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THE$BRAIN$INITIATIVE®
Congressional$Neuroscience$
Caucus$Briefing
Joshua'A.'Gordon,'MD,'PhD
Director,'NIMH
Walter'J.'Koroshetz,'MD
Director,'NINDS
February'26,'2018
THE$BRAIN$INITIATIVE®Neuropsychiatric$Disorders$Leading$
Cause$of$Disability$in$U.S.$
5.1
6.5
8.0
11.8
15.1
16.8
0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 16.0 18.0 20.0
7.**Other*Non3communicable*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
Neurological$Disorders
5.1
Mental$and$BehavioralDisorders
13.6
Leading$Categories$of$US$DALYs$2010
US#Burden#of#Disease#Collaborators,#JAMA,#2013.
THE$BRAIN$INITIATIVE®
“New$directions$in$science$are$launched$by$new$tools$
much$more$often$than$by$new$concepts.$$The%effect%of%a%
concept-driven%revolution%is%to%explain%old%things%in%new%
ways.%%The%effect%of%a%tool-driven%revolution%is%to%discover%
new%things%that%have%to%be%explained.”
Freeman$Dyson$(1997)$Imagined)Worlds)
Harvard$University$Press,$Cambridge,$MA
Where$Does$Scientific$Progress$Come$From?
THE$BRAIN$INITIATIVE®
Original(axial(CT(image(form(Siretom CT(
scanner(circa(1975.(Physicians(were(
fascinated(by(the(ability(to(see(the(brain(
and(ventricles(for(the(first(time.
What$is$Next?
1974 2012
THE$BRAIN$INITIATIVE® What$If$You$Could$See$It$All?$
THE$BRAIN$INITIATIVE®
200#X#200#µm#
Single$Cell$ActivityCortex:wide$Activity
From#the#laboratory#and#collaborations#of#Dr.#Michael#Crair,#Yale#University
Barson,#Hamodi#et#al.#Funded#FY15
What$If$You$Could$See$It$All?$
THE$BRAIN$INITIATIVE®
7
Brain'disorders',, a'leading'source'of'disease'burden'and'cost'in'the'U.S.'
Recent'breakthroughs'are'transforming'how'we'study'brain'structure'and'function
The$BRAIN$Initiative$builds$on$this$recent$progress$to$create$tools$that$will$accelerate$discovery$and$build$the$foundation$we$need$to$reduce$the$burden$of$brain$disorders
The$BRAIN$Initiative®
THE$BRAIN$INITIATIVE®
Goal:"See"the"circuits"in"action"to"understand:
• How"the"brain"moves,"plans,"executes
• How"to"monitor/manipulate"circuits"for"improved"function
• How"disordered"brain"circuits"cause"neuro/mental/substance"use"disorders"
Long3term$goal:$Make"circuit"abnormalities"the"basis"of"diagnostics,"and"normalization"of"circuit"function"the"target"of"intervention
NIH:$Focus$on$Structure$and$Function$of$Brain$Circuits$
Emphasize*
technology*development
FIRST$FIVE$YEARS
Emphasize*
discovery*driven*science
SECOND$FIVE$YEARS
THE$BRAIN$INITIATIVE®
1. Discovering-diversity
2. Maps-at-multiple-scales
3. The-brain-in-action
4. Demonstrating-causality
5. Identifying-fundamental-principles--
6. Creating-human-brain-research-networks
7. From-BRAIN-Initiative-to-the-brain
Seven$High$Priority$Research$Areas
Brain$Cell$Types
Tools$for$Circuit$Diagrams
Technology$to$Monitor$Neural$Activity
Precise$Interventional$Tools
Theory$and$Data$Analysis$Tools
Advance$Human$Neuroscience
Integrate$Approaches
BRAIN$Strategic$Plan
THE$BRAIN$INITIATIVE®
$$-
$$50
$$100
$$150
$$200
$$250Millions
Data
