The following content is provided under a Creative
Commons license.
Your support will help MIT OpenCourseWare continue to
offer high quality educational resources for free.
To make a donation or view additional materials from
hundreds of MIT courses, visit MIT OpenCourseWare at
ocw.mit.edu.
PROFESSOR: So when we talked about learning, we said that
everything we know comes from learning except that which is
given to us by our genes.
Our knowledge of how to walk around in the world, to read,
to think, to talk, to feel, the values that we have, the
hopes we have, the fears we have, they're all learned
through experience.
And then we talked about another approach to thinking
about how we learn things through memory, and today I'm
going to talk about what we understand to be the brain
organization of human memory.
And Oliver Sacks, in The Lost Mariner, chapter 2, talks
about one of the two major kinds of amnesia, the loss of
memory due to a brain disorder or a brain injury.
But he has a very nice language from Luis Bunuel
talking about memory. "You have begun to lose your
memory, if only in bits and pieces, to realize that memory
is what makes our life.
Life without memory is no life at all.
Our memories, our coherence, our reason, our feeling, even
our action.
Without it, we are nothing.
I can only wait for the final amnesia, the one that erases
an entire life as it did
my mother's." Right?
So our memories of our lives, what we've done, where we've
been, what mattered to us--
that's a huge piece of who we are.
And he runs into a patient who came into the hospital early
in 1975 with a note saying "Helpless, demented, confused,
and disoriented." He had what we call
clinically Korsakoff's Syndrome.
So these are individuals who have severe alcoholism for
many years, and a subset of those people develop a severe
memory disorder, like this man.
He's 49 years old.
He tells Sacks about his life, details of his life, going
into World War II, that he worked on a
submarine, and so on.
And Sacks says, "a full and interesting life remembered
visually in detail, but for some reason his memories stop
around World War II."
Then he asked him, what year is it?
Remember the year is 1975.
And he says, it's 1945.
What do you mean?
We've won the war, FDR--
Franklin Delano Roosevelt-- is dead, Truman's at the helm.
These are great times ahead.
And Jimmy, how old would you be?
He stopped and he said, well, I guess I'm 19.
That would have been his age, you know, 20 years ago, right?
30 years ago.
So he's stuck in time.
He thinks it's historically a while ago.
He has the completely wrong age.
And Sacks takes out a mirror and throws it at him and says,
what do you--
what happened?
And he says, Jesus Christ, what's going on?
What happened?
Is this a nightmare?
Am I crazy?
Is this a joke?
So it's as if he's lost the last 30 years of his life.
And he's living as if it were 30 years ago.
And then when he walks back in, he's hardly recognized.
Sacks is hardly recognized by the person.
On intelligence, he shows excellent ability, but his
memory-- very quickly, he forgets things.
What is this, I asked him, showing him a photo in a
magazine I was holding.
It's the moon.
No it's not, if it's a picture of the Earth
taken from the moon.
I'm mean, don't forget, in 1945, nobody imagined that we
would be sending up people to the moon, right?
And taking pictures from the moon of the Earth.
You're used to it.
It's nothing to you.
No it's not.
It's a picture of the Earth taken from the moon.
Doc, you're kidding.
Somebody would have to get a camera up there.
Naturally.
Hell, you're joking.
How would you know that?
So he has lost the last 30 years of his life, for all
practical purposes, despite normal
intelligence and normal thought.
So we're going to talk more about how this occurs in
another patient, and more generally, how the brain
supports your ability to learn things.
So here's this remarkable brain.
And in one sense, you could say it's almost all there to
absorb things in life.
You have very small insects that can do a lot with the
genes they're given.
We have big brains to learn the life we lead.
And I'm going to come back at the end to this metaphor, but
the idea that in many ways, your brain as you sit there
right now, or any healthy brain, is kind of like a
symphony orchestra that has many specialized instruments
for learning different kinds of things.
And you feel like a unified whole, and you are, and these
instruments interact with each other.
But just like a symphony orchestra, you know, together
they make a sound.
So imagine you're a Martian who lands outside a symphony
hall, and you hear a symphony playing.
It's something beautiful.
It sounds really interesting.
If you're a Martian on the outside of the symphony hall,
how many instruments are you guessing, how many things
might you guess, are making that sound?
Would you have any idea?
One big one?
Two big ones?
50?
It'd be very hard to guess.
And it's only been in the last 20 years or so that we had
some real clarification on the instruments of
learning in our brains.
So I'm going to talk about three things today.
Anterograde amnesia, the loss of the ability to form new
memories; retrograde amnesia, the loss of memories you
already had; and that idea of memory systems, this idea that
each of us has a symphony of learning instruments in our
brain that empowers us to learn
different kinds of things.
So anterograde amnesia is, again, the inability to
remember new information.
And people mostly talk about two kinds, but as you see,
they're most of life, OK?
Not all of that-- we'll talk about that-- but a lot of it,
such as events you experience or facts you encounter.
So think about this.
All the events you've remembered from your entire
life, all the facts you ever learned in school, at home, on
the computer--
that's a huge amount of what you know.
And a patient like we just described or the patients I'll
describe in a moment lose the ability to remember any event
from the day they become amnesic or remember much in
the way of new information of any kind, in terms of
facts of the world.
So in what sense is memory in the brain
distributed or localized?
In what sense is it in one place or many places?
And this has been a central debate in all of neuroscience,
but in memory, too.
And Karl Lashley, a giant of neuroscience, who worked just
two T stops away at Harvard, said this: "It is not possible
to demonstrate the isolated localization of a memory trace
anywhere in the nervous system.
The engram is represented throughout the brain." The
engram's kind of a magic word in memory and the brain.
The engram is the thing in you that changes in your brain
that is the stuff of a memory.
If you learn today that there's more terrible news in
Japan with the nuclear reactors, and you remember
that because it matters to you, because you care about
the people, there's a physical change in your brain that is
the memory.
If you remember what I'm saying now for more than a few
moments, that is a physical change in your brain.
So all of us in neuroscience are amazed by that.
How can we physically change the brain to be the biological
record of a memory, that we can keep
and use in the future?
And the engram, Karl Lashley said, is represented
throughout the brain.
It's spread throughout the brain.
Here's why he thought that.
So he was working with rats, and they ran a maze.
And you saw how quickly you learned the maze to go from
start to finish to get the food if you're a rat.
