raw_transcripts/lecture_15.txt

Okay.

Good morning, everybody.

I think we're on the mic.

Yeah.

Welcome back.

Unfortunately, last week we had a strike.

Action affected you.

Today, there's no strike.

So please be quiet for the start of the lecture.

So today, this week, returning from last week, all motivation

and consciousness to memory.

We're today going to focus on human memory, a particular

condition that illuminates a lot of our memory.

And on Friday, we'll pick up on animal research.

This holiday on tonight.

What do we know about what the cells are doing?

So in this lecture, you should know about different types

of amnesia.

This is the topic of today, the brain regions involved.

Examples of the neuropsychological tests which would be important if

any of you are interested in going on into clinical

psychology and the functions lost or retained in amnesia and

controversies.

So what is happening here?

Amnesia is defined as a profound loss of memory in

the in the in the presence of relatively preserved cognitive

abilities.

That's a bit of a mouthful.

So what it implies is not some of these just

lost memory.

So we're interested in people who have lost memory and

profoundly not forgot where the book is or where they

park their car or something like that.

Someone who just can't remember any experience of having.

And also they can do other things that have normal

function.

So if you say somewhere else, Alzheimer's and amnesic patients,

the answer is no.

And we'll see you in a moment.

So why is it interesting?

As you'll see in and as you've seen from lots

of lectures in this course, when the system breaks down,

this case amnesia goes that we can learn a lot

about how the system normally functions.

How does healthy memory work when we do have our

memory?

And if you take an example from culture about memory

is a quote from Michael Crichton, who wrote Jurassic Park,

and this is his book, Sphere At the end of

the entire narrative of the book around memories, as though

the characters in the sense the character thought, all we

consist of is memories.

That's who you are in the audience and the way

our personalities are constructed from memories.

Our lives are organised around memories.

You came here today because you had a lecture.

Our culture is built upon memories.

The foundation of shared memories is what we call history

and science.

So this is kind of an attempt to capture the

profound nature of having memory and how devastating we didn't

need it to survive.

What to eat?

Where are you supposed to be?

What you're what to avoid?

All these things that allow us to survive.

What I'm going to talk about today is despite having

a lack of memory amnesia, patients will say, you can

do an amazing range of things.

So here's a YouTube link to something.

I'll show you an example.

It starts with the man with amnesia playing a piano

and remarkably well.

Hopefully the audio work for this.

One man is consigned to live entirely within the.

Present with terrible consequences.

Clive Waring has the worst case of amnesia.

He lost his memory.

And now his wife, Deborah, is the only person he

recognises.

Oh, ho ho, ho, ho!

It really only has less than 30 seconds memory, and

sometimes it's as little as perhaps 7 seconds.

It's as little as a sentence.

I'm going to see your sister down at dances.

Got married recently in New Zealand and said they're having

a party from her.

The Ladies Club title.

A married man will see to know how much he

knows how many guests he didn't put down.

I need to know why I'm going.

She's having a party at her house tomorrow.

She will say no.

I know it is to do with her daughter.

Do you mind have daughters having a party?

Yes.

No.

She's just got married.

She just got married.

And did what country?

She just got married in New Zealand.

Oh.

Yeah.

The sentence he is in.

He will probably have forgotten the sentence before you ask

him a question, and he'll give you an answer.

But while he's giving me the answer.

He's already forgotten the question.

But so bad it is and is worth watching to

the end of it.

I'm not going to court that because it highlights just

that case of Clive wearing just tie for normally tense

and these you can be trying to trying to imagine

how crippling that would be if as I'm talking to

you now, you forgotten why I started the sentence.

What was I talking about?

This is the classic description from Dani's ex, like Clive

Waring, is that it's like waking from a tree.

You know, you woken up in the morning, you're a

bit dazed, and you've been having a really intense dream

about something and it just fades.

And someone says, What were you thinking about in your

dream?

It is really intense for you, but it just evaporates

and you can't remember that.

And they say, certainly Clive says this in the video.

That's like it all the time for him.

And he's really angry because he knows he should know

things, but he can't.

And he says the doctors have been useless, unable to

help.

He's just absolutely straight.

So it's quite it's a quite a side effect of

amnesia.

But let's not forget what he did at the beginning.

He's got no memory.

But how did he remember to play the piano with

absolute expert precision?

So he does have some memory.

And what is the memory he has now as we're

starting this lecture is that's the interesting bit about Clive

and his wife, Deborah.

And also she dies every time he meets his wife,

Deborah, that you saw when he opened the door, He

jumps up and kisses her and cuddles her every single

time.

So she goes to make a cup of tea and

comes back.

He's felt like he's not seen her for years.

And so it's extremely difficult for his wife as well

as her.

So just to highlight the challenges.

So Clive, in that narrative has what's known as organic

amnesia.

There's a there's a he has brain damage that has

caused his amnesia.

There are fascinating.

The psychogenic amnesia is caused by causes where patients suffer

mental health problems and cannot remember things.

We're not going to touch on that today, but they

are they are fascinating and much more complicated.

And I'm talking about the transient amnesia is so epileptic

amnesia is, for example, a schema accompanies.

Is that cause a complete loss that people wake up

from this condition unable to remember what they're doing in

the hospital, where they are, why they're there, what's going

on?

They're amnesic like lies.

But within a couple of days or weeks, it returns

to normal, comes back.

They don't have persistent amnesia.

Clive has this organic, persistent.

He's never remembered anything since his brain damage.

And the other thing Clive has is this non degenerative

form.

He isn't changing.

He's just got the same memory problems day in, day

out.

Degenerative amnesia has come under Alzheimer's disease and other conditions

that keep getting worse.

