Dr. Octavio Choi presents Brain Basics: An Introduction to Cognitive Neuroscience

[Music]

so we're going to start uh in a moment

with um Dr Tavi Choy Octavio Choy um

I'll say I saved my sort of thank you

now for him um Tavi uh is also the

reason that we're having this program um

he is you'll read in your bio uh about

him in the briefing book um just one of

the the premier upand cominging um

psychiatrist and neuroscientist trained

both as an MD and a PhD uh Tavi is um

one of a new wave of um of doctors who

are um you want to change your slides

who are um uh introducing Neuroscience

into their clinical practice as well

Tavi um directs forensic uh Psychiatry

uh here uh in Oregon Works intensely

with the criminal justice system um and

is going to get us kicked off with the

really basic question of how does the

brain work he has the toughest job of

the entire day I told you tens of

thousands of people are trying to figure

out we're giving him about 40 minutes uh

to get us up to speed uh but if there's

one person who can do it it's Tavi and

with that um let me hand it off to

you he microphone microphone's working

uh this is actually probably the

toughest talk I've ever had to put

together trying to explain the brain in

40 minutes um and so uh let's get to it

so I'm an assistant professor at OSU uh

and I am the director of the forensic

evaluation service at the Oregon State

Hospital in that capacity I have the

privilege of living neural law boots on

the ground evaluating criminal

defendants uh with various types of

medical and uh brain conditions and

assessing how responsible they might be

for the offenses um so let's start with

a case that um of something that you

might all be in a position of

considering uh imagine there's an

defendant who was causing a public

disturbance was urinating in public uh

swearing in public and uh this is a

25-year-old man um no criminal history

excellent physical health never miss a

day of work in his life alert oriented

aware intelligent using language and

very well good memory intact memory

could learn new things and basically

when you ask him about why he did it he

just says well I don't I didn't

care I just didn't care now imagine if

two months prior to this incident

a tamping iron 13 in 13 lb 43 in Long

inch and a quart in diameter shot

through his skull and penetrated the

front of his brain would that uh kind of

affect the way you might think about how

guilty this person might be for their ax

might that in fact be a a strong reason

for why they this person behaved the way

they did uh a lot of you are smiling and

nodding your heads many of you know this

is the famous case of Phineas Gage the

most famous uh patient in Neuroscience I

think half of cognitive Neuroscience

textbooks start with the story of

Phineas Gage so uh who is Phineas Gage

he was a railroad Foreman back in 1848

suffered a terrible accident and uh from

the Boston Post he reported it a foran

in a railroad and Cavendish was uh

tamping down you know he was exploding

rocks to make way for a railroad track

and uh you have to put you know

gunpowder or the explosive and you Tamp

it down with a tamping iron which caused

a spark in the Rock and it exploded and

the tamping iron was driven through his

um through his

skull uh you know 100 years later um

back in 2004 uh spinus Gage's skull is

currently at the Harvard Museum uh and

the doctors has got his skull imaged it

in a 3D in a cat scanner created a 3D

model of the skull and was able to

digitally remaster exactly the path uh

of the of the tapping

iron so this is just uh showing off that

you know we have the skull we're kind of

creating a bunch of three slices uh with

this cat scan and reconstructing with

the computer to make a three-dimensional

model that's completely accurate in

every

detail this is part of the computer

Revolution with increase in computing

power you can take these two-dimensional

slices and make threedimensional models

and there you see uh the tapping iron

going through the skull

ouch uh now the amazing thing one of the

amazing things about um phas gauge is

that he survived and in fact he was

treated by a physician named John Martin

harlo who became famous by reporting on

the case of Phineas Gage and here's what

he had to say I'm going to just read

this because he's such a good writer the

equilibrium or balance so to speak

between his intellectual faculties and

animal propensities seem to have been

destroyed he is fitful irreverent

indulging at times in the grossest

profanity which was not previously his

custom manifesting but little difference

for his fellows impatient of restraint

or advice when it conflicts with his

desires at times pertinaciously

obstinate I love that yet capricious and

vacillating devising many plans of

future operations which are no sooner

arranged and they are abandoned in turn

for others appearing more feasible sound

like anyone we know I mean a lot of us

who work through you know with the uh

criminal defendants I mean this

describes a lot you know kind of very

impulsive uh kind of personalities but

the difference with Phineas Gage is that

before his injury

although untrained in the schools he

possessed a well-balanced mind was

looked upon by those who knew him as

shrewd smart businessmen very energetic

and persistent in executing his plans of

operation in this regard his mind was

radically changed so decidedly that his

friends and acquaintances said he was no

longer

gag now uh you know fenus Gage is often

pointed to as sort of the start of the

birth of modern cognitive neuroscience

and why is this he was really for the

first clear example written in the

literature of someone who suffered a

brain injury and had very specific

impairments which pointed to the key

