Key Dates
- February 22, 2022 - BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS): Comprehensive Centers for Human and Non-Human Primate Brain (UM1 Clinical Trial Not Allowed). See NOFO RFA-NS-22-047.
- February 22, 2022 - BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS): Comprehensive Centers for Mouse Brain (UM1 Clinical Trial Not Allowed). See NOFO RFA-NS-22-048.
- February 22, 2022 - BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS): Specialized Projects for Scalable Technologies (U01 Clinical Trial Not Allowed). See NOFO RFA-NS-22-049.
National Institute of Neurological Disorders and Stroke (NINDS)
National Eye Institute (NEI)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
National Center for Complementary and Integrative Health (NCCIH)
This Notice of Intent to Publish is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects for the following Notice of Funding Opportunity (NOFO), which is expected to be published in October 2023, with an anticipated application receipt date in December 2023.
The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative intends to issue a Notice of Funding Opportunity (NOFO) to solicit applications for one or more Data Coordinating Centers (DCCs) to support BRAIN CONNECTS, a networked consortium of Comprehensive Centers and Specialized Projects funded under RFA-NS-22-047, RFA-NS-22-048, and RFA-NS-22-049. The goals of BRAIN CONNECTS awards are to develop the research capacity and technical capabilities for comprehensive brain-wide connectivity mapping in mouse, human, and non-human primate (NHP). BRAIN CONNECTS projects will collect and process unprecedented volumes of anatomical data by scaling up cutting-edge acquisition modalities and analysis methods, to demonstrate the feasibility and potential impact of production, analysis, dissemination, and interpretation of connectivity maps from entire brains. The resulting feasibility data from these awards are expected to inform NIH decisions on program continuation in a potential subsequent five-year funding period for production of brain-wide wiring diagrams.
Through the intended NOFO, NIH expects to fund one or more BRAIN CONNECTS DCCs, which will collaborate with the data generating projects to (1) coordinate activities of the BRAIN CONNECTS Network, (2) develop and harmonize common data processing pipelines, (3) integrate and disseminate data analytic tools and capabilities, (4) establish a unified knowledge base for connectivity data of diverse modalities, and (5) organize and implement outreach and engagement to the wider research community and the general public. Awards will be integrated into the BRAIN CONNECTS Network as a coordinated effort aimed at developing the ability to generate whole-brain wiring diagrams across multiple scales and species.
Background
Since 2014, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has aimed to accelerate the development and application of innovative neurotechnologies, enabling researchers to produce a new dynamic picture of the brain that reveals how individual cells and complex neural circuits interact in both time and space. It is expected that these advances will ultimately lead to new ways to treat and prevent brain disorders.
As one of several federal agencies involved in the BRAIN Initiative, NIH's contributions to the BRAIN initiative were initially guided by "BRAIN 2025: A Scientific Vision," a strategic plan that detailed seven high-priority research areas. This plan was updated and enhanced in 2019 by: "The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures" and "The BRAIN Initiative and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society." This and other BRAIN Initiative Notices of Funding Opportunity (NOFOs) are based on this vision and issued with input from Advisory Councils of the 10 NIH Institutes and Centers supporting the BRAIN Initiative, as assisted by the NIH BRAIN Multi-Council Working Group and Neuroethics Working Group.
The NIH BRAIN Initiative recognizes that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogeneous teams. There are many benefits that flow from a diverse scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.
To support the best science, the NIH BRAIN Initiative encourages inclusivity in research. Examples of structures that promote diverse perspectives include but are not limited to:
- Transdisciplinary research projects and collaborations among neuroscientists and researchers from fields such as computational biology, physics, engineering, mathematics, computer and data sciences, as well as bioethics.
- Engagement from different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
- Individual applications and partnerships that enhance geographic and regional heterogeneity.
- Investigators and teams composed of researchers at different career stages.
