The Advisory Committee to the NIH Director (ACD) working group is a high-level working group established by NIH Director Francis Collins to help shape the vision of the BRAIN Initiative. The working group, co-chaired by Dr. Cornelia “Cori” Bargmann (The Rockefeller University) and Dr. William Newsome (Stanford University), incorporated broad input from the scientific community, patient advocates, and the general public. Their report, released in June 2014 and enthusiastically endorsed by the ACD, articulated the scientific goals of the BRAIN Initiative and developed a multi-year scientific plan for achieving these goals, including timetables, milestones, and cost estimates.
- Cornelia Bargmann, PhD (co-chair)
The Rockefeller University
- William Newsome, PhD (co-chair)
- David Anderson, PhD
California Institute of Technology
- Emery Brown, MD, PhD
Massachusetts Institute of Technology
and Massachusetts General Hospital
- Karl Deisseroth, MD, PhD
- John Donoghue, PhD
- Peter MacLeish, PhD
Morehouse School of Medicine
- Eve Marder, PhD
- Richard Normann, PhD
University of Utah
- Joshua Sanes, PhD
- Mark Schnitzer, PhD
- Terrence Sejnowski, PhD
Salk Institute for Biological Studies
- David Tank, PhD
- Roger Tsien, PhD
University of California, San Diego
- Kamil Ugurbil, PhD
University of Minnesota
Ex Officio Members
- Kathy Hudson, PhD
National Institutes of Health
- Geoffrey Ling, MD, PhD
Defense Advanced Research Projects Agency
- John Wingfield, PhD
National Science Foundation
- Carlos Peña, PhD
Food and Drug Administration
- Lyric Jorgenson, PhD
National Institutes of Health
The human brain is the source of our thoughts, emotions, perceptions, actions, and memories; it confers on us the abilities that make us human, while simultaneously making each of us unique. Over recent years, neuroscience has advanced to the level that we can envision a comprehensive understanding of the brain in action, spanning molecules, cells, circuits, systems, and behavior. This vision, in turn, inspired the BRAIN Initiative. On April 2, 2013, President Obama launched the BRAIN Initiative to “accelerate the development and application of new technologies that will enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of thought.” In response to this Grand Challenge, the National Institutes of Health (NIH) convened a working group of the Advisory Committee to the Director, NIH, to develop a rigorous plan for achieving this scientific vision. This report presents the findings and recommendations of the working group, including the scientific background and rationale for the BRAIN Initiative as a whole and for each of seven major goals articulated in the report. In addition, we include specific deliverables, timelines, and cost estimates for these goals as requested by the NIH Director.
The charge from the President and from the NIH Director is bold and ambitious. The working group agreed that the best way to set this vision in motion is to accelerate technology development, as reflected in the name of the BRAIN Initiative: “Brain Research through Advancing Innovative Neurotechnologies.” The focus is not on technology per se, but on the development and use of tools for acquiring fundamental insight about how the nervous system functions in health and disease. The initiative is only one part of the NIH’s investment in basic, translational, and clinical neuroscience, but neurotechnology should advance other areas as well. To achieve these goals, we recommend that the BRAIN Initiative develop over a ten-year period beginning in FY2016, with a primary focus on technology development in the first five years, shifting in the second five years to a primary focus on integrating technologies to make fundamental new discoveries about the brain. The distinction between these phases is not black and white, but rather is a matter of emphasis and opportunity. Discovery-based science will motivate technology development in the first phase, and further technology development will be needed as the focus shifts to discovery in later years.
In considering these goals and the current state of neuroscience, the working group identified the analysis of circuits of interacting neurons as being particularly rich in opportunity, with potential for revolutionary advances. Truly understanding a circuit requires identifying and characterizing the component cells, defining their synaptic connections with one another, observing their dynamic patterns of activity as the circuit functions in vivo during behavior, and perturbing these patterns to test their significance. It also requires an understanding of the algorithms that govern information processing within a circuit and between interacting circuits in the brain as a whole. The analysis of circuits is not the only area of neuroscience worthy of attention, but advances in technology are driving a qualitative shift in what is possible, and focused progress in this area will benefit many other areas of neuroscience.