principle of the brain that different

parts of the brain do different things

so if you damage different parts of the

brain there'll be specific impairments

that result so the key phrase um is the

equilibrium or balance between his

intellectual faculties and animal

propensities seems to have been

destroyed so his intelligence as he was

thought of back then was intact his

memory was intact he was was able to

have a conversation with you he knew

where he was he could learn new things

all that stuff was intact uh and also

his emotions were intact he was able to

feel happy and sad and all those things

but the balance between those two things

were was destroyed and I would argue

that the best way to summarize Phineas

Gage's impairments uh his brain deficit

was that his conscience was impaired by

that specific brain

injury so what is a

conscience anyone want just want

throughout his conscience was was

impaired in my opinion just my opinion

but so what what do we mean by

conscience Jim Cricket jimy what about

jimy

Cricket

oner okay so it kind of you know helps

you the right between the wrong and is

it a jimy cricket where it's a cognitive

thing where it's like you know the rules

are wrong or is it like an emotional

thing that stops you from doing what you

think is right or wrong

it could be both but what do you think

is more

important yeah anyone have this thing

where you know you're in the middle of a

you know kind of a deserted town in the

middle of the night and you're stopped

at this traffic light at the red light

you know there's no cops around right

but what what do most of us

do we're glued to that to that red

traffic light right we're not going

forward even though we know there's no

chance we're going to get caught so what

is it that's stopping us

the limic brain okay but explain it for

people who don't know what the limic

brain is it's that gut Consciousness

that you can't it's feeling and it has

no cognitive skill building it's just a

feeling yeah I would argue that it's

sort of like this bad feeling in your

body that you get automatically when

confronted with these kind of kinds of

dilemmas and it's that bad feeling I

would argue might be more important than

the rational I know this is wrong kind

of you know cognitive

thinking so uh you know the weird thing

or the interesting thing about Phineas

Gage is he seems to have suffered an

injury that impairs that part of the

brain which allows you to call up bad

feelings in response to something that

you know is

wrong so we'll get back back that back

get back to that in a moment but let's

just go over some basic

neuroanatomy so this is the picture of

the brain that you know many of us are

familiar with um you know this is a

cerebral cortex you can see this is

tough with a split screen I only have

one pointer

so so uh you know this is the Cal cortex

we can see that it's um this is the

surface of the brain we can see it's

split into various loes there's the

frontal lobe in the front there's a

temporal lobe next to the temples the

back of the brain is called the cipal

lobe and the pral lobe is in between um

and here is a top down view so we're

looking from top down you can see the

eyeball so it's like the brain is paint

pointed this way and you can see you

know an odd thing about the brain is

that you know like the left the right

side of your brain controls the left

half of your body and the the left side

of your brain controls the right side of

your body so you guys probably know

people who have suffered strokes and the

interesting thing is that the that the

side of the injury often results in

deficits on the opposite side of the

body these two halves of the brain are

connected by a bridge called the Corpus

colossum it's a huge uh series of

connections that connect the right and

left halves of your brain uh and coffee

brg asked me about split brain

experiments and you know neurosurgeons

have actually cut this bridge it turns

out what happens is that that splits you

into two different people that live in

the same body so it's a really fast

fting thing that we're not going to go

into more in this talk but um there's a

big bridge called a corpus kosum and

then this is a picture of the brain

looking as if the brain is looking right

at you and so you can see the Corpus

colossus's bridge and you can see that

there's stuff buried underneath the

cortex right uh so that's a really

important point so the brain is not just

what you see on the on the surface

there's stuff buried underneath there oh

another thing is you can see that the

brain has lots of convolutions and the

bumps are called gy and the dips are

called

suai and why do you think we have all

these convolutions and dips and suai and

stuff like that what does that

do increase the surface area right so if

the brain is a computer you can pack

more Computing Machinery into that same

area and actually if you look

evolutionarily these are different kinds

of primates and the relative sizes so

here's humans and we have the biggest

brains but we also have the wrinkliest

brains so when you look back in

evolutionary history the brains get

smoother and smoother uh so it's a very

interesting thing that we get more brain

Machinery stuffed in there by all those

f

so okay so another key point is that the

brain is a multi-layered structure it's

not just the cortex what you see on the

surface there's lots of Machinery

underneath there um so a lot of us know

about this Theory called U the Triune

brain which is put forth in the 7s um by

a Harvard psychiatrist named M mlan

basically he posited that when you look

at the Modern human brain you can you

can conceptualize it as being

constructed of three different layers

what do you call the reptilian layer the

lyic system and then the neom ion which

