The Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative is an ambitious multi-agency effort aimed at revolutionizing our understanding of the human brain. Specific goals for NIH contributions to the Initiative were formulated over a year-long planning process that culminated in the release of BRAIN 2025: A Scientific Vision, a seminal planning document produced by a working committee of the Advisory Council to the NIH Director. NIH continues to be guided by this document and by input from the BRAIN Multi-Council Working Group, a committee that includes council members from each of the ten NIH Institutes and Centers (ICs) contributing to the BRAIN Initiative.
The BRAIN 2025 report calls for an escalating budget to reach $500M per year by fiscal year (FY) 2019, for a total 12-year budget of $4.5 billion. This total is reflective of the BRAIN Initiative’s ambitious goals, but it is proposed within the context of overall NIH funding for neuroscience research, which reached $5.7 billion per year in 2015 (see report.nih.gov/categorical_spending.aspx). The BRAIN Initiative ICs support neuroscience research through applications received via NIH “parent” announcements and by specific Funding Opportunity Announcements (FOAs). Investigators interested in research projects falling outside the scope of the BRAIN Initiative are encouraged to contact Institute program staff for advice on avenues for funding.
For the most current list of FOAs, visit here.
Background: BRAIN Initiative Awards in Fiscal Years 2014-2016
NIH’s contribution to the BRAIN Initiative began with 58 awards made in September 2014, totaling ~$46M, followed by an additional 67 awards totaling ~$39M in FY2015, for a total of ~$85M in new and continuing awards. For FY2016, NIH received additional funds that will bring the total for competing and new awards to ~$150M, with new awards made in late September 2016. Details of specific funded awards and past FOAs are available on the BRAIN Initiative website.
Research Areas Supported in Fiscal Year 2016
For FY2016, NIH released a mix of re-issued and new FOAs in all of the research areas outlined above, with the exception of Research Area 1 (Census of Brain Cell Types). Awards from these FOAs will be made in September 2016. The specific new and re-issued announcements in each area are as follows:
- Tools for Cells and Circuits
RFA-MH-16-775 (FOA Re-Issue) Development and Validation of Novel Tools to Analyze Cell-Specific and Circuit-Specific Processes
- Technologies for Neural Recording and Modulation
RFA-NS-16-006 (FOA Re-Issue) New Technologies and Novel Approaches for Large-Scale Recording and Modulation in the Nervous System RFA-NS-16-007 (FOA Re-Issue) Optimization of Transformative Technologies for Large Scale Recording and Modulation in the Nervous System RFA-EY-16-001 (FOA Re-Issue) New Concepts and Early-Stage Research for Large-Scale Recording and Modulation in the Nervous System
- Human Imaging and Neuromodulation
Foundations of Human Imaging
RFA-MH-16-750 (New FOA) Foundations of Non-Invasive Functional Human Brain Imaging and Recording - Bridging Scales and Modalities
Next-Generation Invasive Devices
RFA-NS-16-009 (FOA Re-Issue) Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System
RFA-NS-16-010 (FOA Re-Issue) Clinical Studies to Advance Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System
RFA-NS-16-011 (New FOA) SBIR Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System
RFA-NS-16-018 SBIR Direct to Phase II Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System
RFA-MH-16-810 (New FOA) Non-Invasive Neuromodulation - New Tools and Techniques for Spatiotemporal Precision
RFA-MH-16-815 (New FOA) Non-Invasive Neuromodulation - Mechanisms and Dose/Response Relationships for Targeted CNS Effects
- Understanding Neural Circuits
RFA-EB-15-006 (New FOA) Theories, Models and Methods for Analysis of Complex Data from the Brain
RFA-NS-16-008 (New FOA) Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain
- Technology Dissemination and Training
RFA-MH-16-725 (New FOA) Technology Sharing and Propagation
- Small Business Research (SBIR/STTR)
For FY2016, NIH continues to support BRAIN Initiative Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) FOAs for technology development by small businesses. Each announcement is open for three years, with three receipt dates per year. For more information, see funding opportunities.