And here's what he found, and the results won't amaze you,
to start with.
So what he did is he made--
this is number of errors during learning, so
it's good to be low.
And this is how much neocortex they took out, ranging from
10% to 80%.
And he discovered that the more neocortex you took out,
the worse learner you were.
Now if it didn't happen in some broad sense, we'd say,
well, what part of us is learning it?
You take out more brain, you're less of a good reader.
10% out, 10% percent bad memory.
50% of brain out, 50% of bad memory.
80% of the brain out, 80% bad memory, right?
OK, that makes sense.
But what he was really impressed by is it didn't seem
to him to matter where he took the brain out of the rat.
It just didn't matter.
It's just the percent that he took out.
Whatever percent he took out is how bad
the learner you were.
And we'll come back to that, but that's why I said, it must
be spread everywhere, because wherever I take out brain,
part of the memory is weakened or disappears.
And sometimes people call that mass action for distributed
memory, that's spread throughout the brain
in this mass way.
It's just spread all over the place.
And a single clinical case--
I'll spend a few moments on him for two reasons.
It is the historical case that turned this around, and I have
a particular perspective on this because when I was a
graduate student, I did a lot of work with this single
patient whose case turned around our understanding of
the mammalian brain and memory.
So as I start to talk about it--
I can't tell you what Phineas Gage was really like, beyond
what I read, OK?
Or Broca's patients from the 1900s.
I can tell you what HM, the man we're about to talk about,
was like because I spent many, many hours with him, two
blocks from here, when I was a graduate student in Suzanne
Corkin's lab.
So the structure we'll focus on is something called the
hippocampus.
It looks sort of big in the picture.
It's about the size of about 2/3 of your thumb, one on the
left and one on the right in the insides of the medial part
of the temporal lobes.
A pretty small percentage of the brain.
And you can see it's located here.
Here it is sort of drawn out.
And here's the story of this man.
He died a couple years ago.
There's lots of plays and movies and books in the works.
I can also tell you that when I was a graduate student here,
my fellow graduate students would say, tell us who HM,
what his initials really stand for, as if it really mattered,
particularly.
But I felt privileged to have the secret knowledge of what
his name was.
When he died, they published it.
Everybody knows now, so my secret is out.
Or our secret is out.
He was born in 1926.
At age 16 he had his first major epileptic seizure.
By age 27, he was having many, many seizures a day.
You can have petit mal seizures, where you tune out
from the world.
You can have grand mal seizures that lead to physical
convulsions.
By age 27, the medications were not helping him, in 1953,
very much, that were available.
And he was just sitting in his house just waiting for the
next seizure, basically.
That was his life.
He was a man of normal intelligence and fairly
typical, average background.
Nothing remarkable.
And in order to treat the epilepsy, William Scoville,
the surgeon, resected, or took out surgically, the tissue.
Here's this cartoon of what he took out--
the hippocampus, also the amygdala just in front of it,
also tissue that surrounds it.
And the reason he took it out is the single most likely
place where epileptic seizures start is the hippocampus.
It's kind of a signal, in many ways, that the hippocampus
does something very dangerous.
It's operating in some sort of fast speed lane of
neurobiology.
It's a very sensitive part of the brain, for lack of oxygen,
for diseases.
We'll talk about Alzheimer's today.
It's a very vulnerable part of the brain, but it does
something magical and essential for memory.
And so they couldn't locate where the seizures were
starting, very well, from him in ways they typically do, so
they said, OK.
He has all these seizures.
We don't know what to do.
Let's take out the left and the right hippocampus and the
surrounding tissue.
And in terms of seizure control, it was pretty
successful.
He had to stay on medications from that day 'til a few years
ago, when he passed away.
But he had very, very few seizures
compared to before that.
So it was medically very successful in
terms of seizure control.
It had a giant side effect.
From that day 'til a couple years ago, HM never formed a
new memory for any event, or for all practical purposes,
for any fact that he was exposed to ever again, despite
his normal intelligence and his
otherwise intact abilities.
So they took an MR of HM.
It took a long time to decide they could even take a MR
picture of HM, because they were very worried that if you
put him in a MR scanner, there's magnetic fields, and
often they put in clips after surgery.
Regularly they put in clips after surgery, to keep the
vessels from bleeding.
And they weren't sure what the clips were
made of for a while.
And so they said, well, we can't put him in, because we
could move the clips and kill him, which would be bad.
So they thought it was dangerous.
And they did a huge detective process of going to factory
that made them and talking to people who built it before
they decided-- it took, like, 10 years of research to decide
that the clips were not metal and they could take an MR.
And even here-- here's the top of the brain, normal person.
Here's the hippocampus, the small structure in you--
pretty small.
It's removed in him, but you can see he's got a lot of
brain left, except for these removed structures.
But what happened was he had such a fantastic impairment of
learning new information, it got the
label of a global amnesia.
Global amnesia.
It didn't matter whether tests were hard, like remembering
stuff or multiple choice.
He failed practically every standard test of memory you'd
ever give a person.
Or if it's words or nonsense syllables, faces, clicks,
mazes, public events, assassinations of presidents,
wars, going to the moon, whatever
you think of as famous--
he didn't know they happened at all.
Personal events.
The death of his own parents.
If you asked him how his parents were doing, he would
say something like, I haven't seen them for a while.
He would not know they had passed away.
So no matter how publicly famous something was, no
matter how personally important it was, that
knowledge--
he could remember it for a few seconds, and we'll talk about
that more, but it would drift away
completely within seconds.
No matter how often he heard it, no matter how personally
important it was.
And you could say, what does he say his experience is like?
So Brenda Milner, the neuropsychologist, who did a
lot of the critical original research with him, describing
his case said that he's said, "Every day is alone in itself,
whatever joy I've had and whatever sorrow I've had." I
mean, it sounds very poetic, and it's true, except that for
HM, his memory lasts seconds.
So he doesn't remember any day since 1950 or something.
So I think his experience is more like this. "Right now I'm
wondering, Have I done or said anything amiss?
You see, at this moment, everything looks clear to me."
His mind is clear.
He's smart.
"But what happened just before?" What happened a
minute ago, or two minutes ago, or five minutes ago?
"That's what worries me.
It's like waking from a dream; I just don't
remember." All right?
So when we worked with him here, a few blocks from here,
he wouldn't know who I was.