is cerebral cortex so if you look at a

MRI and here's the nose looking forward

here's the brain uh we consider these

this first most primitive part of the

brain to be called The Reptilian complex

which is the brain stem on top of that

is built a series of structures called

the lyic system and on top of that we

have the covering called the the cortex

cortex literally means

covering so okay so here's the cortex

and what the cortex in general does is

it manages all the computations required

for higher cognition stuff like language

stuff like high order object recognition

telling the difference between a Vango

and a and a rembrand uh Consciousness

being consciously aware of your thoughts

consciously aware of your feelings all

that fancy stuff that we consider being

human is tends to be um computed and

instantiated in the cerebral cortex if

we get rid of that upper layer we see

underneath it a series of a very complex

series of structures that I'm just going

to simplify and call the lyic system for

the hardcore neuroscientists I know that

that's kind of a simplification but

let's just call this middle layer the

lyic system and what this kind of you

know and lyic system does many things

but one of the key things it does is

core evaluation so you know our brains

evolve to Keep Us Alive and what the

lyic system does with core evaluations

is it scans everything on the outside

hearing s sight sounds touches uh

feelings inside our body and it just

scans for anything that you might want

to pay attention to because it's going

to help you survive so things like

donuts things like spiders like sexual

partners right so um if it sees you it's

constantly scanning if it sees something

that that's going to help you survive in

some way it goes dinging linging Ling

and tells the cereal cortex so then you

can actually go towards that donut away

from the spider away from right and it

doesn't and you know that that message

what does that message feel like it

doesn't feel like a message a text

message coming up on your phone it feels

like the feeling of craving like the

feeling of you want to go towards

something or feeling of Terror or fear

to move away so these core valuations

are computations done at a very low

level that scans the entire external and

internal uh environment in order to give

your cerebral your cortex a signal to to

move towards things or move away from

things and those signals feel like

feelings under if we get rid of the lyic

system um underneath that we have the

brain stem which has bunch of basic life

support so the brain stem is actually

the upper extension of the spinal cord

can you guys see okay here I I feel bad

because my pointer doesn't show up on

this thing so I'm sorry maybe I'll we'll

do like a Bono I went to a YouTu concert

and you know a circular stage the half

this Conant is this way and the other

half VI was this way so maybe Midway

I'll switch

over so the brain stem is the upper

extension of the spinal cord and it

handles a lot of basic life support

there are centers there that control

respiration and heart rate and basic

sensory processing uh there are sensors

there that are constantly sampling the

chemical environment of your blood to

make sure there's enough oxygen in it

for instance so lots of basic life

supports done there if you have a stroke

in your brain stem you generally die

like you know you don't have breathing

you

die okay so there's the brain stem on

top of that we have the lyic system that

is kind of constantly looking out for

things at a low level to help you

survive core valuations and on top of

that we have this H thinking brain the

cortex now another key principle that

the brain is hierarchically organized so

you know you are not aware of most of

the things your brain is doing right

anyone here consciously beating their

heart or you know can you forget how to

breathe not really right that's because

your your brain the lower centers the

brain stem the limic system they're

doing lots of things underneath your

underneath Consciousness they're helping

you stay alive and your coach is only

notified when it's just like a

corporation you have your underlings do

most of the grunt work answering the

lowlevel emails and anytime there's

something hm you know I think the boss

needs to know about this because there's

two conflicting emails and not quite

sure how to resolve it that that then

gets bumped up to the next level of the

hierarchy so for instance your brain

syst has basic life support systems uh

including sensors for oxygen levels in

your blood so if there's a low level of

oxygen in your in you know the oxygen

level in this room drops down these

centers are going to start getting very

excited saying H there's something wrong

here something wrong here I need to

notify the boss the brain stems boss is

the lyic system limit system is is is

it's monitoring everything even stuff

outside of your awareness and that

that's really cool like you're you're

not aware of you know the feeling of you

know the air on the back of your left

hand right I mean now you are but you

weren't before but I guarantee you if

there is a feeling of some fuzzy legs

walking on that on that AR suddenly syst

would say this is important I need to

tell the boss and you become aware of it

okay so if you have Dro an O2 that tells

the lyic system Lim system is sampling

lots of things including the feeling in

the back of your hand but if it gets a

message saying your O2 level is dropping

it says I need to tell the boss about

this this just can't go on right and so

then it sends a signal to the cortex

Cort cortex says yes oh I do feel like

I'm suffocating and so I'm going to get

out of here and possibly go

outside but please stay in the

[Laughter]

