In 2014, the Advisory Committee of the (NIH) Director (ACD) Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative®, working group developed a rigorous plan for achieving the Initiative’s scientific vision. The BRAIN 2025: A Scientific Vision 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 the seven major priority areas articulated in the report and outlined below.
Subsequent BRAIN 2.0 companion reports (“The BRAIN Initiative® 2.0: From Cells to Circuits, Toward Cures” and “The BRAIN Initiative® and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society”) have proceeded to further the Initiative’s goals, priorities, and scientific vision, including through the development of three large-scale projects that promise to transform neuroscience research.
BRAIN 2025 Recommendation: 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.
BRAIN 2025 Recommendation: 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.
Monitor Neural Activity
BRAIN 2025 Recommendation: 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.
BRAIN 2025 Recommendation: 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.
Theory & Data Analysis Tools
BRAIN 2025 Recommendation: 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.
BRAIN 2025 Recommendation: 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.
BRAIN 2025 Recommendation: 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.