He wouldn't know why he was here.
He was an extremely pleasant and wonderful research
participant.
A piece of that was-- he was very nice and very pleasant.
A piece of that was he didn't know time was passing.
So if any of you are involved in experiments as
participants, sometimes people enjoy the experiment for about
five minutes but not for the next 55, because they're
getting a lot of measurements to get a good measurement.
For HM, it was never an hour-long experiment.
It was always a minute and a half experiment.
So you had to be very careful not to abuse that situation as
a researcher.
So here's his name, Henry Molaison.
Here's his pictures from his youth and from this.
But you see how he had a complete reversal?
All of a sudden, the removal just two small regions-- the
left and the right hippocampus in the brain--
stopped the creation, of formation of new memories
altogether and in any practical way.
So that shows you that memory's not spread throughout
the brain in a sort of undifferentiated mass-action
way, but that particular parts of the brain play very
particular roles in how memories are formed.
And the hippocampus plays a huge role in that.
Can't see it.
So they had a big project where they brought him from
the nursing home in Connecticut where he was.
They drove him by ambulance to
Massachusetts General Hospital.
They overnight did a something like an eight hour MRI scan on
him, to have the world's most detailed MRI scan you
practically have on anybody.
And then they removed his brain and sent it to a
laboratory in San Diego, where they took his brain and they
sliced it into many, many, many incredibly thin slices
that they're going to post on the web.
And on the web for quite a while was the
slicing of his brain.
He consented to this, all this research effort, and finally
his brain is a gift to research and understanding the
brain and memory.
So let me tell you a couple of experimental results from him,
and then you might think of questions you have about what
a man like this is like, OK?
So we talked about last time about that if you give a list
of words to people, and you try to do it yourself, that
people remember the first words best--
the primacy effect, a long-term memory effect that's
not affected by adding a few seconds of delay--
and a recency affect--
superior memory for the last few words of the list that's
strongly affected by adding in just 10 seconds of delay from
the last word until you recall.
And this is done with other amnesic patients, and not HM,
but a similar disorder.
You can see that their memory is worse overall--
there, the dark line--
but they have some benefit from the
beginning of the list and--
but it's small.
It's not the same as the control--
but they're completely normal, completely normal for the last
two or three words.
So this is what we mean by impaired long-term memory and
spared short-term memory.
But the short-term memory's just moments.
But it's not just an impression you have.
It's a scientific experiment you can do.
Here's another--
we did this last time.
We said, if you read digits to people and ask them to repeat
them back aloud, that we have a limited short-term memory of
seven plus or minus two.
People get to about seven or eight, typically.
So there's a mean test that's given to look at something.
So here's what they do.
Imagine that you do this test, and you were correct for two
digits, correct for three, repeating them back after you
heard them.
Four, five, six, seven, you did well.
And then you made mistakes at eight, which would be very
typical for a human.
So your span, therefore, is seven.
That's how much you can hold in short-term memory.
It varies a little bit from person to person.
And now they're going to do all the rest of the experiment
at one beyond your span.
One beyond what you can do.
One beyond what your short-term memory--
here's the limit of your short-term memory.
Let's add one thing.
And one thing that we know helps memory is repetition.
It's not the best way to learn things, but it is a powerful
way to learn things.
So now they give the entire experiment with eight digits
at a time for this person, one beyond what you could report.
So they give you this, and they give you this.
But they give you one boost, which is every third one, it's
the same sequence over and over again.
So some you hear once and once only.
And one, you hear over and over again.
Is that OK?
Now what would happen if you think, if you hear eight
digits over and over again?
What would happen?
You know this in your own life.
Your Social Security number, telephone numbers, things--
what happens?
Can you learn eight digits if you do it over and--?
Yeah.
It wouldn't be easy, but you get it with repetition.
So here's what happens in typical people.
Here's the repetition.
Here's how well they do for the
non-repeated super-span ones.
They never get that good because they
basically can't do that.
Occasionally they get lucky, but mostly not.
But the ones that repeat, they get better and better.
So repetition is another way to break the bounds of
short-term memory and register something in long-term memory.
But in HM, they did this for hundreds of trials, and he
never got better at the repeated series.
So you could do endless repetition with him, or it
could be personally important.
He wouldn't remember it.
So let me add one more piece to the story.
If I talk to you and say, here are the digits, tell that back
to me, that's an auditory-verbal experiment.
So they're words, and you're hearing them.
You can also test short-term memory and long-term memory
using a visuo-spatial test of blocks.
So you're seeing what the examiner sees, with numbers on
the back of each of these.
The person taking the test just sees these blocks as
black boxes without any number.
You need that because you have a piece of paper with numbers
on it that tell you what to tap.
OK?
So when you give this test, you might see five, seven,
eight, and you would tap with your hand, five, seven, eight,
and the person would tap that back.
And I can tell you what made me pretty nervous when I gave
this test to a person who had a long one?
Because I'd have to read the numbers, practice it, and I'd
be desperately trying to get eight my head, which I could
barely do, maybe.
Because I could tap eight back, so if a person was--
and then we'd do the same thing.
We'd say, if you can do eight, we'll test you at nine and
repeat them.
And here's two findings, and let's talk
about HM for a moment.
So one finding is now, in patients now-- we're going to
switch one thing a little bit.
HM had the left and the right hippocampus removed.
In these patients, they had either the left
or the right removed.
Either the left or the right.
So here's what happens for normal controls, for the
numbers that are beyond their span.
Not too good, low performance, but they benefit from
repetition.
Here's what happens for the patients with left hippocampal
removals for the auditory-verbal
things for the digits.
So they're good for immediate memory for this stuff, but
they're terrible at developing a long-term memory over here,
if it's verbal.
But the patients with the right temporal
ones are just fine.
For spatial things, it's exactly the opposite.
The group that's really impaired are the patients with
a large right hippocampal removal, and the people with
the left hippocampal do just fine.
So we have two separations in the brain for learning things
in the medial temporal lobes.
Neither the left nor the right are involved in short-term
memory, short-term memory lasting only seconds.
The left is important for verbal long-term memories, and
the right is important for long-term spatial memories,
which is very consistent with what we know about left and
right hemispheres for verbal and spatial knowledge.
So let me say a word more about how we think about the
organization of memory, and we'll come back to this chart.
So we're talking here, so far, about what people call
declarative or explicit memory.