room so uh this is a busy diagram this

is um a diagram from one of the um

references that we put in the briefing

book uh one of the latest issues um

articles about the brain circuitry um of

drug addiction and so uh you know don't

get overwhelmed it's easy to get

overwhelmed with these has of diagrams I

just want you to pay attention to three

different areas the amydala the vental

striatum and the orbital frontal

cortex right so have to give some love

to this side the amydala the vental

striatum and the orbital frontal cortex

now the amydala and the vental serum are

part of the lyic system doing those core

evaluations the amydala tends to be

scanning for things that could possibly

be threatening to you and you need to

move away from and when the amigdala

activates that feels like fear get away

the vental striatum is is uh Cally known

as the pleasure center of the brain and

these are all oversimplifications every

brain area kind of does everything but

just to keep things a bit more simple

the vental starem it's called the

pleasure area of the brain and it tends

to be looking out for things like donuts

sexual partners it gets excited when it

sees things that you might be interested

in moving towards and that feels like

pleasure feels like anticipation if it

activates and the thing isn't there like

if you're C if you see you want a donut

but there's no doughnut there if that

activation feels like

craving now um obviously you don't want

to act on every single impulse your

amydala and eventual strim is saying you

don't want to you know unless you're a

presidential candidate you uh you know

you see an attractive sexual partner

you're gonna you know you're GNA

generally want to say you know I I

couldn't resist I'm sorry um but that's

where your cortex comes in so your

orbital frontal cortex is involved in

evaluating the signals coming from the

amigdala and the vental sprum saying it

adds context to what those drives are

telling you to do it says well maybe not

maybe we shouldn't go you know grope

that person or maybe we shouldn't have

that you know six donut you know um or

you know the amydala is like a little

it's the amydala is like a scared little

kid that everything freaks freaks you

know that little kid's out you know so

sees a spider and the midd goes oh my

God there's a spider there's a spider it

gets very active and excited and the

orbital frontal cortex adds context it

says you know what there's a cage around

that spider we're actually in the zoo so

you don't so calm down Amiga it's going

to be fine or you know you know the

vental stum gets very excited you know

seeing a dut and the fral square just

says you know the last couple times you

kind of did overdid it with the donuts

and you felt really bad uh so it kind of

helps modulate and inhibit those drives

that come from underneath in the limic

system well guess part what part of the

brain was damaged in phineous

gauge the orbital frontal cortex the

tamping rod went straight through that

area that's the area that gives

emotional context to the drives and can

inhibit appropriately the drives that

should be inhibited

uh and so uh Antonio deasio and his wife

Hannah Antonio deasio is one of the

Geniuses of Neuroscience he's a

neurologist I don't he used to be in

Iowa I'm not I think he's he's moved

around he's at USC

now some great Folks at

USC um and he did a he studied this area

the brain called the vent so it's the

orbital fral cortex his phous gauges

tamping iron it went through and here's

a side view of the brain with the brain

looking forward this way and then

underneath the vental surface of the

brain eyeballs be here so you're looking

underneath this section of the brain is

called the orbital frontal cortex it's

also called the ventromedial prefrontal

cortex that was the area those damage

and Phineas gauge and he um his lab was

really instrumental in studying stroke

patients to understand what this part of

the brain was doing because the

fascinating thing is if you damage this

part of the brain your memory is fine

you know you know where you are your use

of language is fine your cognition is

fine and also your emotions are fine

they're able to feel happy and sad but

they no longer seem to care about uh

about inhibiting things that we would

find socially kind of

repulsive right so I would argue that

that's what keeps us from urinating in

public even though we have a really full

bladder we're just not going to do it

the reason we don't do it yeah we know

it's wrong but the other reason is we

know we would dive of embarrassment

right and that feeling is it's a feeling

that stops us it's this feeling of I

feel really bad in my body contemplating

doing this and that's what generally

stops us from doing things that and

where did that feeling come

from how do we get that feeling in our

brain were we any of you have babies do

they have problems urinating public AB

we learned that right it's a series of

learned emotional respon it's like you

did something you're in public and then

you felt bad somehow mommy said don't do

that and you felt bad in your body over

time you developed an emotional linkage

of an state of your body with a certain

context that is exactly what this part

of this brain is doing

so um people with damage in this part of

the brain they have something called

emotional Amnesia they can feel emotions

but they just don't store it so they

can't form those linkages between a

context and a feeling in their body that

would ordinarily stop many of us from

doing stuff like urinating public or

groping um

people okay so deasio the way he put it

is this area of the brain holds linkages