And sometimes you have this new terrible specific you can

have brain surgery and end up losing memory for words

then on other things or in the case of Clive.

And what we'll be talking about today is the classic

Amnesic syndrome.

Where is all material?

There's another audio, verbal, written, any information coming to him

that he's trying to recall?

It's it's lost.

So let's dive now from the what is amnesia to

what was causing that.

This is a brain in behaviour.

So it's about the behaviour that's going to the brain.

Well, the first place to start with that is the

most commonly damaged brain area for amnesia is the structure

of the hippocampus.

Now he focuses a picture through a schematic of the

human brain and one of the images from the tutorial

you get on anatomy.

And we talked about the hippocampus in regards to the

impact of stressors and how that stress disrupts memory.

And today we're going to talk about it a bit

about the hippocampus beyond stress in terms of other factors

that can damage it.

And on Friday, we'll come back to the two things

that sort of tests that can be used in animals

we thought about in more detail.

But here's the hippocampus gets his name because it looks

a little bit like a seahorse.

You can see that stylised in the brain of a

human post-mortem brain.

Here it is curled up in the medium term for

lobe.

So where is the hippocampus is in the temporal lobe

and it's in the medial powers.

If we take a coronial section is the temporal lobe,

and here is this folded up structure of the hippocampus.

Here, let me slice through a horizontal or a horizontal

section.

We can see the hippocampus is tucked away here.

There's one hippocampus in each hemisphere, and it's huge in

most mammals in the sense.

Takes up a lot of the brain.

And interestingly, it looks very, very similar.

Here's your hippocampus.

Here's what you have to have.

This would look like a version of your brain.

So the cadaver is level surgically.

You don't want to happen, of course.

But if you had to do that with a bat

or a sheep or a giraffe, it would look almost

identical to yours.

So the evolution is tinkered with these things, but hasn't

really changed the hippocampus.

It's doing something utterly important for giraffes, bats and humans

and whales.

All of them have a very similar looking hippocampus.

There's this stuff around in the neocortex that has radically

changed in humans and other species.

Now, this massive wiring diagram, which is very simplistic because

it's from 1991, contains what they call the element of

an and first described is a sort of general structure

of the visual system.

So you covered sensory systems earlier in the course.

Here's your retina where light arrives on the the different

P and cells in your retina and passes through different

processing sections.

And right on top of that is seeing the hippocampus.

This is getting visual input from your eyes.

So what you're seeing now is getting into your hippocampus.

But as we're thinking out, there's a lot of processing

that's occurring across the entire brain before it reaches your

eye.

So there's a lot of.

So the hippocampus is getting information about highly, highly processed

information.

So it's doing something quite important.

Of course, we'll focus that today.

One of the key things the hippocampus is doing is

memory.

Let's dive into the anatomy a bit more.

Here's that picture I showed you earlier of a cadaver.

Here's the section where they stated The brain is really

microtransaction.

They say that these are the black dots, individual cells

for a human, a healthy human.

And what you've got in the middle here is the

hippocampus.

We've got the cortex, the neocortex on the outside.

And what this very simplistic story is showing us is

that there are all these areas in the neocortex that

associate information together.

So going back to this story here, use the retina.

Here is the early processing of the brain provision.

And then there are all these associative areas here.

And that's what we're looking at here.

Lots of information that feeds into two key areas the

power of the campus, our campus cortex and the prefrontal

cortex.

And I showed here in this slide, we've got the

prefrontal cortex here.

And that sends information to an area called the entering

cortex.

This bit here and then it's around the cortex, as

you'll get a lecture from Solomon is one of the

earliest areas affected in Alzheimer's disease.

There's a lot of interest in what this brain areas

doing, the various more elaborate bits in anatomy but effectively

the main pathway information from your eye and other senses

are reaching the hippocampus.

It's through the interactive cortex.

And they terminate their cells into these areas in here.

And we'll come on to that in more detail on

Friday, the anatomy that's going on inside here.

But suffice to say, today we're looking at this area,

the hippocampus in here.

Here's a diagram from a textbook trying to outline the

hippocampus and how it's linked to other areas for amnesia.

This blue area is the hippocampus.

And what we're highlighting is the meat, the temporal lobe,

and an immediate temporal lobe.

That's the corpus callosum that we now had in a

number of markers.

What we're looking at here is a circuit.

So the hippocampus is receiving that information of the Toronto

cortex.

The arrows are showing us that it's passing up a

white matter pathway equal to phonics, which occurs under the

white matter of the corpus callosum, and that terminates in

the anterior thalamus on these military bodies.

So when you learn your anatomy, that's kind of a

clear pathway through.

And there are also structures that come through this.

You can see the point axis terminating and what's known

as the septal nuclei in the basal forebrain.

So these are subcortical structures.

It's kind of shown within the cortical area, but there

are nuclei here and these then pass on to the

cingulate cortex.

And there's a generic or directly split neocortex behind the

corpus callosum, the spleen of the corpus callosum rupturing meaning

behind and spleen, you being this spleen him here of

the corpus callosum.

So these are all key areas.

And the reason I'm highlighting the area this way, if

you damage each of these areas individually or globally, you

will end up with someone like Clive.

And Clive has very, very just like extensive damage.

So amnesic patients aren't always as bad as Clive as

Deborah.

His wife's or the intro sequence says he has one

of the worst cases of amnesia.

But I certainly met patients who were similarly affected.

And so these are the key brain areas.

Let's walk through these and get to know them a

bit more.

They also come under the term paper circuit, which is

originally the scientists papers had described the circuit for kind

of motivation, emotion and memory that included these areas.

