Sleep Scientist Explains One Concept in 5 Levels of Difficulty

My name's Aric Prather and I'm a sleep scientist at UCSF.

I study the causes and consequences of insufficient sleep,

and I also carry out interventions to improve sleep

among people with insomnia.

Today, I've been challenged to explain the topic of sleep

at five different levels.

Everybody knows a little bit about

what is happening when they sleep,

but I think they'll be surprised

that there's a lot of science in there.

Nice to meet you, my name's Christopher.

Hey Christopher.

And how old are you?

I'm ten.

What grade is that?

I think fifth.

You think fifth?

What is your favorite subject?

Math and science.

Well that's awesome,

because we're going to be talking about science today.

Cool.

And you know what we're going to be talking about?

What?

Sleep.

Favorite part of the day.

Mine too, because I get to spend all day studying it.

Because you know what sleep does for you?

It rests your body, like an electric car.

[laughs] That's exactly right.

It kinda is like recharging your battery, right?

And sleep is so critical for so many parts

of our body and our mind, right?

It plays a really important way that we learn,

and it helps us kind of recover from the day before.

It affects our immune system and our metabolism,

all of these things that we need to kinda be healthy.

Whoa.

So today, we're going to talk about some animals

and how they sleep.

So here's the first one.

What's that?

A giraffe.

Have you ever seen a giraffe in person?

Uh yeah.

They're pretty cool, right?

Mhm.

And so what's really cool about this is that

giraffes need to sleep like everybody else,

and so the way that it does is it kind of slumps over

and it gets down on its legs

and it kind of becomes this ball,

but what's crazy about the whole thing

is they only sleep for like 30 minutes a day.

30 minutes!

Because it can't waste any more time,

because it can't be vulnerable for any longer.

It can get eaten by lions and that kind of thing.

It has kind of evolved in a way that it can still survive

and still get all the restoration it needs

under such a short period of time.

And how does it like recharge, like humans?

So we think it works the same way,

but maybe just like more efficiently.

And so we're still really learning about how this works.

Sleep science itself is kind of a new field.

I had a sleepover on Saturday,

and I didn't sleep at all.

And how did you feel?

Really tired.

Really tired.

Do you think you were a little crankier than usual?

Yeah.

That's actually really interesting,

because what happens is

humans and everything needs to sleep eventually,

and so you can't stay up indefinitely, right?

What do you think happens if you don't sleep?

It affects what you can do in your daily life.

Excellent.

So now I want to tell you about another animal

and how they sleep, okay?

So we have this one.

What's that?

A hippo.

A hippopotamus.

They have a different challenge.

They sleep underwater.

I could never do that, I would pass out.

Right, right!

So how do they do it?

In the area that they live in,

they need to stay cool, right?

And so they spend a lot of time in the water,

and so then as a consequence,

they need to sleep in the water,

but how do they do it?

So it's really fascinating.

What they do is while they're sleeping,

they actually float back up to the surface and breathe

without waking up.

They're able to go about their whole sleep cycles

but still able to breathe,

because their body has adapted in a way

that they can still get the oxygen that they need.

It's a really amazing thing.

What do you think?

That's cool.

Would it be cool to have that power?

Uh yeah.

So now I want to talk about our last animal,

and I think this one is probably the most amazing of all.

Okay, so what's this?

Aww a dolphin.

A dolphin!

Yes.

So dolphins, kind of like hippos,

have to sleep in the water, okay?

But because they're mammals, right, they need to breathe.

Dolphins breathe air.

They have to go up to the surface and breathe, right?

And for an animal like that,

it needs to figure out a way that it can sleep

but also still survive, right?

You know how dolphins sleep?

How?

One half of their brain at a time.

So half of their brain goes to sleep,

and the other half stays awake,

so that they can continue to breathe and swim,

and they do it in this four hours a time,

so like their right part of their brain sleeps,

they're able to go up to the surface and breathe.

Then their left part of their brain sleeps for four hours,

and it goes back and forth, back and forth,

so they can kind of maintain alertness,

still breathe, and survive.

Is that amazing or what?

That's cool.

So what'd you learn today?

I learned how other animals sleep.

What is important about sleeping?

Sleep rests your body,

and you have to rest your body

in order to do your daily things in life.

Hey, I'm Aric.

I'm Dwayne.

Nice to meet you, Aric.

And how old are you, Dwayne?

I'm 16 years old.

Okay, and where do you go to school?

McClymonds High School in Oakland, California.

Excellent, and what's your favorite subject?

AP Chemistry.

That's a serious science.

It is.

