NOT-NS-22-045 - Notice of Intent to Publish a Funding Opportunity Announcement for BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS): Comprehensive Centers for Human and Non-Human Primate Brain (UM1 Clinical Trial Not Allowed)

NOT-NS-22-047 - Notice of Intent to Publish a Funding Opportunity Announcement for BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS): Specialized Projects for Scalable Technologies (U01 Clinical Trial Not Allowed)

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)

The NIH Institutes and Centers contributing to the Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative intend to issue a Funding Opportunity Announcement (FOA) to support Comprehensive Centers to develop and test technologies that can be scaled to brain-wide atlases of mouse circuit connectivity.

Centers will establish data collection, analysis, and dissemination pipelines to demonstrate the feasibility of mapping cell-to-cell connectivity with a minimum resolution of synaptic connections. They will demonstrate the significance of the approach within the context of a chosen CNS sub-volume, by testing specific hypotheses relating circuit structure to function. They will also incorporate toolsets and infrastructure for integrating separately collected data from smaller volumes, as well as from other data collection modalities, and for enabling the neuroscience community to interact with and mine the data for new research questions.

Awards will be integrated into the BRAIN CONNECTS Network, consisting of projects from this FOA and its companion announcements, as a coordinated effort aimed at developing the research capacity and technical capabilities to generate wiring diagrams that can span entire brains across multiple scales.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.

The FOA is expected to be published in Spring 2022 with an expected application due date in Summer 2022.

This FOA will utilize the UM1 activity code. Details of the planned FOA are provided below.

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 Funding Opportunity Announcements (FOAs) 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 traditionally 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 FOAs.

The BRAIN Initiative requires a high level of coordination and sharing between investigators. It is expected that BRAIN Initiative awardees will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings and in other activities such as the annual PI meeting. The data sharing expectations for BRAIN Initiative awards can be found at NOT-MH-19-010.

Plan for Enhancing Diverse Perspectives (PEDP)

This FOA will require a Plan for Enhancing Diverse Perspectives (PEDP) as part of the application. Applicants are strongly encouraged to read the FOA instructions carefully and view the available PEDP guidance material as described in NOT-MH-21-310. 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.

The BRAIN CONNECTS Network

This FOA is one of three companion FOAs initiating the BRAIN CONNECTS Network, a coordinated effort aimed at developing the research capacity and technical capabilities to generate wiring diagrams that can span entire brains across multiple scales. The overarching objective of the first five years of the program is to develop these capabilities through innovation and iterative engineering of technologies including tissue processing, imaging, data analysis, dissemination, and application to fundamental questions of nervous system function. The CONNECTS Network will demonstrate scalability in human and non-human primate (mapping projections at the level of individual cells and axons) and mouse (mapping connections at the level of synapses), applied to sub-volumes of the brain or spinal cord sufficiently large to prove feasibility of whole-brain mapping. The sub-volumes must be justified in terms of their importance for understanding the relationship between structure and function of specific brain circuits. Funded projects are expected to develop key use-cases and test specific hypotheses of high impact for the neuroscience community.

The FOAs will support multiple approaches for imaging and reconstructing brain connectivity, which are expected to be complementary to one another, with different technologies suited for different types of research questions and use-cases. Throughout the funding period, all CONNECTS Network awardees will work cooperatively to further the common goals, and to identify collaborative opportunities as appropriate. The CONNECTS Network will develop and apply metrics for comparison between approaches, and for assessing feasibility and cost of scaling to entire brains.

Through these initiating FOAs, the program will support:

• A portfolio of complementary approaches for imaging and reconstructing brain connectivity, with metrics for comparing and choosing approaches.
• Teams with diverse perspectives from a variety of disciplines including neuroscience, engineering, computational biology, physics, mathematics, computer and data sciences, and bioethics.
• Engineering and innovation efforts aimed at scale-up to map entire brains with high throughput and precise fidelity.
• Demonstration of lossless imaging and reconstruction across large distances required for whole-brain mapping.
• Proof-of-concept datasets, representing large and unprecedented sub-volumes within the brain or spinal cord, aimed at understanding the wiring principles of specific circuits and their implications for neural function.
• New approaches and toolsets for mining and integrating into the neuroscience knowledge base, including morphological, functional, and molecular data.
• New infrastructure for the research community to discover cell types, circuit motifs, wiring principles and circuit elements, and to develop new computational and conceptual models based on these rich new sources of data.

The Network will be supported by the following three FOAs, with planned receipt dates in July 2022 and 2023. A fourth FOA supporting a Data Coordinating Center will be released after awards from the first FOAs are made.

BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS): Comprehensive Centers for Human and Non-Human Primate Brain (UM1 Clinical Trial Not Allowed)

BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS): Comprehensive Centers for Mouse Brain (UM1 Clinical Trial Not Allowed)

BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS): Specialized Projects for Scalable Technologies (U01 Clinical Trial Not Allowed)

Comprehensive Centers

Comprehensive Centers will use the UM1 activity code, which supports cooperative agreements involving large-scale research activities with interdependent components. For human and non-human primate, resolution must be at the level of individual cells and axonal projections. For mouse, resolution must be at the level of synaptic connections. Required elements will include the following research strategy components, each of which will serve to demonstrate feasibility of scale-up to whole-brain data.

• Overall: including justification for choice of technologies, qualifications of the team, and importance of the volume to be mapped for understanding the relationship between structure and function of specific brain circuits.
• Data Collection: including tissue processing, sample handling and imaging.
• Data Management: including data transfer, storage and security.
• Data Processing and Analysis: including 3D registration, segmentation, annotation, error correction, and statistical processing.
• Data Integration and Dissemination: including toolsets for a) integrating separately collected data of the same modality, b) crossing modalities to integrate with the wider neuroscience knowledge base, and c) collaborative data mining and discovery by the neuroscience community.
• Data Application: applying key use-cases to demonstrate the value of the data for shaping and constraining computational and conceptual models of nervous system function at multiple scales.

Specialized Projects

Specialized Projects will use the U01 activity code for development of current or emerging technologies for scalable mapping of brain connectivity. Efforts are expected to complement the Comprehensive Centers with distinct capabilities and competencies, applied to any aspect of the pipeline, from tissue processing to imaging, alignment, segmentation and annotation, error correction, and integration into the larger neuroscience data environment. Although human, non-human primate and mouse are the focus of the BRAIN CONNECTS Network, Specialized Projects may use other species for validation if well justified. Awards will be integrated into the BRAIN CONNECTS Network for joint analysis and comparative assessment of projects across FOAs.