameworks/theories/models to link contiguous levels of analysis (e.g., linking new or existing theoretical, statistical or computational models; using unbiased data-driven approaches, machine learning, artificial intelligence, etc.). Describe how the proposed frameworks/theories/modeling will integrate multiple pieces of information at each of the levels. Describe plans for data analysis and quality control. Clearly define the purpose and role in the explanatory process for the computational frameworks/theories/models across the chosen levels of analysis. Specify the degree to which the computational framework/theory/model will be biologically realistic, an explicit explanation of how mental (behavioral-level) or neurobiological (systems-level) processes will be mapped to their corresponding mathematical concepts, if applicable, and any limitations inherent in the frameworks/theories/model. If necessary to fully describe different chosen traits or functions, describe plans for the development of multiple causal and/or probabilistic frameworks/theories/models
• Describe the choice of data types at each level (genomics [genome, transcriptome, epigenome, proteome, etc.], molecular [pathways, cascades, ion-flux, etc.], biophysical [tensile strength, etc.], physiological, electrophysiological [EEG, ECOG], imaging, stable recording of neuronal spikes, population-level neuronal activity and synaptic activity across spatiotemporal scales, different imaging modalities, etc.) as it relates to generating or validating the proposed model. Describe what novel strategies will be used to integrate and analyze multi-dimensional datasets. Describe how approaches will be developed to work with or reduce the dimensionality of these datasets. Describe how datasets will be integrated in a manner that permits hypothesis testing across various levels of complexity.
• If addressing genetic/genomic level of analysis, describe how the role of known genetic risk factors for neuropsychiatric disorders (e.g., large-scale genome-wide association studies, rare de novo mutations and structural variations, and tissue-specific or cell-type specific transcriptional and epigenetic profiles) will be addressed in generating dysfunction at other levels of analysis. Describe how genomic data and findings from large-scale genomic studies and initiatives, including the BRAIN Cell Census, Allen Brain Atlas, CommonMind, GENCODE, Roadmap Epigenomics Mapping Consortium, International Human Epigenome Consortium, Psychiatric Genomic Consortium, GTEx, ENCODE, PsychENCODE Consortium, Autism Sequencing Consortium, Bipolar Sequencing Consortium, etc., will be leveraged for this purpose.

Experimental Validation

Applicants Should:

Describe how the computational framework/theory/model will be refined and validated through experimental data. Explicitly detail the follow-up strategies that will be used to test and confirm the findings from the proposed computational frameworks/theories/models and indicate how novel strategies will be deployed for iteratively improved model building with a particular focus on causality. Indicate the strategies the will be utilized for iterative refinements of computational frameworks/theories/models. Describe any plans for use of in silico experiments and/or new or existing data from biological experiments that utilize in vitro, in situ or in vivo systems for these refinements. If utilizing in vitro systems, describe how they are well-suited to model or recapitulate complex cellular heterogeneity and interactions in the human brain (e.g., cell-based platforms, such as 3D brain organoids derived from induced pluripotent stem cells)..

• For any proposed biological experiments: Describe how existing tools and measures, such as those from the BRAIN and RDoC initiatives, will be adapted for use in the project. Describe the development of any new tools or measures and document the need for their development to carry out the aims of the project. Describe how cutting edge technologies (e.g., DREADS, optogenetics, advanced microscopy, emerging technologies with spatial and temporal resolution [ECOG array], closed-loop brain stimulation, imaging, etc.) will be used to identify cells/cell populations, structures, and/or processes/functions involved in disease pathogenesis is also encouraged where possible. If prospective phenotypic measurements inhumans are described, indicate to what extent detailed, standardized, and validated measurements were used (e.g., PhenX Toolkit, NIH Toolbox, RDoC) where available and appropriate.
• Describe how available data will be leveraged and/or new data generated to develop, refine, and validate your framework/theory/model. Indicate the extent to which data from human populations (e.g., clinical phenotypes, genotypes, imaging, electrophysiology, etc.) will be utilized. Describe any use of animal data and detail how the use of this data is appropriate in the context of the human trait or function under investigation (i.e. how these data are able to represent or inform our understanding of the human trait or function in question). If using animal models, indicate whether the models are etiologically relevant, with the same genetic modification as human patients for construct validity. If directly addressing behavior, indicate the extent to which non-human primate and human data will be incorporated. Provide justification any new data collection that will be done as part of the project.

