the nih brain initiative koroshetz.pdf · 2017. 10. 20. · the brain initiative® 1. discovering...
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THE BRAIN INITIATIVE®
The NIH BRAIN Initiative
Walter Koroshetz, M.D.Co-Chair, NIH BRAIN Multi-Council Working Group
Director, National Institute of Neurological Disorders andStroke, NIH
THE BRAIN INITIATIVE®
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7. Other Non-communicable Diseases
6. Chronic Respiratory Diseases
5. Diabetes, Urogenital, Blood, andEndocrine Diseases
4. Musculoskeletal Disorders
3. Neoplasms
2. Cardiovascular and CirculatoryDiseases
1. Neuropsychiatric Disorders
Percent of Total U.S. DALYs
U.S. Burden of Diseases: 291 Diseases and Injuries
Leading Categories of DALYs 201018.7
NeurologicalDisorders
5.1
Mental and BehavioralDisorders
13.6
US Burden of Disease Collaborators, JAMA, 2013
THE BRAIN INITIATIVE®The Next Great American Project
“So there is this enormous mystery waiting to be unlocked, andthe BRAIN Initiative will change that by giving scientists the toolsthey need to get a dynamic picture of the brain in action andbetter understand how we think and how we learn and how weremember. And that knowledge could be – will be –transformative.”
-- President Obama, April 2, 2013
Three years ago, PresidentObama announced a newgrand challenge: The BrainResearch through AdvancingInnovative Neurotechnologies(BRAIN) Initiative
THE BRAIN INITIATIVE®
We need to be able to see the circuits in action to:• Understand how the brain moves, plans, executes• Understand how to monitor and manipulate circuits for
improved function.• The disability that patients with neuro/mental/substance abuse
disorders suffer is a direct result of disordered brain circuits.
Goal: Make circuit normalization/compensation the targetof intervention
Molecular/StructuralPathology
Molecular/StructuralPathology
CircuitDysfunction
CircuitDysfunction
Neuro/MentalFunctional Disability
Neuro/MentalFunctional Disability
Focus on Circuit Structureand Function
THE BRAIN INITIATIVE®
“New directions in science are launched by new toolsmuch more often than by new concepts. The effect of aconcept-driven revolution is to explain old things in newways. The effect of a tool-driven revolution is to discovernew things that have to be explained.”
Freeman Dyson (1997) Imagined Worlds HarvardUniversity Press, Cambridge, MA
Where Does Scientific ProgressCome From?
THE BRAIN INITIATIVE®
6Original axial CT image form Siretom CTscanner circa 1975. Physicians werefascinated by the ability to see the brainand ventricles for the first time.
1974 2012
What is Next?
THE BRAIN INITIATIVE®CLARITY: Neuroanatomy
for the 21st Century
Deisseroth et al, Stanford
THE BRAIN INITIATIVE®
1. Discovering diversity: Identify and provide experimentalaccess to the different brain cell types to determine theirroles in health and disease.
2. Maps at multiple scales: Generate circuit diagrams thatvary in resolution from synapses to the whole brain.
3. The brain in action: Produce a dynamic picture of thefunctioning brain by developing and applying improvedmethods for large-scale monitoring of neural activity.
4. Demonstrating causality: Link brain activity to behaviorwith precise interventional tools that change neural circuitdynamics.
Seven High Priority Research AreasBrainCell
Types
Tools forCircuit
Diagrams
Tech. toMonitorNeuralActivity
PreciseInter-
ventionalTools
THE BRAIN INITIATIVE®
5. Identifying fundamental principles: Produce conceptualfoundations for understanding the biological basis ofmental processes through development of new theoreticaland data analysis tools.
6. Advancing human neuroscience: Develop innovativetechnologies to understand the human brain and treat itsdisorders; create and support integrated human brainresearch networks.
7. From BRAIN Initiative to the brain: Integrate newtechnological and conceptual approaches produced ingoals #1-6 to discover how dynamic patterns of neuralactivity are transformed into cognition, emotion,perception, and action in health and disease.