Research Areas Supported in Fiscal Years 2014-2015
In FY2014 and 2015, NIH funded BRAIN Initiative awards in the following research areas:
- Census of Brain Cell Types
RFA-MH-14-215 Transformative Approaches for Cell-Type Classification in the Brain (2014: 10 awards totaling $12.9 million)
- Tools for Cells and Circuits
RFA-MH-14-216, RFA-MH-15-225 Development and Validation of Novel Tools to Analyze Cell-Specific and Circuit-Specific Processes (2014: 10 awards totaling $6.4 million, 2015: 15 awards totaling $11.3 million)
- Technologies for Neural Recording and Modulation
RFA-NS-14-007, RFA-NS-15-003 New Technologies and Novel Approaches for Large-Scale Recording and Modulation in the Nervous System (2014: 11 awards totaling $8.0 million, 2015: 6 awards totaling $3.7 million)
RFA-NS-14-008, RFA-NS-15-004 Optimization of Transformative Technologies for Large Scale Recording and Modulation in the Nervous System (2014: 8 awards totaling $4.8 million, 2015: 5 awards totaling $3.5)
RFA-EY-15-001 New Concepts and Early-Stage Research for Large-Scale Recording and Modulation in the Nervous System (2015: 23 awards totaling $5.6 million)
- Human Imaging and Neuromodulation
Next-Generation Human Imaging
RFA-MH-14-217, RFA-MH-15-200 Planning for Next Generation Human Brain Imaging (2014 9 awards totaling $4.3 million, 2015: 5 awards totaling $1.7 million)
Next-Generation Invasive Devices
RFA-NS-15-006 Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (2015: 2 awards totaling $3.0 million) RFA-NS-15-008 Clinical Studies to Advance Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (2015: 1 award totaling $1.4 million)
- Understanding Neural Circuits
RFA-NS-14-009, RFA-NS-15-005 Integrated Approaches to Understanding Circuit Function in the Nervous System (2014: 10 awards totaling $9.7 million, 2015: 7 awards $7.2 million)
- Technology Dissemination and Training
RFA-MH-15-215 Short Courses in Computational Neuroscience (2015: 3 awards totaling $0.4 million)
Fiscal Year 2017
The 2017 fiscal year represented a transition point for the BRAIN Initiative, as the initial FY2014 awards were three years in duration, with the expectation that promising research projects as well as newly proposed applications could enter into a second phase starting in FY2017. To fund the ambitious goals of this transition, NIH initiated the FOAs in the following Research Areas:
1. Census of Brain Cell Types
BRAIN Initiative Cell Census Network (BICCN)
Recent technological advances in high throughput analyses of molecular, anatomic, and physiological measurements at the single cell level promise to open a new era calling for a unified brain cell census. This cell census effort will identify unique cell type markers for understanding and accessing neural circuits, and unveil the regulatory code that controls cell type formation, maintenance, and transition in health and disease. In 2014, the BRAIN Initiative awarded 10 grants to pilot classification strategies and generate data/metadata for this comprehensive brain cell census. From these pilot projects, multiple brain regions from different organisms are being studied using a variety of advanced technologies, and awardees are collaborating on defining standards to describe experiments and data sets.
The following announcements for FY2017 intended to expand NIH support for cell census data and relevant tools by launching a coordinated set of awards under the auspices of a BRAIN Initiative Cell Census Network (BICCN). The overarching goals of the consortium are to (1) create a comprehensive 3D common reference mouse brain cell atlas that integrates molecular, anatomical, and physiological annotations of brain cell types, and (2) generate reference brain cell atlases from postmortem healthy adult human and/or non-human primate brain samples.
- Comprehensive Mouse Brain Cell Atlas:
This FOA supports a Comprehensive Center or Centers to adopt scalable technology platforms and streamlined workflows to generate a 3D brain cell reference atlas encompassing molecular, anatomical, and physiological annotations of brain cell types in mouse, and to incorporate additional genetic and other advanced cell-specific targeting approaches and tools to facilitate this goal.
- Brain Cell Data Center:
This FOA supports a Brain Cell Data Center that will work with the BRAIN Cell Census projects and other interested researchers to establish a web-accessible information system to capture, store, analyze, curate, and display all data and metadata on brain cell types and their connectivity. The Cell Data Center is expected to lead efforts to (1) establish spatial and semantic standards for managing heterogeneous brain cell census data types and information, (2) collect and register multimodal brain cell census data to common brain coordinate systems, (3) create searchable 2D and 3D digital brain atlases for cell census data, and (4) generate a unified and comprehensive brain cell knowledge base that integrates all existing brain cell census data and information across diverse repositories.
