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more done. This

1:03

program is sponsored by the

1:05

Cauvly Prize which honors scientists

1:07

for breakthroughs in astrophysics, nanoscience,

1:09

and neuroscience. The

1:11

Cauvly Prize is a partnership among

1:13

the Norwegian Academy of Science and

1:16

Letters, the Norwegian Ministry of Education

1:18

and Research, and the

1:20

US-based Cauvly Foundation in Los

1:22

Angeles, California. I'm

1:29

Alan Olga and this is Clear

1:31

and Vivid, conversations about

1:33

connecting and communicating. This

1:39

year's Cauvly Prizes will be announced two weeks

1:42

from now on June 12th and

1:44

we'll be here then to talk with some

1:46

of the winners in two special episodes of

1:48

Clear and Vivid. And for

1:50

the next two weeks I'll be catching

1:53

up with and celebrating previous Cauvly laureates.

1:56

Today my guests are Carla Schatz and

1:58

Marcus Rakel. both winners

2:00

of the Cauley Prize in Neuroscience.

2:03

Carla's award was for her work figuring

2:06

out how our brains wire themselves up.

2:09

Her goal today is to build on

2:11

that research to make aging brains more

2:13

resilient. Marcus Raco was

2:15

rewarded for his breakthrough discovery that

2:17

our brains never rest. Even

2:20

when we don't seem to be doing much, our

2:22

brains are busy preparing for the future. Like

2:25

Carla, he too sees this insight

2:27

providing new approaches to helping aging

2:29

brains, especially those afflicted

2:31

with Alzheimer's disease. First

2:34

up, Carla Schatz, who I had the pleasure of meeting

2:36

back in 2016 when I was in Oslo helping host

2:40

the award ceremony. Carla,

2:44

it's great to see you again. You

2:46

know, I still have the most wonderful

2:48

memories of being together

2:50

in Oslo, and there was

2:53

a reception for all of us. And I

2:55

just remember having a glass of champagne with

2:58

you. And I think you joined

3:00

my brother and sister-in-law, and it was just

3:02

a really special moment. So it's great to

3:04

see you. It's great to see

3:06

you. And I remember that time in Oslo, you

3:09

gave the Cauley lecture, and

3:11

your brother was in the audience

3:13

who had previously suffered a really

3:15

serious accident, apparently. Yes,

3:18

you're right. That's right. He had

3:20

a spinal cord injury from a

3:22

mountain biking incident, and he's still

3:25

really struggling. But he is

3:27

miraculously still able to move,

3:30

and he's got the most amazing attitude

3:33

about the injury and about

3:35

life. And I think

3:37

he understands that with the

3:40

situation these days in terms

3:42

of really still not understanding

3:44

how to encourage

3:47

full nerve regeneration, that

3:49

it's mind over matter,

3:51

and his mind is

3:53

amazing. So he has

3:55

succeeded. I thought it

3:57

was very touching that you began the lecture. by

4:00

saying the fact that he was there at all was

4:03

because of the miracle of

4:05

neuroplasticity. Probably I've been studying neuroplasticity

4:07

for my entire career. For

4:10

me, the question is like, what

4:12

does plasticity mean at the level

4:14

of cells in the brain and

4:16

nerve cells? And

4:19

that really leads us

4:21

to the synapse, which

4:24

is this crucial connection

4:26

between nerve cells. The

4:29

synapse is the place where

4:31

computations happen in the brain and

4:34

where the information from one cell

4:36

is relayed to another cell across

4:39

a gap. And synapses change.

4:42

And the changes in those

4:44

connections and synapses lead to changes

4:47

in circuits. That's what I've been

4:49

studying my whole career in the sense that

4:53

I've really been wanting to understand how

4:55

circuits get set up

4:57

in the first place and tuned up by

5:00

experience. And the tuning itself

5:02

is plasticity because experience

5:05

is driving changes

5:08

in the numbers, the location,

5:10

and the strength of synapses. So

5:13

when our brains change, our

5:15

synapses change, which is always a very

5:17

positive thing. And that

5:20

is plasticity in action. And

5:23

that seems to be laid

5:25

into the foundation of the development of

5:28

a human. The idea that you

5:31

have this incredible ability to learn as

5:33

a baby or a young child, and

5:36

then that's pruned away after

5:38

you know basic things, right? Absolutely.

5:42

Patricia Kuhl, who studies

5:44

language learning in children,

5:46

very young children, loves

5:48

to say that we are all

5:51

born citizens of the world. In

5:53

other words, we are

5:56

able to hear and learn

5:58

and speak multiple languages. during

6:01

these early periods of plasticity.