Resource 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.
• Plans should include sharing clinical and genotypic data with the NIMH Repository and Genomics Resource (NRGR), genotype-phenotype data with the database of Genotypes and Phenotypes (dbGaP), and/or clinical and associated genotype and phenotype data to the NIMH Data Archives (NDA), as appropriate.
• The NIH Genomic Data Sharing Policy will apply to any large scale human or non-human genomic data generated under this project, as well as the use of these data for subsequent research https://gds.nih.gov/03policy2.html ).
• Applicants should refer to the NIMH guide notice NOT-MH-15-012; NOT-MH-14-015; NOT-MH-09-005 for NIMH specific data and biospecimen sharing expectations.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Form only available in FORMS-D application packages for use with due dates on or before January 24, 2018.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study: All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

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.

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 Grants.gov

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 business day.

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

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

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

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 process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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.

Participation of NIH Intramural Scientists:

An NIH intramural scientist may serve as a co-investigator, collaborator, or consultant. However, an Intramural scientist may not receive salary, equipment, supplies, or other remuneration from awards resulting from this FOA. The Intramural scientist must obtain written approval of his/her NIH Institute Scientific Director for the amount of resources that may be allocated to the project. The approval must also specify that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research. The participation of an intramural scientist is independent of, and unrelated to, the role of the NIMH Project Scientist. The involvement of Intramural scientists needs to be consistent with NIH Policy and all applicable federal laws and regulations: http://www1.od.nih.gov/oir/sourcebook/ethic-conduct/ethical-conduct-toc.htm.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant 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.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

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 review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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?

Do the PD(s)/PI(s) clearly describe which neuropsychiatric problem they plan to investigate and how the proposed physical sciences perspective or approach could bring novel insight to neurobiology and neuropsychiatric disorders? How well does the project address connecting contiguous levels of analysis in the context of a neuropsychiatric disorder? How well do the aims test and advance the convergent neuroscience-based approaches of the project? If the aims of the application are achieved, how will scientific knowledge in neuropsychiatric research be advanced? Does the proposed work have a strong likelihood of revealing causal linkages across contiguous levels of analysis in the context of brain function and dysfunction related to psychiatric disorders? If the project includes a genetic level of analysis, does it signify an important advancement in explaining genetic causality across levels?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

To what extent does the project utilize the combined physical/computational/mathematical sciences, neuropsychiatric, and neuroscience research expertise to address linking contiguous levels of analysis? How will the project benefit from the unique scientific expertise represented by the PD/PI (and/or key personnel)? To what extent is there complementary and synergistic expertise? To what extent is the project management plan appropriate to optimize the management of a multidisciplinary, milestone-driven 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?

How novel is the project's application of multidisciplinary-based approaches and perspectives (neurobiological, physical, mathematical, computational sciences, engineering, etc.) to linking contiguous levels of analysis? To what extent does the application propose novel strategies for establishing causal linkages across contiguous levels of analysis? Does the application represent an innovative solution which overcomes current scientific or technical barriers? To what extent does the application propose novel strategies for integrating and analyzing multi-dimensional datasets, to reduce their dimensionality, and facilitate hypothesis testing across various levels of complexity? Will cutting-edge technologies be used where available?

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 problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

How well does the project integrate approaches from the orthogonal fields (i.e. physical/computational/mathematical sciences and neuropsychiatric research) to address linking contiguous levels of analysis? Does the project propose to understand causality in the context of a specific human trait or function? To what extent was sufficient and appropriate justification provided for the choice of the contiguous levels of analysis proposed to be linked? Were at least three contiguous levels of analysis proposed? If not, was the choice of two levels appropriately and adequately justified? To what extent are the multidisciplinary approaches, including the computational and biological aspects of the proposed project, appropriately integrated? To what extent are the described choices of data type, data set, and computational framework/theory/model, etc. appropriate for connecting the chosen levels of analysis in the context of the neuropsychiatric phenotype under investigation? If the genomic level was included in the proposed project, was adequate reference made to findings from unbiased genome-wide studies and was the use of this information appropriate for connecting the chosen levels of analysis in the context of the neuropsychiatric phenotype under investigation? If a candidate approach was proposed, was this approach adequately justified using findings from unbiased genome-wide studies and to what extent was a broad context proposed for the candidate? To what extent are the methods and approaches proposed appropriate for establishing causal linkages across contiguous levels of analysis? Are key technical barriers and dependencies identified? Are existing data leveraged when possible? If new data collection is proposed, is the justification appropriate and compelling? If use of animal data or model organisms is proposed: is it appropriate in the context of the human trait or function under investigation? To what extent are the experimental approaches or biological data chosen to test and validate the computational model adequate and appropriate? To what extent are the proposed methodologies for developing the computational frameworks/theories/models appropriate? To what extent are the methodologies for integrating multi-dimensional datasets to reduce their dimensionality and facilitate hypothesis testing across various levels of complexity appropriate? Are existing tools and measures utilized and leveraged appropriately? If new tool development is proposed, is it appropriately justified?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