- Specialized Brain Cell Phenotyping Centers:
This FOA supports a group of Specialized Centers to provide mouse brain data and/or tools that complement the output of the Comprehensive Center(s), and to initiate efforts to provide data/tools for human and non-human primate brain cell types. The focus of each Specialized Center will be on one or more of four specific types of data and resources: (1) Molecular Signatures, which includes transcriptional, proteomic, and epigenetic information; (2) Anatomy, including cell morphology and anatomical connectivity; (3) Functional Measures, such as electrophysiology or measures of functional connectivity; and (4) Cell-Specific Targeting, including development of novel tools, advanced approaches, or essential information for accessing and manipulating brain cell types.
- Specialized Centers for Atlases of Human and Non-Human Primate Brain Cell Types:
This FOA is for a group of Specialized Centers that will adopt scalable technology platforms and streamlined workflows to accelerate progress towards establishing reference cell atlases of human and non-human primate brains. As primate brains are several orders of magnitude larger than the mouse brain in size and number of cells, these Centers will serve as a pilot program to implement high throughput approaches and to establish experimental feasibility towards the generation of comprehensive brain cell atlases in larger brains. Centers may focus on one or a few select brain regions, and are expected to develop and assess scalable and multiplexed approaches for comprehensive cell type surveys.
2. Tools for Cells and Circuits
For FY2017, NIH re-issued the previous announcement for Development and Validation of Novel Tools to Analyze Cell-Specific and Circuit-Specific Processes (MH-17-220).
3. Technologies for Neural Recording and Modulation
For FY2017, NIH re-issued the three previous announcements for New Concepts and Early Stage Research (EY-17-001), New Technologies and Novel Approaches (NS-17-003), and Optimization of Transformative Technologies (NS-17-004) for Large-Scale Recording and Modulation in the Nervous System.
4. Human Imaging and Neuromodulation
Next-Generation Human Imaging
Development of Next Generation Human Brain Imaging Tools and Technologies: Stage 2
In FY2014 and FY2015, NIH issued FOAs for Next-Generation Human Brain Imaging, with 14 awards that support planning activities and proof of concept development of novel and transformative ideas for non-invasive imaging of human brains. In 2017, as a follow on to these FOAs and other advances in the broader research community, NIH initiated Stage 2 awards for full development of novel and breakthrough technologies for noninvasive brain imaging. The goal is to generate tools and methods that elucidate brain structure and function at levels that are currently unachievable, and that can be practically used in humans, regardless of health or disease state.
This goal will likely require expertise of interdisciplinary teams, including investigators with proficiency in physical sciences and engineering, as well as neurobiologists and clinical and behavioral scientists. The awards are intended to provide the necessary resources to meet the inherent challenges of technical development within an award period of up to four years. Academic/industry partnerships are encouraged, and efforts can and should address any of the steps along the path of brain imaging data acquisition, including hardware and probe development, data analysis, and validation.
Proof of Concept Development for Next Generation Human Brain Imaging
This FOA supports early stage development of entirely new or next generation noninvasive human brain imaging technologies and methods that will lead to transformative advances in our understanding of the human brain. The opportunity is for unusually bold and potentially transformative approaches, with funding for small scale, proof of concept development projects based on exceptionally innovative, original and/or unconventional concepts
- Foundations of Human Imaging
For FY2017, NIH re-issued the previous announcement for Foundations of Non-Invasive Functional Human Brain Imaging and Recording - Bridging Scales and Modalities (MH-17-235).
- Next-Generation Invasive Devices
For FY2017, NIH re-issued previous announcements for clinical (NS-17-006), as well as translational-to-clinical (NS-17-005) phased awards for Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System, including re-issues of the corresponding SBIR FOAs (NS-17-007 and NS-17-008).
- Non-Invasive Neuromodulation
For FY2017, NIH re-issued the previous announcements calling for new tools and techniques (MH-17-240), as well as mechanisms and optimization (MH-17-245), of Non-Invasive Neuromodulation.
5. Understanding Neural Circuits
For FY2017, NIH re-issued the announcements for:
Theories, Models and Methods for Analysis of Complex Data from the Brain
Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain
Exploratory Team-Based Projects for Understanding Brain Circuit Function (see below)
Integrated Approaches Funding Opportunities
In 2014 and 2015, NIH issued FOAs for Integrated Approaches to Understanding Circuit Function in the Nervous System, resulting in 17 awards totaling $17 million per year, with each award lasting three years. The explicit, short-term goal of the first phase is to foster a set of interdisciplinary team projects in preparation for the second phase to start in FY2017, when larger multi-component awards will support full-scale, team-science programs for understanding how circuits create and contribute to cognitive and behavioral capabilities.
