Dr. Eddie Chang: The Science of Learning & Speaking Languages | Huberman Lab Podcast #95

- Welcome to the Huberman Lab podcast

where we discuss science and science-based tools

for everyday life.

[upbeat music]

I'm Andrew Huberman,

and I'm a professor of neurobiology and ophthalmology

at Stanford School of Medicine.

Today, my guest is Dr. Eddie Chang.

Dr. Eddie Chang is the chair of the neurosurgery department

at the University of California at San Francisco.

Dr. Chang's clinical group focuses on the treatment

of movement disorders including epilepsy.

He is also a world expert

in the treatment of speech disorders

and relieving paralysis that prevents speech

and other forms of movement and communication.

Indeed, his laboratory is credited with discovering ways

to allow people who have fully locked-in syndrome,

that is, who cannot speak or move,

to communicate through computers and AI devices

in order to be able to speak to others in their world

and understand what others are saying to them.

It is a truly remarkable achievement that we discuss today,

in addition to his discoveries about critical periods,

which are periods of time during one's life

when one can learn things, in particular, languages,

with great ease as opposed to later in life,

and we talk about the basis of things

like bilingualism and trilingualism.

We talk about how the brain controls movement

of the very muscles that allow for speech and language

and how those can be modified over time.

We also talk about stutter,

and we talk about a number of aspects of speech and language

that give insight into not just how we create

this incredible thing called speech

or how we understand speech and language,

but how the brain works more generally.

Dr. Chang is also one of the world leaders

in bioengineering,

that is, the creation of devices that allow the brain

to function at supraphysiological levels

and that can allow people

with various syndromes and disorders

to overcome their deficits.

So if you are somebody who is interested

in how the brain works normally,

how it breaks down and how it can be repaired,

and if you are interested in speech and language,

reading and comprehension of information of any kind,

today's episode ought to include some information

of deep interest to you.

Dr. Chang is indeed the top of his field

in terms of understanding these issues

of how the brain encodes speech and language

and creates speech and language

and, as I mentioned, movement disorders and epilepsy.

We even talk about things such as the ketogenic diet,

the future of companies like Neuralink,

which are interested in bioengineering

and augmenting the human brain, and much more.

One thing that I would like to note is that in addition

to being a world-class neuroscience researcher

and world-class clinician, neurosurgeon,

and chair of neurosurgery,

Dr. Eddie Chang has also been a close, personal friend

of mine since we were nine years old.

We attended elementary school together,

and we actually had a science club

when we were nine years old

focused on a very particular topic.

You'll have to listen in to today's episode

to discover what that topic was

and what membership to that club required.

That aside, Dr. Chang is an absolute phenom

with respect to his scientific prowess,

that is, both his research and his clinical abilities,

and he's one of these rare individuals

that, whenever he opens his mouth, we learn.

Before we begin, I'd like to emphasize that this podcast

is separate from my teaching and research roles at Stanford.

It is, however, part of my desire and effort

to bring zero-cost-to-consumer information

about science and science-related tools

to the general public.

In keeping with that theme,

I'd like to thank the sponsors of today's podcast.

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And now for my discussion with Dr. Eddie Chang.

Eddie, welcome.

- Hi. Hi, Andrew.

- Great to be here with you.

This has been a long time coming.

Just to come clean,

we've known each other since we were nine years old.

- Yeah.

- But then there was a long gap

in which we didn't talk to one another.

I heard things about you,

and, presumably, you heard a thing or two about me,

for better or for worse. [Eddie laughs]

And then we reconnected years later

when I was a PhD student and you were a medical student.

We literally ran into each other

in the halls of the University of California San Francisco

where you're now the chair of neurosurgery,

so it all comes full circle.

When you were at UCSF, you were working with Mike Merzenich,

and I know that name

might not be familiar to a lot of people,

but he's sort of synonymous with neuroplasticity,

the ability of the brain and nervous system

to change in response to experience.

So for our listeners,

I would just love for you to give a brief overview

of what you were doing at that time

because I find that work so fascinating,

and it really points to some of the things that can promote

and maybe hinder our brain's ability to change.

- Oh, wow. That's fantastic.

So we did bump into each other serendipitously back then,

and, at the time, I was a medical student at UCSF

studying with Mike Merzenich.

In particular, I was studying how the brain organizes

when you have patterns of sound.

And in particular, we were studying the brain of rodents

and trying to understand how different sound patterns

organize the frequency representation

from low to middle to high frequency maps

in the brains of baby rodents.

And one of the things that I was very interested in

was trying to understand

how the patterns of the natural environment,

let's say the vocalizations of the environment

that the rat pups were raised in,

or just the natural sounds that they hear,

how that shapes the structure of the brain.

And one of the things we did was to try an experiment

where we raised some of these rat pups in white noise,

continuous white noise that was essentially masking

all of those environmental sounds.

- And what was the consequence of animals being raised

in white noise environment?

- Well, one of the things that we didn't expect

but we found, which was quite striking,

is that there's this early period in brain development

where we're very susceptible

to the patterns that we hear or see.

In neuroscience, we call this a critical period

or a sensitive period.

And we have this for our eyes,

but we also have it for our ears.

And one of the most striking examples of this

is that any human can essentially grow up in a culture

where they hear different speech sounds

from one language to another,

and it's like after a couple of years,

you lose sensitivity to sounds

that are not part of your native language

and you have high sensitivity

for the languages of your native culture.

And that's pretty extraordinary

that human brain has that flexibility

yet, at the same time, has that specialization for language.

And so we were trying to think about how do we model this,

for example, in rodents, who obviously don't speak,

but we're just understanding how sounds

and environmental sounds

modulate and organize the auditory cortex.

And one of the things that we found that was quite striking

was that if you basically mask environmental sounds

from these rat pups,

the critical period,

this sensitive period where it's open to plasticity,

it's open to change, it's open to reorganization,

that window can stay open much, much longer.

And in one way, it sounds like that's a good thing,

but on the other hand, it's also a retardation.

It actually slowed the maturation of the auditory cortex.

It was ready to close when these rat pups were really young,

but by raising them in white noise,

we found out that you could keep it open

for months beyond the time period that it normally closes.

And so I think one of the things it taught me

was that it's not just about the genetic programming

that specifies some of this sensitive period,

but it's also a little bit about the nature

of the sounds that we hear

that help keep that window for the critical period

open and closed.

- That's fascinating.

And I know it's difficult to make a direct leap

from animal research to human research,

but if we could speculate a little bit,

I can imagine that some people grow up in homes

where there's a lot of shouting and a lot of inflection,

maybe people are very verbose.

Maybe others grow up in a home

where it's quieter and more peaceful.

Some people are going to grow up in cities.

I just came back from New York City,

it's like all night long,

there's honking and sirens and it's just nonstop,

and then I return here where it's quite quiet at night.

Can we imagine that the human brain

is going to be shaped differently

depending on whether or not one grows up

in one environment or another?

And would that impact their tendency

to speak in a certain way as well as hear in a certain way?

What do we know about that?

- Well, I think that, from my perspective,

it's really clear that those sounds that we are exposed to

from the very earliest time, even in utero, in the womb,

where the sound is hearing the mother or father or friends

while in the womb

actually will influence how these things organize.

And so there's no question that the sounds that we hear

are going to have some influence,

and those sounds are going to structure

the way that those neural networks actually lay down

and will forever influence how you hear sounds,

and speech and language

is probably one of the most profound examples of that.

- I get a lot of questions

about the use of white noise during sleep.

In particular, people want to know

whether or not using a white noise machine

or a machine or a program

that makes the sound of waves, for instance,

if it assists their infant in sleeping,

is it going to be bad for them

because it's flooding the auditory system

with a bunch of essentially white noise

or disorganized noise?

Do we have an answer to that question?

- Not yet.

I think that what you're asking

is a really important question

because parents are using white noise generators

almost universally now, and for good reasons.

You know, it is hard to have kids up at night.

I've got three kids of my own and was very tempted

to think about how to use some of these tools

to just soothe them and get them to bed,

especially when I was, like, so tired and exhausted.

But I think that there is a cost,

you know, to think a little bit about.

You know, we're not exposed

to continuous white noise naturally.

There is a value to having really salient, structured sounds

that are part of our natural environment

to actually have the brain develop normally.

So whether or not that has an impact,

you know, while you're sleeping, it's not clear.

I don't think that those studies have been done.

What was really clear was that if you raise these baby rats

in continuous white noise, not super loud,

but just enough to mask the environmental sounds

that that was enough to keep, you know, the auditory cortex,

the part of the brain that hears,

in this really delayed state

which could essentially slow down the development

and maturation of the brain.

- And one could probably assume

that slowing the maturation of areas of the brain

that are responsible for hearing

might, I want to underscore,

might impact one's ability to speak, right?

Because isn't it the case that if people can't hear,

they actually have a harder time enunciating

in a particular way, is that right?

If I were to not be able to hear my own voice,

would my speech patterns change?

- Well, I think part of it

is that, over time, we develop sensitivity

to the very specific speech sounds in a given language,

and the sensitivity improves

as we hear more and more and more of it.

And then on the other hand,

we lose sensitivity to other speech sounds at the same time.

But as part of that process,

we also have a selectivity, a gain,

a specialization even for those sounds,

even relative to noise,

noisy backgrounds and things like that.

I tend to think about it

like what is the signal-to-noise ratio?

And so the brain has its own ways

of trying to increase that signal-to-noise ratio

in order to make it more clear.

Part of that is how we hear

and how it lays down a foundation

for that signal-to-noise ratio,

and so you can imagine a child

that's raised continuously in white noise

would be really deprived of those kind of sounds

that are really necessary for it to develop properly.

So I think with regard to those tools for babies,

I think we should study it,

we should try to understand this definitively.

I think what we saw in rodents

would tell us that there is potential,

you know, things that we should be concerned about.

But, again, it's not really clear,

if you're just using at night, whether it has those effects.

- I guess the critical question

that a number of people are going to be asking

is did you decide to use a white noise machine or not

to help keep any of your three children asleep?

- Well, I think the short answer is no.