- Participation of individuals from diverse backgrounds, including groups historically underrepresented in the biomedical, behavioral, and clinical research workforce (see NOT-OD-20-031), such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
- Project-based opportunities to enhance the research environment to benefit early- and mid-career investigators.
The 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 NOFOs.
Plan for Enhancing Diverse Perspectives (PEDP)
This NOFO will require a Plan for Enhancing Diverse Perspectives (PEDP) as part of the application. The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions. Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material as described in NOT-MH-21-310.
BRAIN CONNECTS Awards
The BRAIN CONNECTS DCC(s) will be charged with supporting awards from the following NOFOs:
RFA-NS-22-047 UM1 Comprehensive Centers for Human and Non-Human Primate Brain
RFA-NS-22-048 UM1 Comprehensive Centers for Mouse Brain
RFA-NS-22-049 U01 Specialized Projects for Scalable Technologies
Details and PI contact information can be found by searching NIH RePORTER for awards from each of the three NOFOs.
Comprehensive Center UM1 awards will establish full production pipelines, from sample collection through data integration, analysis, and dissemination, applied to sub-volumes that are sufficiently large to prove feasibility of whole-brain mapping. From these sub-volumes, specific hypotheses will be tested to understand relationships between circuit structure and function and the neural substrates for complex behaviors. Centers will also incorporate toolsets and infrastructure for integrating additional data of the same and different modalities, and for enabling the neuroscience community to interact with and mine the data for new research questions.
Specialized Project U01 awards are expected to complement the Comprehensive Centers with distinct capabilities and competencies, to develop and scale up any aspect(s) of the pipeline, from sample processing, data acquisition and analysis, to integration with the larger neuroscience data environment and dissemination to the research community.
The funded CONNECTS awards include diverse mapping technologies and associated data processing and analytic approaches. For human and NHP, the common goal is to establish high-resolution region-to-region connectivity at the level of axonal projections. For mouse, the goal is local and long-range cell-to-cell connectivity at the level of synaptic connections. A variety of acquisition and analysis methods will be scaled to unparalleled throughput and unprecedented tissue volumes.
The BRAIN CONNECTS Network
BRAIN CONNECTS DCC(s) will be responsible for coordinating consortium efforts of the BRAIN CONNECTS Network. All CONNECTS award recipients contribute to the activities of the Network, which is governed by a Steering Committee consisting of award PIs and an NIH representative. Expectations and requirements for each project are published in the Cooperative Agreement Terms and Conditions of each NOFO and include agreement to accept and implement common policies and guidelines as approved by the Steering Committee. The DCCs will coordinate the following requirements of CONNECTS Network members to:
- Optimize data production and analysis, including dissemination of best practices and collective evaluation of procedures, resources, and emerging technologies.
- Establish common data release and resource sharing policies, develop uniform procedures for data standardization and quality assurance, and agree on consensus metrics for assessing scalability, benchmarking performance, and comparing between approaches.
- Submit data for quality assessment to ensure scientific rigor, and share algorithms and software source code with other Network members for scientific evaluation, while maintaining confidentiality and adhering to NIH intellectual property policies.
- Coordinate and collaborate with other U.S. and international groups that may be generating complementary datasets, and as needed, establish working groups including outside experts to address specific issues of high importance to the broader field.
BRAIN CONNECTS DCC Requirements
The BRAIN CONNECTS DCC(s) will be integrated into the BRAIN CONNECTS Network and will collaborate with CONNECTS data generating projects to accomplish the following five Critical Elements:
1. Coordinate activities of the BRAIN CONNECTS Network.
The DCC(s) will coordinate the efforts of the Network consortium, including the requirements outlined above and any new activities agreed upon by the Network Steering Committee during the course of the project.
2. Develop and harmonize common data processing pipelines.
DCC applications must propose to harmonize and optimize processing, analysis, and dissemination of data from one or more of the following data acquisition and analysis modalities:
- Electron microscopy and automated segmentation and classification of cells and synapses, integrated with transcriptomic cell-type data by positional and morphological correlation.