And good news, we're talking about science today.

Yeah.

In fact, we're talking about sleep.

Oh okay. And sleep science.

Do you sleep?

I do, I try. [laughs]

You try, we all gotta try.

You've probably heard about sleep as this kind of,

you know, it's a biological process

that happens in your brain.

It's really important for your body,

but it's a lot more complex than that.

Sleep is made up of different parts.

You know, when you think about sleep,

what do you think about?

Resting, relaxing, really shutting down your brain,

taking some time off of a busy schedule and work day.

But being off is not just being off.

There's lots of things that are happening.

We're gonna kind of talk

about those different pieces of sleep.

Okay.

So our sleep is made up of different types, okay?

The first one is called non-rapid eye movement sleep,

or non-REM, okay?

Or NREM.

And then the other one, which might not be a surprise,

is called REM.

Rapid eye movement sleep.

And those are the two main types of sleep that happen.

The way that we measure that as a sleep scientist

is that we'll actually bring people into the lab

where they can do this at home,

where we put electrodes on their scalp

while they're sleeping,

and that allows us to measure the brain activity

that's going on during the night.

Okay.

Are you like able to tell how much sleep someone's getting

or what their sleep schedule is by REM?

When we measure all of that, we're able to see

how much time someone's asleep,

and how many times they wake up and stuff during the night.

You know, we're also really interested

in kind of, the amount of non-REM sleep someone gets

and the amount of REM sleep that someone gets,

because each part of those types of sleep

do different things for the body.

And so it's important to get both of those.

And so within non-REM sleep,

there are three stages ranging from N-1 to N-2 to N-3.

So not particularly clever in our naming,

but that's how we know what stages they are.

And what they do is it moves

from lightest to deepest sleep, okay?

N-1, it's more kind of light, wakefulness sleep,

kind of in and out of sleeping.

Then you go into N-2,

which is where we spend 45 to 55 percent of our sleep.

And it's more this kind of light sleep,

but then we get into kind of the really restorative sleep,

and that's N-3.

And in N-3, when we look at someone's EEG wave,

we see these big slow waves,

and it's called slow wave sleep.

And so we spend about 20% of our sleep in slow wave sleep,

though it can vary on a day to day.

Oh wow.

Okay?

When do you think you experience the most REM?

Well I've heard that you don't really go

into like a deeper sleep,

so I'm guessing like N-3,

or really any of the N's at all, really,

if you are on technology right before you sleep.

And also if there's too much light,

or if you're listening to music while you're asleep

or anything like that,

you're not experiencing deep sleep, right?

You know, some of that is totally accurate,

that like when your brain's more engaged

by being on your phone or doing things that you really enjoy

or things that stress you out

or any of those types of things,

it's harder to get to sleep

and to kind of fall into that deeper levels of sleep.

Most of the REM sleep, this dreaming sleep,

happens in the second half of the night.

Oh.

Okay?

So we wake up a lot during the night,

and we just don't remember it.

And you'll go back down into deep sleep,

and then up again into REM,

you know, in kinda these cycles.

Oh wow.

Do you ever take naps?

I do.

Okay.

How long are the naps that you take?

Anywhere from between one to six hours.

One to six hours?

That's a long nap.

It is a long nap.

Okay.

Usually we want to keep naps, like 20 to 30 minutes.

When people drop into deep sleep,

and then they're woken up out of a nap,

most people report that they feel way worse

than they did before they took the nap,

and that's because you've been in deep sleep,

and it's this term called sleep inertia.

So what are the stages of sleep?

So N-1 being like light sleep,

still a lot of brain activity going on.

I can imagine that happens right after you fall asleep.

Asleep.

And then N-2 being light, moderate activity in your brain,

still sleep, but still kind of consciously aware,

and N-3 being the deepest form of sleep.

I want to know if you agree,

sleep is the coolest thing you've ever heard of.

It really is.

[laughs]

Right now, it definitely is

the coolest thing I've ever heard of.

So tell me, where are you in school?

What do you study?

I'm a fourth year Chemistry student at USF.

So pretty science-y.

Yes, pretty science-y.

Excellent, because today for this level,

we're talking about sleep.

Great.

How much sleep do you get, typically?

During the summer?

Like 10 hours. 10 hours?

And during the school year, maybe five?

Wow.

Yeah.

And so, how much do you think you need?

I mean, I've read that six is ideal

for people in my age range.

It turns out, for people that are

between the ages of 18 and 65,

the agreed upon amount of sleep

that people should get is between seven and nine hours,

and it's really at least seven hours per night,

to maintain optimal health as an adult.