You study some material, you get tested on it.
What did you study?
And people sometimes make a difference between
two kinds of things.
So episodic memory might be if I ask you--
OK, I need a volunteer in your seat.
It's really easy, this one.
OK, thanks.
I saw some people getting ready to go.
Well, OK.
OK, what did you have for breakfast this morning?
And you don't have to answer honestly if its embarrassing.
You can just give us a standard--
(LAUGHING) I'm not looking to make--
yeah.
AUDIENCE: Cereal.
PROFESSOR: Cereal.
How about you?
AUDIENCE: What?
AUDIENCE: Yogurt.
PROFESSOR: Yogurt.
Cereal and yogurt.
Two excellent healthy answers.
OK.
So now I'm going to ask you--
if I could ask you first.
How many feet in a yard?
AUDIENCE: Three.
PROFESSOR: Excellent.
OK.
And now I'm going to ask you, when and where
did you learn that?
OK?
And you might go, I don't know.
I just learned it.
Right?
Or if I ask you, capital of France.
AUDIENCE: Paris.
PROFESSOR: Paris.
Excellent answer.
When was the shocking moment when this was revealed to you?
When you said, I'll never trust the world again--
yes.
Who knows, right?
So what you're learning is, episodic memory is memory for
specific events, like what I did last night, what I had for
breakfast, specific time and place.
Semantic memory is what we could call generic memory.
We know lots of things about the world, but we might not
know when or where we learned.
So that's a distinction psychologists find useful to
think about.
So how about in HM?
We said he can't remember digits, or faces,
or things like that.
How about generic memory?
So here's an experiment that I was involved in, where we
said-- because there were some debates
about this at the time.
So we gave HM a multiple choice test where he saw words
or phrases that entered the language after the onset of
his amnesia.
So we thought he wouldn't learn them, but we didn't know
for sure, from just everyday experience.
And by the way, I should tell you, he watched tons of
television.
What his experience was like watching television is an
interesting question.
You should be thinking now about questions you want to
ask about HM.
In a moment, I'll come back to that.
But look at-- so, he has four choices for the word
amniocentesis, including the correct one, but he picks "an
infectious inflammatory disease of the
intestines." apartheid?
In front of him is the correct answer, two other answers, and
he picks, "the separation of young cows that have not yet
given birth to calves."
Boat people? "People who cater bon voyage parties," which is
completely the wrong--
Brainwash, "a fluid that surrounds and bathes the
brain." Granola, "a portable keyboard wind instrument."
Software, "expensive clothing made of a soft, twilled
fabric."
What's going on with him?
Are these, like, crazy weird answers?
Or how would you-- what do we think is going on with him?
Why is he picking these?
The other one is right in front of him.
What's he doing?
AUDIENCE: Looking at words he knows.
PROFESSOR: Yeah.
He's doing what teachers teach you in school.
Take apart the word into its parts, right?
And so he goes, software, soft clothes that you wear.
But what does that mean?
He's missed, in every sense, the advent of computers and
software in the world.
The idea, the concept, the words--
it's as if it didn't exist, because in 1953, although
software existed, it wasn't a very popular concept.
Most people didn't know about the concept of that.
In 1953--
the way we looked at these, these were not words that were
in the dictionary in the 1950s.
So now, what would you like to know about a man like HM?
Yeah.
AUDIENCE: So obviously he couldn't remember something
that happened two hours ago, but if you're having a
conversation with him, would he not remember what you guys
were talking about?
Or could he remember the context of the conversation?
PROFESSOR: Right.
So you're saying, he wouldn't remember something two days
ago, but you're talking with him.
What's that like?
Right?
So let me give you one experimental
thing and then an exper--
so one experiment they did is they left him with something
like six numbers, well within the span, and said, remember
these numbers.
And it could be, you know, 1, 2, 3, 4, 5, 6-- well, that
wouldn't work so well.
2, 4, 6, 8, 9.
They leave the room for 15 minutes.
They come back in.
He's an excellent subject.
He's going, 2, 4, 6, 8, 9.
2, 4, 6, 8, 9.
What were the numbers?
2, 4, 6, 8, 9.
They go, that's excellent.
Was there any trick you did to do that?
Or did you just--
And he'd go, oh, oh, oh.
What were the numbers?
As soon as a thought is out of the forefront of
his mind, it's gone.
So, yeah.
He would not recognize us, and we spent many hours with him.
A striking thing, which was amazing at first and then
sometimes irksome if you worked with him-- and he was a
delightful guy--
was that he would tell you a story from his past.
And he didn't have a huge array of stories, because they
were all from a long time ago.
And he would tell you about a gun collection he had.
And he would tell he had three guns, and they had this
property and that property.
He'd finish the story, and if you just stayed quiet for a
moment, he would forget that he told you the story, but it
would be vaguely on his mind because he
just told it to you.
And he would say to you, hey, did I tell you about my gun
collection?
And he would tell you, almost verbatim, the same story.
You'd just wait a moment.
He forgot that he told you this story, but it's slightly
on his mind because you just told you it.
And he goes, hey, did I tell you my--
he could tell you this until you could bear it no longer.
So it was kind of amazing how short his
short-term memory was.
Without this part of the brain,
it's just a few seconds.
His conversations were OK, but I would
call them pretty shallow.
I don't know how to put it.
You know, when you talk with somebody and you're on the
phone, and they're doing something
else, and you can tell--
for him it was a little bit like that.
He was-- so, good social convention.
He would smile.
He would chat with you.
But if what you were talking about depended on remembering
something from three sentences ago in any detail, gone.
Just seconds, unless he's practicing and practicing and
practicing without doing anything else.
Yeah.
AUDIENCE: So he did have the capability to learn
procedurally.
PROFESSOR: Yes.
We're going to come to that.
So the question is, did he ever learn-- he had other
kinds of learning that were amazingly
completely normal in him.
Procedural memory, you're absolutely right.
And we'll come to that just in about 20 minutes, OK?
Exactly right.
And if I don't answer that well, make me do that again.
OK?
But yeah.
Yeah?
AUDIENCE: Was he able to remember that he couldn't
remember things?
PROFESSOR: Yeah.
Really good question.
Was he able to remember that he couldn't remember things?
Yes, he knew he had a bad memory.
So now the question is, in what sense did he know he had
a bad memory?