And there are two key areas, key types of amnesia

in the literature.

There's what's known as hippocampal amnesia, which is areas disrupted

by the hippocampus and the phonics.

But there's also course some easier, which is we'll see

is linked with thiamine deficiency.

There's more affected by the the bodies of the anterior

thalamus here.

So we'll mostly focus on hippocampal amnesia today.

But there are cases where they suffered a particular damage

that leads to to these particular areas.

Now, of course, the cough was the clinician that spotted

a number of cases and they all came in with

severe alcohol poisoning, really drinking an enormous amount.

They should have died, but they didn't.

But they ended up with really, really like low wearing

severe amnesia.

They didn't have hippocampal damage, but they did have in

thier anterior thalamic, miliary body damage.

And we know that these areas important from these kind

of clinical case studies that this seems to operate as

a circuit which isn't necessary, if you like to remember

what I'm saying to you.

Now if you remember what I'm saying a couple of

sentences ago, you can hear inside your head your anterior

thalamus, and you remove the bodies and the hippocampus.

So what causes amnesia?

Sometimes physical damage, head trauma or surgery?

Viral diseases are one of the common reasons you can

end up.

Encephalitis is one of the most common causes.

Other common causes are loss of blood flow, a schema

or anoxia.

When someone is, as you know, being carbon monoxide poisoning

is a classic example.

And finally, we talked about Corsica syndrome, which is a

low thymus, a thiamine is a key molecule.

A key molecule.

What he needs to process and do a number of

things for your body.

One of those is keep the brain is processing areas

in the brain.

Now, earlier in the course, in the end of my

slides for the first lecture, I talked about this patient,

H.M. Really classic important case.

Brenda milner is the scientist still alive in her late

hundreds and early hundreds is well over 100.

And she studied patient H.M. where he had his bilateral

temporal medial temporal lobes removed the areas we talked about

in that circuit.

Here's the diagram of his brain.

I mean, this is a classic case of amnesia, dense,

just like life.

But he didn't have amnesia before surgery and after surgery,

he did align the scientists to see that if you

intervene with that area, you would result in that dense

amnesia.

Now, we can go from a very severe that's a

huge amount of brain tissue to remove from somebody's brain.

They do not do that anymore.

They're very much, much more selective in surgery.

You don't have to have that level of damage.

Here's patient P.J..

Now, this is a study reported by Van and Ableton,

and here's an MRI.

This is from 2004.

See, MRI scans clinical and it's a bit fuzzy.

But what the arrows point to is an area of

darkness in the sky.

And what that means is water in his brain.

And you can see here what looks like a nice

organised brain has two kind of holes here.

Unfortunately for patient B.J, they got into a fight in

a bar and had a snooker cue forced through their

face in a fight and it skewered the patients and

misery bodies.

They survived a bit like Phineas Gauge, the person on

a on Bach countryside.

But that patient and the period they lived after the

say after having this new cookie removed and the damage

alleviated has severe amnesia despite it disrupting just one small

areas of brain injury bodies.

If you go back to another reason that can cause

amnesia is encephalitis, we can see a case study by

this very famous researcher in amnesia, Larry Squire.

This is Patient EPI.

He's been reported in lots of studies.

And this is an MRI scan of his brain.

It should all look.

This is a scan where the grey grey matter in

the blade brain is dark.

And these areas of white show where there's a lot

of fluid, but the tissue is not normally presents.

And effectively, this patient had a really bad case of

encephalitis affecting the damage to the brain very much like

patient.

H.M. As if they'd had surgery to remove their hippocampus

and patient.

EPI is extremely dense.

The amnesic.

Again, flipping back, you don't always have to have this

extensive massive damage.

Patient y are who will come on the later in

this in the slides.

Here's a healthy MRI scan.

This is the hippocampus on a coronial section curled up

nicely in the medial temporal lobe.

And here it is flattened in this patient who unfortunately

suffered severe carbon monoxide poisoning, just survived.

It had to be revived after being revived, had quite

severe amnesia really affecting their life.

Finally, we can get onto Ischaemia where this is not

anoxia is not like a loss of oxygen environment, but

something in the body that caused a loss of blood

supply.

This can be a stroke, for example, very targeted stroke.

And here's the healthy brain we looked at earlier, and

here is the disruptors.

You can see the nicely laid out cells in our

in the hippocampus.

This nice line of cells.

We'll talk about those cells next week, sorry, this week

on Friday.

And here you can see this area here, nicely organised

in the patient healthy brain and utterly disrupted inside this

patient who had quite severe amnesia, but relatively normal brain

otherwise.

So amnesia can sometimes result from acts massive damage or

very small amounts of damage.

That's the brain.

Let's turn it back to studying what happens to that

brain damage.

So let's look at those patients in different studies.

First thing we'll look at is what can they do

in amnesia?

And then we'll move on to what can they not

do.

Think a bit more about what this tells us about

long term memory and we'll pick up some controversies where

there's been disagreement.

So starting with spared functions.

Oh, I talked to.

So let's just take Clive notes, take the way he

talks about to his wife.

In that interview.

We would say that Clive's general cognitive abilities in that

interview were pretty good.

His IQ seemed quite normal.

It wasn't.

We didn't see him do an IQ test, but I

can tell you his IQ was very high.

His language was entirely normal.

You could hear Clive talking away, perfect prosody, very good.

He was attending to what his.

His wife said he could see Deborah coming in the

door.

He acted appropriately.

We get into executive functions and the last lecture on

this course, that is the ability to organise your behaviour

to achieve goals.

And he was perfectly fine.

So you can say all that.

To say, Look, we watched Clive just now.