6:03

And then, if you don't

6:06

use a language, and you

6:08

really have to use it in here at both, then

6:11

those connections are lost. And

6:13

I think there's a

6:16

lot of very beautiful examples of

6:19

this kind of losing it, or

6:22

pruning, as you say, where synapses are

6:24

removed. Why does the pruning

6:26

take place? Well, that's

6:28

a cosmic question. Why

6:32

shouldn't we just be able to retain

6:35

all of these capacities until

6:38

we need to use them? Yeah, I'd go for that.

6:40

Yeah, me too. And actually, a corollary

6:44

is, why can't we

6:46

put all those capacities back later? But

6:50

anyhow, the process of

6:52

learning actually

6:55

allows the used

6:57

synapses to grow and

6:59

stabilize. So, in

7:01

order to have room to

7:05

really create and stabilize connections

7:07

that we're going to use throughout our life, some

7:11

connections that aren't used have to be

7:13

removed. So, there would be a lot

7:15

of arguments for why that

7:17

would be good in an evolutionary way. I mean,

7:20

one is that energetically, probably

7:23

there's nothing more energetically expensive,

7:25

except maybe in the heart,

7:28

for maintaining synapses. They need

7:30

a lot of energy to

7:32

work. So, there's a lot

7:34

of argument for efficiency in

7:37

terms of removing the ones that are not moved.

7:39

There's also the issue of space. It

7:43

seems to me that there's only a certain amount of real

7:45

estate in the brain. We still need

7:47

room to learn other things, absolutely.

7:49

And by the way, that's partly

7:51

why, even though this pruning process

7:54

happens extensively in brain

7:56

development, eliminating the unused

7:59

possibilities. It also

8:02

happens throughout life at a much lower

8:04

rate. So people

8:06

understand that even

8:08

learning in adult, obviously we can still learn

8:11

in adulthood. It's just not at the same

8:13

amazing rate or ability or

8:15

flexibility. But even learning in the

8:17

adult does involve both

8:20

the formation and stabilization

8:22

of new connections and

8:25

also the removal even then to

8:27

keep the efficiency going of

8:29

connections that are not used as much. So

8:33

it happens throughout life. Let

8:35

me ask you about the word stabilization, which

8:37

you just used. The

8:40

impression I get, and you have

8:42

to guide me and let me know how close

8:44

I am to understanding this, the impression I get

8:46

is that as you

8:48

learn something, you're

8:50

stabilizing it more and more. The

8:52

more you hit the nails, the deeper it goes into

8:54

the piece of wood, the more stable it is. Is

8:56

that in the neighborhood?

8:59

Absolutely. It's definitely in the neighborhood.

9:01

So I think what I mean

9:03

by stabilization is first, I

9:05

guess I have to back up. I'm really

9:08

glad you asked this question about the use

9:10

of the word because as

9:13

we learn, new

9:15

connections are formed. So

9:17

new synapses are formed even in

9:19

our old brains when we're

9:21

adding knowledge. And

9:24

as they form, they're delicate

9:27

and unstable to start with. And

9:30

then they grow and become

9:32

stable. It's

9:36

like building where you're adding

9:40

structural material to the

9:42

synapse to stabilize it so

9:44

that it's not trembling and

9:47

unstable. And that's amazing. And how do we

9:49

know that? So neuroscientists

9:52

now have pioneered methods that

9:54

I find really awesome in

9:56

which it's possible to make

9:58

a little... window

10:01

on the brain, in this case

10:03

of mice, and when

10:06

mice are learning simple tasks

10:08

like, for example, running

10:11

in a maze and remembering where the good food is

10:13

or reaching for

10:15

a little food

10:18

reward with their little delicate

10:20

fingers, you can peer into the brain

10:22

and watch the individual

10:24

neurons in that part of

10:27

the brain that's doing the learning, and those

10:30

neurons form new synapses and you

10:32

can literally see them formed. So

10:35

we know learning requires

10:37

new synapses to be formed, but

10:39

then the most amazing

10:42

experiment to me is that neuroscientists have

10:44

also figured out a way to

10:47

target those newly formed

10:49

synapses and remove

10:51

them artificially,

10:54

and when that

10:56

happens, the mice forget

10:59

what they just learned. So

11:01

we know that synapses have

11:03

to grow and become stabilized

11:05

and remain and that

11:07

forms a substrate for memory. You

11:10

know, for me the thing that is most, I

11:13

know, heartbreaking and something I'm

11:15

really interested in at the

11:18

moment is

11:20

what happens in the brain of people

11:23

who have Alzheimer's disease where

11:25

they literally not only

11:27

can't recall but really can't form

11:30

new memories and have lost their

11:32

memories with the disease.