between the facts that compose the

situation and the emotion previously

paired with

it and I would say that is actually a

major part of what the conscious is this

is where this is one of the main brain

areas where con the the conscience uh is

instantiated okay and you know in

general fenus gauge was an important

case of some someone who suffered a

specific brain injury and had a specific

deficit thereby showing a key principle

that different parts of the brain do

different things that's principle is

called functional

specialization uh and actually the man

sitting there Michael Posner is one of

the key people who established uh that

that principle on the

brain and so uh you know this idea that

different parts of the brain do

different things that might sound like a

really obvious idea uh to modern day

people but it was not an obvious idea

hundred years ago and in fact there was

a raging debate between the holists and

the localists uh so P Pier Floren was

one of the main proponents of holism

which said like you know the brain is a

is a computer and all parts of it are

undifferentiated so really you know

impairments have to do don't have to do

with the location of the impairment it

has to do with the size of the

impairment of of the damage right so

every brain part is kind of

interchangeable France Joseph Gaul uh

was a opponent of localism they said no

no brain areas are highly specialized

okay different parts of the brain do

different things but he took it a little

too far he's the he's the main guy

between uh for the theory of phenology

uh which you guys know phenology right

bumps on the surface of your head means

you're criminal it means you're a good

person I have a very bumpy head I don't

know what that I uh I shaved my head to

go into Meditation Retreat a few years

ago and I was like oh my God I'm never

shaving my that's why my hair is kind of

like you know I I've God would hate me

but he he took it too far you know he

said you know the the brain is divided

into areas and there's an area for

acquisitiveness and there's a area for

sublim whatever Sublimity is and an area

for mirthfulness and he very there's one

area of the brain that does that and

that that's nonsense that's taking it

too far um because when you think about

it any task that you do like let's say

you're reading right when you think

about what that task involves it

involves looking at looking at words so

there's a visual system involv it right

then you it's understanding the word so

there's you know there's processing of

what that visual signal means it might

invoke memories right so and those

memories might invoke kind of behaviors

and decisions you want might want to

make each of those different uh

qualities of that task is done in

different parts of the brain so even

something as simple as reading a single

word activates different parts of the

brain uh associated with those

Elementary tasks does that make sense

and that's what Dr posner's work with

his colleagues at the at Washington

University established in a series of

super elegant studies I I love reading

those

studies when I read those studies I feel

like oh I understand the

brain okay so actually the you know

localism is taking it too far holism is

also taking it too far there's this in

between thing called distributed

processing and that's the principle that

I just elucidated where you know it's

not that there's one part of the brain

that does you know a single thing but

there you know any task that you have

has Elementary cognitive operations and

each of those Elementary operations are

done by different part of the brain does

that make sense so it's a collection of

specialized modules that get gets

invoked dynamically depending on the

task that's at hand right okay good

nodding heads good um now um phas gauge

was a loss of function study uh you know

a tamping iron went through a certain

part of his brain you know and he lost

some ability and so people started to

make correlations between parts of the

brain and the and the parts and what you

know what kind of functions that uh are

done by that part of the brain uh many

of us are probably familiar with Strokes

Strokes um stroke patients so that's

another loss of function study where

part of your brain gets knocked out and

by studying what kind of impairments

result from that you can make inferences

about what that brain area is useful for

right make

sense uh in fact you know some of the

seminal studies um early studies on

brain localization were had to do with

aphasias or language deficits and so you

guys heard of broka and wariki these are

two famous scientists neurologists

around the turn of the century who

studied uh some fascinating par uh

patients who had language deficits in

different parts of their brain let me go

over here for a little bit

so broka Pier uh uh broka was a French

neurologist who found that a bunch of

his patients lost the ability to

vocalize language so they could

understand language when you spoke to

them and they could do execute command

you know you know if you said set them

for them to do something indicating that

they understood language but they were

they had a really hard time generating

language and speaking so he discovered

that these patients had a damage in an

area of Cortex called broa area and

interestingly that brokus area is right

next to the part of the brain that

controls the motor muscles of the lips

and tongue so damage to this area um

results in impairments where patients

can understand language but they have a

hard time generating

language is

it boy is it that Landing

[Music]