I mean, I obviously did a lot of work thinking

and work on this and thought about it carefully,

but there are other kinds of noise,

or, I wouldn't even call it noise,

other sounds that you can use

that can be equally soothing to a baby.

It's just that white noise has no structure,

and what it's doing

is essentially masking out all of the natural sounds.

And I think the goal

should really be about how do we replace that

with other more natural sounds that structure the brain

in the way that we want to be more healthy.

- Well, I know that

after you finished your medical training,

you went on to, of course, specialize in neurosurgery.

And last I checked, you spend most of your days

either running your laboratory or in the clinic

or running the department,

and your clinical work and your laboratory work

involves often removing pieces of the skull of humans

and going in and either removing things

or stimulating neurons,

treating various ailments of different kinds,

but your main focus these days, of course,

is the neurobiology of speech and language.

And so for those that aren't familiar,

could you please distinguish for us speech versus language

in terms of whether or not

different brain areas control them?

And I know that there's a lot of interest

in how speech and language and hearing

all relate to one another.

And then we'll talk a bit

about, for instance, emotions

and how facial expressions could play into this,

or hand gestures, et cetera.

But for the uninformed person,

and for me, to be quite direct,

what are the brain areas that control speech and language?

What are they really,

and especially in humans, how are they different?

I mean, we have such sophisticated language

compared to a number of other species.

What does all this landscape look like in there?

- Yeah, well, that's a fascinating question,

and I'm going to just try to connect a couple of the dots here,

which is that in that earlier work during medical school,

I was doing a lot of what we call neurophysiology,

putting electrodes into the auditory cortex

and understanding how the brain responds to sounds,

and that's how we actually mapped out these things

about the sensitivity to sensitive periods.

That experience with Mike Merzenich

and thinking about how plasticity is regulated in the brain

and particular about how sound

is represented by brain activity

was something that, you know, was really formative for me.

And because I was a medical student

and was going back to my medical studies,

it was that in combination

with seeing some awake brain surgeries

that our department is really well known for.

One of my mentors, Mitch Berger,

really pioneered these methods

for taking care of patients with brain tumor

and be able to do these surgeries safely

by keeping patients awake and by mapping out language.

- So they're talking and listening,

and you're essentially in conversation with these patients

while there's a portion of their skull removed,

and you are stimulating

or, in some cases, removing areas of their brain,

is that right?

- That's exactly right, and the only thing off there

is it's not essentially, it is just that.

The only difference between the conversation

that I might have with my patient

who's undergoing awake brain surgery

is that I can't see their face and they can't see my face.

We actually have a sterile drape

that actually separates the operating field,

and they're looking and interacting

with our neuropsychologist,

but I can talk to them and they can hear my voice

and vice versa.

And it's a really, really important way

of how we can protect some of those areas

that are really critical for language,

at the same time, accomplish a mission

of getting the seizures under control

or getting a brain tumor removed.

- And is that because occasionally

you'll encounter a brain area,

maybe you're stimulating

or considering removing that brain area,

and suddenly a patient will start stuttering

or will have a hard time formulating a sentence?

Is that essentially what you're looking for?

You're looking for regions

in which it is okay or not okay to probe?

- Exactly, so the first thing that we do

is that we use a small electrical stimulator

to probe different parts of the areas

that we think might be related and important for language

or talking or even movements of your arm and leg.

That's what we call brain mapping.

And we use a small electrical current

that's delivered through a probe

that we can just put at each spot.

And the areas that we're really interested in

are, of course, the areas that are right around the part

that is pathological, the part that's injured,

or the part that has a brain tumor that we want to remove,

so we can apply that probe

and transiently, meaning temporarily, activate it.

So if you're stimulating the part of the brain

that controls the hand, the hand will move, it will jerk.

Sometimes a fist will be made, something like that.

Other times, while someone is counting

or just saying the days of the week,

you can stimulate in a different area

that stops their speech altogether.

That's what we call speech arrest.

Or if someone is looking at pictures

and they're describing the pictures

and you stimulate in a particular area,

they stop speaking or the words start coming out slurred

or they can't remember the name of the object

that they're seeing in the picture.

These are all things that we're listening really carefully

while we apply that focal stimulation.

That's what we call brain mapping.

- What are some of the more surprising,

or maybe even if you want to offer

one of the more outrageous examples of things

that people have suddenly done or failed to be able to do

as a consequence of this brain mapping?

- Well, I think the thing to me

that has been the most striking

is that, you know, some of these areas you stimulate,

and altogether, you can shut down someone's talking.

So a person says, "I wanted to say it,

but I couldn't get the words out."

And even though I've seen this thousands of times now,

it's still exciting every time that I see it because,

it's exciting because you're seeing the brain,

it's a physical organ, it's part of the body,

outside of the veins on top of it,

it doesn't look like a machine.

But when you do something like that

and you focally change the way it works,

and you see that because the person can't talk anymore

and they say, "I know what I want to say,

but I couldn't get the words out,"

you're confronted with this idea

that that organ is the basis of speech and language

and way beyond that, obviously,

you know, for all the other functions

that we have for thinking

and feeling our emotions, everything.

So that, to me, is a constant reminder

of, you know, this really special thing that the brain does

which is compute so many of the things that we do,

and in particular in the area

around speech and language, generating words,

something that is really unique to our species,

is just extraordinary to see.

Again, even though I've seen it thousands of times,

it's just having that connection

because it doesn't look like a machine,

but it is doing something that is quite complicated,

precise, and remarkable.

- Do you ever see emotional responses

from stimulation in particular areas?

And do you ever hear or see emotional responses

that are associated with particular types of speech?

Because, for instance, curse words are known to,

people with Tourette's often will curse,

not always, sometimes they'll have tics or other things.

But what I learned from a colleague of ours

is that curse words have a certain structure to them.

There's usually a heavy

or kind of a sharp consonant up front, right,

that allows people, at least as it was described to me,

to have some sort of emotional release.

It's not a word like murmur,

which has kind of a soft entry here,

I'm not using the technical language,

and you pick your favorite curse word out there, folks.

I'm not going to shout out any now or say any now,

but that certain words have a structure to them

that, because of the motor patterns

that are involved in saying that word,

you could imagine it has an emotional response unto itself.

So when stimulating

or when blocking these different brain areas,

do you ever see people get angry or sad

or happy or more relaxed?

- Oh, well, definitely I've seen cases

where you can invoke anxiety, stress,

and I think that there are also areas that you can stimulate

and you can also evoke the opposite of that,

sort of like a calm state.

- I think that brain area is slightly hyperactive in you,

or at least more than me.

In all the years I've known you,

you've always been, at least externally, a very calm person.

I mean, I always find it amusing

that you work on speech and language

and you have a very calming voice.

And I'm being really serious.

I think that there's a huge variation in that, right,

in terms of how people speak and how they accent words.

- Absolutely, yeah.

So there are areas,

for example, the orbitofrontal cortex that we showed

that if you stimulate there...

The orbitofrontal cortex is a part of the brain

that's above the eyes.

That's why they call it orbitofrontal,

meaning it's above the eye or the orbit

and in the frontal lobe, and it's this area right in here.

It has really complex functions.

It's really important for learning and memory.

But one of the things that we observed

is when you stimulate in there,

people tended to have a reduction in their stress,

and it was very much related to their state of being,

meaning that if someone was already kind of feeling normal

and you stimulate there, it didn't do much.

But if someone was in a very anxious state,

it actually relieved that.

And then we've seen the corollary of that

which is true, too,

which is that there are other areas

like the amygdala or parts of the insula

that if you stimulate,

you can cause an acute temporary anxiety,

a nervous feeling,

or if you stimulate the insula,

people can have an acute feeling of disgust.

So, you know, the brain has different functions

and these different nodes that help process the way we feel.

Certainly, I think that, to some degree,

neuropsychiatric conditions reflect an imbalance

of the electrical activities in these areas.

One of the things that was something I will never forget

was taking care of a young woman with uncontrolled seizures.

We call that epilepsy.

It's a medical condition where someone

has uncontrolled electrical activity in the brain.

Sometimes you can see that as convulsions

where people are shaking and lose consciousness.

There are other kind of seizures that people can have

where they don't lose consciousness,

but they can have experiences that just come out of nowhere

just as a result of electrical activity

coming from the brain.

And about six years ago, I took care of a young woman

who was diagnosed psychiatrically

with anxiety disorder for several years.

It turns out that it wasn't really an anxiety disorder.

It was actually that she had underlying seizures,

an epilepsy activating a part of her brain

that evokes, you know, anxious feelings.

- How was that discovered?

Because I know a lot of people out there have anxiety.

I mean, in the absence of a brain scan,

how or why would one suspect that maybe they have a tumor

or some other condition

that was causing those neurons to become hyperactive?

- Yeah, that's really important

because so many people have anxiety,

and the vast, vast majority are not having that

because they're having seizures in the brain.

I think one of the ways that this was diagnosed

was that the nature

of when she was having these panic attacks

was not triggered by anything.

They would just happen spontaneously.

And that's what can happen with seizures sometimes.

They just come out of nowhere.

We don't fully understand what can trigger them,

but they weren't things

that were typically anxiety-provoking.

This is something that just happened all of a sudden.

And because you brought it up,

this is not something that you can see on an MRI.

We could not see and look at the structure of her brain,

with an MRI, that she was having seizures.

The only way that we could actually prove this

was actually putting electrodes into her brain

and proving that these attacks that she was having

were localized to a part called the amygdala,

it's a medial part of the temporal lobe, which is here,

and associating the electrical activity

that we were seeing on those electrodes

with the symptoms that she had,

and she ultimately needed a kind of surgery

where she was awake in order to remove this safely.

- Speaking of epilepsy,

a number of people out there have epilepsy

or know people who do.

Are the drugs for epilepsy satisfactory?

You know, I think about things like Depakote,

you know, and adjusting the excitation

and inhibition of the brain.

I mean, are there good drugs for epilepsy?

We know there are not great drugs

for a lot of other conditions.

And how often does one need neurosurgery

in order to treat epilepsy?