He looked entirely normal.

But as a neuropsychologist, which is what we into the

realm of amnesia, we want to study that.

We organise psychological tasks that are quantifiable and have psychometric

properties so we can we can have numbers that come

out of them, we can analyse and make predictions.

There's a standardised test called the Waste Weschler Adult intelligence

scale, which can tell you how someone's IQ is and

what their attention is like.

And Clive will have been assessed and defined to be

very high on this particular test.

And there are other tests like the Wisconsin cause sorting

task will come on to a test for executive functions

and we will come back to that at the end.

Again, Paul Burgess, we'll talk about this later.

And then there are other things that you might show

people, pictures of camels or a tiger, for example, and

say, what is this animal?

And if they've got a normal functioning knowledge, they will

tell you what that camel is or the tiger or.

And you can make that harder and harder with complicated

objects that most people wouldn't know.

Now, all of that makes sense.

We heard Clive do all that.

But what about short term memory?

So we come on in these lectures, the distinction between

long term memory and short term memory.

Now, if Clive was able to have that conversation with

Deborah and respond, she said to him, guess, guess what

your daughter's up to.

He had to hold that information in mind and say,

I had no idea that was an appropriate answer for

Clive to say.

I have no idea if he blurted out elephants.

That would have been absolutely make no sense.

Right.

He had to have heard what his wife Deborah, said

and then respond.

Well, he couldn't do was remember what she said in

the sentence before that his daughter was getting married in

another country.

And so we can see that functionally in Clive.

But scientists have found ways to study that you need

numbers to be able to say Clive is getting worse

or he's stable or or and so on.

And part of the reason we need these kind of

tests is we might want to know whether we want

to do neurosurgery or take an intervention.

You can't do that without these tests.

And so one of these tasks will be span.

Another is the course he blocks on.

And let's take a look at the.

The judge.

The judges found first really simple tests developed going back

to Donald Hebb and others of getting people a sequence

of numbers.

So what they'll do is sit with Clive and say,

okay, Clive, focus on me now.

I'm going to give you some numbers and tell me

what you heard.

And you can say Clive one four.

And Clive probably say one four.

Great.

So he can remember the numbers one four.

But if he said to Clive, okay, I'll give you

one, I'll read out the list here that is used

for all the clinical work.

143928675.

Very likely Clive might say seven five, but he wouldn't

remember the numbers earlier in that sequence.

He's unable to remember what the start of the sequence

was.

And you can do.

If you have those questions.

I like your point.

So he seems to remember what the questions were.

He said, no idea, or so you might likely remember

what the question was.

But you're right.

After a certain number of if you gave him nine

numbers is very likely to say, sorry, what is this

about?

And you know, he don't remember it even knows.

But if you say, can you tell me the number

is one to repeat back 1 to 1 two, because

we heard in there.

So we have very, very small digits than is what's

number.

So you can have a digits of one or maybe

zero.

If they can't hold that, that's extremely, extremely rare.

Maybe someone have a digit span if they're a genius

memory, sort of, you know, maybe they can remember up

to 20 numbers or so, probably more if they're very,

very clever.

But you can do this forwards and backwards as well.

So and if you're doing experiments, you might repeat numbers

where people tend to get better.

So hidden in a sequence of numbers, you might go

through the first sequence and the next and there can

be some hidden repeats, but that's not what we're getting

on since the main thing is that this is one

way of assessing memory amnesia.

Another one is to not use numbers but just visual

information.

So someone has problems of language and they can't remember

words or what you're saying.

You can still use this visual task, which is that

the patient sits opposite you across the table.

If you are the clinician, you see these numbers on

the blocks that the patient opposite can't see the numbers.

And what the clinician will do is tap out a

sequence with their fingers over the blocks and the patient

has the top back the same sequence, either in the

same order or in reverse order.

And again, if they've got a good memory, they'll tap

the right sequence through.

But if it's forgotten, they'll struggle to remember what the

sequence was.

So this is, of course, in long span.

Now, another way of looking at memory going beyond the

short term test is to get into what's known as

procedural or implicit memory.

And there's many different types of this.

So one of the key ways of studying what's known

as procedural memory, we'll get on in a moment to

taxonomy.

The memory is to how people one of the earliest

studies that came up with a way of looking at

this was to say, Well, maybe there are other types

of memory that Clive, that I can't remember what Deborah's

asked, and he can remember how to play a piano,

how And in fact, people found people like Clive could

learn new tasks, procedures for doing things, but be unaware

of it.

So here's one classic example.

In this in this psychometric task, people are shown a

star on a piece of paper, but they can only

see it through a mirror.

So there's a piece of cardboard looking and they can't

see the piece of paper directly.

They can only see it through a mirror and they're

given a pen and just write really simple.

Can you just draw on the inner bit of the

star lists that you're going to draw exactly along the

stars edge and draw around it?

Now, if you just looking directly at a star, you

should be able, if you're most of you in the

room, to be able to do that perfectly, I'd imagine

all of you would do it perfectly.

But if you're looking through a mirror, every move that

you make is reversed.

It's really hard.

You've got to reverse your movements.

So it's very hard.

And so the average person when they're doing this makes

30 errors that go outside the line 30 times, trying

to make their way round the star.

And if you say, Right, okay, great, you do that,

and I do it again.

And another session, they'll get down to say, 12 errors.

You know, they'll get down and eventually you keep giving

them this task by the end of the whole day.

So lots of trials, they'll get down to making maybe

five errors.

So they've got better and better messages over the day.

You get them back, the next day they'll make more

errors as they've gotten a bit very quickly, they'll get

back down to this and then on the third day

of coming back doing this task, they're not flawless, but

they're making very few errors.

