Neuroscience Caucus Briefing · 2018-08-20 · THE$BRAIN$INITIATIVE® Congressional$Neuroscience$ Caucus$Briefing Joshua'A.'Gordon,'MD,'PhD Director,'NIMH Walter'J.'Koroshetz,'MD

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.


“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?


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?$


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?$


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®


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


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


$$-

$$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


New$(FY2017) Since BRAIN$Began$(FY2014)

Number'awards 110 345

Number'investigators 178 504

Investment $169.6M $548.3M

NIH$BRAIN$Initiative$Awards


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


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


https://www.braininitiative.nih.gov/resources/publication.aspx

NIHAFunded$BRAIN$Researchers$Publish$Findings

Over$315 publications$have$emerged$

from$NIH$BRAIN$Initiative$to$date


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


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


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


• New$technologies$for$circuit$mapping

• New$interventional$tools$for$functional$

circuit$interrogation$across$scales

Ting%Hao Huang*et*al.*Development*2016;143:4073%4084


Crair,*M.*Yale*University,*BRAIN*Initiative*Project*funded*FY15*


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:


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



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.


• 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


www.braininitiative.nih.gov/resources/BRAIN_PPP/index

http://www.braininitiative.nih.gov/resources/BRAIN_PPP/index


BRAIN$Researchers$Improve$Treatment$

Options$for$Chronic$Disorders

http://www.youtube.com/watch?v=xejclvwbwsk

http://www.youtube.com/watch?v=IOHtUzW02cg

Other$videos

http://www.youtube.com/watch?v=xejclvwbwsk

http://www.youtube.com/watch?v=IOHtUzW02cg


• 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


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


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

https://grants.nih.gov/grants/guide/notice-files/NOT-NS-18-008.html


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


• 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&


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]

Documents

Neuroscience Caucus Briefing · 2018-08-20 · THE$BRAIN$INITIATIVE® Congressional$Neuroscience$ Caucus$Briefing Joshua'A.'Gordon,'MD,'PhD Director,'NIMH Walter'J.'Koroshetz,'MD