With these considerations in mind, the working group consulted extensively with the scientific community to evaluate challenges and opportunities in the field. The following areas were identified as high priorities for the BRAIN Initiative. These goals are intellectually and practically expanded in Sections II and III of this report.
#1. Discovering diversity: Identify and provide experimental access to the different brain cell types to determine their roles in health and disease. It is within reach to characterize all cell types in the nervous system, and to develop tools to record, mark, and manipulate these precisely defined neurons in the living brain. We envision an integrated, systematic census of neuronal and glial cell types, and new genetic and non-genetic tools to deliver genes, proteins, and chemicals to cells of interest in non-human animals and in humans.
#2. Maps at multiple scales: Generate circuit diagrams that vary in resolution from synapses to the whole brain. It is increasingly possible to map connected neurons in local circuits and distributed brain systems, enabling an understanding of the relationship between neuronal structure and function. We envision improved technologies—faster, less expensive, scalable—for anatomic reconstruction of neural circuits at all scales, from non-invasive whole human brain imaging to dense reconstruction of synaptic inputs and outputs at the subcellular level.
#3. The brain in action: Produce a dynamic picture of the functioning brain by developing and applying improved methods for large-scale monitoring of neural activity. We should seize the challenge of recording dynamic neuronal activity from complete neural networks, over long periods, in all areas of the brain. There are promising opportunities both for improving existing technologies and for developing entirely new technologies for neuronal recording, including methods based on electrodes, optics, molecular genetics, and nanoscience, and encompassing different facets of brain activity.
#4. Demonstrating causality: Link brain activity to behavior with precise interventional tools that change neural circuit dynamics. By directly activating and inhibiting populations of neurons, neuroscience is progressing from observation to causation, and much more is possible. To enable the immense potential of circuit manipulation, a new generation of tools for optogenetics, chemogenetics, and biochemical and electromagnetic modulation should be developed for use in animals and eventually in human patients.
#5. Identifying fundamental principles: Produce conceptual foundations for understanding the biological basis of mental processes through development of new theoretical and data analysis tools. Rigorous theory, modeling, and statistics are advancing our understanding of complex, nonlinear brain functions where human intuition fails. New kinds of data are accruing at increasing rates, mandating new methods of data analysis and interpretation. To enable progress in theory and data analysis, we must foster collaborations between experimentalists and scientists from statistics, physics, mathematics, engineering, and computer science.
#6. Advancing human neuroscience: Develop innovative technologies to understand the human brain and treat its disorders; create and support integrated human brain research networks. Consenting humans who are undergoing diagnostic brain monitoring, or receiving neurotechnology for clinical applications, provide an extraordinary opportunity for scientific research. This setting enables research on human brain function, the mechanisms of human brain disorders, the effect of therapy, and the value of diagnostics. Meeting this opportunity requires closely integrated research teams performing according to the highest ethical standards of clinical care and research. New mechanisms are needed to maximize the collection of this priceless information and ensure that it benefits people with brain disorders.
#7. From BRAIN Initiative to the brain: Integrate new technological and conceptual approaches produced in Goals #1-6 to discover how dynamic patterns of neural activity are transformed into cognition, emotion, perception, and action in health and disease. The most important outcome of the BRAIN Initiative will be a comprehensive, mechanistic understanding of mental function that emerges from synergistic application of the new technologies and conceptual structures developed under the BRAIN Initiative.
The overarching vision of the BRAIN Initiative is best captured by Goal #7—combining these approaches into a single, integrated science of cells, circuits, brain, and behavior. For example, immense value is added if recordings are conducted from identified cell types whose anatomical connections are established in the same study. Such an experiment is currently an exceptional tour de force; with new technology, it could become routine. In another example, neuronal populations recorded during complex behavior might be immediately retested with circuit manipulation techniques to determine their causal role in generating the behavior. Theory and modeling should be woven into successive stages of ongoing experiments, enabling bridges to be built from single cells to connectivity, population dynamics, and behavior.