11:34

And this is where the system

11:36

breaks down because of the neurodegenerative

11:39

disease. Correct. It's not a natural

11:41

process, right? That's right, and so

11:43

then the question is whether any of the

11:45

natural processes that we know

11:47

exist in the brain that

11:49

are underlying the process of forming

11:52

memories at synapses and building

11:54

circuits for those memories, are

11:57

those normal processes in some way

11:59

being hijacked in the

12:01

disease to cause too much

12:04

removal of synapses. So

12:06

in other words, do they become

12:08

unstable and that

12:11

leads to removal? And if

12:13

you lose enough synapses, you're

12:15

losing memories and what's

12:18

even more to the point is that you

12:20

can't form new ones. You

12:31

know, since we talked last, I

12:34

gave a lot of thought, I have given

12:36

a lot of thought to this idea of

12:39

perhaps you're helping us re-achieve this

12:41

ability of rapid learning that we

12:44

had as children, as

12:46

babies and children. And

12:48

every time I get so far

12:51

in thinking about that, I come up

12:53

against a kind of serious question,

12:56

what would my brain be giving up to enable

12:58

me to do that? There's only a certain amount

13:00

of brain there and if I'm devoting it to

13:02

what all the things I did as

13:05

a baby before I

13:07

shaped the precise targeted things

13:09

I needed to do to get through life, am

13:12

I going to give up some of those? I mean,

13:15

that is the whatever 64 million

13:18

dollar question, of course, you know, we

13:21

can talk about this idea of taking

13:24

a pill that would reopen these early

13:27

learning periods and you know, I think the concern

13:29

there would be that when you reopen them, you

13:32

would make the synapses unstable

13:34

again, I'm wiggling my fingers,

13:36

you know, to indicate that

13:39

and and the instability

13:41

of those synapses might

13:44

mean that you would lose things that

13:46

you had learned, which

13:49

could be, you know, a disaster.

13:51

So on the other hand, let's

13:54

just let's just think about it for a

13:56

minute in terms of therapeutics though, rather than...

14:00

So I mean, I would like the pill because I

14:02

want to learn how to speak French without an accent.

14:04

But you know, you're right. What would I give up

14:06

English? I have no idea. Nobody knows. But

14:10

I think you have a comedy

14:12

science fiction movie. It's actually all

14:14

right. Yeah, well, it's already a

14:17

comedy. So why not? It's a

14:19

divine comedy, right? Thinking

14:21

about the brain. And now let's

14:24

go back to the pill. Mm

14:27

hmm. So-called pill. The so-called

14:29

quote pill. And

14:32

ask, well, what if we gave the

14:35

pill and

14:37

reopened this wonderful

14:40

learning period? Would

14:42

it be possible to acquire

14:44

new memories? So

14:48

I don't think you could get back to your old ones

14:50

necessarily, but maybe one

14:52

could create new connections because

14:54

so many have been lost. So

14:56

you could recognize your

14:59

friends again and so on because you'd have to

15:01

you know, you'd have to relearn it. So

15:03

I think in cases

15:05

where there might be a lot of synapse

15:08

loss and cognitive loss, I

15:10

might be willing to try this

15:12

so-called pill. So

15:19

tell me in your wonderful organization

15:21

Bio X, where

15:23

you're bringing different viewpoints together

15:26

to study things in fresh ways. Are

15:28

you are you working on any of these things that we've

15:30

just been talking about? Well,

15:33

yes, for sure. Since I'm getting to be

15:35

very old now, I'm

15:38

much more interested in what goes on

15:40

in neurodegenerative disorders than I used to

15:42

be when I was studying babies brains.

15:44

So personally, of course, I'm very

15:47

interested in that. You

15:49

know, the Bio X

15:51

is Bio plus let X equal

15:54

chemistry, physics, engineering,

15:57

the clinical

15:59

sciences. way beyond neuroscience, you

16:01

know, also cardiovascular

16:04

cancer biology. It's

16:06

this wonderful, the X is

16:08

the interdisciplinary crossroads of disciplines.

16:11

So there are many of

16:13

us neuroscientists who have

16:17

drawn the X Kool-Aid and

16:19

are involved in a

16:21

lot of interdisciplinary collaborations,

16:24

for example. So I am,

16:26

you know, running bio X at

16:28

the moment, but also involved

16:30

so, you know, experimentally. The other really

16:32

exciting thing is that at Stanford, we

16:34

do have a new program, which

16:37

is called the brain resilience program. You'll

16:39

like that term. I think

16:41

we all are thinking about mechanisms

16:44

for brain resilience and restoring

16:47

resilience to aging brains.