So at least seven hours.

When we look at across all of the data that is available

on like sleep and health,

and sleep and psychiatric illness and those types of things,

the largest risk is when people get five hours or less.

What do you think is responsible for driving

how much sleep you need, and things like that?

I mean, I know sleep is kind of regulated

by the thalamus and the suprachiasmatic nucleus

sending signals to the pineal gland

to which kind of secretes melatonin,

which tells us when it's time to go to sleep.

Right.

You can do part of this level,

and you can do the other part, clearly.

Got some expertise under your belt, and that's awesome,

because I think that everyone should know more about sleep.

And so the way that we think about what drives sleep

are two independent but related processes

and so they have kind of lame names.

Process S and process C,

and what you've kind of described is process C,

and that's the master clock, right?

And it helps regulate kind of the rhythms

like all over your body, all your cells,

and all those kind of things.

It drives the release of melatonin from the pineal gland,

and melatonin comes online under darkness,

so when the sun goes down, your brain knows

okay it's time to start getting ready for sleep,

and so you start releasing melatonin,

which really kind of sets the table for sleeping.

I'm from Hoi, so we have very long days.

We have early sunrises, late sunsets.

Does that signify less sleep,

because we have a shorter amount of time

for melatonin to be released?

Yeah, no, that's a really great question,

and the same is true in places where

the sun never goes down during the summer,

and when it's dark all the time during the winter,

and it turns out light isn't the only thing

that kind of gates your circadian rhythm.

But I think the thing that's really important,

again there are two processes,

that the other one is the S process,

and that one's just kind of

a really important driver of sleep.

One name we call it is the homeostatic sleep drive.

Kind of the longer you're awake,

the sleepier you get.

You stay up, you get sleepy.

Time goes by, you get sleepier.

Time goes by, you get sleepier.

But it's actually kind of a fundamental principle

for how sleep is regulated,

and it's really kind of akin to like a balloon, okay?

So you wake up in the morning and your balloon is flat.

You've kind of like drained out all of the sleepiness.

But then as you kind of go throughout the day,

it kind of fills up, so you use your energy,

it gets filled up.

And then it gets filled up more

as you get towards nighttime, right?

And then when it's at this optimal amount

is when you kind of go to sleep

and let out all of the sleepiness again.

And this is really what underlies

why napping can also be bad for you.

So napping's not inherently bad,

but if you actually let out some of this air during the day,

it's going to take longer for the balloon

to get bigger, right, I see

to where you feel sleepy, right?

Right.

What did you learn about sleep today?

I learned about the two processes,

process S and process C.

I learned about the circadian rhythm,

and it doesn't only rely on melatonin,

but it also relies on your eating

and a whole bunch of other factors

that affect your circadian rhythm.

Hi, I'm Aric.

Mave.

Thank you for joining us.

What do you do?

Where are you at in school?

So I'm at UC Berkeley, I'm a psychology student

studying cognitive neuro-science

and I just started my third year.

Congratulations.

Thank you.

So a lot of brain stuff.

A lot of brain stuff.

Great.

I'm biased because I study one of the other

sub-critical parts of the brain, the cerebellum.

So that's good, because that's why you're here,

and so we're talking about sleep today,

and really about kind of what is the brain machinery

through which we go through consciousness

to unconsciousness and that transition.

Great.

Okay.

The best way to think about this transition

is really called, it's a flip flop switch, okay?

So this term comes from engineering,

and the idea is that in sleep,

you basically have kind of this all of nothing experience.

Certainly people kind of drift off to sleep,

but then all of a sudden you're unconscious, right?

So it seems like it's this flip flop between

the arousal system and the sleep promoting system,

and it's certainly regulated,

and we'll get a little bit into that,

but they're certainly kind of made up

of two reciprocally inhibitory processes.

Okay, so we have the ascending reticular activating system.

It originates in the brain stem,

and there's a dorsal and a ventral arm to this,

and so the dorsal arm has neurons, cholinergic neurons,

that go up to the thalamus

and then it projections into the fore brain,

and then there's the ventral arm,

and this is comprised of a whole bunch

of different types of neurons,

so there are monominergic,

so there's kind of dopaminergic neurons

that come from the periaqueductal gray,

serotonergic ones from the dorsal raphae nuclei,

histaminergic neurons that come

from the tuberomammillary nucleus of the hippothalamus,

and then noradrenergic neurons

from the locus coeruleus,

and so all of those are kind of working in tandem

to kind of drive wake within the brain.