Or can it be treated most often just using pharmacology?

- Yeah, great question.

Well, a lot of people have seizures

that can be completely controlled

by their medications, a lot.

But there's about a one-third of people who have epilepsy,

which we define as anyone who's had three or more seizures

that, you know, about a third of them

actually don't have control

with all of the modern medications that we have nowadays.

And some of the data suggests

that if you have two or three medications,

it actually doesn't matter necessarily

which of the anti-seizure medications it is,

but there is data suggests

if you've just tried two or three,

the fourth, fifth, sixth, and beyond

is not likely to help control it.

So we are in a situation, unfortunately,

where a lot of the medications are great for some people,

but for another subset, they can't control it,

and it comes from a particular part of the brain.

Now, fortunately, in that subset,

there's another part of that group

that can benefit from a surgery

that actually either removes that part of the brain,

and nowadays, we'll use stimulators now

to sometimes put electrical stimulation

in that part of the brain to help reduce the seizures.

- And you said a third of people with epilepsy

might need neurosurgery?

- Well, what I mean by that

is, like, they continue to have seizures

that are not controlled by all medications,

and there's going to be another subset of those

that may benefit from a surgery.

It's probably not that whole third, it's a subset of that.

It's just to say that epilepsy

can be really hard to get fixed.

And for people where the seizures come from one spot

or, you know, an area, then surgery can do great.

If it comes from multiple areas

or if it comes from the whole brain,

then we have to think about other methods to control it.

Fortunately, nowadays, there's actually other ways.

Surgery now, to us,

doesn't just mean removing part of the brain.

Half of what we do now is use stimulators

that modulate the state of the brain

that can help reduce the seizures.

- I've heard before that the ketogenic diet

was originally formulated in order to treat epilepsy

and, in particular, in kids.

Is that true, and why would being in a ketogenic state

with low blood glucose reduce seizures?

- That's a great question.

And to be honest, I don't know actually

if it was originally designed to treat seizures,

but I can tell you for sure that for some people,

just like with some medications,

it can be a life-changing thing.

It can completely change the way that the brain works.

And it's not something that's for everybody,

but for some people, there's no question,

and it has some very beneficial effects.

I think it's to be determined still,

like why and how that works.

- I've heard similar things about the ketogenic diet

for people with Alzheimer's dementia,

that there's nothing particularly relevant

about ketosis to Alzheimer's per se,

but because Alzheimer's changes the way

that neurons metabolize energy

that shifting to an alternate fuel source

can sometimes make people feel better,

and so a number of people are now trying it.

But it's not as if blood glucose and having carbohydrates

is causing Alzheimer's.

And people get confused often

that just because something can help

doesn't mean that the opposite is harming somebody.

So I find this really interesting.

Sometime I'll check back with you about what's happening

in terms of ketogenic diets and epilepsy.

But you said that in some cases, it can help.

Has that observation been made

both for children and for adults?

Because I thought that, originally,

the ketogenic diet for epilepsy

was really for pediatric epilepsy.

- Yeah, that's right.

So a lot of its focus has really been on kids with epilepsy,

but certainly it's a safe thing to try,

so a lot of adults, you know, will try it as well.

- Interesting.

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I'm curious about epilepsy for another reason.

I was taught that epilepsy is an imbalance

in the excitation and inhibition in the brain.

So you think about these electrical storms

that give people either grand mal,

you know, shaking and kind of convulsions.

But years ago, I was reading a book,

a wonderful book actually,

called "Einstein in Love" by Dennis Overbye.

It was about Einstein and I guess his personal life.

People who knew him

claimed that he would sometimes walk along,

and then every once in a while would just stop

and kind of stare off into space

for anywhere from a minute to three to five minutes,

and it was speculated that he had absence seizures.

What is an absence seizure?

And the reason I ask is I occasionally will be walking along

and I'll be thinking about something and I'll stop.

But in my mind, I'm thinking during that time,

but I realize that if I were to see myself from the outside,

it might appear that I was just kind of absent.

What is an absence seizure?

Because it's so strikingly different in its description

from, say, a grand mal convulsive seizure.

- Sure, well, like I mentioned before,

depending on how the seizure activity spreads in the brain

or how it actually propagates,

if it stays in one particular spot

and doesn't spread to the entire brain,

it can have really different manifestation.

It can represent really differently.

So absence seizure is just one category

of different kind of seizures

where you can lose consciousness basically,

and what I mean by that is that you're not fully aware

of what's going on in your environment, okay?

So you're sort of taken offline

temporarily from consciousness,

but you could still be, for example, standing,

and to people who are not paying attention,

they may not even be aware that that's happening.

- What are some other types of seizures?

- Well, you know, I think some of the other kinds,

the classic ones are temporal lobe seizures.

So these are ones that come from the medial structures

like the amygdala and hippocampus.

Oftentimes people, when they have seizures coming from that,

they may taste something very unusual like a metallic taste

or smell something like the smell of burning toast,

something like that.

There are some people, with temporal lobe seizures,

will have deja vu.

They will have that experience

that you've been somewhere before,

but that's just a precursor to the seizure.

And it just highlights that when people have seizures

coming from these areas,

they sometimes hijack what that part of the brain

is really for.

So the amygdala and hippocampus, for example,

are really important for learning and memory.

It's not surprising that when people have seizures there

that it can evoke a feeling of deja vu

or that it can evoke a feeling of anxiety.

And the areas that are right next to it, for example,

these areas are really important for processing smell.

So these areas are right next to each other

so you can have these kind of complex set of symptoms,

the weird taste, the smell of toast,

and then a feeling of deja vu,

that's classic for a temporal lobe seizure,

and it's because those parts of the brain

that process those functions are right next to each other.

- I'm told that I've had nocturnal seizures,

and I've woken up sometimes from sleep

having felt as if I was having a convulsion,

the sort of sense of buzzing in the back of the head.

This happened to me two or three times in college.

Well, I woke up and my girlfriend was very distraught,

like, "You were having a seizure."

I was having full convulsion in my sleep.

Is that correct?

Is there such a thing as nocturnal seizures?

What do they reflect?

They eventually stopped happening,

and I couldn't tether them to any kind of life event.

I wasn't doing any kind of combat sport

or anything at the time,

I wasn't drinking alcohol much,

it's never really been my thing.

What are nocturnal seizures about?

- [Eddie] Oh, well-

- And do I need brain surgery?

[Andrew laughs] [Eddie laughs]

- Nocturnal seizures are just another form.

Like, again, epilepsy and seizures

can have so many different forms

and not just, like, where in the brain,

but also when they happen.

And there are some people who, for whatever reason,

it's very timed to the circadian rhythm.

It's actually not just happening at night,

but a certain period at night

when people are in a certain stage of sleep

that the brain is in a state

that it's vulnerable to having a seizure,

and so that's basically just one form of that.

Again, it's not just about where it's coming from,

but also when it's happening and how that's timed

with other things that are happening with the body.

- Interesting.

Well, it eventually stopped happening

so I stopped worrying about it.

I haven't had seizures since.

Returning to speech and language,

when I was getting weaned in neuroscience,

I learned that we have an area of the brain

for producing speech

and we have an area of the brain for comprehending speech.

What's the story there?

Is it still true

that we have a Broca's and a Wernicke's area?

Those are names of neurologists, presumably,

or neurosurgeons that discovered

these different brain areas.

Maybe you could familiarize us

with some of the sort of textbook version

of how speech and language are organized in the brain,

maybe share with us a little bit of the lesion studies

that led to that understanding,

and then I would love to hear a bit

about what your laboratory is discovering

about how things are actually organized,

because from some discussions you and I have had

over the last year or so,

it seems like, well, let's just be blunt,

it seems that much of what we know from the textbooks

could be wrong.

- Well, I love that question

because, for me, it's very central to the research we do,

and it's where the intersection

between what we do in the laboratory in our research

interfaces with what I see in patients.

And one of the things that fascinated me

early on in my medical training

was in doing some of these brain mapping

or watching them with my mentor

or taking care of patients that had, you know, brain tumors

in a certain part of the brain

was that, a lot of times, what I was seeing in a patient

did not correlate with what I was taught in medical school.

And, you know, some people will think,

well, this might be an exception,

but after you see it for a couple times

and if you're kind of interested in this problem,

you know, it poses a serious challenge

to what you've learned

and how you think about how these things operate.

And that actually got me really interested

in trying to figure this out

because, earlier, we talked about

just this extraordinary thing that the brain is doing

to create words and sentences,

and that's the process by which I'm getting ideas out

from my mind into yours.

It's an incredible thing, right?

It's the basis of communication,

high information communication between two individuals

that's really unique to humans.

So in historical times,

how this works has been very controversial

from day one of neuroscience.

A long time ago, people thought the bumps on your head

corresponded to the different faculties of the mind.

So for example, if you had a bump here,

it might be corresponding to intelligence

or another one over here, you know, to vision

and these kind of things.

That's what we nowadays call phrenology,

and that was kind of the starting point.

A lot of that has been, of course, debunked,

but when you see those little statues

of different brain partitions on someone's head,

that's essentially how people

were thinking about how the brain worked back then,

a couple hundred years ago.

Modern neuroscience began when,

actually, it was very much related

to the discovery of language.

So modern neuroscience,

meaning moving beyond this idea that the bumps on the scalp

corresponded to the faculties of the mind,

but there were things

that actually were in the brain themselves,

and they weren't corresponding to things

that you could see superficially,

like on the scalp or externally,

that it was something about the brain itself.

I mean, it seems so obvious now,

but back then, this was the big academic, you know, debate.

And the first observation

that I think was really impactful in the area of language

was an observation by a French neurosurgeon

named Pierre Broca.

And what he observed was that in a patient,

not that he did surgery in,

but that he had seen and taken care of,

that the person couldn't talk.

And, in particular, they called this individual Tan

because the only words that he could produce was tan, tan.

For the most part,

he could generally understand the kind of things

that people were asking him about,

but the only thing that he could utter from his mouth

were these words, tan, tan.