- Fluorescence microscopy and tracing of axonal projections, densely labeled by antibodies to endogenous markers, or sparsely labeled by injection of fluorescent tracers or virally expressed fluorescent proteins.
- Nucleotide barcode library expression, followed by bulk sequencing of micro-dissected tissue, or by in-situ sequencing of cell bodies and axons combined with transcriptomic cell-type identification of single barcoded cells.
- Axonal projection and fiber orientation data collected from the same brains using multiple imaging modalities, including high-gradient-strength diffusion MRI, polarization-sensitive optical coherence tomography, and high-energy coherent phase-contrast X-ray tomography.
On an ongoing basis, the DCC(s) will convene projects producing and analyzing data of the same modality, to develop consistent data and metadata standards and practices, to agree on quality assurance protocols, and to implement shared archiving and dissemination strategies. This effort will leverage the BRAIN Initiative Data Infrastructure, which is funded under RFA-MH-20-600 and related NOFOs (for more information see https://braininitiative.nih.gov/research/data-science-and-informatics/informatics-program), for data sharing and development of cloud-based analytic tools. The DCC(s) will also be responsible for developing metrics and implementing processes for assessing scalability and comparing between approaches. In addition, the DCC(s) will coordinate the development of new capabilities to facilitate continued innovation for the BRAIN CONNECTS program, to enable processing of datasets approaching exabytes in magnitude, including new approaches to data compression, as well as protocols and consensus policies for sharing reduced derivative data to the neuroscience research community.
3. Integrate and disseminate data analytic tools and capabilities.
For each data modality, DCC(s) are expected to instantiate a unified environment for cooperative or competitive development of visualization and analysis toolsets, and for online algorithms with potential for scale-up to brain-wide capabilities. The resulting software tools and analysis products will be broadly distributed, for democratized access and analysis by the neuroscience research community. Online platforms must be compatible with data submitted to the BRAIN Initiative Archives, and must include architecture for data validation, shared annotation, error correction and ground truth comparisons, as well as query and statistical analysis of embedded features.
4. Establish a unified knowledge base for connectivity data of diverse modalities.
Collectively, the DCC(s) will engage and extend the integration goals of the data generating projects, to bridge modalities and initiate a unified representation of brain connectivity data. Strategies might include development of standards and data models at points of intersection between modalities, such as common coordinates and similarity matching algorithms. The DCC(s) are expected to leverage the efforts and products of the BRAIN Initiative Cell Atlas Network (BICAN), including cell-type taxonomies and common coordinate frameworks, as well as the standards development efforts of the BRAIN Initiative Data Infrastructure archives and associated projects.
5. Organize and implement outreach and engagement to the wider research community and the general public.
The DCC(s) will organize and enhance ongoing and new efforts by the data generating projects to disseminate their products to the research community. In addition, they will extend and unify efforts to engage and train a new and more diverse generation of biomedical researchers, as proposed in each project’s research strategy, and as elaborated in each Plan for Enhancing Diverse Perspectives. They will also develop resources and a vision for disseminating BRAIN CONNECTS aspirations and outcomes to the general public, to enhance scientific literacy and to fully leverage the impact of new understanding of the brain’s wiring principles and the implications for treating brain disorders.
Funding Information
Estimated total of $6M per year
1-3 awards
NA
TBD
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
Indian/Native American Tribal Government (Federally Recognized)
County governments
Independent school districts
Public housing authorities/Indian housing authorities
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Non-domestic (non-U.S.) Entity (Foreign Organization)
Regional Organization
Eligible Agencies of the Federal Government
NIH Intramural Program
Applications are not being solicited at this time.
Inquiries
Please direct all inquiries to:
Kari Johnson, PhD
National Institute of Neurological Disorders and Stroke
BRAIN-CONNECTS-Inquiries@nih.gov
and Human Services (HHS)