down it's hard to hear this person

having a whole lot of time expressing

language cookie

jar you wouldn't call this person fluid

right she has damage in broke his area

now there's another area called wor

Niki's area which is close to the

auditory cortex where it uh with the

part of the manand process is uh

incoming sound signals damage to the W's

area results in a language deficit in

which people can generate language just

fine they're talking up a storm but once

you but they can't understand language

spoken language they can understand

written language which comes in through

a different pathway through the visual

cortex but they can't understand spoken

language so when you ask them to do

something in a verbal command they

respond with very fluent nonsense so

here's an example what are you doing

today we stayed with the water of here

at the moment and talk with the people

for them over there they're diving for

them at the moment they'll save in the

moment heal of water very soon for him

with luck for him so we're on a cruise

and we're about to we will s right here

and they'll save their hands right there

for them so that's brok's area so those

early studies were super uh interesting

and important for establishing again the

different parts of the brain do

different

things um s also around the turn of the

century a guy named broadman uh had a

microscope a novel technology at the

time um and uh by studying he by

stamping little core samples from

different areas of the cortex and

looking at them under the microscope he

could see that cells look different in

different parts of the brain and he

hypothesized that the reason those cells

look different is because those these

brain areas are specialized and do

different things so this is a broadman

map and you might many of you might have

seen this we still use this map of brain

areas which he numbered like area 17 is

primary visual cortex and

neuroscientists still refer to brokas

areas uh so it's another indication that

if you look at the at the microscopic

level of different parts of the brain it

looks different and that that that

supports a theory that different parts

of the brain do different

things any questions so far or yeah this

is all good okay so um now broka I

should have I learned this thing trigger

alert trigger alert I hadn't heard this

before yesterday I need to warn you for

anything that might potentially be

traumatic um

and my tone of voice was a little

sarcastic I don't mean that um but um

bernicki and broka um you know they

discovered where the where the damage

was in their patients's brain by they

had to wait until those patients died

and then they had to slice up those

brains literally with a knife and then

find little goobers and stuff then like

oh okay this you know this is seems to

be where the problem is now you can

imagine that's an incredibly slow

process right like you have you know

five really interesting patients and you

have to wait 10 or 20 years until they

die or you know unethically hope that

they die sooner now wouldn't wouldn't

the whole Enterprise be a lot more

efficient if you could look to see where

the damage was in the living person

right that would be fantastic right and

so that's what the Imaging revolution

has done to help us um so I'm going to

talk about s the evolution of brain

Imaging so the X-ray we all know about

x-rays invented or discovered by renen

um he reported in in a a meeting in 1895

that he discovered these X-rays and this

is the very first x-ray he took over

wife's hand and you can see the ring and

his wife was repeated to have said I

have seen my death when she saw this

scan now x-rays are amazing uh x-rays

work by shooting um um high-intensity

waves called x-rays through a person's

body and on the other side is a

photographic plate and then some stop

x-rays more than others like bones stop

X-rays and you know really well leading

to light areas in the X-ray and tissues

tend to soft tissues tend to stop them

not so well they go through and so the

photographic plate gets start so they're

called shadow

pictures um and here's a skull X-ray and

you know the the dream was maybe we can

see the brain with this x-ray stuff

right but the problem was U the brain is

inside this thing called the skull and

the skull is a really dense thing that

stops most X-rays and so it's really

hard to see also with an x-ray a

threedimensional thing is flattened into

two Dimensions so it becomes really hard

to tell anything apart that's why

Radiologists get paid the big bucks they

see something something this and they

can they can turn that into a three

dimensional image in their

heads so for a long time the brain was

called The Dark Continent we had no way

of Imaging it now I think around the um

50s 60s someone had the body idea of of

injecting air into the brain because air

is very not dense uh and compared to

brain tissue we might be able to tell

the difference in the X-ray so the um

the brain has a series of interconnected

fluid canals called the ventricles right

the ventricles make cerebral spinal

fluid and bathe the brain in fluid uh

someone had the bride idea of taking a

syringe of air injecting it through the

brain and injecting air into the system

and then you'd be able to see the bubble

of air with an

x-ray later on people said you know we

actually don't need to go right through

the brain we can go through the spinal

cord with a spinal tap kind of procedure

and that was a lot better um but still

these are the kind of images you get

right it's going to be hard to tell Pro

I me you can tell some if someone has a

major problem with their ventricles you

can tell something's going on but it's a

low resolution image and I like seeing

this to remind us how far we've come you

inject the air bubble and then you

they're in this chair that kind of puts

you in different positions and then you

take x-rays in those different positions

as the air bubble moves to kind of this

was supposed to be an incredibly painful

procedure and the joke was that this uh

this um procedure was uh therapeutic

because the patient whatever their

complaint was never came back to you

again so this was the

60s okay um shooting ahead the CAT scan

um it was invented in the 60s The

Beatles were an incredibly important

part of developing the CAT scan the CAT

scan was developed by Emi which is also

the record label the be the Beatles Emi

ended up with a just a ton of money from

the Beatles albums they said what can we

do with all this money an engineer uh

you know at Emi said I know what to do

with that money with the rise of

computing power I can develop a new kind

of X-ray that will take a series of of

x-ray images in in a rotational Manner

and with my computer algorithms can

reconstruct a three a two-dimensional

and then a threedimensional structure of

the brain um and um you know amazingly

it worked so when you look at a cat

scanner this is the inside what this is

is a spinning x-ray where you have an