16:49

And what do you mean by resilience in

16:52

particular? Well, that's a good question.

16:54

I mean, what I mean by resilience

16:56

is the ability of the brain to

16:58

restore itself to a healthy

17:00

function, for example, or

17:03

to be resistant to,

17:06

so resilient to resistant to

17:08

loss of cognitive

17:10

abilities and other aspects of

17:13

function as

17:15

we age or in the context

17:17

of neurodegenerative disorders. So

17:19

rather than calling it a program

17:21

in neurodegeneration, which is

17:25

kind of negative, let's call

17:27

it a resilient. Yeah, let's call

17:29

it resilience, because that's the goal. Let's

17:32

get to the goal rather

17:35

than where we are now. So

17:37

are there any hints about what

17:39

contributes to resilience that we

17:41

can take to the grocery store? Well,

17:44

let there are no pills yet either.

17:47

But I mean, you know, I'll

17:49

tell you, the most fundamental aspects

17:51

of resilience really have to

17:53

do with cardiovascular health. And everybody knows that,

17:55

but it's serious. And it's

17:58

worth thinking about brain resilience. really

18:01

also requires cardiovascular

18:04

resilience and good brain

18:06

oxygenation. And we all know

18:08

that, and our mothers know that and everything. So, but

18:11

there are a lot of promising leads.

18:15

And one of the leads really has to do also

18:17

with keeping the immune system

18:20

happy and not inflamed.

18:24

And there are people across the world and

18:26

here at Stanford who are really studying aspects

18:29

of inflammation in

18:31

neurodegenerative disorders. And

18:33

I think practice makes perfect. So actually

18:36

really for both of us, using our

18:38

brains all the time is really helpful

18:40

because it's not

18:42

just use it or lose it during development, it's

18:44

also now. And

18:46

so I think it's not

18:49

just cardiovascular exercise, but exercising

18:52

those connections. And

18:54

there are a lot of molecular

18:57

approaches where people are actually looking

18:59

for molecules that

19:01

seem to confer resilience, especially

19:04

in mice models. And

19:06

then lastly, very interesting work

19:08

in human genetics, looking

19:11

at centiogenarians who

19:13

are healthy agers who seem

19:16

to manage even at the age of

19:18

100 plus to have healthy brains is

19:20

to ask what's in their genome that

19:24

is different from the rest of us that

19:27

allows them to maintain

19:29

their mental sharpness even

19:32

as they age. And so, I'm

19:35

hoping the next 10 years, not longer,

19:38

will be yielding some

19:40

important clues that could become something

19:43

that we could go to the grocery store

19:45

for. Well, I

19:47

tell you, my brain grows every time I

19:49

talk with you. And I'm glad

19:51

we could have this talk today. It's just been

19:53

terrific. Well, it's absolutely wonderful. It's

19:55

such an honor to talk to you and

19:58

see you again. I

20:00

look forward to another opportunity to see you in

20:03

person, so be well and take care. You

20:05

too, Carla. When

20:12

we come back from our break, I continue

20:14

catching up with previous Cauvly laureates by

20:17

talking with Marcus Rakel. He

20:19

was awarded the 2014 prize

20:21

in neuroscience for research

20:23

that upended the conventional wisdom about how

20:26

our brains go about their work. Our

20:32

program is sponsored by the

20:34

Cauvly Prize, which honors scientists

20:36

for breakthroughs in astrophysics, nanoscience,

20:38

and neuroscience that transform

20:40

our understanding of the very big,

20:43

the very small, and the

20:45

very complex. From

20:47

scientific breakthroughs like the discovery

20:49

of CRISPR-Cas9 and the detection

20:51

of gravitational waves to

20:54

inventing new fields of research, Cauvly

20:56

Prize laureates push the limits of what

20:58

we know and advance science in ways

21:01

that could not have been imagined. The

21:04

Cauvly Prize is a partnership among

21:06

the Norwegian Academy of Science and

21:08

Letters, the Norwegian Ministry of Education

21:10

and Research, and the

21:12

U.S.-based Cauvly Foundation in Los

21:14

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get more done. This

22:21

is clear and vivid continuing our

22:23

special episode spotlighting past winners of

22:25

the Cauvly Prize. I

22:27

first met Marcus Rakel several years ago

22:29

when filming for the PBS series The

22:31

Human Spark. He introduced me

22:33

to the surprising fact that our brains are just

22:36

as active when we seem to be not doing

22:38

much of anything as when

22:40

we're busy working or thinking hard. You

22:44

know ever since we talked the

22:46

first time I've been thinking over

22:48

and over about your work on

22:51

the default mode network. It just

22:53

fascinates me because

22:55

I come from a

22:57

time when people popularly said

22:59

that we only use a part of our brain

23:01

or we're not using our brain all the time but

23:04

your work shows that we use our

23:06

brain, all our brain, all the time

23:08

right? That's exactly right. Yeah this notion

23:11

that you only use 10% of your

23:14

brain is a

23:16

crazy idea. Yeah what's it all there

23:18

for? You're not going to use it.