Like, I know I can't draw very well, amongst many other
things I can't do very well.
But if you talked to him, he'd say, yeah, I
don't have a good memory.
But he's looking at you, and he's going, like, I don't know
where I am, who you are, or what I'm doing.
Everything is vague, for many, many years.
I must have bad memory.
Like, you would too, like a science fiction movie.
You woke up, you didn't know who you were, where you were,
what you were doing, and you can't remember anything except
from the most distant past.
You'd go, something is not good with my memory.
But you're smart, so you would know that.
What I don't know is if you woke him up at 2 AM and you
said, HM, how's your memory?
I don't know if he'd go, well, I'm a famous amnesic, of
course it's terrible.
I don't know if he knew it as a fact, like we might know
about what we're good and not good at, or he just knew it by
constantly being aware that he didn't know anything he ought
to know via memory.
Does that make sense?
Anything else about--?
Yeah.
AUDIENCE: How does one explain scientific consent to--?
PROFESSOR: Oh, this is good.
It's a very interesting question.
Informed consent.
So technically he was conserved by the state once
his family had passed away.
But, you know, his intelligence was fine, so you
had to be a little bit careful to do it right.
But you could tell him, we're going to do an experiment.
We're going to test your memory for words.
Is that OK with you?
And he'd say yes.
Of course, if you had him read a 12-page document, by the
time he got to page 12-- but you could talk him through it.
His intelligence was fine.
You could worry about the edges, if there--
so I think the investigators felt an extra ethical thing,
also, not to ask him to do anything that a person
might say no to.
He was a wonderful participant, but it was an
extra responsibility for the reason you're saying.
AUDIENCE: Does that mean he was happy all the time?
PROFESSOR: Was he happy all the time?
Excellent question.
He was a very sort of mellow--
yeah.
Well, you could think for a moment whether having no
memory would make you happy or sad.
So he couldn't hold a job.
He couldn't sustain a human relation because he would
never know he'd met you before.
So, those are things we often think of as pretty big in our
happiness, the kind of the work we do, in some broad
sense, and the people we relate to, right?
And those were all gone for him.
On the other hand, he didn't exactly realize that.
He didn't realize he didn't work.
He didn't realize he didn't have relations he might be
expected to have, because he'd forget that about as fast as
he could think about it.
So I--
he was kind of a very, I would say, mild, happy person.
So there's three possibilities that crossed my head.
And scientifically, we can never figure them out.
One of them is, maybe just he was that way.
I mean some people are just mellow and happy, right?
They don't have-- without amnesia.
Second possibility is-- he had removed, also, the amygdala.
We'll talk about that later in the course.
That's a structure that's pretty important for some
aspects of emotion and feeling.
So that could have been relevant.
The third one is, but this is kind of getting to your
question, which was just--
intuitively, I feel like this.
Again, this is not science but is just a feeling.
That what makes us mostly sort of happy or sad?
For me, it's mostly relatively recent things that went well
or didn't go well, or things I'm sad about recently, and
things on my horizon.
Things I'm worried about, or things I'm looking forward to.
And you guys might be different, but I don't get
that worked up these days about second grade.
At the time I'm sure it was pretty emotional about it.
So if you think about him, he doesn't remember anything
recent that was good or bad.
He doesn't remember anything coming up that's interesting,
or threatening, or risky, or unpleasant.
So he lives in this constant now.
You know, people tell you, live in the moment.
Nobody could have lived more in the moment than he did.
It's impossible to live more in the moment when the
previous moment you can consult is from
30, 40 years ago.
So, yeah, he was pretty happy, and a pretty pleasant guy.
Essentially, I don't think most of us want that life,
although he's probably happier than many people who have all
their memories.
One thing he's the opposite of, just to remind you--
we talked about it now, but just to make it clear-- it's
the opposite of television amnesia.
What happens in soap operas and murder movies or comedy
shows when they get bonked on the head?
Television amnesia.
They forget who they are and where they came from, right?
And then they marry their worst enemy or something like
this, to make the story go forward.
That's television amnesia.
But after that, they're kind of fine, right?
They're kind of operating but they just
forgot where they come--
that we never see after brain injuries.
We never see a person who forgets who they are but gets
around fine in the world.
HM is the opposite.
He remembers stuff from before, but he
can't learn new things.
Opposite of TV amnesia.
Any other questions about HM?
Yeah.
AUDIENCE: As he got older, could he recognize
people from his past?
AUDIENCE: Yes, and let me talk a little bit about that.
If I don't answer that, let me know.
So let me talk about this.
This sort of touches on this, loss of already-known
information.
And if I don't answer you well, just put your
hand up again, OK?
So it's easy to test learning new things, because you can
give somebody something in the laboratory and you see
if they learn it.
Knowing things they should have known from
before is much harder.
Different people know different things, in the past.
So here's how they'd test it.
And here's a thing that people have discovered, which is
people are pretty unknowledgeable, mostly, about
faces of people who were famous at the
time they were famous.
But if you're, like, 20, you don't know people who were
famous before you were born.
Mostly.
There's some exceptions.
So they'd take faces from different decades, and they'd
show you them and they'd ask you, do you know who this is?
So do you know who this is?
This is Lindbergh.
Frank Sinatra.
Bob Hope.
Does that name even ring a bell?
I know.
This is totally--
however old you are is totally how you do on this test.
Lyndon Baines Johnson, president of the United States
after Kennedy.
Douglas MacArthur, the general.
This, you might.
Richard Nixon.
McCarthy, as in McCarthyism.
Golda Meir.
Elvis.
OK now.
If you--
pretend you became amnesic.
You became amnesic.
Pretend you're old enough to become amnesic in 1990.
This is if you're feeling--
would you know this face, in 1990?
Let's say 1980.
Let's make it simple.
1980?
No.
Would you know this face?
No.
OK.
But you know them now.
So that tells you that you can put faces to decades, roughly.
You know, 1980, only Barack Obama's family knew Barack
Obama's face, right?
And now we all do.
Temporally limited retrograde amnesia.
So this is how well you do-- higher is better--
in decades.
In 1960, here's HM.
So here's faces that were famous in the '20s, '30s, and
'40s, before he became amnesic,
and he's pretty normal.
These are public faces.
And then he's terrible for the '50s and
'60s, after his amnesia.
So his memory for faces from the past is pretty normal.