Coordination/Informatics
Neuroethics
Training/Dissemination
Human9Imaging/Modulation
Understanding9Circuits
Neural
Recording/Modulation
Cell/Circuit9Tools
Cell9Types
Overall$Support$for$High$Priority$Research$Areas
Funding9for9New9
and9Non@
Competing9Awards
2014 2015 2016 2017
$2509
$2009
$1509
$1009
$509
$09
$3009
$$in$M
illions
THE$BRAIN$INITIATIVE®
New$(FY2017) Since BRAIN$Began$(FY2014)
Number'awards 110 345
Number'investigators 178 504
Investment $169.6M $548.3M
NIH$BRAIN$Initiative$Awards
THE$BRAIN$INITIATIVE®
0
100
200
300
400
500
600
700
800
2014
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
Millions
21st1Century1Cures
Base1Budget
$4.2B$$$$$Projected total1for1lifetime1of1BRAIN
$550M$$$BRAIN1Funding1through12017:1~12%1
of1the1total
BRAIN$Funding$to$Ramp$Up
THE$BRAIN$INITIATIVE®
1st$meeting$of$
the$BRAIN$
MCWG
August&2014
BRAIN$
Initiative$
announced
April&2013
BRAIN&2025&
Report$
released
June&2014
1st$NIH$BRAIN$
awards
September&
2014
1st$BRAIN$PI$
Meeting
November&
2014
Neuroethics$
Division$
established
August&2015
1st$BRAIN$
Initiative$
Alliance$
discussion
July&2015
4th$BRAIN$PI$
Meeting
April&2018
BRAIN$Initiative$Alliance$website$launches
November&2016
BRAIN InitiativeInvestigators Meeting
A$Timeline$of$BRAIN$at$NIH
21st Century$
Cures$Act$
signed$into$law
December&2016
PublicJPrivate$
Partnership$
Program$
established
September&
2015
4th$NIH$
BRAIN$
awards
May,&
October,&
December&
2017
THE$BRAIN$INITIATIVE®
https://www.braininitiative.nih.gov/resources/publication.aspx
NIHAFunded$BRAIN$Researchers$Publish$Findings
Over$315 publications$have$emerged$
from$NIH$BRAIN$Initiative$to$date
THE$BRAIN$INITIATIVE®
Discoveries$from$BRAIN$Priority$Areas
BRAIN&Initiative&Cell&Census&Network:
• Provide(a(comprehensive(reference(of(all(different(cell(types(in(human,(monkey,(and(mouse(brain
• $250(Million(invested(over(the(next(5(years
• 9(funded(projects(to(support(4(parts(of(the(network:
Brain(Cell(Data(Center
Mouse(Brain(Cell(Census(Center
Mouse(Brain(Cell(Census(Collaboratory
Human(and(Nonhuman(Primate(Brain(Cell(
Census(Collaboratory
THE$BRAIN$INITIATIVE®
Data$from$Cell$Census$Informs$Projects$
Targeting$Distinct$Cell$Types
K.#Chan#et#al.#2017#Nature'Neuroscience
Lab#of#Viviana#Gradinaru,#California#Institute#of#
Technology
Lab#of#Karel#Svoboda,#Janelia Collaboration#Kith#NIH
THE$BRAIN$INITIATIVE®
BRAIN$Initiative$Cell$Census$
Network$GoalsAnticipated*outcomes
• Essential)knowledge)on)diverse)cell)types)and)their)3D)organization
• An)open9access)3D)digital)mouse)brain)cell)reference)atlas
• A)comprehensive)neural)circuit)diagram)in)mouse)brain
• Precision)tools)to)monitor,)map)or)modulate))the)activity)of)specific)cells
THE$BRAIN$INITIATIVE®
• New$technologies$for$circuit$mapping
• New$interventional$tools$for$functional$
circuit$interrogation$across$scales
Ting%Hao Huang*et*al.*Development*2016;143:4073%4084
Discoveries$from$BRAIN$Priority$Areas
Crair,*M.*Yale*University,*BRAIN*Initiative*Project*funded*FY15*