23:20

That's right. I think one of the

23:23

curious things about it is that even

23:25

when we think we're doing nothing or

23:28

focused on nothing much just letting

23:30

our mind wander and drift the

23:32

default mode network is still pumping

23:34

away. Yes. I think

23:36

definitely pumping more vigorously than when

23:38

you're applying yourself to a specific

23:41

task. It kind of slows down

23:43

during that period as the impression I get anyway.

23:45

Yeah well that was how we kind of discovered

23:47

the thing in the first place was these

23:50

funny things that were going

23:52

down when you engaged in

23:54

a demanding task. That

23:56

coupled with the fact that the cost of

23:59

running your brain very

24:01

little no matter what you're doing.

24:03

If you're just laying quietly, gazing

24:05

at the scenes around you

24:08

or sleeping and so forth, it's

24:10

still very costly. Am I right

24:12

that before you did

24:14

all this work on the default

24:17

mode network, the signals

24:19

that were coming from it were thought

24:21

to be by most scientists just

24:23

noise that could be subtracted from

24:25

the whole operation? Yeah, there was

24:28

what we called the global signal

24:30

and the trick was just to subtract it

24:32

away. And you got

24:35

these beautiful pictures of the brain when

24:37

you were reading a word or you

24:39

were saying a word or doing whatever

24:41

and the background was black. But

24:45

what was not really

24:47

conveyed at that time was

24:49

that the change that we

24:51

were depicting was a few

24:53

percentage. We were very good at

24:56

doing this. But we were throwing

24:58

most of what the brain was doing out

25:00

the window. I've heard you

25:02

say a couple of times that

25:04

the brain is a kind of a prediction

25:06

machine. Yes. What's it busy

25:08

predicting? I think prediction is

25:10

an important part of survival, if

25:13

you will. In other words,

25:15

if you've learned something in the past that's

25:19

important in terms of

25:21

your survival, it's

25:23

important to keep that on board and

25:25

to bring that to your

25:28

attention when you're about

25:30

to engage in something that's relevant

25:32

to that concern. So

25:34

in prediction, there's an element of

25:36

memory and then

25:39

the ability to utilize

25:41

that memory for future

25:43

activities, either as a

25:46

warning or as an encouragement or whatever

25:48

else it might be. So

25:50

let me ask you over some examples that

25:52

occur to me. And I'm curious to know

25:55

if there are examples, as far

25:57

as you're concerned, of the

25:59

default mode. in operation. For

26:01

instance, I'm not sure

26:04

what I'm going to say next when

26:06

I speak to somebody. I

26:08

have a general impulse that I'm aware of, but

26:11

the precise words I use seem

26:13

to come to as a kind of

26:15

momentary inspiration. Are they coming from the

26:17

default mode network? They're

26:20

coming from the default mode of

26:22

the brain. There is

26:24

a default mode network which is this very

26:26

interesting collection of areas that run all the

26:29

way from the front of the brain to

26:31

the back of the brain. But

26:34

the notion of a default mode

26:36

involves all of the other networks

26:39

within the brain and their

26:41

ongoing conversation. There is

26:44

a pecking order here. You have various

26:46

parts of the brain, your hippocampus,

26:49

which some people say is part

26:52

of the default mode network, but

26:54

then you have the amygdala and other parts

26:56

of the brain that are concerned with emotion

26:59

and other things. And

27:01

if you get serious about looking at this,

27:03

and this is one of the things that's

27:05

really fascinated me, is

27:07

that there is ongoing activity in all

27:10

parts of the brain. I

27:12

was trying to pin down the operations of

27:14

the default mode network. It's some of the

27:16

things it's focused on when it's churning

27:19

away. So I tried focusing

27:22

the network on what word is

27:24

coming out of me next, but

27:26

that apparently isn't. Most of that

27:28

work is done by other networks.

27:32

Well, it's a combination of these

27:34

things. And what's so really interesting

27:38

is that you not

27:40

only have the networks, but you

27:42

have very specific, if you will,

27:44

conversations between them. And this is

27:47

where I think

27:49

one of the important advances in

27:51

imaging, it's not only where things

27:54

are happening, but is what's

27:58

going on over time. I

28:00

like to think of it like a symphony

28:02

orchestra. I used to be

28:04

a noble player in a symphony orchestra. I

28:06

may have mentioned that to you. But

28:10

the music that comes out

28:12

is rhythmically coordinated between the

28:14

first violins, second violins, percussion,

28:16

you know, the whole thing.

