T
BRAIN
I
A T
NATIONAL I NSTITUTES OF H EALTH
T H E R E I S TH I S E N O R M O U S MYST E RY WA IT I N G TO B E
U N LO C K E D, AN D TH E B RA I N I N IT IAT IVE WI L L C HA N G E
T H AT BY G IVI N G S C I E NT I STS T H E TO O LS T H EY N E E D
TO G ET A DYN AM I C P I CT U R E O F T H E B RA I N I N ACT I O N
A N D B E T TE R U N D E R STA N D H O W WE T H I N K A N D
H O W W E L E AR N AN D H O W WE R E M E M B E R. A N D T HAT
K N O W L E D G E C O U L D B E WI L L B E T RA N S F O R MAT IV E.
P R E S I D E N T BARAC K O BA MA , A P R I L 2 , 2 0 1 3
W H AT
I S
T H E
BRAIN
I N I T I A T I V E ?
Brain Research through Advancing Innovative Technologies (BRAIN) Initiative
The BRAIN Initiative will accelerate the development and application of new technologies to produce dynamic
pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of
thought. These technologies will open new doors to explore how the brain encodes, stores, and retrieves vast
quantities of information, and shed light on the complex links between brain function and behavior.
The National Institutes of Health (NIH), the Defense Advanced Research Projects Agency (DARPA), the
National Science Foundation (NSF), and the Food and Drug Administration (FDA) are leading this national effort.
Momentum is growing and additional partners are getting involved. President Obama has called for the BRAIN
Initiative to be an all hands on deck effort and has encouraged participation from the private sector as well.
WHY NOW?
100 million Americans suffer from devastating brain
disorders at some point in their lives neurodevelopmental
disorders (such as autism), mood and anxiety disorders
(such as depression and post-traumatic stress disorder),
neurodegenerative diseases (such as Parkinsons and
Alzheimers diseases), among many others (such as
epilepsy and stroke). Knowing more about the brain has
TH E H U MAN B RAI N
the potential to improve so many areas of human health.
A recent revolution in modern neuroscience creates
HAS 86 B I LLION
a unique opportunity to unlock mysteries of the brain
with the promise of ultimately helping people with brain
N E U RONS ALONG
WITH OTH E R CE LLS
THAT MAKE M OR E
disorders. Recent progress has given us:
Exciting insights into brain structure
Advanced technologies for recording hundreds of
neurons at once
New methods for precisely manipulating activity
THAN 100 TR I LLION
CON N ECTIONS.
within brain circuits
Massive and complex data sets rich with valuable
information
The time is right to inspire a new generation of
researchers to undertake the most groundbreaking and
integrated approach ever contemplated to understanding
how the brain works in health and disease.
This is a moment in science when our knowledge base,
our new technological capabilities, and our dedicated
and coordinated efforts can generate great leaps
forward. The answers to the mystery of how organized
circuits of cells interact dynamically to produce behavior
and cognition will not come easily, but the public health
need and the scientific opportunity are so great that there
has never been a better time to undertake this challenge.
N I H ROLE
WHY FOCUS ON CIRCUITS?
NIH Director Francis Collins convened an esteemed
60 years of studying one neuron at a time has
group of experts in neuroscience to develop a
taught us a lot about individual neurons. Imaging
scientific plan for this bold endeavor. The group
technologies have enabled us to observe the
spent over a year and a half in extensive consultation,
activity of thousands of neurons in the living brain.
getting feedback from the basic, translational, and
But there remains a gap in our knowledge of what
clinical research communities, in addition to patient
happens in the middle of this spectrum within
advocates and the general public. The resulting
the complex networks of neurons that form neural
June 2014 report, a 12-year scientific vision,
circuits. This is the level at which most of human
spells out the NIHs role in the BRAIN Initiative
(www.nih.gov/science/brain/2025).
12-YEAR SCIENTIFIC VISION
Overall Aim: To map the circuits of the brain, measure
the fluctuating patterns of electrical and chemical
cognition and behavior is generated. At any
moment, thousands to millions of interconnected
cells are rapidly transmitting information between
themselves via chemical signals and electrical
activity. We must understand how these
circuits work to capture the full sense of what is
activity, and understand how their interplay creates
happening in the healthy brain and what goes
our unique cognitive and behavioral capabilities.
awry in disease.
Advanced genetic techniques can label nerve cell circuits in real time at the level of single cells. This image depicts the
circuitry a fly uses to smell. Credit: Liqun Luo, Stanford University, Palo Alto, CA
3
Brainbow is a technique that maps individual nerve
cells with a wide array of colors in order to chart the
circuitry of the nervous system. Credit: J. Livet and
J.W. Lichtman, Harvard University
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SCI E NTI FIC GOALS
To achieve the long-term vision of the BRAIN
Initiative, NIH is prioritizing seven scientific goals:
Parts list: Identify and provide experimental
access to the different brain cell types to
determine their roles in health and disease.
Maps: Generate circuit diagrams that vary in
resolution from synapses to the whole brain.
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.
THE BRAIN INITIATIVE HAS
ENORMOUS POTENTIAL
FOR SOLVING PERSISTENT
Causes: Link brain activity to behavior with
MYSTERIES OF BRAIN
precise interventional tools that change neural
circuit dynamics.