And what eventually had happened

was this individual passed away,

and the way that neuroscience was done back then

was basically to wait until that happened

and then to remove the brain

and to see what part of the brain was affected

in this patient that they called Tan.

And what Broca found was that there was a part

in the left frontal lobe,

so the frontal lobe is this area like I described earlier,

which is, you know, up behind our forehead, up here,

and in the back of that frontal lobe,

he claimed that this was the seat of articulation

in the brain.

He literally used something like that in French,

the seat of articulation,

meaning that this is the part of the brain

that is responsible for us to generate words.

About 50 years later, the story becomes more complicated

with a German neurologist named Carl Wernicke.

And what Wernicke described

was a different set of symptoms

in patients that he observed a different phenomenon

where people could produce words,

but a lot of the words,

and they were fluent in the sense

that, like, they sound like they could be real words

but from a different language, for example.

And some of us call that, like, word salad or jargon.

They were essentially making up words,

but it was not intentional.

It was just the way that the words came out.

But in addition to that, he observed that these people

also could not understand what was being said to them.

So we could be having a conversation,

and I'd be asking you, "Am I a woman?"

And you might nod your head,

you know, just because you're not processing the question.

And so here are two observations.

One is that the frontal lobe is important

for articulating speech,

creating the words and expressing them fluently.

And then a different part of the brain

called the left temporal lobe,

which is this area right above my ear,

that is an area that I think was claimed

to be really important for understanding.

So the two major functions in language,

to speak and to understand,

were kind of pinned down to that,

and we've had that basic idea in the textbooks

for, you know, over 200 years.

- It's certainly what I was taught.

- [Eddie] Is that right?

- Oh, yeah, and certainly what we still,

we still teach undergraduates, graduate students,

and medical students that.

- Well, that's what I learned, too, in medical school.

And what I saw in reality

when I started taking care of patients

was that it's not so simple.

In fact, part of it is fundamentally wrong.

So just in a nutshell,

nowadays, after, you know, looking at this very carefully

over hundreds of patients,

we've shown that surgeries,

for example, in the posterior part of the frontal lobe,

a lot of times, people have no problem talking at all

whatsoever after those kind of surgeries,

and that it's a different part of the brain

that we call the precentral gyrus.

The precentral gyrus is a part of the brain

that is intimately associated with the motor cortex.

The motor cortex is the part of the brain

that has a map of your entire body

so that it has a part that corresponds to your feet,

it has a part that corresponds to your hands.

But then there's another part

that comes out more laterally on the side of the brain

that corresponds to your lips, your jaw, your larynx,

and we have seen that when patients have surgeries

or injuries to that part of the brain,

it actually can really interrupt language,

so it's not as simple

as just moving the muscles of the vocal tract,

but it's also important for formulating

and expressing words.

So that's Broca's area

that I think the field now recognizes

not just because of our work,

but many other people that have studied this

in stroke and beyond,

is that the idea

that that is the basis of speaking in Broca's area

is fundamentally wrong right now,

and we have to figure out how to correct the textbooks

that we kind of understand that

so that we can continue to make progress.

Now, in terms of the other major area

that we call Wernicke's area in the posterior temporal lobe,

that has held,

I think, quite legitimately for some time.

So that is an area that you have to be super careful

when you do surgery there.

That's an area where,

if you have a mistake there and you cause a stroke

or you remove too much of the tumor there,

you go too far beyond it,

then the person can be really, really hurt.

Like, they'll have a condition that we call aphasia

where they may not be able to understand words,

they may not be able to remember the word

that they're trying to say.

They know what they're trying to say,

but they can't remember the precise word

that goes with the object that they're trying to think of.

They may even produce words

that I described before are like word salad or very jargony.

So, you know, they might say something like tamiranai.

That's not a real word,

but it sounds like it could be, you know?

And that's just because that part of the brain

has some role not just in understanding what we hear,

but also actually has a really important role

in sending the commands to different parts of the brain

to control what we say.

- Not long ago, you and me

and my good friend Rick Rubin

were having a conversation about medicine and science,

and Rick asked the question,

"What percentage of what you learned

in graduate and/or medical school do you think is correct?"

And you had a very interesting answer.

Would you share it with us?

- I don't know. I don't remember the exact.

But I would say

that with regard to the brain in particular,

I would say about 50%

gets it right and accurate and is helpful,

but another 50% is just the approximation

and oversimplification of what's going on.

The example that we talked about,

language is just an example of that.

It's just there are things that make it easier to learn

and easier to teach and easier to even think about,

and that's probably why we continue teaching

in the way that we do.

But I think as time goes on,

the complexity of reality of how the brain works

is, well, first of all,

we're still trying to figure it out,

and second of all, it is complex

and it's still incomplete story.

- It's early days.

And we'll get into some of the technical advances

that are allowing some correction of the errors

that the field has made.

And, look, no disrespect to the brain explorers

that came before us,

and the ones that come after us will correct us, right?

That's the way the game is played.

But what I'm hearing

is that there are certain truths that people accept,

and then there's about half of the information

that is still open for debate

and maybe even for complete revision.

One thing that I learned about language

and the neural circuits underlying language

is that it's heavily lateralized,

that these structures, Broca's and Wernicke's

and other structures in the brain

responsible for speech and comprehension of speech

sit mainly on one side of the brain,

but they do not have a mirror representation

or another equivalent area

on the opposite side of the brain.

And for those that haven't poked around in a lot of brains,

certainly you, Eddie,

have done far more of that than I have,

but I've done my fair share in nonhuman species

and a little bit in humans,

almost every structure,

almost every structure has a matching structure

on the other side of the brain,

so when we say the hippocampus,

we really mean two hippocampi,

one on each side of the brain.

But language, I was taught, is heavily lateralized,

that is, that there's only one.

So that raises two questions. One, is that true?

And if it is true, then what is the equivalent real estate

on the opposite side of the brain doing

if it's not doing the same function

that the one on, say, the left side is performing?

- Well, that's one of those things

that is, again, like mostly true, not 100%.

And what I mean by that is that it's complicated.

So for people who are right-handed,

99% of the time, the language part of the brain

is on the left side.

- And what is the equivalent brain area

on the right side doing if it's not doing language?

- Well, you know, the thing that's incredible

is if you look at the right side

and you look at it very carefully,

either under an MRI

or you actually look at the brain

under slides in a microscope,

it looks very, very similar.

It's not identical, but it looks very, very similar.

All the gyri, which are the bumps on the brain

that, you know, have the different contours

and the valleys that we call sulci,

those all look basically the same.

Like, there is a mirror anatomy on the left and right side,

and so it's not been so clear

what's so special actually about the left side

to house language.

But what we do know,

and this is what we use all the time in assessing

and figuring out, you know, this before surgery,

is if you're right-handed,

99% of the time, the language is going to be

on the left side of the brain.

- Is handedness genetic in any way?

I mean, when I grew up, - Yes.

- a pen or a pencil or crayon

was placed into my hand presumably, or I started using...

My father was left-handed,

and then where he grew up in South America,

they forced him to force himself to become right-handed.

They actually used to restrict the movement of his left hand

so he was forced to write...

And then you have hook lefties and hook righties.

And I know this is a deep dive

and we probably don't want to go

into every derivation of this,

but so for somebody who's left-handed,

naturally just starts writing with the left hand,

there's some genetic predisposition to being left-handed?

- Absolutely. No question about it.

Handedness is not entirely but strongly genetic.

So there is something that ties all of this,

and what does handedness, for example, have to do

with the part of your brain that controls language?

Well, it turns out that the parts that control the hand

are very close to the areas

that really are responsible for the vocal tract.

Again, part of the motor cortex

and part of this brain area called the precentral gyrus.

And there are some theories

that, because of their proximity,

that these parts of the brain

might develop together early in utero

and they might have a head start compared to the right side,

and because they have a head start

that things solidify there.

This is one theory of why this happens.

In people who are left-handed,

it still turns out that the vast majority of people

have language on the left side,

but it's not 99%, it's more like 70%.

So if you're left-handed,

it's still more likely that the language part of your brain

is going to be on the left side,

but there's going to be a greater proportion, maybe 20, 30%,

where it's either in both hemispheres or on the right side.

And just to make this a little bit more interesting

is that when people have strokes on the left side,

and if they are lucky enough to recover from those strokes,

sometimes that involves reorganization,

this term that we call plasticity earlier,

where the areas around where the stroke

take on that new function

in a way that they didn't have before.

That can certainly happen in the left hemisphere,

but there are also instances where the right hemisphere

can also start to take on the function of language

where it was once on left and then transfers to the right.

So the thing that I think about a lot

is that the machinery

probably exists on both sides,

but we don't use them together all the time.

In fact, we may strongly bias one side or the other.

Just like we use our two hands in very, very different ways,

it's a little bit the same with the brain.

Well, it's because of what we do with the brain

that actually is why we use the hands in different ways.

And the same thing goes for language,

which is that, again, the substrates, the organ,

the language organ, the part of the brain that process it

probably has very similar machinery

on the left side as the right,

and the right may have the capability to do it,

but in real, everyday use,

the brain specializes one of the sides

in order for us to use it functionally.

That's a theory.

- You're bilingual, correct?

- Yeah.

- [Andrew] You speak English and Chinese?

- Yeah.

- For people that are bilingual and that learn two or more,

well, bilingual is two, obviously,

but learn both languages

or let's say more languages from an early time in life,

do they use the same brain area to generate that language?

Or perhaps they use the left side to speak English

and the right side to speak Chinese?

Do we know anything about bilingualism in the brain?

- Well, I think we know a lot

about bilingualism in the brain.

The answers are still out there, the final answers on it,

and part of the answer is yes, absolutely,

we use some parts of the brain very similarly.

We actually have a study in the lab right now

where we're looking at this

where people who speak one language or another

or are bilingual,

and we're looking at how the brain activity patterns occur

when they're hearing one language versus the other.

And what's striking to see, actually,

is how overlapping they really can be.

Even though the person may have no idea

of the language that they're hearing,

the English part of the brain is still processing that

and maybe trying to interpret it

through an English lens, for example.