So.

Right.

And they know how to do this task and they've

learned how to do mirror drawing with this particular set

up.

So this type of procedural memory.

Now, what's amazing about this is that that score sequence

you're looking at, there is not a healthy person and

someone with amnesia.

And the interesting thing is that they would learn how

to do this pretty much just as fast as a

healthy person.

But on day three, they're surprised.

The reason this surprise is they've never seen this before.

There's no memory of sitting down.

They don't know how to do.

They've never seen the experience and not met the researchers

to them as an uneasy, but yet they know how

to do the skill suddenly got this ability.

So it shows this dissociation between things you can be

conscious and aware of and abilities and memories you're not

conscious that you had.

Another way to do this is as perceptual priming.

This is devised by Elizabeth Warren's.

And so this starts out as an easy version showing

a white and a more difficult version shown on the

left.

So in this particular task, if we focus on the

right hand side, the person is presented with a blank

piece of paper and said, okay, we're going to turn

over this to show you the next picture on the

page.

And I turn over the presentation with the sequence of

dots or this sequence of scrambled dots and it's okay.

Yes.

Guess what these dots are.

There are some there are some thing you can name.

What are they?

And if you've never done this before, you'd have no

idea.

If you had to guess, you might say I could

be anything.

Could be the house, could be anything.

I don't know.

But then they flip the page over to the next

image and they say, What do you think this is?

I know it's not a house.

Something else Maybe you don't know exactly.

You cannot guess what that might be.

Okay, look it over again.

Now it's getting a little clearer what this might be.

And on the last page, you flip over and.

Okay, okay.

If the person's got normal memory, normal functions that he

hasn't caused us an elephant.

I can name the elephant.

Okay.

So they get they can name the elephant on the

last page.

What the clinician will do is repeat this again and

say, okay, here's.

And they'll do that with a whole load of animals.

So you're not just getting one elephant, you're getting you're

getting a seagull or a canoe or whatever.

It's just those little dots.

And so the person might see this and say, Is

it the canoe?

No, they're wrong.

And I go forward and I say, Is it the

elephant?

Yes, it's the elephant.

They've learned that that sequence of dots.

And if you do this again and again, this time

they see this this sequence in dogs.

They can say elephants.

Now, they don't necessarily know.

Sometimes they might know, but they might not necessarily know

why This feels like it's the elephant, particularly this one

here, because it's really difficult to guess.

But the key point of this work is that amnesic

patients likewise can still do this.

He can still guess well above chance that that sequence

of dots is an elephant.

And he's surprised again.

No idea how he knows, but his brain has learned

to associate those dots with elephants.

And what's been shown is that that involves areas of

neocortex and other areas of the brain that are not

the hippocampus.

Hippocampus can help because you can remember things, but this

type of rapid naming of dots can be done by

other brain areas.

So you can do this in amnesic.

Another classic is before we move on to the other

things that are lost.

Example of preserved.

Yeah.

If you're you to.

He only played one time.

He could only play what he'd learned there.

It's very difficult to learn new sheet music, as far

as I know.

I don't.

I don't.

There's a whole Wikipedia page all about Clive, and he

may well tell us whether he has learned, but my

memory is that it's this type of learning can be

done.

And a good point is, if you came back to

Clive in a month's time and said, Right, can you

name this elephant?

He's already forgotten that.

But have also had many normal, healthy people.

Like if I came back to you in a year's

time and said, Right, what was that?

With these dots, you might remember if I was only

an elephant I showed you.

But if I showed you a whole ton of animals

and things, you wouldn't remember it.

This is something in the immediate area of learning.

But yeah, it's a good question.

As I say, I don't know the exact answer, but

it's very likely he couldn't learn.

And again, the challenge is finding styles, specifically tasks.

You can go metrics and numbers out.

So here is a task developed by Barbara Knowlton and

others published in Science some time back and has been

reused in lots of studies, and they tested it on

both patients with Parkinson's, Huntington's or amnesic cases, the brains

of different patients.

And what they found was that what they did in

this ask is take a sequence of cards that only

show one of these at a time and a whole

sequence of these cards for these cards.

But they keep flipping through them and saying, okay, when

you see a card, let's take the latest item.

And you say, okay, what with each of these cards

is going to give you, you going to have to

guess whether it's going to be sunny or rainy today

based on the card.

And then they guess you might say, well, I've no

idea, but I'm going to get some.

And they're told, yes, you're right, that son.

And he's the son.

Perfect.

Okay.

Next card, son.

Right.

They said, Well, you guessed right.

And I've been told, no, you're wrong, that that was

done.

And they go and they see the cards and they

have to learn what the association is between a card

and an outcome.

And of course, this goes back to our reinforcement learning

lecture last week where I talked about the idea.

If you watched the movie of the idea that you'd

need that motivational circuit, the dopamine to learn this association.

And so what's really important here is that it's not

100% probable.

So if you given this card 80% of the time,

it will lead to say something and 20% it will

be right.

So you can't by using one shot experience memorise, you've

got to learn over lots of trials.

What each card is associated with.

All of them will give you some rain.

But these two, for example, might give you some more

of the time.

And these.

Right more of the time and was exciting and why.

This is published in one of the world's leading science

journal Science was that amnesic patients could have learned that

rule over 50 trials.

They could they could learn what this is they don't

get as an doctor.

Guess some well done Huntington's and Parkinson's patients.

Damage destroys them.

And about the last week, they struggle to learn that

rule their VCA, that whole circuit to do it opening

is disrupted the VCA and that circuit is not disrupted

and classic amnesia.