x-ray SCE that's spinning in a circle

and there's a photographic plate and

it's taking like a million x-rays right

and then magically if you do take a

million different you know x-rays from

different angles reconstruct that with

the computer you can now start to look

at brain

tissue so this is the first uh CAT scan

um and can you see see anything here

there's a dark spot right there so it's

fantastic it's always great when the

first cat scan shows something you can

actually do something about so this

turned out to be a tumor that was

reected uh and you know houndsfield went

up went on to win the Nobel Prize and it

it was all

good uh the MRI is a technology that

we're most of us are familiar with it's

our modern Imaging method uh and it's a

much bigger machine so here's a person

here's you know and the MRI and it take

you know hours of physics to explain

exactly how it works works but uh

suffice it to say that the MRI can

interrogate magnetic signals all

throughout your brain and because your

brain is made of different different you

know comp compositions of water and fat

and different kinds of molecules it can

actually distinguish those magnetically

so those have different magnetic

properties that can be converted to an

image um and so and the MRI resolution

is uh depended on magnetic field

strength so the early MRIs were 0.35

Tesla then there were 1.5

Tesla then you went up to 3.0

Tesla then you went up to the modern

research uh scanners have seven Teslas

and if you compare the difference

between the 0.35 Tesla and the Seven

Tesla there is a remarkable Improvement

in

resolution uh the world's most powerful

MRI is being constructed there's a

that's a person inside there um it's

going to generate an almost 12 Tesla

signal which is just enormous and with

that with that enormous magnetic

strength the voxal or the brain elements

that get get image gets smaller and

smaller so we're getting incredibly

we're going to get incredibly high

resolution um pictures of the brain and

like many big science projects keep

keeps getting pushed

back uh now that's loss of function

studies um which are really useful but

it's sort of a kind of like if you want

to figure out how your iPhone work it's

like if you took an ice pick and stabbed

different parts of your iPhone and said

oh well this doesn't seem to work

anymore right it's kind of a slow

laborious process so what we'd really

like to do is study the intact

functioning brain what is the normal

function structure and function of the

brain and so that's where functional

Imaging studies come in and that's

really a revolution so the two main ways

to visualize brain activity these days

are with pet and with epari uh and a pet

studies are amazing and uh they can't

and they can do things that fmri can't

do I'm going to focus mostly on fmri

which is used more uh pet requires

injection of radioactive particles and a

lot of patients kind of don't like that

so much so fmri it's all done with

magnets so it's safe and it's even

holistically beneficial so fmri so the

thing with fmri to really a key point is

that you know although these pictures

are very pretty and it looks like we're

looking at brain activity we are not

looking at brain activity we are looking

at an indirect measure of brain activity

we're actually looking at a vascular

response to brain

activity so the fmy visualizes a

vascular response to brain activity not

brain activity

itself and so you know the principle is

if a part of your brain is working hard

it's going to recruit more blood flow

that extra blood flow is going to change

the magnetic properties of that part of

the brain and that can be visualized on

the

fmri so the fmri actually visualizes

what's called a relative oxygenation

level which is an indirect measure of

brain activity because your brain's

working hard recruits more blood blood

oxygen level goes up and that can be

seen on the

MRI now so uh this is an important slide

and I you know I see the references in

the briefing book in this you know

there's many limitations of EP we're

looking at a correlation of vascular

response to brain activity and all

correlations are imperfect and there's

people who've made their careers

studying how th those things can be

mismatched uh the other thing to really

understand is that this is a highly

processed image this is not just a

photograph of your brain activity this

is a highly refined image with many

steps and statistical assumptions behind

it uh there's a lack of standardization

so that one lab's FMI machine has a

bunch of settings that aren't the same

is another lab's fi machine so you can

imagine if this gets into court and it's

really been resisted in courts because

you know one one lab's FMI you know

image can look very different from

another ones if all the settings are

different right there hasn't been

standardization in the same way that DNA

analysis has been completely

standardized from Lab to

lab um and also some of the statistical

assumptions have been shown to be faulty

in fact there's a major paper this year

that was incredibly disturbing to fmri

researchers that showed that based on an

obscure setting in the software of most

fmri software packages that up to 70% of

the results might just be

BS so it's still a new technology it's

developed in the 90s but it's still

relatively new uh fmis is being used

more and more in fact Sarah Fel Ying

will um present I hope on her elegant

studies showing or I'm not going to tell

her what she's going to present but

she's done very elegant work looking at

adolescence engaging in therapy seeing

what parts of their brain are active and

using those FMI images to refine what

kind of therapeutic interventions uh

might be U the most

effective so different parts of the

brain do different things that's how we

get these colorful maps that you can see

if you open up any web

page another key principle brain areas

are wired together right they talk they

do these different things and they talk

to each other they form these local

circuits right so this is a circuit that

we've talked about already there's the

amygdala the part of the lyic system

that gets really excited over things

that are scary the vental striem the

part of the brain that gets excited over

things that like donuts

um and the orbital FAL cortex it says

hey maybe we shouldn't follow every

impulse that we that we you know that we

might have and in fact you know what's

uh hope what Dr Compton I think will

talk about is how this circuit gets

corrupted uh with as you develop a drug

addiction when you look at the

microscopic level of what these wires

are composed of they're composed of a

brain cells so here's a high resolution

picture of a brain cell with a cell body

a the wire which is called the axon and

then the end of it which is called the

axon terminal and so this is the basic

Computing unit of the brain and you know

what's what's interesting about this is

that this is a chemical electrical