So the short answer is that with bilingualism,

there are shared circuitry,

there's this shared machinery in the brain

that allows us to process both, but it's not identical.

It's the same part of the brain,

but what it's doing with the signals

can be very, very different.

And what I mean by that precisely

is not the instantaneous detecting of one sound to the next,

but the memory of the sequences of those particular sounds

that give rise to things like words and meaning,

that can be highly variable from one individual to the next,

and those neurons are very, very sensitive

to the sequences of the sounds,

even though the sounds themselves

might have some overlap between languages.

- Fascinating.

Okay, so we've talked about brain areas

and a little bit about lateralization.

I want to get back to the hands

and some things related to emotion in a little bit.

But maybe now we could go into those brain areas

and start to ask the question,

what exactly is represented or mapped there?

And for people who perhaps aren't familiar

with brain mapping and representation and receptive fields,

perhaps the simplest analogy might be the visual system

where I look at your face, I know you, I recognize you,

and certainly there are brain areas

that are responsible for face recognition.

But the fact that I know that that's your face,

and for those listening, I'm looking into Eddie's face,

the fact that I know that that's your face at all

is because we are well aware that there are cells

that represent edges and that represent dark and light,

and those all combine

in what we call a hierarchical structure.

They sort of build up from basic elements

as simple as little dots,

but then lines and things that move, et cetera,

to give a coherent representation of the face.

When I think about language,

I think about words and just talking.

If I sit down and do a long podcast

or I think about asking you a question,

I don't even think about the words I want to say very much.

I mean, I have to think about them a little bit,

one would hope,

but I don't think about individual syllables

unless I'm trying to, you know, accent something

or it's a word that I have a particular difficulty saying

or I want to change the cadence, et cetera.

So what's represented in the neurons,

the nerve cells in these areas?

Are they representing vowels, consonants?

And how do things like inflection...

Like I occasionally will poke fun at upspeak,

but there's, I think, a healthy, a normal version of upspeak

where somebody's asking a question,

like, for instance, what is that?

That's an appropriate use of upspeak

as opposed to saying something that is not a question

and putting a lilt at the end of the sentence,

then we call that upspeak,

which doesn't fit with what the person is saying.

So what in the world is contained in these brain areas,

what is represented,

to me, is perhaps one of the most interesting questions,

and I know this lands square in your wheelhouse.

- Sure, let's get into this, Andrew,

because this is one of the most exciting stuff

that's happening right now is understanding

how the brain processes these exact questions.

And you asked me earlier,

you know, what is difference between speech and language?

Speech corresponds to the communication signal.

It corresponds to me moving my mouth and my vocal tract

to generate words,

and you're hearing these as an auditory signal.

Language is something much broader.

So it refers to what you're extracting

from the words that I'm saying,

we call that pragmatics

and sort of are you getting the gist of what I'm saying?

There's another aspect of it that we call semantics.

Do you understand the meaning

of these words and the sentences?

There's another part that we call syntax,

which refers to how the words are assembled

in a grammatical form.

So those are all really critical parts of language,

and speech is just one form of language.

There's many other forms like sign language, reading.

Those are all important modalities for reading.

Our research really focuses on this area

that we're calling speech,

again, the production of this audio signal

which you can't see but your microphones are picking up.

There are these vibrations in the air

that are created by my vocal tract

that are picked up by the microphone

in the case of this recording,

but also picked up by the sensors in your ear.

The very tiny vibrations in your ear are picking that up

and translating that into electrical activity.

And what the ear does at the periphery

is translates all sounds into different frequencies.

So its main thing to do is to take a speech signal

or any other kind of sound and decompose it,

meaning separate that sound into different kind of signals.

And in the case of hearing, what it's doing

is separating it out into low, middle, high frequencies

at a very, very high resolution.

It's doing it very quickly,

and it's doing it in a really fine way

to separate all of those different sounds.

So if you look at the periphery

near the nerve that goes to your ear,

those nerve fibers,

some of them are tuned to low frequencies,

some of them are tuned to high frequencies,

some of them are tuned to the middle frequencies,

and that is what your ear is doing.

It's taking these words

and splitting them up into different frequencies.

- And for those of you out there

that aren't familiar with thinking about things

in the so-called frequency space,

bass tones would be lower frequencies

and high-pitched tones would be higher frequencies,

just to make sure everyone's on the same page.

So the sound of my voice, the sound of your voice,

or any sound in the environment

is being broken down into these frequencies.

Are they being broken down

into very narrow channels of frequency,

or are they, I want to avoid nomenclature here,

or are they being binned as fairly broad frequencies?

'Cause we know low, medium, and high,

but, for instance, I can detect

whether or not something's approaching me

or moving away from me

depending on whether or not it sweeps louder

[imitates sound approaching]

or [imitates sound receding], right, towards or away.

It's subtle, and of course it's combined

with what I see and my own movement,

But how finely sliced

is our perception of the auditory world?

- Oh, extraordinarily precise.

I mean, we take these millisecond cues,

the millisecond differences

between the sound coming to one ear,

let's say your right ear versus your left,

to understand what direction that sound came from.

Those are only millisecond differences,

and that's how precise this works.

But on the other hand,

it does a lot of computation on this

it does a lot of analysis as you go up,

and a lot of our work is focused on the part of the brain

that we call the cortex.

The cortex is the outermost part of brain where we believe

that sounds are actually converted into words and language.

So there's this transformation

where, at the ear, words are decomposed

and turned into these elemental frequency channels,

and then as it goes up through the auditory system,

hits the cortex.

There are some things that happen obviously

before it gets to the cortex,

but when it gets to cortex,

there's something special going on,

which is that that part of the brain

is looking for specific sounds.

And specifically what I mean by that

is the sounds of human language,

so the ones that are the different consonants and vowels

in a different language.

One of the ways that we have studied this

is looking in patients who have epilepsy.

And in a lot of these cases

where the MRI looks completely normal,

we have to put electrodes surgically on a part of the brain.

The temporal lobe is a very, very common place,

so we've done a lot of our work

looking at how the temporal lobe processes speech sounds

because we're looking for where the seizures start,

but then we're also doing brain mapping

for language and speech so we can protect those areas.

We want to identify the areas that we want to remove

to cure someone's seizures,

but we also want to figure out the areas

that are important for speech and language

to protect those so that we can do a surgery

that's effective and safe.

And so in our research,

and why it's become a really important addition

to our knowledge

is that we have electrodes directly recording

from the human brain surface.

A lot of the technology we work with right now

is recording on the order of millimeters,

and they can record millisecond time resolution

of neural activity,

and what we see is extraordinary patterns of activity

when people hear words and sentences.

If you look at that part of the brain

that we call Wernicke's area

in this part of the temporal lobe,

this whole area lights up when you hear words or speech.

And it's not in a way

that is like a general light bulb warming up

and it's generally lit up,

but what you actually see

is something much, much more complicated,

which is a pattern of activity,

and what we've done in the last 10 years

is try to understand what does that pattern come from?

And if we were to look at each individual site

from that part of the brain, what would we see?

What parts of words are being coded by electrical activity

in those parts of the brain?

Remember, the cortex is using electrical activity

to transmit information and do analysis,

and what we're doing is we're eavesdropping

on this part of the brain as it's processing speech

to try to understand what each individual site is doing.

- And what are those sites doing,

or could you give us some examples

of what those sites are doing?

So, for instance, are they sites that are specific for,

or we could say even listening for consonants or for vowels

or for inflection or for emotionality?

What's in there?

- [Eddie] Okay, well-

- What makes these, what makes these cells fire?

- Yeah, what gets them excited?

- Yeah. - What gets them going

is hearing speech.

In particular, there are some of these really focal sites,

again, just on the order of millimeter

or, at some level, single neurons

that are tuned to consonants, some are tuned to vowels,

some are tuned to particular features of consonants.

What I mean by that are different categories of consonants.

There's a class of consonants

that we call plosive consonants.

This is a little bit of linguistic jargon,

but I'm going to make a point here with that

is that certain classes of sounds, when you make them,

it requires you to actually close your mouth temporarily.

- Hmm. Now I'm going to be thinking about this.

So plosive, like plosive,

like saying the word plosive requires that.

- Exactly, so what's cool about that

is that we actually have no idea

what's going on in our mouth when we speak.

We really have no idea.

- Some people definitely have no idea.

[Andrew laughs] [Eddie laughs]

- Well, not just like in terms

of what you're saying sometimes,

but actually like how you're actually moving,

you know, the different parts of vocal tract.

And I have a feeling if we actually required understanding,

we would never be able to speak 'cause it's so complex.

It's such a complex feat.

Some people would say it's the most complex motor thing

that we do as a species is just speaking.

Not, you know, the extreme feats of acrobatics

or athleticism but speaking.

- And especially when one observes, you know, opera

or people who, you know, freestyle rappers.

And of course it's not just the lips. It's the tongue.

And you've mentioned two other structures

Pharynx and larynx are the main ones.

Can you tell us, just educate us at a superficial level

what the pharynx and larynx do differentially?

'Cause I think most people aren't going to

be familiar with that. - Okay, sure.

So I'll talk primarily

about the larynx here for a second,

which is that if you think about when we're speaking,

really, what we're doing is we're shaping the breath.

So even before you get to the larynx,

you got to start with the expiration.

So we fill up our lungs and then we push the air out.

That's a normal part of breathing.

And what is really amazing about speech and language

is that we evolved to take advantage

of that normal physiologic thing, add a larynx,

and what the larynx does is that when you're exhaling,

it brings the vocal folds together.

Some people call them vocal cords.

They're not really cords. They're really vocal folds.

They're two pieces of tissue that come together,

and a muscle brings them together.

And then what happens

is when the air comes through the vocal folds

when they're together,

they vibrate at really high frequencies,

like 100 to 200 hertz.

Yours is probably about 100 hertz.

The average- - Whereas yours is 200.

[Andrew laughs]

- No, no. Most male voices are around 100, okay?

And then the average female voice around 200 hertz.

- Well, and as you know, I've always had the same voice.

- Yes, yes, the same- - This was a point of shame

when I was a kid.