And so what was fascinating was that they got this

dissociation between amnesia able to learn, and Parkinson sometimes is

not able to learn.

But when you test them an hour later, have you

seen these stimuli?

Which of these eight cards and there's four of these

and four other ones did you look at Parkinson's patients

and Huntington's?

Yeah, it's obvious it was.

I spent ages looking at these cards as these four.

They know what they saw.

They can recognise the stimuli, but Clive Waring and other

amnesia patients would have no idea that they seen these

cards.

So you have this association with learning a rule and

being able to remember the stimuli.

What did you see before you recognise it?

So this this is this is this implicit with this

learning of the rule is described as habit learning.

Like your brain is constantly learning habits all the time,

sitting down, setting up laptops where you turn to when

you leave this.

You been in lectures here lots of times.

You're not thinking very hard about where the doors are.

You have a habit ingrained in your brain.

That's what's the amazing things that are stated in these

amnesic patients.

But what is lost?

Okay, so we're going to measure that.

What appears to be lost is cut encapsulated by this,

what's known as episodic memory.

Memory for events and episodes which were personally experienced.

The things that happened to you.

So, Clive, to go back to that video I showed,

Deborah asks him and says, I'm going to tell you.

Let me tell you, divorce is getting married.

She's getting married.

Australia.

She's getting married soon.

I'm trying to remember exactly what he said.

I'm sure I didn't get it right, but that is

the gist of it.

He's then tested on.

Well, do you remember what's happening tomorrow?

He has no idea.

So he's failed to remember.

And she asked him several questions.

He can't remember any of them.

This all comes under episodic memory, personally presented events, information

that was given to him or episodes made or experience

that he experienced himself.

Episodic memory.

Now, there's two types of amnesia when we delve down

into this.

What we've just looked at was anterograde amnesia.

So Clive Waring had a lesion in his brain, and

this is his life after that lesion.

His inability to remember whatever his wife is telling him

is known as an interim great amnesia.

He can't remember that his daughter's getting married and told,

but he might remember that he has a daughter.

He wasn't surprised as my daughter's getting married.

I have a daughter.

Do I really have a daughter?

He didn't say that.

Except that he knew he had a daughter.

There's no loss of memory he could have.

There's all sorts of things that Clive knows about happened

in the past.

But there's a period typically in amnesia just close to

the lesion where he had his damage.

But perhaps, for example, let's say his daughter, this is

this is a fictitious narrative.

It's something that happened to his daughter.

This quite significant just before his lesion, his brain damage

is quite likely.

He would not remember that.

And whenever his wife brought it up, he'd be surprised.

And what's important here is that his brain was perfectly

healthy when he learned that information, but it had not

been stored in some way that made it.

Safe or protected.

Where is the memory that he has a daughter from

some time back in his life when he was an

adult has been protected.

He has retained that despite their amnesia.

So you have some retrograde and there's constant anterograde amnesia

in the classic amnesia syndrome.

So how do we test the I'm sorry, great amnesia?

Let's focus on how we test that on the classic

test.

To do that, to look at episodic memory in a

laboratory or at a clinic is to give people this

task where you're shown a abstract picture like this, isn't

it?

Is the real stress complex figure based on the clinicians

that develops it and they give it, the person is

given another piece of paper.

And so can you draw this out as carefully as

you can, do this really carefully?

Drew exactly what you see on this paper, nothing else.

And then after 50 minutes, they're given a blank piece

of paper.

And so, okay, I showed you a piece, a drawing.

Please, can you redraw that?

And again, Clive would have no idea that he has

a drawing or something, but sometimes the amnesic have some

sense they had too.

Earlier on, I showed you patient brain with really small

selective damage.

Here's on the far right of this nine he's is

a control participant who's drawn out the shape.

Each of these are patients with a brain with really

severe damage.

They've all drawn that shape perfectly relatively perfectly.

And the control participants and a fantastic job, they've drawn

it themselves.

So they they've got a better memory than if you

just seen the picture.

You can see they've gotten the lines across.

Yes, they're not perfect.

But each of these participants here, they've remember these are

amnesic patients.

And remember something arises.

And that in itself is kind of fascinating.

That is something, remember, for retained, but a vast amount

is lost.

So there seems to be some preserved information about this

going into that's very likely.

Is that implicit memory for something about the context of

that.

But it's a great question as to why we still

don't fundamentally understand all the things that occur in amnesia,

and that would be an example of it.

Semantic memories.

You got that memory for Clive.

What was he told in that short chat with his

wife?

Another memory type that's really key is the ability to

remember facts information independently from the initial experience.

So an example of that is knowing what is this

for English speakers and people in the room?

You're hearing this lecture in English.

So you should know that this this diagram here is

a tiger.

That's the knowledge you gained over many experiences.

Now, it's unlikely that you remember the first time you

learn Tiger.

You may do, but many people have grown up in

the first languages.

English Well, I had no idea when I learned I

was very young.

John Another example one was the capital of Peru is

a fact.

I also have no memory of when I first learned

that Lima is the capital of Peru.

So there's much later in life, there's still, for me,

a semantic memory.

I have no idea when I learned that site.

These are just classic examples.

Clive Waring in that interview knew what a daughter was.

He was straight in questions.

A lot of the things he has, a lot of

facts he knows about the world and these are retained.

And Larry Squire, who I put his picture up next,

the patient NPR there.

In fact, Larry Squire, there's a short 50 minute movie.

And this section you can watch where he talks through

declarative memory and taxonomies of memory and history of amnesia.

It is quite helpful if you want some more information.

But here, what was developed by Larry Squire and many

others, Neal Cohen is an example.

