the nih brain initiative koroshetz.pdf · 2017. 10. 20. · the brain initiative® 1. discovering...

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


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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


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


“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?


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


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


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


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


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


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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


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


Walter J. Koroshetz, M.D.DirectorNational Institute of Neurological Disorders and StrokeEmail: [email protected]: http://www.ninds.nih.gov/

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Follow me @NINDSdirector

Thank You!

the nih brain initiative koroshetz.pdf · 2017. 10. 20. · the brain initiative® 1. discovering...

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