Folks, my voice never changed. I always had the same voice.

This is a discussion for another time.

- Yeah, well, it's a great voice,

you know, a great baritone voice,

but I know in your voice, it's a low-frequency voice.

And the reason why men and women

generally have different voice qualities

is it has to do with the size of the larynx

and the shape of it, okay?

So in general, men have a larger voice box or larynx,

and the vibrating frequency, the resonance frequency

of the vocal folds when the air comes through them

is about 100 hertz for men and about 200 for women.

So what happens is,

okay, so you take a breath in,

and then as the air is coming out,

the vocal folds come together and the air goes through.

That creates the sound of the voice that we call voicing,

and that's the energy of your voice.

It's not just your voice characteristic,

it's the energy of your voice.

It's coming from the larynx there, it's a noise.

And then it's the source of the voice.

And then what happens is that energy,

that sound goes up through the parts of the vocal tract,

like the pharynx into the oral cavity,

which is your mouth and your tongue and your lips.

And what those things are doing

is that they're shaping the air in particular ways

that create consonants and vowels.

So that's what I mean by shaping the breath.

It just starts with this exhalation.

You generate the voice in the larynx,

and then everything above the larynx is moving around,

just like the way my mouth is doing right now,

to shape that air into particular patterns

that you can hear as words.

- Fascinating, and immediately makes me wonder

about more primitive or non-learned vocalizations

like crying or laughter.

Babies will cry, babies will show laughter.

Are those sorts of vocalizations

produced by the language areas like Wernicke's,

or do they have their own unique neural structures?

- Yeah, interesting question.

So we call those vocalizations.

A vocalization is basically where someone

can create a sound, like a cry or a moan,

that kind of sound,

and it also involves the exhalation of air.

It also involves some phonation at the level larynx

where the vocal folds come together

to create that audible sound.

But it turns out that those are actually different areas,

so people who have injuries in the speech and language areas

oftentimes can still moan, they can still vocalize,

and it is a different part of the brain,

I would say an area that even nonhuman primates have

that can be specialized, you know, for vocalization.

It's a different form of communication

than words, for example.

- The intricacy of these circuits in the brain

and their connections to the pharynx and larynx is just,

it's almost overwhelming

in terms of thinking about just how complicated it must be,

and yet some general features and principles

are starting to emerge from your work

and from the work of others.

If we think about that work

and we think about, for instance, Wernicke's area,

if I were to record from neurons in Wernicke's area

at different locations,

would I find that there's any kind of systematic layout?

For instance, in terms of, you talked about sound frequency,

we know that low frequencies

are represented at one end of a structure

and high frequencies at the other.

This is true actually, at least from my earlier training,

within the ear itself, within the cochlea,

the early work of von Bekesy and from cadavers, right?

They actually figured this out from dead people,

which is incredible.

A fascinating literature people should look up.

And in the visual system,

we know that, for instance, you know, visual position,

where things are is mapped systematically.

In other words,

neurons that sit next to each other in the brain

represent portions of visual space

that are next to each other in the real world.

What is the organization of language

in areas like Wernicke's and Broca's?

For instance, I think of the vowels, A, E, I, O, U,

as kind of a coherent unit,

but do I find the A neurons are next to the E neurons

or next to the A, E, I, O, U.

Is that vowel representation also laid out in order,

or is it kind of salt and pepper, is it random?

- That's been one of the, like, most important questions

we've been trying to answer for the past decade.

So there is a part of the brain

that we call the primary auditory cortex,

and the primary auditory cortex

is deep in the temporal lobe.

And if you looked at that part of the brain,

there is a map of different sound frequencies.

So if you look at the front of that primary auditory cortex,

you'll find low-frequency sounds,

and then as you march backwards in that cortex,

it goes from low to medium to high frequencies.

It's organized in this really nice and orderly way.

And it turns out there's not just one.

There's, like, mirrors of that tone frequency map

in the primary auditory cortex.

The areas that are really important for speech

are on the side of that.

And we now think that speech

can go straight to the speech cortex

without having to go through the primary auditory cortex,

that it has its own pathway to get to the part of the brain

that processes speech.

And when we've looked at that question about is there a map,

the short answer is yes, there is a map,

but it is not structured universally across all people

in a way that we can clearly see right now.

It is like a salt and pepper map

of the different features in speech.

So before, we talked about these sounds

that are called plosives.

You make a plosive when the mouth

or something in the oral cavity closes temporarily,

and when it opens,

that creates that fast plosive sound.

So when you say dad

or, you know, like the B in ball,

that kind of thing,

you will notice that your lips actually close,

and then it's the release of that

that creates that particular sounds, okay?

So those are the sounds that we call plosive.

Those are like ba da ga, pa ta ka,

Those are a certain class of consonants

that we call plosive sounds.

There is another class of sounds

that we call fricatives in linguistics.

Fricatives are created by turbulence

in the airstream as it comes out through the mouth,

and the way that we make that turbulence

is getting the mouth and the lips to close

almost until they're completely shut

or putting the tongue to near the teeth

to almost get it completely shut

but just have a narrow aperture,

that creates a turbulence in the airflow

that we perceive as a high-frequency sound.

So those are the sounds like sha and tha,

those kind of things.

Those are, if you look at the frequencies,

they're higher frequencies,

and those are created by specific movements

that you constrict the airflow to create turbulence,

and we hear it as sha, sa, tha.

- So if I say that.

- [Eddie] Exactly.

- And as opposed to a plosive where I'd say explosive.

- [Eddie] Right.

- Of course, I'm emphasizing here.

Well, this explains something and solves a mystery,

which is recently I've been fascinated by the work

of a physician scientist back east,

Dr. Shanna Swan, who's done a lot of work

on things that are contained in pesticides and foods

that are changing hormone levels,

and she refers to phthalates, which is spelled...

So it's both a plosive and a tha,

so it's combining the two,

and it's one of the most difficult words

in the English language to pronounce,

second only perhaps

to the correct pronunciation of ophthalmology.

[Eddie laughs] [Andrew laughs]

So it's a combination of a plosive

and one of these tha sounds,

and that's probably why it's difficult.

- That's exactly right.

In fact, we have a term for that.

That's called a consonant cluster.

So sometimes syllables will just have one consonant,

but when we start stacking certain syllables in a sequence,

and there's rules that actually govern which consonants

can be in a particular sequence for a given language,

that makes it more complicated.

And certain languages

have a lot more constant clusters than others.

- For instance- - So for instance,

Russian, for example, has a lot of consonant clusters.

English has a lot of them.

There are other languages that have very, very few.

For example, Hawaiian.

Hawaiian has an inventory

of about 12 to 14 different phonemes,

14 different consonants and vowels.

English, on contrast,

has about 40 different consonants and vowels.

So languages have different inventories.

They can overlap for sure,

but different languages use different sound elements,

combine and recombine those elements

to give rise to different words and meanings.

- Can we say that there is a most complicated language

out there, or among the most complicated?

Would it be Russian?

- It's definitely high up there.

English is up there, too, actually. Yeah, German as well.

- And in terms of learning multiple languages

during development,

my understanding is that if one

wants to become bilingual or trilingual,

best to learn those languages simultaneously

during development, ideally before age 12,

if one hopes to not have an accent in speaking them later.

Is that correct, or do you want to revise that?

- Well, basically, the earlier,

and the earlier is better,

the more intense it is and the more immersive it is,

the longer, you know, that you can be exposed to that

is really important.

A lot of people can get exposed to it early

and basically lose it.

Even though it's, quote, unquote,

during that sensitive period,

unless it's maintained, it can be very easily lost.

Then I think another aspect of it that's very interesting

is some of the social requirements for it too.

It's pretty clear that you can only go so far

just listening to these sounds from a tape recording

or something like that.

There's something extra about real human interactions

that activates the brain's sensitivity

to different speech sounds

and allows us to become specialized for them

for a given language.

- So returning to what's mapped,

what the representations are in the brain,

I'm starting to get a picture now

based on these plosives and these tha sounds.

And what I find so interesting and logical about that

is it maps to the motor structures

and the actual pronunciation of the sounds,

not necessarily to the meaning of the individual words.

Now, of course, it's related to the meaning

of the individual words,

but it makes good sense to me

why something as complex as language,

both to understand and to generate,

would map to something that is essentially motor in design

because, as you point out, I have to generate these sounds

and I have to hear them generated from others.

However, there's reading and there's writing,

and writing is certainly motor,

reading involves some motor commands

of the eyes and et cetera.

Where do reading and writing come into this picture?

Are they in parallel with, as we would say in neuroscience,

or are they embedded within the same structures?

Are they part of the same series of computations?

- Yeah, so to address the first part

is that we've got this map

of these different parts of consonants and vowels,

and when we look at how they lay out

in this part of the brain that we call Wernicke's area,

we've spent a lot of time really just dissecting this

millimeter by millimeter.

The term that you used is very apropos.

It's salt and pepper. It's not random.

There is this kind of selectivity

to these individual speech sounds.

And one point I want to make about it is this,

is that in English, for example,

there are about 40 different phonemes.

Phonemes are just consonants or vowels

or individual speech segments.

But these articulatory features that you refer to,

for example, the characteristic sounds

that are generated by specific movements in the mouth,

you can more or less reduce that

to about 12 different features.

Okay, these are specific movements of the tongue,

the jaw, the lips, the larynx.

There are about 12 of these movements,

and just like you said, Andrew,

by themselves, they have no meaning.

They're just movements.

But what's incredible about it

is that you take these 12 movements

and you put them in combinations

and you start putting them in sequence.

We as humans use those 12 set features

to generate all words.

And because we can generate

nearly an infinite number of words

with that code of just 12 features,

we have something

that generates essentially all possible meaning

because that's what we do as humans, we generate meanings,

I'm trying to communicate one idea to another,

which, to me, is extraordinary.

A parallel would be, for example, DNA.

There's four base pairs in DNA,

but with those four base pairs in a specific sequence

can generate an entire code for life.

And speech is the same way.