The key person here was that long term memory can

be split between explicit memory he describes as declarative memory,

an implicit memory or non declarative memory.

So explicit memories are things like Clive Clive wearing saying,

you know, I do, I do know this or I

don't know that my daughter's getting married tomorrow.

Yes, you can.

You can say yes or no to that.

But how did he play the piano?

It's not a yes, no question.

He used to move his fingers in a particular way.

He could tell you what is happening, but he just

knows how to do it.

It's like riding a bicycle.

You don't really think about it.

You just kind of do it.

And that's what's described here is non declarative skills and

habits and emotional responses to things like priming that can

occur, knowing that that was an elephant given the dots.

So how did you know that?

I just know might be the answer.

And within declarative memory, we're drawing a distinction between episodic

memory events and times, the things that happened, and semantic

memories of facts and figures and things.

And the controversy will now look at.

So that's that's the kind of where we got to

in general agreement these things will exist and that there

are this side of the pathways, damage and amnesia.

Going to end the lecture and the last 8 minutes

or so on controversies.

And one of them has been the brain areas involved

in supporting recognition, memories, semantic memory.

So here, if we look down here, the events of

episodic memory.

You can split if your scientist in two things, you

can recollect, go back in time and remember and say,

Yeah, I was in this lecture theatre in the past.

It was on a monday.

I remember that.

Or you can say you were familiar.

So what classically might be meeting somebody and knowing what

their name is and who they are versus meeting somebody?

You think I know you, but I don't know what

your name is or who you want to know how

I know you, but I just know who you are.

And that's the similarity.

Now, some of the work is shown, and I just

highlighted that example, a feeling of knowing that's what this

slide is running over.

An example here is recognising someone you seen before, not

knowing the name of who they are.

Now, that's fine, I can tell you that.

But if I want to do a test badly, one

of the key forefathers of like a lot of working

memory and neuropsychological assessments developed the task of the two

and people test.

We have to remember people in names or visual shapes

of an either figure or you have to do a

recognition task.

You are given a spotlight, a whole sequence of names

like Jill, Ashley or Doors to memorise really boring doors.

Unless you are tested on that always, you can recognise

those names.

The reason you estimate this side really hard is that

you want us to equate record recall with recognition.

And we're much better recognition because the information's in front

of us.

I was shown here are a number of patients, so

with this test, the rules and people is standardised.

The score of ten is normal and plus or minus

two captures.

And those people I was shown in prior work.

Is that patient?

We are on another case.

This patient John, we're amazingly good if we are really

good are recognising which of these doors you give that

door and they pick it out.

You can even see the colours change the bit.

They recognise this door from having seen 12 doors with

that particular door really good at it and patient John

Similar, but they cannot remember the name.

So the fact this guy's call, Tom Webster utterly forgotten,

absolutely devastated on the on recall side are the patients

suddenly have terrible on both scores.

So what what it shows is generally amnesia damages both

the ability to recognise things like names and pictures and

recall things.

But sometimes the damage can be selective and preserve, says

some other areas of the brain must be doing this

recognition memory.

And that's been somewhat controversial.

Controversial?

The argument is the hippocampus is not essential.

This brain area for tasks using familiarity.

What about semantic memory?

So if I'm going around the world like Clive and

trying to Deborah sitting there, trying to teach Clive about,

say, what a tsunami is.

So it's anomalies are not really discussed in the literature,

in the culture before a certain point.

Big tsunamis came in and killed lots of people and

culture.

So this Endeavour might be trying to explain to Clive

all about tsunamis.

And he's going have a really hard time remembering what

a tsunami is.

And eventually, with all the research shows, he will never

learn new facts.

Clive is so densely amnesic, he can't learn new science

information.

So H.M.

He talked about his famous patient.

He could not remember new word definitions being done.

And the other patient I talked to about both episodic

and semantic information, they can't learn new things.

However, there was a startling discovery in 1997.

Away from, in fact, pretty much in the offices where

the lecture Friday is Fridays lectures at the Institute of

Child Health.

Finally, Volker Kardon is a client, is the lead clinician

for the clinical neuropsychology team for the paediatric pathway in

the ICU in Great Ormond Street.

And her team led the discovery in 1997 of a

group, a number of patients who couldn't remember anything like

Clive come in, no memory, couldn't get a cup of

tea.

They forget who you are.

Yeah, I had amazing knowledge about the world.

And one of those patients I mentioned a second ago

was John, this patient, John.

John went on to pass a GCSE in history.

You got a He didn't get an A-grade, but he

remembered lots of facts.

Somehow this patient, John, had learned over repeated, repeated repetition

facts about the world.

What this tells us is that the neocortex, John, John

and all these patients has severe hippocampal damage.

My patient, while John's hippocampus was shrunken, the key thing,

the word his early onset, all of them had damaged

in childhood, really early in life.

So these are their their neocortex, the survival supplies for

this gradual learning, or there's something about their hippocampus when

damaged early in life, still able to pull off this

trick.

You still don't know the exact mechanism.

It's very hard to study in humans, these things.

So this has been controversial and caused a lot of

disagreement.

But the current no doubt there's no dispute.

These children have grown up with eyes and memory and

can't remember what happened to them over their lives in

terms of experiences they don't know facts about.

They know they got a brother, for example, but they

don't.

You said, Don't you remember your 14th birthday when Joe

came and it was a disaster?

No.

No memory.

Most people remember the disastrous birthday they might have had.

They won't have that ability.

Finally, I'm going to touch on the last moments of

this lecture on consolidation.

So here's patient H.M. Here's the dense.

I'm Terry Great amnesia.

He had utterly after the surgery he lost all capacity

to learn new things.