His memory for faces from the onset of his amnesia forward
is terrible.
Is that OK?
Does that answer your question reasonably?
But here's another really weird thing that people
observed in many cases, which is kind of hard to understand,
but it's been observed in many cases.
So here's another patient.
He was a bus driver in Washington, DC.
He moved to work in a drugstore in Boston, then a
mattress factory in Boston.
Then he was hospitalized at the Boston VA in November 1965
with a huge hematoma on the right temporal parietal-- a
big bleeding.
And he was pretty aphasic and stuporous.
He couldn't answer questions.
In a month, digit span, his short-term memory returns.
He states the date as approximately something like
September 1965.
He has a severe anterograde amnesia.
For example, he fails to learned the names of the
nurses he sees every day.
But when asked-- this is the striking thing.
When asked, where do you live?
He says, I live in Washington, with certainty, as if he lost
all these memories from before.
By March, he starts to learn the nurses' names.
He's recovering his memory capacity.
He couldn't remember that he'd moved to Boston, but he
doesn't fight the idea that he lives in Boston.
Then he remembers that he worked at a drugstore.
Then he remembers that he worked in a mattress factory.
And by the time that he's discharged, it's only the last
24 hours before he went into the hospital that he's lost.
So two things.
There's a coupling between the anterograde amnesia and the
retrograde amnesia.
He can't learn new things, but he lost old things.
And as the anterograde amnesia resolves, the retrograde
amnesia resolves, in some sense, in temporal order.
It's really odd, but it's been observed many times.
So there is some link between what the hippocampus does and
memory for the past.
Now in some ways, it's really hard to study these things in
detail in a patient like HM.
But some other patients give us another perspective.
Although every one of these examples is not quite perfect.
Here's patients who undergo treatment for depression with
electroconvulsive therapy.
And appropriately--
in movies like One Flew Over the Cuckoo's Nest, wrongly
used electroconvulsive therapy is wrong.
For some patients with severe depression who fail to respond
to medications and who have suicidal ideation--
literally attempt to take their lives or talk a lot
about it in a believable way to family and physician--
electroconvulsive therapy can be very helpful.
It's a hard choice to make, and a complicated one.
Here's what happens.
Patients typically go-- and it varies-- but they go in for
the electroconvulsive therapy.
And nowadays, it's done, typically, only in the right
hemisphere.
In this study, done some years ago around
1972, it was bilateral.
They put electrodes on both sides of the brain.
They passed current and they induced a seizure.
And they do that something like every second day for
about 10 days.
It's a very aggressive form of treatment, certainly.
But for some patients, the depression just lifts, and
they're no longer talking about taking their lives.
So for some people it seems to work when other things don't.
During the course of the treatment, these patients
develop and anterograde amnesia.
They become HM-like.
While they're in the hospital, they become HM-like.
They can't learn new things.
They forget the nurses.
You can test them formally.
And so Larry Squire did the following experiment with
these kinds of patients.
So we don't know that it's the hippocampus that's the
critical thing in these patients, but they
look a lot like HM.
And we know that the hippocampus has
a low seizure threshold.
That's why it occurs so often as the locus of epilepsy.
So what they did is they took television shows.
And this is another world than you can possibly imagine.
I grew up in a world where there were basically three
television stations.
And you're feeling sad for me already, right?
And so everybody knew what was on those
three television stations.
But they took shows that weren't very successful, that
were on for one season only.
So they weren't super popular, but a lot of people saw them.
And there were only three television
networks and stations.
So now what they did is they tested them on these events or
other things like that before they had ECT-- so this is
their knowledge before they had ECT.
Of course they remember recent things, 1971, better than
stuff from years ago.
We all do.
But the striking thing is that when these patients got ECT,
during the course of their amnesia they only lost memory
for TV shows from the last two years.
They didn't lose those memories.
These are the very same patients.
The very same patients before they got ECT and while they're
getting ECT, they lose memory only for the last two years of
TV shows and not all the other ones.
Or the same thing you can do with famous public events.
So this is what people call a
temporally-limited retrograde amnesia.
It goes back for some years, the knowledge you already had.
And here's the amazing thing.
When these patients go home, their memory largely comes
back and so does their knowledge of the TV shows.
It's as if it's in their brain.
They don't have access to it, for the last two years of
information.
But it's still sitting there and they regain that access.
Two more examples on this.
So here's an example--
because with humans it's always tough.
So they do the same thing with monkeys.
With monkeys, they could create a surgical lesion like
HM and train them on material.
They knew exactly what they learned.
Here they had the surgery either 2, 4, 8 or
12, or 8, 16 weeks.
And you can see the monkeys with the hippocampal damage
were performing poorly if they learned the material 2 or 4
weeks ago but not 8 or 16 weeks ago.
Again, a temporally-limited retrograde amnesia.
So we're getting the idea that the hippocampus is important,
not only for forming new memories--
and this is kind of wild.
It's still important for you to remember stuff from a week
ago, a month ago, and a couple years ago.
And it takes years for your memory to become independent,
or what people call consolidated, so that it no
longer depends upon the hippocampus.
So the hippocampus both is required to form a new memory,
and it seems like it's necessary to remember that
memory from months to years, before that memory becomes
independent of the hippocampus.
So right now in you, it's as if you had a neurochemistry
team finishing your memories from the end of eighth grade.
We're done.
We're moving on to ninth grade!
Because it takes years for your hippocampus to no longer
be required to get those memories that you
acquired years ago.
And the same thing-- they did these famous faces, like the
ones I showed you before?
So these had to be somewhat older people.
Here's activation in the 1990s, if they were looking at
famous faces and the experiment was done in the
late 1990s.
So recent faces, hippocampus turned on, but not for '80s,
'70s, or '60s, or '50s, or '40s.
Again, they said the hippocampus is required to
retrieve memories that's in the rest of your brain for
some time period, but then after much time passes, it's
no longer required.
So this just summarizes those things.
So now, Tyler, if we could do the film.
We're going to how you an amnesic patient.
Most amnesic patients are like this man.
Very intelligent, very verbal.
Not dramatic, but with terribly impaired memory.
So last part of the talk is this idea of memory systems
and procedural memory, the idea that you're a symphony of
the neural systems that learn different things.
So your brain is like the university, right?
Department of Chemistry, department of Biology,
department of Brain and
Cognitive Science, or Economics.