THE$BRAIN$INITIATIVE®
200#X#200#µm#
Single$Cell$ActivityCortex:wide$Activity
Prism#of#Mesoscope
From#the#laboratory#and#collaborations#of#Dr.#Michael#Crair,#Yale#University
Barson,#Hamodi#et#al.#Funded#FY15
Microscope$Reveals$Activity$at$Multiple$Scales$Simultaneously
Brain#activity#measured#while#mice#run#on#a#treadmill:
THE$BRAIN$INITIATIVE®
Scientists(reconstructed(this(zebrafish(larva’s(brain(wiring(from(
16,000(slices.(Credit:(Hildebrand,(Engert,(Lichtman – Nature
• Develop(and(improve(large?scale(monitoring(of(neural(activity to(produce(a(dynamic(picture(of(the(brain
• Link(brain(activity(to(behavior(via(interventional(tools
Discoveries$from$BRAIN$Priority$Areas
THE$BRAIN$INITIATIVE®
BRAIN$Researchers$Create$Versatile$Probes$to$Interrogate$Circuitry
Dr.$Polina Anikeeva (MIT)$is$part$of$
a$Bioelectronics$Group$who$works$
at$the$interface$of$materials$
science,$electronics,$and$
neurobiology$to$create$devices$to$
manipulate$and$record$neural$
activity.$This$machine$makes$
flexible$neural$probes,$as$shown$
below.
THE$BRAIN$INITIATIVE®
• Next%generation%human%imaging%
technologies%(phase%2%awards)
• Foundations%of%human%imaging
• Noninvasive%neuromodulation
• Next%generation%DBS%devices%for%a%
range%of%disorders
• Public%Private%Partnership%Program
Researchers%are%improving%on%FDAB
approved%Deep%Brain%Stimulation%to%
incorporate%feedback%from%brain%to%
automatically%adjust%brain%stimulation%
from%pacemaker
Discoveries$from$BRAIN$Priority$Areas
www.braininitiative.nih.gov/resources/BRAIN_PPP/index
THE$BRAIN$INITIATIVE®
BRAIN$Researchers$Improve$Treatment$
Options$for$Chronic$Disorders
http://www.youtube.com/watch?v=xejclvwbwsk
http://www.youtube.com/watch?v=IOHtUzW02cg
Other$videos
THE$BRAIN$INITIATIVE®
• Of#345#BRAIN#awards,#80#projects#
involve#human#subjects#research
• Therapeutic#projects#in#BRAIN:#16#
awards#targeting#nine#distinct#disorders
– Developing#individualized#algorithms#in#DBS#
devices#for#Parkinson’s#disease#
management
– Using#DBS#stimulation#to#disrupt#circuit#
dysfunction#in#OCD
– Building#nextQgeneration#device#therapy#for#
cognitive#impairment#associated#with#TBI
• In#FY2017,#four#R01#grants#awarded#for#
neuroethics research
Blindness
Stroke
Parkinson’s$DiseaseObsessive$Compulsive$Disorder
Traumatic$Brain$Injury
Epilepsy
BRAIN$Funds$Tool$Developmentto$Improve$Health
THE$BRAIN$INITIATIVE®
2015%Overdose%Deaths:%
52,404%Any%Drug
33,091%Any%Opioid
Opioid%OD%Deaths%US,%2000?2015
266 260 253242 234
222
0
50
100
150
200
250
300
201020112012201320142015
OPIOID$M
ME$IN$BILLIONS
Source:%IMS%Health,%U.S.%Outpatient%Retail%Setting
Opioid%morphine%milligram%
equivalents%(MME)%dispensed%fell%
by%over%15%%from%2010?2015
Opioid$Prescriptions$have$started$to$Decrease$but$Opioid$Fatalities$are$still$Increasing
• ~64,000)deaths)from)drug)overdose)in)2016
• ~20,100)deaths)from)fentanyl/related$drugs
THE$BRAIN$INITIATIVE®
NIH$on$the$Opioid$Epidemic$and$Chronic$Pain• Address&rise&in&opioid+related&fatalities&via&3&pillars:
– Improve&overdose+reversal&and&prevention&interventions
– New&medications,&technologies&to&treat&opioid&addiction
– ID&safe,&effective,&non+addictive&interventions&for&chronic&pain
New$Notice:$NIH$welcomes$BRAIN$Initiative$applications$
targeting$central$nervous$system$nociceptive$and$pain$circuits
https://grants.nih.gov/grants/guide/notice+files/NOT+NS+18+008.html
BRAIN$Funds$Projects$Developing$Tools$to$Improve$Health
THE$BRAIN$INITIATIVE®
NIH$BRAIN$Initiative$2
Neuroethics
Neuroethics$Division$of#the#BRAIN#
Multi0Council#Working#Group#is#charged#
with#providing#input#on#how#to#address#
neuroethics#questions#raised#by#BRAIN#
Initiative#research
Neuroethics#Division#holds#topical#workshops#on#key#issues
• Ethical(Issues(in(Research(with(Invasive(&(Non5Invasive(Neural(Devices(in(Humans(
• Workshop(on(Research(with(Human(Neural(Tissue(
Neuroethics#Division#is#developing#Neuroethics(Guiding(Principles(for(NIH(BRAIN(
Initiative
• Principles#will#serve#as#an#overarching#neuroethics#framework#
• Will#include#practical#suggestions#on#how#to#integrate#neuroethics#into#BRAIN0funded#
research
THE$BRAIN$INITIATIVE®
• Need$ongoing$dialogue$between$neuroscience$researchers,$neuroethicists,$
funders,$and$other$stakeholders
• The$Guiding$Principles$serve$to$inform$this$dialogue,$and$are$framed$by$two$
general$points:
1)$Pursuing$neuroscience$research$is$an$ethical$imperative
2)$Neuroethics$is$vital$to$neuroscience$research
DRAFT$Neuroethics$Guiding$Principles$
for$the$NIH$BRAIN$Initiative
NIH$BRAIN$Initiative$A
Neuroethics
THE$BRAIN$INITIATIVE®Updating$the$NIH$BRAIN$
Strategic$Plan:$Beyond$2020$
BRAIN&2025&Report:"First&years&[should]&
emphasize&technology&development&and&
validation,&with&a&growing&emphasis&on&
problem;driven&neuroscience&after&FY2020&
THE$BRAIN$INITIATIVE®
New$panel$of$outside$scientific$experts$will$advise$the$
NIH$Advisory$Committee$to$the$Director$on$updating$
BRAIN&2025 to$guide$the$second$half$of$the$Initiative
Goals:
– Review$the$NIH$BRAIN$Initiative$progress$
– Identify$new$topics$and$questions$that$now$can$be$
interrogated$given$the$emerging$set$of$tools$and$
technologies,$within$a$solid$ethical$framework$to$
ensure$the$research$is$of$the$utmost$value$to$the$
public$it$intends$to$serve
– Identify$valuable$areas$of$new$and$continued$
technology$development
– Consider$the$unique$contributions$that$the$NIH$
BRAIN$Initiative$can$make$to$neuroscience
Working$Group$of$Outside$Experts$to$Advise$NIH$BRAIN
• The Website is a platform for funding opportunities, news, events, achievements, resources, and more related to the BRAIN Initiative.
A L L I A N C E
www.braininitiative.org
• The Alliance’s Mission is to coordinate and facilitate communications from its members related to the BRAIN Initiative.
NIH$Collaborates$with$Federal$&$Non5Federal$Groups
Walter'J.'Koroshetz,'M.D.
Email:'[email protected]''
Follow'us' @NINDSdirector
@NIMHDirector
Thank'You!
https://www.braininitiative.nih.gov/
Joshua'A.'Gordon,'M.D.,'Ph.D.
Email:'[email protected]