But they asked him questions before the surgery and just

before it.

Very few details.

But you go back into his childhood and he could

remember.

So he lost.

He lost the memory of an uncle who died very

sadly.

And his childhood memories are fantastic.

What was argued around from that information was that it

seems like the hippocampus in that circuit we've been looking

at is damaged in amnesia, is critical for inquiry into

memories.

But then over time that becomes consolidated.

Consolidated is strengthened.

Those memories become strengthened and stored in a much more

robust way, and then they become independent of the hippocampus.

So let's take another patient.

So that was H.M. But here's a patient p Z

who had a diary.

He kept a meticulous diary.

So you can go back and work out how much

of his diary did he remember and what matters.

And Sir Mark showed in a paper study was that

it was like up and up linearly.

I just went up backwards over time.

And there are a range of ways to probe this

with a diary or with photographs of famous people.

If you're an American, these are famous celebrities.

You might recognise one or two if you're lucky, and

there are standardised ways of interviewing people as highlights.

So most of these suffer from some retrograde amnesia, but

it's variable pace, I think is a case of patient

RB Where we went a few years back, another case

l.D.

This famous face, no memories their entire life back to

childhood.

It's hard to study few standardised tests if you're not

motivated, it's very hard to study and all the stimuli

are very hard to match how salient they are.

And it's hard to know whether those memories are going

back up and synthesised or episodic.

So that's one of the other debates.

And what scientists think is going on is that when

you first acquire memory, your neocortex or go back to

that slide on the hippocampus, the neocortex, signs of.

Mason is at the campus and creates links and binds

together information between areas in the neocortex, which, of course

talk to each other, connect connections between the cells.

But over time, these connections between these great areas become

strengthened and able to operate, and the connections with the

hippocampus become downregulated not necessary for the retrieval of the

memory.

And that's that is the standard model of consolidation.

Very simple model that if you remember things initially, like

H.M. learns that he's got a uncle, he's who's died

very sad.

He uses hippocampus to bind it, but he then has

his hippocampus removed.

It doesn't have a chance to strengthen or the fact

there was a fire in his and his in his

an environment of his young really early along back in

his childhood.

It does get strengthened and he can remember it because

his neocortex has got that memory strengthened and consolidated.

Now that was argued against in 1997 by two scientists,

Maurice Moscowitz.

And then they tell you argue that actually the details

and never really there.

If you go back to these kind of the pollen

and the fire is not detail in nature and cannot

tell you when you could when he was alive about

the details of it that in fact, as we get

as things go on, they argue the visual details get

strengthened with the hippocampus and MCO, the medial temple who

are strengthened.

That view was updated in 2011 in this journal article

by Whittaker Moskovitz to argue that there's a transformation that

occurs in the brain for detail.

And here's just one case example from Pelosi and colleagues

who are on the case who absolutely could not recall

things from their life, the detail they could recognise, not

the things that happen to them.

So we can see this distinction between vivid, rich detail

of recall and massive dishonesty and retrograde amnesia.

But there's no gradient, and it's this episodic loss that's

occurring.

So I'm just going to end on a few last

points.

Let's take an example of this kind of consolidation.

This is an amnesic taxi driver.

I was fortunate to study with Eliot and McGuire at

UCL.

He was hippocampus, was disrupted bilaterally, very severe damage damages,

hippocampus like Clive wearing.

I stepped out to get him a cup of tea

and came back.

He reintroduced himself to me and said Hello, but we've

been talking for some time.

I gave him I gave him the compass with an

arrow on it.

He couldn't see the compass.

It was hidden so I could measure his direction pointing.

I just I could just point to various places around

London.

We're standing in the middle of Queen's Square.

Where is London Bridge?

I'd be very surprised if you do see it.

The audience could point from here to London Bridge.

I can't do it if you take a London taxi

driver.

He spent 40 years.

He knows exactly about London Bridge.

He knows where Peter Street is.

He knows where all the streets in London, they have

to memorise it to be London taxi drivers.

And this is the chart.

A little little white dots of all the taxi drivers

with healthy brains we measured on in the black dots

this amnesic and he doesn't know how he knows this,

but he knows these directions.

We then were able to put him into a virtual

reality simulation of London back in 2006 and have him

drive round a virtual simulation of London.

And here's a route driven across the virtual simulation by

a group of ten healthy cat taxi drivers.

And in black.

Here's his route.

So it was terrible.

He was really bad at actually navigating.

So we had this knowledge of things, but his ability

to actually find his way in London in a virtual

simulation was terrible.

And what we found was that if he had to

go on minor roads, he couldn't remember.

But the major A-roads he could had been consolidated.

So he had this.

Some of his knowledge that we repeated have been strengthened.

Finally, Demis Hassabis, who was in Newcastle before he's founded

the company DeepMind, ran some studies asking patients to imagine

things like, Can you imagine lying on a sandy beach?

If you ask most people's room, they'll give you a

long, long description, all sorts of things happening.

But if you ask Clive Waring or patients, he was

tested.

They gives you a bit of a vague answer.

They report various things, but it's a bit vague.

And in particular they're missing all of the references to

where things are, things the normal, healthy person.

Things are behind them and they're left there.

But this is all missing.

And what damage some of the elements.

They can't actually imagine the scene.

You can imagine objects like a football.

They have problems processing, constructing the world.

So what this means is that where we are in

2022, the hippocampus is necessary for amnesic to remember things,

but it goes into imagination as well.

Clive Waring would not be able to imagine his daughter's

wedding.

This is what this work shows.

So here's the overview of what we talked about today

for time.

I won't read it out and can't read this and

there's a great review in 2008.