28:21

It's a very, very organized

28:24

relationship that's both spatial in

28:27

the orchestra and

28:29

in the brain. And

28:31

timewise, how much time does it

28:33

take to go from the front of the default

28:35

mode network to the back? And

28:38

what is the time difference between the

28:41

amygdala and a default mode network, for

28:43

example, or the

28:45

motor system, for that matter? So

28:48

we have this ongoing orchestra

28:50

or community conversation going on

28:53

in our head all of

28:55

the time, making

28:57

of this very

28:59

expensive organ and

29:02

preparing for things to come. It's

29:05

kind of fascinating to me. It

29:07

is. And as you describe it, it

29:10

sounds like the amygdala and

29:12

its emotional duties are

29:15

very important. Sounds like the big

29:17

role for the default mode network

29:20

in keeping you alive, if

29:22

the amygdala says, oh, I'm afraid of this.

29:25

Yes, well, something like the

29:28

amygdala comes along, you know, in

29:30

the background there and says, oops.

29:32

Yeah, right. I see trouble. Don't

29:36

go there. It's either a snake or a garden

29:39

hose. And

29:41

don't take any chances with this. You got

29:43

it. Well, I get

29:45

into trouble when you don't need to. Yeah, right.

29:47

Yeah. But you know,

29:49

the other thing that kind of fascinates me

29:51

at times, and I'm sure you must have

29:53

experienced this, is

29:58

you've been puzzling about something. For

30:00

me, it's oftentimes the praying. You know, why

30:03

in the devil did we organize it this

30:05

way? And you go

30:07

to bed and you're kind of laying there and thinking

30:09

about it, and all of a sudden something pops out.

30:13

Like holy cow. And so I'm

30:15

using it up and write it down because I don't

30:17

want to forget it. Right. It's

30:20

been something that's been worked on in the

30:22

background in your brain. That's right. And

30:25

in the unconscious part of the brain, working away

30:27

at solving this problem. See, to me, it's like,

30:30

what's that person's name? And in the middle of

30:32

the night, or just as you're going to sleep,

30:34

say, oh, I got the name now. Or

30:36

it's looking for the solution of a

30:39

creative problem. How do I make this

30:41

scene work between these two characters? How

30:43

do I develop this theme without

30:45

looking like I'm just talking to the

30:47

audience about a theme? How do

30:49

I have it come out of the characters? That

30:52

sounds to me like something that the default

30:54

mode network would be interested in

30:56

solving after a certain period

30:58

of time. But I can't get in touch

31:00

with it. I can't force it to come

31:02

up with the answer, can I? That's right.

31:04

Yeah. And you know, my best

31:07

example when I'm trying to explain this to somebody

31:09

is you see somebody coming down the street and

31:12

you know this person, but you

31:14

can't think of his name or her name.

31:17

And you know, this is going to be

31:20

an embarrassing encounter. And

31:23

so they come and you've fumbled your way through

31:25

this whole thing. And as you're walking away a

31:28

bit later, all of a sudden that

31:30

name just kind of pops out of

31:33

nowhere. Yes, right. Now, now,

31:35

now what's going on there? How

31:38

big a role is the default mode

31:40

network playing in that? I don't know

31:42

specifically, but my sense

31:44

of it is given its central

31:46

position in all of these relationships

31:49

that the default mode notion,

31:52

including all of these networks, is

31:55

responsible for what's going on. Right. Who

31:58

are the major players in this? story. Well,

32:02

you can kind of guess at

32:04

that. We don't know that for sure. But,

32:07

you know, this aha moment where

32:09

something occurs or you remember a name.

32:12

And at

32:14

my age now, I occasionally feel

32:16

embarrassed as I think about somebody

32:18

and I can't remember their name

32:20

or something like this. It's especially

32:22

embarrassing if it's one of your

32:24

children. I

32:27

haven't gotten to that yet, but I've

32:29

got 11 grandchildren now and you

32:31

got to be careful here. Yeah,

32:33

right. Right.

32:39

So I spend a lot of my time

32:41

in my various jobs as an actor, as

32:43

a writer. I spend a lot of

32:46

time trying to get in touch with my unconscious,

32:48

where all the good stuff is, where the

32:50

deep work is going on.