Theoryand DataAnalysis
Tools
AdvanceHumanNeuro-science
IntegrateApproaches
Seven High Priority Research Areas
THE BRAIN INITIATIVE® The BRAIN Initiative®
2014 NIH BRAIN awards• 58 awards, $46 million
2015 NIH BRAIN awards• 67 awards, $38 million• 130+ investigators, 8 countries
outside the US
2016 NIH BRAIN awards• 100+ awards, $150+ million• 170 investigators in the United
States and 8 other countries in FY16• Since FY14, 13 countries total are
involved in US BRAIN projects
THE BRAIN INITIATIVE® Optical InstrumentationDeeper – anywhere in the brainFaster – whole volumes rather than single image planeMore precise targeting
3-photon imaging of hippocampalneurons >1mm deep in themouse brain – Cornell (Xu)
SCAPE imaging of cortical neuronscolored by deconvolution –Columbia (Hillman, Paninski)
THE BRAIN INITIATIVE® Probe DevelopmentSensors: voltage, transmitters/modulators, activity history,activated synapses, MRI for calcium
Activators/inhibitors: chemical-genetic, photo-switchableligands, GPCR signaling, synaptic plasticity
GFP-basedfluorophor
MutatedOpsin
Fast response tovoltage changes
FRET donorfor brightsignal
Voltage imaging of single neurondynamics in mouse cortex in vivo –Stanford (Schnitzer/Lin)
New optogenetic serotonin sensorwith high SNR in cultured cells – UCDavis (Tian)
GFP Linked bacterialprotein mutated to bindserotonin
THE BRAIN INITIATIVE®
Dr. Arnold Kriegstein and colleagues identify candidate entryreceptor for Zika virus in neural stem cells
Single cell RNA-seq analysis ofdifferent cell types during earlydevelopment (Cell Stem Cell)• Examined expression of several
candidate entry receptors for Zikavirus
• Candidate AXL is highly expressedin several cell types, includinghuman radial glial cells
• Loss of radial glia founderpopulations leads to microcephaly
• AXL expression pattern isconserved in mice, ferrets, andhuman iPSCs – models forinfectivity and developmentaleffects of Zika virus
Exciting New Discoveries
THE BRAIN INITIATIVE®
Dr. Sarah Stanley and colleagues develop a system for using radiowaves outside the head to control neural activity in mice
Electromagnetic waves were used to manipulate specific ionchannels to modulate neural activity and feeding behavior (Nature)
• Iron nanoparticles were tethered to temperature-sensitive TRPV1• Radio waves or magnetic fields activated glucose-sensing neurons in the
mouse hypothalamus, leading to increased plasma glucose levels, loweredinsulin levels, and stimulated feeding behaviors
• Genetically-manipulated TRPV1 selective to chloride ions were also created• Electromagnetic waves
inhibited the sameclass of neurons,leading to decreasedplasma glucose,higher insulin, andsuppressed feeding
Schematic of “Radiogenetics” System
Exciting Advances
THE BRAIN INITIATIVE® BRAIN NeuroethicsBRAIN Neuroethics Working Group
• A consultative ethics group to work with BRAIN leadershipand BRAIN investigators• Co-chaired by Dr. Christine Grady and Hank Greely
• First meeting was on Feb 9, 2016 with BRAIN PIs conductinginvasive human studies
• Second meeting was Aug 3-• Workshop on privacy, ethics of research with invasive
neurotechnologies, data sharing; long-term obligationsto patients with invasive neural devices
• Yuste and Goering (2016) On the necessity of ethicalguidelines for novel neurotechnologies. Cell 167:882-885
• Request for Information (RFI): Guidance for Opportunities inNeuroethics closed July 29
• New funding opportunity planned for FY 2017, informed byRFI input
THE BRAIN INITIATIVE® BRAIN Initiative Alliance
Mission Statement: The aim of the BRAIN InitiativeAlliance is to coordinate and facilitate
communications from its members related to theBRAIN Initiative.
Short Term Focus: Launched website that serves as a single point ofcommunication for all BRAIN Initiative-related announcements of
funding opportunities and accomplishments
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THE BRAIN INITIATIVE® International Partnerships
Goals:• Develop a coordinated program to foster
collaborative research in areas of mutualinterest within the BRAIN Initiative
• Jointly support research projects involvingForeign and U.S. scientists; exchange ofscientific information• Funding for projects in Denmark provided by
Lundbeck Foundation• Funding for projects in Canada provided by
Brain Canada• Funding for projects in Australia provided by
the Australian National Health and MedicalResearch Council
THE BRAIN INITIATIVE®
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Foreign Performance Sites
FY14 FY15 FY16
Performance Sites (Foreign)
THE BRAIN INITIATIVE®2015 & 2016
BRAIN Investigators MeetingMeeting offers opportunity for BRAIN investigators tointeract across project areas, funding agencies
2nd Annual Meeting: December 11-12, 2015• Almost 500 attendees
• Scientists and clinicians, federal staff,non-government foundations, scientific press
• Over 190 scientific poster presentations
3rd Annual Meeting: December 12-14, 2016• Expand 2016 meeting to include public/open session(s)• Anticipate upwards of 1000 in attendance• Includes sessions on the EU Human Brain Project and Global Efforts in
Neurotechnology Development
THE BRAIN INITIATIVE®
3D NeuralReconstruction• PI: Jeff Lichtman, PhD
and colleagues, Cell• Automated serial
sectioning of mousecortex
• Imaging with a scanningelectron microscope
• Virtual, 3D reconstructionand analysis
• Nanometer scale
http://braininitiative.nih.gov/
Exciting New Discoveries
THE BRAIN INITIATIVE®
Walter J. Koroshetz, M.D.DirectorNational Institute of Neurological Disorders and StrokeEmail: [email protected]: http://www.ninds.nih.gov/
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Thank You!