FUNCTION, SPINNING OFF
Fundamental principles: Produce conceptual
TECHNOLOGIES THAT
foundations for understanding the biological basis
of mental processes through development of new
theoretical and data analysis tools.
SEED NEW INDUSTRIES,
Human neuroscience: Develop innovative
AND OPENING THE DOOR
technologies to understand the human brain and
treat its disorders; create and support integrated
brain research networks.
TO N EW TR EATM E NTS
From BRAIN Initiative to the brain: Integrate
DISOR DE RS OF TH E
new technological and conceptual approaches
produced in the other goals to discover
FOR DISEASES AN D
N E RVOUS SYSTE M .
how dynamic patterns of neural activity are
transformed into cognition, emotion, perception,
and action in health and disease.
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WHAT WILL IT TAKE TO ACCOMPLISH THIS GRAND CHALLENGE?
Collaborations
Rigorous standards and accountability
Cross traditional neuroscience boundaries in
Pursue human and non-human studies in parallel to
interdisciplinary collaborations with geneticists,
chemists, engineers, physicists, information
scientists, and others
Work with industry partners, who will bring experience
developing products for use in patients
reach scientific goals as expeditiously as possible
Consider the ethical implications of research
on the brain
Ensure accountability to taxpayers and the community
of basic, translational, and clinical neuroscientists
New technologies
Integrate spatial and temporal scales, to go from
cells to circuits as well as functions that can take
milliseconds, minutes, or a lifetime
Establish platforms to preserve and share data
Validate and disseminate technologies
Substantial, sustained commitment
More than a 10-year research effort
Years 1-5: technology development and validation
Years 6-10+: discovery-driven research to
answer fundamental questions
Above: With lightsheet microscopy, activity in nearly every brain cell of the zebrafish can be monitored during behavior.
Credit: Misha B. Ahrens & Phillip Keller, HHMI, Janelia Farm Research Campus
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TH E CHALLE NG ES
A FOCUSED, SUSTAINED
The brain is the most complex organ in the
INVESTMENT IN THE BRAIN
body; it may take decades for discoveries in
basic neuroscience to lead to new treatments
and cures for brain disorders. Researchers
must first develop the tools for studying the
INITIATIVE HAS THE POWER
TO CHANGE THE FUTURE.
brain to gain a fundamental understanding of
how it works. This knowledge will provide
much needed insights for solving the medical
mysteries plaguing patients.
In the 21st century, brain disorders
neurodevelopmental and neurodegenerative
will be the most disabling and most costly
chronic diseases.
5 million+ Americans suffer from Alzheimers
disease. The cost of caring for these individuals
is $200 billion+/year. Medicare and Medicaid
OPPORTUNITIES
Cochlear implants help more than 200,000
people overcome profound deafness. The
same leap forward may be possible to restore
vision for those with profound blindness. By
understanding how the neurons in the retina
and brain process streams of information
from the visual world, it should be possible to
devise intelligent retinal prostheses or other
spending on Alzheimers disease alone dwarfs
devices to restore sight.
the NIHs total neuroscience research budget.
Brain Computer Interfaces are being
2.4 million+ Americans have schizophrenia.
After 20 years of intense effort by the
pharmaceutical industry, there are still no
fundamentally new drugs.
From 2000 through 2011, more than 235,000
service members were diagnosed with a
traumatic brain injury.
In 2009, an estimated 248,418 children (age
developed for patients paralyzed by injuries
or stroke. But the technology needs better
speed, reliability, and dexterity, which can
come from better understanding of how the
brain elicits targeted movements.
Deep brain stimulation has been used as a
treatment for Parkinsons disease, chronic
pain, and depression. The current technology
could be improved through the development
19 or younger) were treated in U.S. emergency
of electrodes capable of adapting stimulation
departments for sports and recreation-related
parameters in real-time using feedback from
injuries that included a diagnosis of concussion
neural activity, ultimately serving as sensors
or traumatic brain injury.
as well as stimulators.
7
New high-resolution, non-invasive imaging techniques produce detailed diagrams of neural tracts, enabling new analyses of how
brain regions are connected. Credit: Washington University University of Minnesota Human Connectome Project consortium
On the cover: Map of the wiring diagram of specific brain circuits, now called the connectome in the human brain.
Credit: Harvard/MGH-UCLA Human Connectome Project consortium
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H O W T H E B R A I N W O R K S A N D G I V E S R I S E TO
O U R M E N TA L A N D I N T E L L E C T U A L L I V E S W I L L
B E T H E M O ST E XC I T I N G A N D C H A L L E N G I N G A R E A
O F S C I E N C E I N T H E 2 1 S T C E N T U R Y.
N I H D I R E CTO R F R A N C I S C O L L I N S , J U N E 4 , 2 0 1 4
T H E B R A I N I N I T I AT I V E I S O N E PA R T O F T H E N I H S
I N V E ST M E N T I N BA S I C , T R A N S L AT I O N A L , A N D C L I N I CA L
N E U R O S C I E N C E. TO L EAR N M O R E AB O UT TH E N I H
B R A I N I N I T I AT I V E , V I S I T : www.nih.gov/science/brain
August 2014