It's like you've got these fundamental elements

that, by themselves, have no meaning,

but when you put them together

give rise to every possible meaning.

So with regard to your second point

about reading and writing, it's a fascinating question.

Speech and language is part of who we are as humans.

That's part of how we evolved,

and it's hardwired

and, you know, molded by experience.

Reading and writing are a human invention.

It's something that was added on

to the architecture of the brain.

And because reading and writing

are fairly recent in human evolution,

it's essentially too quick

for anything to, like, have a dramatic change

in, let's say, a new brain area

or some kind of specialization.

Instead, what happens is that whenever any kind of behavior

becomes ultra specialized in any of us or any organism,

we can sort of take some areas

that are normally involved with vision, for example,

and specialize it for the purpose of reading.

So all of us have a part of our brain

in the back of the temporal lobe

that interfaces with the occipital visual cortex

that we call a visual word form area.

There's actually a part of the brain that is very sensitive

to seeing words, like, either typed or handwritten.

There's a part of the brain that also is sensitive

to seeing things like faces.

So these are things that are all conditioned

on what's important, you know, to survive.

So reading and writing are an invention,

and there are things that have mapped

to functions that the brain already has.

And one of the really important things

about reading and writing

is that when we learn to read and write,

especially with the reading part,

it maps to the part of the brain

that we've been talking about,

which is the part that's processing speech sounds.

So some of us kind of think about it,

these are two different things.

One is hearing sounds through your ears,

the other is reading

where you're actually seeing things through your eyes

and then getting into the language system.

Well, it turns out that the auditory speech cortex

is the primal and primitive fundamental area

that's really important for speech,

and what happens with the reading

is once it gets through that visual cortex,

it's going to try to map those reading signals

to the part of the brain

that's trying to make sense of sounds,

the sounds of words, what we call phonology.

Now, why is this important?

It has a lot of relevance to how we learn to write.

And in some kids with dyslexia...

Dyslexia is a neurological condition

where a child, in some cases, an adult,

has trouble reading, for example.

And in many of those cases,

it's because that mapping between how we see the words

to the way that the brain processes the sounds

is something different,

it's a little bit different

than people who can read really well.

So when you're reading, a lot of times,

you're actually activating the part of the brain

that is processing the words that you hear.

- What is the current treatment for dyslexia?

I've heard that it's a deficit

in some of the motion processing systems

of the visual system.

You know, people, their eyes are jumping

as opposed to more linear reading across,

or I suppose if it were Chinese it would be...

You know, I don't want to presume

people are always reading English.

Or I suppose if it's Hebrew,

they're going from the opposite side of the page.

What can be done for dyslexia?

And do any of the modern treatments for dyslexia

involve changing things from the speech side

as opposed to just the, quote, unquote, reading side,

given that speech and reading are interconnected?

- Yeah, absolutely.

So, again, I think in the beginning,

people might have thought

this was purely a visual abstraction

or something really just about the visual system,

but there's been more recognition

that it could be both or it could be either,

depending on the particular instance.

It's very clear that there are many kids with dyslexia

where the problem is a problem of a phonological awareness.

So, you know, it can be very hard to detect

because they may understand the words that you were saying,

but because the brain is so good at pattern recognition,

sometimes even if the individual speech sounds

are not crystal clear, it can compensate that,

so that you can have an individual who can hear the words

but not be able to essentially hear them

when they're reading those same words.

And so what can happen with that

is that you can have this disconnection

between what they're seeing

and what they need in order to hear it as words

and process it as language.

And so skilled readers

usually need that route first.

They've got to map the vision to the sound

in order to get that sort of like foundation.

But then over time, the reading has its direct connection

to the language parts of the brain,

and we don't necessarily always need to map to sounds.

You know, you can basically develop a parallel route,

and we, as readers, actually use both all the time.

So for example, if it's a new word

that you've never seen before,

sometimes you try to, like, pronounce it in your mind,

you know, and try to hear what that word is.

Even though you're not actually saying it,

you're trying to just generate

what those sounds might be like.

And that's the part where we're kind of relying

on how we learn to read in the first place,

which is mapping those word images

to the sounds that, you know, go along with them.

But in other times, if you're a really proficient reader,

you're just seeing the words

and you can map them directly to meaning

without having to go through that process.

- Yeah, I'm a big fan of listening to audiobooks,

and of course I also listen to podcasts quite a lot,

but I also am a strong believer,

based on the research that I've seen,

that reading books, physical books,

it could be on a Kindle, I suppose,

but reading a physical book is useful

for being able to articulate well and structure sentences

and build what are essentially paragraphs,

which is what I'm required to do

when I do solo episodes of the podcast.

I've noticed over the years

as text messaging has become more popular

and there's essentially an erosion of punctuation

or the need to have complete sentences,

and now that's sort of transferred to email as well.

It's become acceptable

to just say, you know, fragmented sentences in email.

It seems likely that it's starting to impact

the way that people speak as well.

And I don't think this has anything to do with intelligence

or education level,

but are you aware of any evidence

that how we read and what we read

and whether or not we consume information

purely through reading or mainly through auditory sources,

does it change the way that we speak?

Because, after all, Wernicke's and Broca's area

and the other auditory and speech production areas

are heavily intermeshed,

and so it would make perfect sense to me that what we hear

and the patterns of sound that are being communicated to us

would also change the way that we speak.

- Yeah, that's a really fascinating point.

There is this idea

that there's, like, this proper way to speak,

like that there's the right way, for example,

what are the appropriate, you know...

Like, for example, in school, you're oftentimes told, like,

"You should say it like this,

not say it like that," you know?

And every language kind of has that.

It turns out that that's really unnatural.

Languages, and speech in particular, change over time,

it evolves, and it can happen very quickly.

You know, the things that we call dialects, for example,

are just different ways of speaking,

and someone can just be in one environment

and change from one dialect to another,

and some people, it kind of is really fixed.

And there is this idea that, you know, like in school

that we're told that there's this right way,

but in reality, that's not true.

Like, language change and speech change

is completely normal and happens all the time,

and it can be really dramatic.

Like, certain cultures and communities,

if they are isolated,

they can develop a whole new language,

a whole new set of words, for example,

and new ways and dialects that are independent from people

to the point where it's unintelligible even to others.

And so the basic idea is that sound change

is part of the way it works,

and the brain is very sensitive to those kind of changes.

- Speaking of learning new languages,

I'm assuming it's possible to learn new languages

throughout the lifespan, correct?

- [Eddie] Yeah.

- I've also heard these kind of fantastical stories

of somebody has a stroke

and then suddenly, spontaneously, can speak French fluently,

whereas prior to the stroke, they could not.

Is there any merit to those stories whatsoever?

[Eddie laughs]

I find it very hard to believe

that there was a complete map representation

of a language in somebody's brain

that they were completely unaware of,

and then because of damage to a brain area,

that capacity to speak that language was somehow unveiled.

It just seems too wild,

and I don't want to say good to be true

because nobody wants a stroke,

but it just seems out outrageously implausible.

- Well, there are aspects of that

that certainly are implausible.

So I don't know of any true case that I've ever seen

or experienced myself or even read about

where, for example, there was an injury to the brain

that resulted in loss of,

well, essentially a gain of function,

meaning, like, just all of a sudden

started speaking another language.

So for example, if you had a stroke

and you never spoke French,

and then you had it

and then all of a sudden you're speaking,

that, I've never heard of and never seen.

However, there is a condition that is well acknowledged

and I have seen one case of this

called a foreign accent syndrome,

which is peculiar because there are people

who have an injury to the part of the brain

where it sounds like they're starting

to speak this other language,

but they're not actually speaking the language,

it just sounds like it.

And this goes back to what we were talking about earlier

about these areas that are really important

for speech control of the vocal tract,

this area in the precentral gyrus.

People have documented

where, you know, patients have had strokes there,

and after that, it sounds like they're speaking Spanish

as opposed to English

or it sounds like they have the intonational properties

of French or Russian

as compared to their original native language.

They're not learning all the rest of it,

like the meaning and the grammar, et cetera,

but they're adopting some of the phonology,

and part of that is just because it's not working

the way it normally does.

So there is something

actually called a foreign accent syndrome

that people can have after a stroke.

- Interesting. I'm curious about auditory memory.

When I was a kid, I used to get into bed at night,

and I'd close my eyes and I would replay conversations

that I had heard during the day or people's voices.

I actually can remember calling your house

when we were young kids,

and because I don't speak any Chinese

but I'd have to ask for you,

I'd say, I think it was, Eddie [speaking Chinese].

- Yeah.

- Yeah, and then whoever answered the phone

would go get you, and then I'd say [speaking Chinese],

which I believe means thank you, right?

That's the total of the Chinese that I speak, by the way,

but I will never forget that.

I'll just never forget it, I hope.

I suppose if I have a stroke or something of that sort,

at some point, I'll forget it

and I won't know that I've forgotten it.

But in all seriousness, I remember that to this day.

I couldn't spell that out, I wouldn't know how,

certainly not in Chinese,

but even a transliteration,

I couldn't do using English letters.

Where are memories of sounds stored?

Because within our days and across our lives,

we have an infinite number of auditory experiences,

just like we have an infinite number of visual experiences.

Where are they stored,

and what is the structure of their storage?

What am I calling upon,

besides, of course, the motor commands

that are required to say what I just said in Chinese,

which I won't repeat again,

'cause I somehow managed to get it right the first time,

or at least not terribly wrong,

then I don't want to botch it the second time.

Where is that stored, and how does that work?

And, more importantly,

as I speak my native language, English,

am I pulling from a memory bank?

Because it doesn't feel like it.

I'm just telling you what I want to say.

I'm doing my best to communicate clearly and succinctly.

I'm usually not so good at the succinct part.

But where is the bank of information?

On my keyboard on my computer, I have the letters,

and I have certain elements of punctuation and the space.

What am I pulling from? Am I pulling from those plosives?

But if so, how can I do it so quickly?

Even for people that speak slowly,

it appears more or less fluid.

This, to me, is overwhelmingly impressive

that the brain can do that.

How does it do that?