chemical system so the dendrite has the

cell body has lots of extensions that

sniff around the chemical environment

looking for things that it makes it

excited chemicals that make it excited

if it gets excited it generates an

electrical charge that then gets sent

down the axon in an electrical impulse

at the other end it releases chemicals

called neurotransmitters which then

continues the brain

communication that's why the brains are

uh you can you can control brains with

electrical you can put an electrode in

someone's brain turn it on and see weird

things happen you can also give people

uh drugs right medications different

kinds of chemicals and that will affect

brain function that's because it's

affecting the the chemical environment

which gets picked up by the neuron does

that make

sense okay and this is a high resolution

view of what the end of one axon with

the start of a new neuron so here's a

two neuron circuit here's the axon The

Wire right and then it's connecting to

the second neuron and this connection is

called the synapse right so I'm going to

show you a high resolution view of the

synapse so the electrical impulse called

the action potential comes down at the

end it releases chemicals called

neurotransmitters in this case

acetylcholine those neurotransmitters

diffuse across the synapse and bind to

receptors so here's a re receptor it

binds to the receptor and what that

binding does is open up the pore which

allows electrically charged uh molecules

to come in which can continue the

Electrical uh

process uh here's an incredibly

impressive example of brain wiring

diagrams Carl daero is a name you should

all be aware of he is 100% guaranteed to

win the Nobel Prize uh one of the things

his lab uh invented was a a method of

making the brain Clear so this is a

mouse brain and he made it clear once

you make it clear you can fluorescently

label uh brain cells and look at

circuitry at a whole brain level so

here's one of the really impressive

videos from his lab where he's showing

you the mouse brain he's showing you how

they're taking two dimens you know two

dimensional slices which they're going

to feed into a computer to construct a

completely accurate three-dimensional

model high resolution model you zoom in

you can see you know this is the whole

brain these are the axons you can see

you know axons coursing back and forth

and it's all in the computer so you can

rotate you can make parts of it

transparent so now the computer's

reconstructing the three-dimensional

model which is then you can then rotate

and you can then fly through the brain

look at cellular level resolution I mean

imagine this 100 years ago this is an

incredible credible

technology Carl

diero

yeah this is the part of the brain

called hippocampus which is important

for memory and again he's just slicing

through these are the cell bodies you

can see these wires are the axons here

he's labeled different sets of neurons

with different colors

you can then take each slice reconstruct

it with a computer make a

three-dimensional model and this is not

an artist rendition this is an actual

part of the brain with all the wiring

intact okay um in the in the human

beings we can uh image this with

diffusion tensor Imaging uh diffusion

tensor Imaging allows us to see the

wires in the brain does that because

when you look at neurons they um they

have water in them and water tends to go

up and down the Axon DTI Imaging looks

at the the movement of water molecules

and from that you can infer um where the

connections in the brain

[Music]

are so we have these very high

resolution DTI Imaging maps of different

um these are all the different kind of

wires in the brain and we get we get

those wires by looking at where molecu

molecules of water are going back and

forth okay I'm gonna just finish up with

one last

slide so I talked about the brain it

does core evaluation you know the lmic

system is looking out for things that

helps you survive Donuts sexual partners

spiders move away from move towards

right and then the upper hearts of the

brain the cortex puts those core

valuation into context it's cognitive

context saying well you know you ate

your six dut and you didn't feel so good

emotional context where you felt bad in

your body when you over binged on Donuts

before so it says maybe we shouldn't

listen to the core valuation so much and

that's built up through past experiences

so if you see a donut you know your

ventum goes dingl lingling ding lingling

uh so that creates that feeling of Drive

of wanting to move towards that donut

and I'm from Portland so that's why

there's so many donuts in my talk we

have fantastic

Donuts uh you know and that you know it

brings up facts and reasons Donuts are

good Donuts are Tasty Donuts have 8,000

calories it also brings up emotional

context of these linkages of what

happened and how you felt the previous

times you eat donuts these are all

connected in a circuit right and then

from the activity of those of the

circuit you come up with a with the

decision eat or don't

eat um and if there defects in either

brain areas or their connections you're

going to have impaired decision- making

and a lot of what happens with drug

addiction is that this circuit gets

corrupted over time so you make worse

and worse

decisions I just want to make a shout

out for this is the last slide so um you

know how do we change the Cog the way we

think about things generally with

psychodynamic therapy with therapy kind

of reframing what some with the

cognitive mean meaning of something is

right um how do we work on the emotional

context well we have therapies like CBT

which change the kind of emotions we

actually link to a certain

situation and um Sarah I might talk

about her work or not but she's doing

fabulous work looking at different ban

areas that are activated by different

kinds of therapy uh to guide what really

what what's what are the active

ingredients that make therapy

effective now you can control the you

know the co core valuations with

medications and with new techniques that

I hope our other speakers will talk

about Mar and fireman are is going to

talk about medications that it might

affect the activity of these of these

levels maybe turning down the vental

stardum activity a little bit so you

have less craving and Virginia kusan

Carlson and Kathleen Grant I hope we'll

talk about just some fabulous research

using dreads which are uh designer drugs

that can activate receptors in just

specific very specific neural circuits

to turn them up or down so imagine there

was a tiny little spot in the vental

spum that led to craving for cocaine

imagine there was just one spot there

imagine if you can selectively turn down

the activity of just that one spot and

get rid of craving for cocaine that's

the promise of the the of the kinds of

approaches that these guys are trying to

do we have a great day ahead of us thank

you so much for being here and it's a

pleasure to to talk to you guys thank

you