32:54

And I've heard you say

32:56

that no degree of

32:58

introspection provides any access to the

33:01

default mode network. Does that mean

33:03

that all the default modes are

33:05

as hard to reach? Am

33:08

I wasting my time trying to get in touch with

33:10

them? Because it seems to me that one way I

33:12

can get in touch with them is through an associative

33:14

process, trying to remember the name

33:16

of that person coming down the street. Yeah,

33:19

I think it's your friend to begin

33:22

with and it's organized

33:25

in ways we're still trying

33:27

to figure out for sure. But

33:30

the mere fact that you are

33:32

engaged into something that is important

33:35

for you to understand more deeply,

33:37

you're trying to figure out something, whether

33:40

it's a perspective of a musician

33:43

or an actor or a scientist or

33:45

so forth, I

33:47

find myself puzzling about things.

33:50

And what's so interesting

33:53

is that oftentimes suggestions

33:55

pop out in

33:57

curious ways. And

34:00

all I can think about is I planted a

34:02

seed in my brain

34:04

some way or other,

34:06

and it continues to

34:08

work on this problem,

34:10

despite whatever else I'm

34:12

doing in the meantime. And

34:15

it then speaks back

34:17

to me in some curious way.

34:21

Is the amount of time and

34:23

the pressure you put on yourself

34:25

the exclusion of other worries, other

34:28

concerns, and the focus on the

34:30

problem, does that increase

34:32

the ability of the default modes

34:35

or the network to function more

34:38

fully, more fruitfully? I

34:41

think it could be both ways. I

34:43

think it could be more fruitfully, more

34:46

productive, and so forth, as well as

34:48

not less productive, depending

34:50

upon how things are

34:53

organized in there. Sounds

34:55

a little bit like how important it is to

34:57

your survival. Yes. I

35:00

think it is. I mean, there must

35:03

be a prioritization in there in some

35:05

way. I've never used that term before

35:07

in this conversation. But

35:11

something like that, there is a

35:13

priority of things that you

35:16

are obsessed with thinking about and

35:19

other things that are more casual. And

35:25

the result of that interest is

35:27

reflected in what comes to your

35:29

mind, if you will, that becomes

35:31

conscious as you think about it.

35:34

I'm thinking of the scientist whose name I can't

35:36

remember right now, who famously was

35:39

searching for the structure of a

35:42

molecule and dreamt

35:44

of a snake in a circle

35:46

eating its own tail, and

35:48

woke up and said, I got it. It's

35:50

circular. Yeah, that

35:53

would be a great example of

35:57

what really fascinates me about it. how

36:00

our brain is working. We start

36:02

out with the fact that it's working all the

36:04

time. Right. And that isn't

36:07

just like your car idling in

36:09

the driveway as you're... there's

36:11

more sophisticated stuff going on in

36:13

there. And what

36:16

you've been thinking about consciously clearly

36:18

has an impact on that, for

36:21

better or worse. It

36:23

interests me that you see a benefit

36:26

to our health. And

36:28

I think you said that Alzheimer's one day

36:30

may be characterized as a disease of

36:32

the default mode network.

36:35

Is there any news on that

36:37

front? I wish there were. I

36:41

still believe that because if you look at

36:43

the anatomy of the pathology in Alzheimer's

36:46

disease, it

36:48

is the anatomy of the default mode network for

36:51

the most part. And

36:53

so somehow, rather, taking

36:56

advantage of that and what we

36:58

know about those constituents, I

37:01

would like to think that over time

37:03

this will help us understand the pathology,

37:06

how to manipulate it in such

37:08

a way as to either slow

37:10

the process down or

37:13

to cure it. It's

37:15

a real problem and it's a

37:17

personal one to me because there's

37:19

a high incidence of that in

37:21

our family. My sister recently died

37:23

of Alzheimer's disease. I'm sorry to

37:25

hear that. Yeah. So what kind

37:27

of assault could it

37:29

be on the default

37:32

mode network that would cause

37:34

it and what

37:36

could be done to remedy it?

37:38

Does anybody know anything about that

37:40

yet? Well, the literature on Alzheimer's

37:43

disease is enormous. And

37:45

of course, we have this

37:47

array of drugs being used

37:49

to slow it down or

37:51

make you better. And

37:55

of course, that's a very sad tale

37:57

because even though it seems to have

38:01

like mice who have Alzheimer's

38:04

genes, is pretty

38:06

ineffective in treating people. And

38:09

so, you know, and

38:11

we've got the billions of the disease.