In you are multiple very specialized learning circuits
that are good for learning different things.
So this idea of a memory system, a particular part of
the brain that has a particular learning process.
And a key concept in that is, so far we've been talking
about what people would normally call memory--
explicit or direct testing.
You know, what did you study?
What year is it?
You're asked directly to do something.
But another way to show memory and learning is through
changes in performance with practice.
So people will sometimes call the first kind declarative
memory, where you directly have conscious memory about
facts and episodes.
You know that you know something, or
that something occurred.
And then the other kind, we'll talk about now, procedural
memory, accessible only through performance and
knowing how.
Now with these kinds of skill learning or procedural memory,
we see how people get better when they practice.
Getting better is a change in your behavior that's learned
and a change in your brain that performs.
This is for your performance.
So here's the experiment that was the original one Brenda
Milner did with HM, where you have to
trace a star in a mirror.
You see your hand in a mirror, but you don't have direct view
of your hand.
Have any of you done something like this for some odds and
ends reason?
Anybody?
Sometimes--
do I see a hand?
No.
OK.
It's surprisingly hard.
The horizontals and verticals are pretty easy.
The diagonals, as you move your hand, you
go, oh, it's no problem.
I just reverse everything.
And you see your hand just drift the wrong way.
And you go, OK, no, no, no, no.
I just have to go 45 degrees difference.
I can do it.
And you're controlling your hand, but then you move again
and it still goes the wrong way.
And so at first, you make lots of mistakes.
We understand this because you have such automaticity between
what you see and how you move all the time, that the mirror
reverse, you have to overcome that automatic relationship.
So at first you make a lot of mistakes and move slowly.
You practice, and you get better.
Here's the remarkable thing with-- so here's HM.
Each of these dots is the next time he does it consecutively.
He gets better from doing it over and over again.
That's not a shock.
Here's the shock.
He comes the next day, he keeps the learning he had and
he gets better.
He comes in day three, he keeps learning.
Now for him, a day is like infinity, for memory.
When he comes in the room, he says, what do I do with this?
You'd go, well, we did it the last two days.
Don't you know?
He said, no, I have no idea.
Have you done this before?
No.
You can give him multiple choice of different things he
might have done.
He'll pick the wrong thing.
When you come in on day three and you're this good, you're
pretty proud.
In fact, vain.
You're going, like, I can do this.
I'm awesome.
Just let me at it.
Because you know that you did it.
You know how good you are through practice.
He has no idea, but his learning is entirely normal.
Not just better than you'd think?
Just as good as you.
So a memory system in his brain, different than the
hippocampus, has kept that memory, uses that memory.
And the amazing thing is that this means that that's also
true in you, as far as we understand these things.
When you learn a physical or mental skill, a lot of it is
learned in a way that has nothing to do with your memory
that you learned the skill.
It's all by doing.
And it doesn't depend on the hippocampus.
And some years later, I did this again a little bit.
Here's his performance first, second, third day, a week
later, two weeks later, and a year later.
Complete retention for a man who can forget within moments.
A year later, a skill.
He forgets that he did it ever within moments.
So another kind of task that people do-- same idea.
A motor skill you can lose, it's called rotary pursuit.
There's a disc like this that revolves around a platter that
turns pretty fast.
Your job is to maintain contact between--
this was sort of sad before video games, right?
This is about as interesting as 1940s games got.
It was whizzed around, and it's fast enough that it's not
easy to do.
And at first your hand goes off it, but with practice you
get really good at revolving with a rotating disc.
And HM and patients like him learned that very well.
Another motor skill.
So who's bad at learning this?
Which part of the brain is your instrument for learning
skills through practice?
So our best evidence comes from patients with a very
difficult disease called Huntington's disease.
It's a genetic rare disease.
Its onset is in the 30s or 40s.
These patients get severe motor problems and movement
problems, and then, over time, cognitive ones
and psychiatric ones.
There's no treatment for it.
So this is the caudate withering away in a patient
with Huntington's disease compared to a healthy
person's, post mortem.
Or if you look at an MRI, here's your basal ganglia.
Here's the withered away basal ganglia in the patients with
Huntington's disease.
And there's a brief--
can we do, Tyler-- there's a brief video of a patient with
early-stage Huntington's disease.
So it's not the most severe problem they have, but when
they do one of these motor kinds of tasks--
here's normal typical people learning a motor task, getting
better on it.
It's good to be high on this graph.
Here's the patients with Huntington's disease showing
no learning at all.
And this is a test that an amnesic
patient would learn normally.
So very convincing-- and you could say, well, if they have
a motor problem, they're not going to get a motor skill.
So one thing they do is they make the platter turn very
slowly, so at the beginning they're doing just as well.
And they still show no learning at all.
So there's a lot of other evidence sparked by this that
just shows that the basal ganglia is an instrument
that's essential for us to learn physical or motor
skills, perceptual skills, and a variety of
cognitive skills as well.
Things where we practice, practice, practice to become
excellent--
basal ganglia is doing a lot of that work for you.
The last kind of learning I'll talk to you about, and the
last disease, is a sort of odder form of learning called
repetition priming.
It's a change in performance because of
something you did recently.
And if I give you a concrete example, it'll feel better.
So here's one of many examples.
Imagine you study a list of words like stamp, landmark,
speak, clock.
You study a list of words like these.
I can give you an explicit or declarative memory test.
What words did you see?
You'd recall them.
Or which word did you see, that we'd do multiple choice.
That's regular memory that we know depends on the
hippocampus.
I can also give you weird test like this, which says, tell me
the first word you think of that starts with STA.
Now if you have good memory, you'll go, do you want me to
give you stamp?
Is that the point?
And you go, no, no, no.
And they go, oh, it's a Freudian thing.
You want to know some weird things I'm gonna think of.
And you go, no, no, no.
Just tell me the first word you think of, OK?
And you can give many answers that are all perfectly fine.
You can give stall, stand, staccato, star, many STA
words, and all of them are fine.
That's all you have to do.
But if you saw stamp, one particular completion of this,
about 10 minutes ago, you're biased or primed to come up
with that word.
Not all the time, but much more than by chance.
A recent experience biases you to behave in a certain way.
And here's the remarkable thing.
When you do this experiment with HM, if you just had the
list of words and you wait about 20
seconds, here's your recall.
Now you're not surprised that recall from a healthy person
is about seven words, right?