How well does the project environment promote collaborations and transdisciplinary research? To what extent does the environment facilitate the operation of a single cohesive project which integrates the physical sciences with neuroscience/neuropsychiatry?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Project Management Plan

Is the Project Management Plan adequate and appropriate to ensure coordination of the different elements of the project? To what extent would this plan ensure that all elements would operate in a synergistic and integrated manner within and across sites? To what extent does the plan include adequate procedures to assure reliability and quality control, comprehensive transparency of data reporting, and sharing of resources? To what extent does the application include adequate plans for maintenance of close collaboration and effective communication among members within and across application sites? To what extent are the plans for data standards and data integration adequate to the need of the project? To what extent are adequate plans presented for the completion of the project following the loss of a key member of the group? To what extent are there adequate plans for providing education and regular cross-training opportunities for group members?

Milestones and Timelines Plan

To what extent are the proposed milestones and timelines reasonable and appropriate to achieve the aims of the application?

Data and Samples Plan:

Are all proposed uses of existing data and samples adequately described?

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

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

Not Applicable

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

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

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

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Adequacy of plans to integrate expertise from fields outside of neuroscience.
• Adequacy of focus on a human trait or function relevant to psychopathology
• Adequacy of plans to validate the conceptual frameworks, theoretical approaches and computational explanatory models developed through explicit follow-up strategies and experimental approaches.
• Use of the MPI mechanism for at least one of the linked applications to include at least one PD/PI with expertise in orthogonal sciences (e.g., data/computational science, physics, engineering, mathematics, environmental sciences) and one PD/PI with synergistic expertise in neuroscience/neuropsychiatry.

Adequate milestones that include clear and objective criteria for success, cover the required elements of this application, and which are unambiguous, quantifiable, and scientifically justified to allow NIMH staff to assess progress.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH's purpose is to support and stimulate the recipients' activities by involvement in, and otherwise working jointly with, the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

All awards supported under this FOA and the companion collaborative U01 FOA (PAR-17-176) will be governed by the Convergent Neuroscience Network for Psychiatry (CNN-Psych) Steering Committee, composed of the PDs/PIs of each project, NIMH Project Scientist(s), and the NIMH Program Officer to assist in monitoring and developing scientific content and direction of the program.

The PD(s)/PI(s) will have the primary responsibility to:

• Define objectives, approaches, and to plan and conduct the proposed research and assume responsibility and accountability to the applicant organization and to the NIMH for performance and proper conduct of all research supported in this initiative, in accordance with the Terms and Conditions of Award.
• Adhere to the agreed upon milestones.
• Provide leadership in thought, ideas, and actions; working with the organization, structure, and advisors of the CNN-Psych and the Steering Committee for the cooperative agreement.
• Serve on the CNN-Psych Steering Committee. The PD/PI and any MPI are required to serve as members of the Steering Committee. Key personnel from projects may also serve in addition to PD/PIs. The Steering Committee members from each project should collectively represent both the physical sciences and neuropsychiatric research components of the U01.
• Respect the governance of the CNN-Psych Steering Committee and all CNN-Psych policies agreed upon by the Steering Committee and approved by NIH Program Staff.
• Coordinate and attend at least monthly CNN-Psych Steering Committee meetings. The PD/PIs will be responsible for preparing concise proceedings or minutes (two or three pages), which will be delivered to the members of the CNN-Psych within one week of the meeting.
• Accept close interaction with, and participation of, NIH staff in aspects of management of within project activities and on the coordination of CNN-Psych activities; cooperating and assisting in implementing the recommendations of the CNN-Psych Steering Committee to facilitate coordination amongst all the U01 grantees under this FOA and its companion PAR-17-176.
• Communicate and publish major findings in a timely manner. Publication or oral presentation of work done under this agreement will be accompanied by appropriate acknowledgment of NIMH support, including the assigned cooperative agreement award number.
• Ownership of all analytic tools, protocols, and assays developed during the course of the research rests with the respective PD/PI(s) who generated them.
• The Awardee Institution and/or Research Project Leader's Institution will retain primary custody of, and have primary rights to, data as specified under the NIMH approved data and research resource sharing plans (described above). The Government, via the NIMH Project Scientist(s), will have access to data generated under this cooperative agreement and may periodically review the data consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The NIMH Project Scientist (or designated alternate in the event the Project Scientist is not available) will have substantial programmatic/scientific involvement to:

• Coordinate and facilitate the interactions among the research teams supported under this FOA.
• Serve as a resource with respect to other ongoing NIH activities that may be relevant to this effort to effectively leverage existing NIH resources and infrastructures and provide expert advice to the awardees on specific scientific and/or analytic issues.
• Assist in the design, development, and coordination of the different stages of the study within their role a Project Scientist and a participant on the Steering Committee.
• Review analysis plans to ensure that they are within the scope of this effort and consistent with the results of peer review.
• Serve as a voting member(s) of the Steering Committee.
• Participate in Steering Committee meetings and conference calls.
• Serve on Steering Committee sub-committees or CNN-Psych working groups and assist the Steering Committee in developing operating guidelines and consistent policies for dealing with situations that require coordinated action.

In addition, an NIMH Program Officer has usual stewardship responsibility for monitoring the conduct and progress of the project to ensure milestones are accomplished in accordance with the timeline. The Program Officer carries primary responsibility for periodic review and approval of the study protocol in relation to stated recommendations regarding continuance of the project, receives all required reports and determines that satisfactory progress is being made, and attends the Steering Committee meetings as a non-voting participant. The Program Officer negotiates throughput, quality control, validation, and cost goals with the awardees as necessary, suggests reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not being met, and may recommend withholding of support, suspension, or termination of a U01 award for lack of adherence to required policies and/or procedures.

The NIMH reserves the right to phase out or curtail the collaborative project (or an individual award) in the event of (a) failure to complete milestones as mutually agreed upon with program staff (b) substantial shortfall in consortium participation and collaboration with other awardees, (c) substantive changes in the agreed upon methodologies and tools with which NIMH cannot concur, (d) human subject ethical issues that may dictate a premature termination, or (e) results that substantially diminish the scientific value of study continuation.

Areas of Joint Responsibility include:

All awardees under this FOA will be governed by the Steering Committee composed of the PDs/PIs of each grant, NIMH Project Scientist(s), and the NIMH Program Officer to assist in monitoring and developing scientific content and direction of the program. The PD/PI and any MPI are required to serve as members of the Steering Committee. Key personnel from projects may also serve in addition to PD/PIs. The Steering Committee members from each project should collectively represent both the physical sciences and neuropsychiatric research components of the U01. Each project, project being either a single U01 supported under this FOA or a collaborative U01 set supported under PAR-17-176, will have two votes in Steering Committee decisions, one representing neuroscientists and one representing the physical scientists on their team. The Steering Committee will select, by majority vote, a Chair from among the PDs/PIs for a two-year term.

The Steering Committee will:

• Ensure synergistic functioning and coordination across grants supported under this FOA.
• Assist in monitoring and developing scientific content and direction of the projects.
• Identify synergies across projects.
• Identify scientific and policy issues that need to be, or can benefit by, being addressed at the CNN-Psych level and develop recommendations to Program Officials and Project Scientists for addressing such issues.
• Coordinate CNN-Psych publications.
• Establish, as necessary, subcommittees to ensure progress of the individual Projects and the CNN-Psych.
• Share data and resources among the members and with the broader scientific community in a timely manner, as per the data sharing plan and the Steering Committee recommendations, in accordance with the NIH and NIMH data sharing guidelines (NOT-MH-15-012; NOT-MH-14-015; NOT-MH-09-005) and GDS policy.
• Guide and evaluate the progress and direction of the research conducted by the awardees.
• Coordinate and attend monthly meetings of the Steering Committee to review progress and identify emerging opportunities for strategic partnerships, and decide optimal research approaches and protocol designs as warranted.
• Schedule and organize at least one annual in-person meeting at which CNN-Psych investigators will present their scientific progress and participate in group discussions.
• It is expected that decisions made or actions taken by the Steering Committee will be by consensus, or majority vote when needed; each project, project being either a single U01 supported under this FOA or a collaborative U01 set supported under PAR-17-176, will have two votes in Steering Committee decisions, one representing neuroscientists and one representing the physical scientists on their team, with the NIMH Project Scientist (or alternate) having one vote. The NIMH Program Officer will not have a vote. Outside consultants/experts may be asked to participate in Steering Committee meetings and discussions, but not have a vote on committee decisions. Membership on the Steering Committee becomes effective upon issuance of the Notice of Grant Award.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Geetha Senthil, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-402-0754
Email: [email protected]

Kathy Anderson, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-5944
Email: [email protected]

Susan Koester, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3563
Email: [email protected]

Alexei Kondratyev, Ph.D
Center for Scientific Review
Telephone: 301-435-1785
Email: [email protected]

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.