38:13

It's like, you know, amyloid

38:15

beta is one of the things that

38:17

creates these plaques, and then there's the

38:20

thing called tau tangles

38:22

in there. And

38:24

we've kind of made a criminal out of A

38:26

beta. And one of the things

38:29

that I think we need to be thinking

38:31

about is, why in the devil is it

38:33

there in the first place? It clearly was

38:35

not put there so we could get Alzheimer's

38:37

disease. What's its real purpose,

38:39

and how is that

38:42

regulated, and

38:44

what goes wrong with the manner in

38:46

which it's regulated and dealt with? And

38:50

I think we, you see hints

38:53

of that kind of thinking, but

38:55

not enough. I think

38:57

we're, as we get better at

38:59

looking at this and looking at

39:01

in a more holistic way, looking

39:04

at the brain more, you know, it's fine

39:06

to know something about a given individual

39:08

neuron, but there's 100 billion of them

39:10

up there. It's

39:12

a little like, you know, it's a little

39:14

like dropping down into Times Square, grabbing

39:16

one citizen out of Times Square,

39:19

taking him off to a lab or her

39:21

off to a lab and studying and in

39:24

hopes you will understand New York City. That's

39:27

perfect. Perfect. Well, you've

39:30

certainly done an enormous amount of

39:32

work in collectivizing our knowledge of

39:35

the brain so that we can

39:37

understand it so much better. You've been responsible

39:40

for a paradigm shift in how we regard

39:42

the brain. And it's so exciting

39:44

to talk to you about that. I thank

39:46

you for taking the time to explain it

39:48

to me further. It's my pleasure to

39:51

share these ideas with other people,

39:54

hopefully somewhere or other, although I'm running

39:56

out of time here. to

40:00

see these become useful ideas in

40:02

the care of people with neurologic

40:05

problems. Of course. Well, I'm sorry

40:07

you and I have run out of time. I'd

40:09

love to hear more. Maybe next time we meet.

40:11

Alrighty. My pleasure is

40:13

seeing you again. Me too. This

40:23

program is sponsored by the

40:25

Cauley Prize, which honors scientists

40:27

for breakthroughs in astrophysics, nanoscience,

40:29

and neuroscience. The

40:31

Cauley Prize is a partnership among

40:33

the Norwegian Academy of Science and

40:35

Letters, the Norwegian Ministry of Education

40:37

and Research, and the

40:40

U.S.-based Cauley Foundation in Los

40:42

Angeles, California. Carla

40:45

Schatz is Professor of Biology

40:47

and Neurobiology at Stanford University.

40:50

She's also the director of Stanford

40:52

BioX, whose goal is

40:54

to facilitate interdisciplinary research and

40:57

teaching in the areas

40:59

of bioengineering, biomedicine, and bioscience.

41:02

Marcus Rakel is the Wolf Distinguished

41:04

Professor of Medicine at Washington

41:07

University School of Medicine in St.

41:09

Louis. This

41:11

episode was edited and produced by

41:14

our executive producer Graham Ched, with

41:16

help from our associate producer Jean

41:18

Chamais. Our publicist is

41:21

Sarah Hill. Our researcher

41:23

is Elizabeth Ohini, and

41:25

the sound engineer is Erica Hwan. The

41:28

music is courtesy of the Stefan-Kernig

41:30

Trio. Next

41:40

in our series of conversations, I talk

41:42

with two more past Cauley Laureates. David

41:45

Jewett shared the 2012 astronomy prize

41:47

for discovering a huge part

41:49

of our solar system that

41:51

was previously unknown, the Kuiper

41:53

Belt. If you could see a

41:56

picture of it, if you could go outside the solar

41:58

system and turn back and take a picture. it

42:00

would look like kind of a fat

42:02

donut surrounding the solar system, with the

42:04

inner edge of the hole in the

42:06

donut being where Neptune's orbit is, and

42:08

that extending out to some very large

42:11

distance. It's what the solar system was

42:13

like in the beginning, basically before the

42:15

planets came to be. Sharing

42:17

the 2012 astronomy prize

42:19

with David Jewett was Jane

42:21

Liu. She joined him in

42:23

the hunt for what at that time wasn't thought to

42:26

exist when she was a graduate

42:28

student. It took a long

42:30

time and you get disappointed

42:32

a lot, and I do remember saying things are

42:34

not going well. We've been doing this for a

42:36

while now. Like, are we going to do this

42:38

forever? And he said, Jane,

42:40

if we find this thing, we'll never have to

42:42

work again. I didn't quite know what that meant.

42:45

Like, will we be so rich? But I do

42:47

distinctly remember him saying that. And it sounded so

42:49

good. I said, OK, we'll

42:51

keep going. David Jewett

42:54

and Jane Liu, next

42:56

time on Clear and Vivid. For

42:59

more details about Clear and Vivid and to

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sign up for my newsletter, please

43:04

visit alanalda.com. And

43:06

you can also find us on Facebook

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and Instagram at Clear and Vivid. Thanks

43:11

for listening. Bye bye. Tired

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