This synthetic approach will enable penetrating solutions to longstanding problems in brain function, but we also emphasize the likelihood of entirely new, unexpected discoveries that will result from the new technologies. In some sense, BRAIN Initiative scientists who apply the new activity-monitoring technology will be like Galileo looking into the heavens with the first optical telescope. Similarly, new perturbation tools and quantitative approaches are likely to yield extraordinary insights into the relationship between brain activity and mental functions. We expect to discover new forms of neural coding as exciting as the discovery of place cells, and new forms of neural dynamics that underlie neural computations.
Over the course of our deliberations, specific themes emerged that should become core principles for the NIH BRAIN Initiative.
- Pursue human studies and non-human models in parallel. The goal is to understand the human brain, but many methods and ideas will be developed first in animal models. Experiments should take advantage of the unique strengths of diverse species and experimental systems.
- Cross boundaries in interdisciplinary collaborations. No single researcher or discovery will solve the brain’s mysteries. The most exciting approaches will bridge fields, linking experiment to theory, biology to engineering, tool development to experimental application, human neuroscience to non-human models, and more, in innovative ways.
- Integrate spatial and temporal scales. A unified view of the brain will cross spatial and temporal levels, recognizing that the nervous system consists of interacting molecules, cells, and circuits across the entire body, and important functions can occur in milliseconds or minutes, or take a lifetime.
- Establish platforms for sharing data. Public, integrated repositories for datasets and data analysis tools, with an emphasis on ready accessibility and effective central maintenance, will have immense value.
- Validate and disseminate technology. New methods should be critically tested through iterative interaction between tool-makers and experimentalists. After validation, mechanisms must be developed to make new tools available to all.
- Consider ethical implications of neuroscience research. BRAIN Initiative research may raise important issues about neural enhancement, data privacy, and appropriate use of brain data in law, education and business. These important issues must be considered in a serious and sustained manner. BRAIN Initiative research should hew to the highest ethical standards for research with human subjects and with non-human animals under applicable federal and local laws.
- Accountability to NIH, the taxpayer, and the basic, translational, and clinical neuroscience communities. The BRAIN Initiative is extremely broad in interdisciplinary scope and will involve multiple partners both within and outside the NIH. Oversight mechanisms should be established to ensure that BRAIN funds are invested wisely for the ultimate benefit of the public and the scientific community.
To guide the BRAIN Initiative and ensure that these goals and principles are evaluated and refreshed as appropriate, we recommend that a scientific advisory board be established, to be composed of scientists who are experts in the diverse fields relevant to the Initiative — neuroscience, molecular biology, the clinical sciences, the physical and quantitative sciences, and ethics. The rapid pace of technological and conceptual change in neuroscience almost ensures that some portions of this report will be obsolete within several years. A cohesive and rigorous scientific advisory board will be invaluable in responding to future challenges.
As part of the planning process, the working group was asked to estimate the cost of the BRAIN Initiative. While we did not conduct a detailed cost analysis, we considered the scope of the questions to be addressed by the initiative, and the cost of programs that have developed in related areas over recent years. Thus our budget estimates, while provisional, are informed by the costs of real neuroscience at this technological level. To vigorously advance the goals of the BRAIN Initiative as stated above, we recommend an investment by the NIH that ramps up to $400 million/year over the next five years (FY16-20), and continues at $500 million/year subsequently (FY21-25). A sustained, decade-long commitment at this level will attract talented scientists from multiple fields to the interdisciplinary collaborations that are essential to the BRAIN Initiative and its ambitious goals.
Full report- “Brain 2025, a scientific vision” (HTML version)
Full Report- “Brain 2025, a scientific vision” (PDF version)