The currently funded projects are exploratory in nature, with a goal of integrating cutting edge technologies for circuit interrogation at cellular and sub-second resolution, and merging them with sophisticated analytic methods to develop new theories of specific circuit contributions to behaviors in model organisms, including rodents, non-human primates, zebrafish, and fruit flies. In addition, human research studies using invasive recording and modulation technologies with relatively high spatiotemporal precision were initiated with FOAs in 2016 and 2017 for Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (listed above).
For FY2017, NIH issued a family of FOAs supporting research that integrates multiple technologies for assessing circuit function in the brain, ranging from two-year, small exploratory research projects to large team-based research grants with extensive, elaborated goals and a 5-10-year time horizon (see below). All FOAs in this family emphasize the use of cutting-edge methods of activation and recording to understand the behavior of circuits at cellular and sub-second levels of spatial and temporal resolution. Basic research approaches using human or non-human subjects (from invertebrates to non-human primates) were welcomed.
Integrated Approaches – Family of Mechanisms GOALS and SCOPE of WORK
|FY17 Concepts||Exploratory Projects to establish feasibility/validity||Research Projects toward extensive, elaborate goals|
|Individual Lab or Small, Multi-PI team||Targeted BRAIN Circuits Projects (R21): 2-3 year scope of work||Targeted BRAIN Circuits Projects (R01): 4-5 year scope of work|
|Multi-Component, Team Approach Science||Exploratory Integrated Approaches Research Projects (U01): 4-5 year scope of work||Integrated Approaches, Team-Research Programs (U19): 5-10 year scope of work|
- Team-Based Research Programs for Understanding Brain Circuit Function
This FOA supports integrated, interdisciplinary research teams from prior BRAIN technology and/or integrated approaches teams, as well as new projects from the greater research community that focus on examining circuit functions related to behavior, using advanced and innovative technologies. The goal is to support programs using a team-science approach that can realize meaningful outcomes within 5–10 years. Awards were made for 5 years, with a possibility of one competing renewal. Awards address overarching principles of circuit function in the context of specific brain systems, such as sensation, perception, emotion, motivation, cognition, choosing, and taking action. Awards incorporate theory-/model-driven experimental design and offer predictive models as deliverables. Awards seek to understand circuits of the brain by systematically controlling stimuli and/or behavior while actively recording and/or manipulating relevant dynamic patterns of neural activity and by measuring the resulting behaviors and/or perceptions. Awards employ approaches guided by specified theoretical constructs, and may employ quantitative, mechanistic models where appropriate. Awardees are required to manage their data and analysis methods in a standardized framework that will be developed and used in the project. Budgets are commensurate with multi-component teams of research expertise - including neurobiologists, statisticians, physicists, mathematicians, engineers, computer scientists, and data scientists, as appropriate - that seek to cross boundaries of interdisciplinary collaboration.
- Exploratory Team-Based Projects for Understanding Brain Circuit Function
This FOA was a re-issue of Integrated Approaches to Understanding Circuit Function in the Nervous System, to support exploratory research projects that seek to integrate cutting edge technologies to develop new theories of specific circuit contributions to brain function. The goal is to foster new interdisciplinary team projects in preparation for larger multi-component awards in future years of the BRAIN Initiative.
- Targeted Projects for Understanding Brain Circuit Function
This complementary pair of FOAs sought R01 and R21 applications proposing innovative approaches that are in an earlier stage of development, and/or of smaller scale of approach than sought in the larger Team-Research Programs FOAs. These projects may be individual labs or small, multi-PI teams. Awards specify tractable, specific research goals on the circuit mechanisms of specified behaviors or neural systems. Awarded projects incorporate theory/model-driven experimental design, and employ quantitative approaches where appropriate. R21 awards are 2 year exploratory projects to establish feasibility and supporting data for potential subsequent R01 funding. R01 awards are non-renewable within BRAIN Initiative FOAs with specific, feasible research goals as endpoints. Budgets are commensurate with single-lab or small, multi-PI teams of investigators focused on a specified scope of work elaborated in the specific aims.