You tried that yourself.
HM, sadly, has no score because he always
goes, like, what list?
So no recall.
Multiple choice recognition, where there are three choices,
here's typical people, HM about chance.
The probability above chance--
that you give stamp as the completion to
STA if you saw stamp--
if I showed you star, probably you'd give star.
The specific word you saw 10 minutes ago?
Perfectly the same in HM as normal control subjects.
He was just as influenced by that word he saw 10 minutes
ago as you are, to give you that answer.
So this got people very excited, because they said,
now we can experimentally and scientifically study something
that Freud talked about as a very vague idea, the cognitive
unconscious.
He's not conscious that he saw a list of words 10 minutes
ago, but it's making him choose to behave in
a certain way now.
Now you have both things in you, as far as
we understand it.
You can both remember you saw the word list, but if you
switch your thinking a little bit, your behavior a little
bit, the unconscious system gets into the driver's seat.
Because the people with good memory were giving stamp often
but no more or less than HM.
So unconscious.
So what part of the brain does this kind of memory?
And our insight to that comes from Alzheimer's disease.
So HM's kind of amnesia is extremely rare.
Huntington's is quite rare.
Alzheimer's is tragically common.
In fact, they went to East Boston, the area near Logan,
and knocked on doors of people's homes.
Not people in nursing homes.
At home.
And they estimated--
and there's debates about this back and forth.
But about half the people over 85 who answered the door
qualify for diagnosis of Alzheimer's disease.
About half over 85.
There's debates about this.
There's debates about whether all of us would get it if we
lived long enough.
But as American society gets older, as us baby boomers all
move into our '60s, '70s, and '80s, there's going to be a
heck of a lot of people around with Alzheimer's disease.
And some of you have probably experienced this, with
grandparents if nothing else.
It's a very devastating disorder for the patient, for
the spouse or family.
It's a very challenging disorder.
So what is Alzheimer's disease?
Well behaviorally, it's an insidious
and progressive dementia.
Dementia means, unlike HM, it's many losses of abilities.
Unlike HM.
HM had his surgery one day, boom.
That was it.
Alzheimer's starts very slowly and gets worse
and worse over time.
The biggest problem early on is memory, the most common
problem but over time, language, thinking,
concentration, spatial thinking, sometimes mood and
personality, all of these get altered over time.
In the brain when you look at the changes, you see that the
changes occur especially in the hippocampal region-- so
that's why the memory problem is like HM--
and also in some other parts of the cortex, but not so
much, for example, in basal ganglia, that we just spoke
about as important for procedural memory.
Here's a control brain and equal-aged Alzheimer's brain.
The reason why these gyri, this whole side widened is
because of widespread neuronal shrinkage or death.
And what's happening inside the brain, when you look at
post mortem, there's sort of neurofibrillary tangles and
plaques that are associated with the diseases.
The tangles are something about the
cells that have died.
The plaques are thought to be maybe part of the process that
leads to the disorder, but there's a debate about
that to this day.
And if you look, on post mortem, where the tangles are,
the tangles up here, you can see they're most dense in the
hippocampus or near the hippocampus, like HM.
And so that's why we think so many patients with Alzheimer's
have an HM-like memory problem and then more
problems after that.
So here's a healthy person top of the brain.
Here's the left and right hippocampus in an 81-year-old.
And here in an 80-year-old Alzheimer's patient, the
hippocampus has withered away, both sides of the brain,
bilaterally.
So one more brain perspective on this.
This is a SPECT scan, that just shows you where there's
blood flow and metabolism.
Top of the brain, bottom of the brain.
Here's the insides of the temporal lobes in a healthy
elderly adult.
Look how much worse--
this is HM.
He looks pretty good, right?
You have to look really hard to see that the hippocampus is
missing because it's such a small structure.
And here's an early-stage Alzheimer's patient.
Lots of the tissue is there, but a lot of-- you know, it's
not functioning because there's so much damage.
Here's the medial temporal lobes but also cortical areas
that are compromised.
OK, again.
Not their biggest problem, but in terms of thinking about
different parts of the brain and what parts
of memory they do--
So these are amnesic patients, including HM, Alzheimer's
patients, and green in controls.
So recall of the list, what words were on the list,
explicit memory bad in the two patient groups.
Recognition pretty poor.
Word stem completion, the kind of thing that we said is
completely normal in HM, that's impaired
in Alzheimer's disease.
So we think that kind of priming depends on the
neocortex, the part of the brain that's also injured in
Alzheimer's.
Because we know it doesn't depend on the hippocampus,
because the patients with
hippocampus-only damage are fine.
So we end up with a picture like this of something on
memory systems.
For explicit or declarative memory, from patients with
amnesia, we know it depends on the medial temporal lobe.
Left, verbal; right, spatial.
For skill learning, anything you practice many times to get
better at, we know from Huntington's disease, that
depends on the basal ganglia.
For kinds of priming, recent experience altering something
about brain organization, Alzheimer's disease, we know
from that that it's likely mediated by the neocortex.
These are from patient studies, but the imaging
studies are very well aligned with these things.
So we think it's true not only of patients, but of you, in
terms of the instruments of your brain.
So now we have not only episodic memory
and semantic memory.
We talked about procedural memory.
We talked about priming.
I didn't talk about conditioning today, but we've
talked about that before.
So I have two more slides to add on conceptually.
So in what sense was Karl Ashley right or wrong when he
said memory's all over the brain?
Here's how we think about it now.
We think he was right that all of your brain is learning.
Practically all of your brain is plastic.
It changes with experience.
But different parts of your brain are
learning different things.
The basal ganglia is learning how to
be skilled at something.
The neocortex, how to gain knowledge and shift your
representation of knowledge, like in priming.
The medial temporal lobe on the left is learning verbal
facts, and the right is nonverbal
facts or spatial facts.
So all of your brain is learning, but it's learning
different things.
And in that sense we end up with this metaphor that-- you
know, just like there's a string section and a
percussion section or something like that, in you,
there's all these different instruments that are highly
tuned in the way they're organized to learn all the
different things you learned.
They're all pretty useful instruments to have.
And without these patients and the imaging studies, we
wouldn't have known that.
You would be like the Martian.
One instrument?
A thousand instruments?
Well, we know there's multiple ones, and we know pretty much
which structures are essential for them.
Thanks.