- Well, first of all,

I am impressed that 35 years later... [laughs]

- Well, I had to get ahold of you. [laughs]

- Yeah, so I am impressed, 35 years later,

that you can still remember that.

- But only that.

- That's fine, but I'm still very impressed.

But it clearly was something important to you.

So the short answer is that memory is very distributed.

So it's almost like the question that you asked me

is ill posed 'cause you asked me where?

Well, it's not one specific area.

It's actually really distributed.

It's not just one particular area.

In fact, I'm fairly certain

that if we were to injure that part of the brain

called the Wernicke's area,

you may still even have memories of that.

People can have injuries of Broca's area

or certainly the precentral gyrus

and be able to sing "Happy Birthday," for example,

when it's embedded in melody

or highly rehearsed things like counting

despite not being able to speak, which is incredible, right?

It's like you can see a patient,

for example, who can't really put together a sentence.

You ask them, "How are you feeling today?"

And they can't even utter a word.

But then you ask them to count sometimes,

and they'll get up to any number really.

And so there are some things

that are really built into our motor memory

and it's distributed.

It's not one particular part of the brain,

it's actually multiple areas

where that memory is distributed.

And thank God that's the way it is

because it's very rare

in the kind of surgeries that I do

where you go in, you remove a piece of the brain,

that someone forgets these kind of long-term memories

or these long-term motor skills that they have.

That's very, very rare.

It's the number one question a patient will ask me,

like, "Am I going to be the same?

And am I going to remember, you know, my wife?

Or am I going to remember,

you know, these thoughts of my birthday

when I was 10 years old?"

And I've never really seen that kind of severe amnesia

unless it's a very, very severe injury

that involves almost the entire brain, and thank God.

So a lot of that information

is really distributed across the entire brain.

- Speaking of storage of and ability to speak,

you are doing some amazing work

and have achieved some pretty incredible,

well-deserved recognition for your work

in bringing language out of paralyzed people,

essentially allowing people

who are locked into a paralyzed state

or otherwise unable to articulate speech

using brain-machine interfaces,

essentially translating the neural activity

of areas of the brain that would produce speech

into hardware,

wires and things of that sort,

artificial, non-biological tools

in order to allow paralyzed people to communicate.

We will provide a link

to some of the popular press coverage of that work

and the original papers.

But if you would be so kind

as to tell us what those experiments look like,

who these people are who are locked in

and that you allow to communicate,

and then especially interesting to me,

some of the directions that you're taking this now,

which is beyond just, you know, people being able to think

about what they want to say

and words coming out on a screen or through a microphone,

but actually making the interactions

between these people and the real world

more elaborate and more real.

If that seems mysterious to people,

I'm going to let Eddie tell you what they're doing with this

rather than put any more detail on it.

- Oh, okay. Well, thanks for asking about this.

This has really been some of the exciting recent work

from the lab.

So for the last decade,

we've really been focusing on the basic science,

meaning trying to understand

how the brain extracts and produces speech sounds and words.

We've done a lot of work trying to figure out

how these parts of the brain

control these individual elements

that give rise to all words and meanings.

And so it was about six years ago

where we realized we actually have a pretty good idea

of how this code works.

We had identified all of these different elements

that we could decode in epilepsy patients, for example,

when they had electrodes on the brain

as part of their surgeries,

we could decode all of the different consonants

and vowels of English.

That was about six years ago.

So a natural question was this,

which is if we understand that electrical code,

can we use that to help someone who is paralyzed

and can't get those signals out of the brain

to speak normally?

And that's in the setting of people who are paralyzed.

So there are a series of conditions,

they include things like brain stem stroke.

The brain stem is the part of the brain

that connects the cerebrum, which is the top part,

does our thinking and a lot of the motor control,

speech, language, everything,

and the brain stem is what connects that

to the spinal cord and the nerves

that go out to the face and vocal tract.

So if you have a stroke there,

basically, you could be thinking all the wild, creative,

intelligent thoughts you have in the mind and the cerebrum,

but you can't get them out into words

or you can't get them out to your hand to write them down.

So that's a very severe form of paralysis

called brain stem stroke.

There's another kind of conditions

that we call neurodegenerative

where the nerve cells die basically, or atrophy,

in a condition called ALS,

and that's a very severe form of paralysis.

In its extreme form,

people essentially lose all voluntary movement.

- So Stephen Hawking would be a good example

of someone with ALS, Lou Gehrig's disease?

- He's an example of someone who had ALS

but not a great example of what typical course of ALS.

So for reasons not clear,

the progression of his disease largely stabilized

to the point where he could twitch, you know, a cheek muscle

or move his eyes, let's say.

In most people, it's very rapid,

and many people, they die from it, actually,

you know, within a couple of years of diagnosis, so-

- Yeah, he lived a long time in that-

- He lived a long time-

- That slanted-over state

in his wheelchair. - Right, exactly.

But he wasn't breathing,

you know, through a tube in his throat, for example,

because people with severe ALS,

the muscles to their diaphragm and their lungs

essentially give out as well.

They get weakness there and then they can't breathe anymore.

So that's another form of paralysis.

And so in our field,

these are kind of like the most devastating things

that can happen.

I'm not going to really try to compare, like, what's worse,

you know, having a brain tumor or a stroke, it's all bad.

But this condition of what we call being locked in

refers to this idea

that you can have completely intact cognition

and awareness but have no way to express that,

no voluntary movement, no ability to speak.

And that is devastating

because psychologically and socially,

you know, you're completely isolated.

That's what we call locked-in syndrome,

and it's devastating.

I've seen that throughout my career,

and it's really heartbreaking

because you know that the person is there

but you can't see, they can't communicate.

So we've been studying this patterning

of electrical activity for consonants and vowels,

and essentially, once we figured out a lot of these codes

for the individual phonetic elements,

we took a little bit of a detour,

or at least part of the lab

started to focus on this very specific question.

For people who have these kind of paralysis,

could we intercept those signals

from the brain, the cerebral cortex,

as someone is trying to say those words,

and then can we intercept them

and then have them taken out of the brain through wires

to a computer that are going to interpret those signals

and translate them into words?

So about three years ago,

we started a clinical trial.

It's called the BRAVO trial. It's still underway.

And the first participant in the BRAVO trial

was a man who had been paralyzed for 15 years.

When he was about 20 years old,

he came to the United States,

was actually working in the Sonoma area

and he was in a car accident,

and he actually walked out of the hospital

day after that car accident,

but the next day, had a complication related to it

where he had a very large stroke in the brain stem,

and that turned out to be devastating.

He didn't wake up from that stroke for about a week.

He was in a coma for about a week.

And when he woke up from that coma,

he realized that he couldn't speak or move his arms or legs.

And as he told me or communicated to us,

that was absolutely devastating.

He wanted really to die at that time.

- Could he blink his eyes or move his mouth in any way?

- He could blink his eyes,

he had some limited mouth movements

but couldn't produce any intelligible speech.

It was, like, completely slurred and incomprehensible.

And he survived this injury.

A lot of people who have that kind of stroke

just don't survive.

But he survived.

And I also realized that he's just an incredible person,

like a force of nature in terms of his optimism,

in terms of his ability to make friends

despite his condition.

The way he actually communicates,

because he has a little bit of residual neck movements,

is that he improvised and had his friends

basically put a stick attached to his baseball cap.

And because he could move his neck,

he would essentially type out letters on a keyboard screen

to get out words.

In fact, this is how he communicated was through a device

that he would essentially peck out letters one by one

by moving his neck

to control this stick attached to his baseball cap.

- How many years did he use that method of communication?

- [Eddie] For about 15 years.

He hadn't really spoken for about 15 years.

- Oh, goodness.

- Yeah. So it was a devastating injury.

But, you know, there's something to be said

about the human spirit,

and if there's anyone who embodies it, it is Pancho,

that's his nickname, the first participant in our trial.

He has that human spirit, he persevered,

and, in fact, you know, could thrive

in his community, basically, and friends,

being able to communicate

in this very slow and inefficient way.

Maybe part of that spirit is why he volunteered

to be the first person in this trial.

It was a clinical trial, an experiment. It was a study.

This is not an approved therapy by any means.

This was really something that had not been done before,

and we had a lot of ideas about it, but we didn't know.

You know, we had proven a lot of this could be true

in some people who are normally speaking,

but to actually put it into someone who's paralyzed,

number one, where we don't know the code is the same.

Number two is someone who's not been speaking for 15 years,

whether those signals are actually still there or not.

So it was part of a clinical trial.

It was, you know, something that our hospital

and also the FDA, you know, had to approve

and looked at very carefully,

but given a lot of the work that we had done,

there was some basis for why this might work.

And so about two and a half years ago,

we did a surgery where we implanted electrodes

onto the parts of the brain that we've been talking about,

these areas that control the vocal tract,

the areas that control the larynx,

the areas that control the lips and tongue and jaw movements

when we normally speak.

These are areas that presumably may be active,

that was our hope, in his brain,

but he just couldn't get those out

to control his mouth in a normal way.

And he underwent a surgery,

a brain surgery where we put an electrode array

and we connected it to a port that was screwed to his skull.

And the port actually goes through his scalp,

and he's lived with this now for the last three years.

It is a risk of infection.

These ports eventually have to become wireless

in the future.

But we've figured out a way to keep that port there

where we can essentially connect him to a computer

through that port.

So he has an electrode array that's implanted

over the part of his brain that's important for speech,

it's connected to a port,

and then we connect a wire to that port that translates

those what we call analog, you know, brainwaves

and converts them into digital signals.

And then a computer takes those digital signals

from those individual sites from the speech cortex

and translates those into words.

- Can you describe for us the first time that Pancho spoke

through this engineered device?

What was that experience like for you?

And, at least from what he conveyed to you,

what was that experience like for him?

Because as somebody who was essentially locked-in,

except for this, you know, rather crude pecking device,

although I'm thoroughly impressed by how adaptive

or adaptable Pancho was,

and his friends engineering that device for him

is really nothing short of clever

because otherwise he would be truly locked in, right?

But what was that moment like? I can only imagine.

- That moment was incredible.