6. Technology Dissemination and Training
- Research Resource Grants for Technology Integration and Dissemination
The BRAIN Initiative is currently funding projects at various stages in the technology cycle, including early stage development, proof-of-concept experiments, and optimization and iteration with end-users. This FOA addressed an additional critical component of the technology cycle - dissemination of technologies and associated resources, including their integration into neuroscience research. It is anticipated that projects will engage in one or more of the following activities: distribution of cutting edge tools (e.g., vectors, sensors, probes, electrodes, or models), dissemination of established resources to new user groups, training end users in new technologies, providing access to specialized facilities, and/or increasing the scale/efficiency of resource production and delivery. Applications strictly focused on technology development were not considered responsive to this FOA, although use of existing techniques to develop new reagents or genetic lines of clear value were appropriate. In addition, iterative refinement of technologies and associated resources, with incorporation of end-user feedback, in order to disseminate to larger communities were appropriate. The proposed resources demonstrate value to the research community, and are highly relevant to specific goals of the BRAIN Initiative as described in the BRAIN 2025 Report.
- Research Career Enhancement Award for Investigators to Build Skills in a Cross-Disciplinary Area
This FOA supports mentored career enhancement awards in research areas that are highly relevant to the BRAIN Initiative. This career enhancement program supports the development of research capabilities for the BRAIN Initiative, with specific emphasis on cross-training independent investigators who are either trained in neuroscience and seeking to enhance or develop their research program in a quantitative or physical discipline (e.g., physics, chemistry, engineering, computer science, mathematics) relevant to the BRAIN Initiative, or vice versa. The research project conducted under this award should enhance the candidate’s ability to significantly contribute to or lead projects that investigate questions central to the goals of the BRAIN Initiative. Eligible candidates were independent investigators at any faculty rank or level.
- BRAIN Initiative Fellows: Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship - Active Now
The purpose of the BRAIN Initiative Fellows (F32) program is to enhance the research training of promising postdoctorates, early in their postdoctoral training period, who have the potential to become productive investigators in research areas that will advance the goals of the BRAIN Initiative. Applications were encouraged in any research area that is aligned with the BRAIN Initiative, including neuroethics. Applicants were expected to propose research training in an area that complements their predoctoral research. Formal training in quantitative perspectives and analytical tools was expected to be an integral part of the proposed research training plan. In order to maximize the training potential of the F32 award, this program encouraged applications from individuals who have not yet completed their terminal doctoral degree and who expect to do so within 12 months of the application due date. On the application due date, candidates may not have completed more than 6 months of postdoctoral training.
For FY2017, NIH issued a new announcement for BRAIN Initiative Fellows: Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship.
7. Small Business Awards
For FY2017, NIH continued its support for BRAIN Initiative Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) FOAs for technology development by small businesses.
For more information, see Funding Opportunities and Announcements.
8. Data Coordination
A number of BRAIN Initiative awards are expected to begin to produce significant amounts of data in FY2018 and beyond. For FY2017, NIH issued three, new related FOAs. In each case, the data coordination activity is in the context of a scientific sub-domain related to existing BRAIN Initiative awards and to other closely related scientific areas.
- Experimental Standards
The purpose of the first FOA (MH-17-256) was to provide short term support (up to two years) to enable investigators from a particular research sub-domain to develop standards for new experimental protocols that are being used - or could be used - as part of the BRAIN Initiative.
- Data Archives
The purpose of the second FOA (MH-17-255) was to provide support for the creation and management of data archives that will hold data related to the BRAIN Initiative. The data that will be deposited in the archive need not be restricted to data sets funded by BRAIN Initiative awards, but applicants were expected to explicitly define the scope of the data archive. The data archive is expected to use relevant standards that describe BRAIN Initiative experiments. Such standards may be developed under the previous FOA, or may already exist. Each data archive will develop a data submission pipeline ensuring appropriate quality control standards for laboratories who intend to upload data. The data archive will provide an interface that is accessible to anyone with a web browser. The data archive will make appropriate query tools and summary data easily available to allow the research community to check whether data of interest are held in the archive.
- Integration and Analysis
The purpose of the final FOA (MH-17-257) was to encourage the development of new data analysis and visualization tools, or to modify existing tools for BRAIN Initiative data. Tools that integrate different types of data were also invited under this concept. Such integration tools might link data across multiple scales or across different species. The focus for integration tools in this FOA is mainly in finding the data and applying metrics for data alignment, standardization and normalization for further analysis. All tools must make use of relevant standards and will be built to enable easy integration with relevant data archives.
- Research on the ethical implications of advancements in neurotechnology and brain science
This FOA sought R01 applications proposing to address core ethical issues associated with research focused on the human brain and resulting from emerging technologies and advancements in research and development supported by the BRAIN Initiative. The goal is to support efforts that are both complimentary and integrative with the transformative, breakthrough discoveries being supported through the BRAIN Initiative.