So if we just think about drugs that are available

inducing wakefulness, we can certainly,

kind of the dopaminergic ones jump out, right?

So we have amphetamines that kind of drive those signaling,

and then modafinil, which is a wake promoting drug

for people that have kind of excessive day-time sleepiness

that maintains alertness throughout the day.

In terms of the dopamine,

if you're taking amphetamines,

that's usually to promote, as you said, wakefulness,

but does that actually improve the quality of your sleep?

How reliable are those kinds of interventions?

For the role that they play

with respect to the sleep-wake system

is really kind of amping up the wake system, right?

And so certainly that has like down stream consequences

for the sleep system, because now the flip flop switch

is kind of pushed in a much stronger direction,

and we have to kind of rely on what regulates sleep

to get it pushed back to sleep.

And do we know much about why,

or which stages of the sleep cycle are affected?

You know, if you take amphetamines,

is it then when you go to sleep,

that you're not able to transition

through each of the sleep periods,

or is that less clear? You know, so I think

that's less clear.

In some ways, you know, getting back to this idea

of this wake-sleep system,

we have this sleep system that is kind of the counterpoint

to this wake arousal system, and so

the primary nucleus region

is the ventral lateral pre-optic nucleus,

also called VLPO, and that has particular neuron outputs

that release GABA and galanin,

which work in an inhibitory way

on kind of the wake promoting ones.

And so, it's kind of this delicate balance

of these two systems that are ongoing.

In your cognitive neuro-science training, right,

it sounds like it's pretty specific and focused

in a particular part of the brain, the cerebellum,

and one thing that I'm interested in

is you bring a participant into the study,

have you ensured that they got a good night's sleep?

Have you asked them about their sleep?

Well in most studies, probably it is advised

for your participants before they come in

to get a good night's sleep,

so those would be recommendations that you would lay out,

you know, in communication with the participant,

before they come in.

You know, what we do in our studies,

is we actually track people, for say a week,

and they have to get in within this range of amount of sleep

and then it has to be both amount of sleep

and how stable it is.

That variability can kind of impact it

and certainly might have an impact on the machinery

that's happening in the brain.

I often think that people, many people think

that they can get by on very little sleep

where the less than average amount of sleep,

from what I know from the research,

you know if you actually test those people

on different batteries of cognitive tasks,

you often find that their performance is slightly worse

than they had anticipated.

Yeah.

So what did you learn about sleep today?

I guess I learned a system that is,

you know, very heavily regulated and influenced

by some of these older conserved

sub-cortical systems in the brain,

and that there's, as you called it,

like a flip flop function between wakefulness and sleep

that's regulated by these specific dopaminergic,

neurogenergic, like neurotransmitters,

that manifest in different sub-cortical parts of the brain.

So now we have sleep on your brain.

That was all I wanted to hear.

Good to see you again, Yue.

Yes, good to see you.

Really glad that you could join us.

So we've been talking about sleep today,

various levels of complexity.

But now with you, I really want to talk about

what do we know about sleep and the aging brain.

Can you tell me a little bit about

some of the work that you've been doing in that area?

So I'm a epidemiologist,

so we do a lot of work

on the epidemiology of sleep

and development of neurodegenerative diseases

including both Alzheimer's and Parkinson's disease,

so ADMPD.

We mainly work on population studies.

We work on thousands and even millions of population,

and we use statistical modeling to find out

the association between different sleep disturbances

and also genetics related to sleep disturbances

and link that to their risk of developing ADMPD.

So how strong is the link?

Our study has found really strong associations

looking at these populations, for example, with sleep apnea.

We've done one meta-analysis and it's showed that

those with sleep apnea, they have a ratio of 1.26,

which means that those who have sleep apnea

have 26% elevated risk of developing Alzheimer's

compared to those without sleep apnea.

So it's interesting, so I also saw

that there was also a recent meta-analysis

around sleep disturbances and dementia risk,

and in that study, they looked about 250,000 people

in this meta-analysis,

and they followed them around for 10 years,

and you know, when they pulled all the samples together,

they found there was a 1.2 fold increased risk

for developing all caused dementia,

so it sounds like both sleep apnea

and then maybe sleep disturbances more generally

are associated with increased risk for dementia.

When I think about that, I think about how

sleep lives in the brain,

these neurodegenerative diseases live in the brain,

and so what do we know about the causality of this?

Could it be that individuals

who have early onset of say, Alzheimer's,

have then poor sleep kind of as a consequence of that?

Yeah, so I think what's really fascinating

is all these bio-directional relationships

that's being identified in animal studies especially,

showing that sleep changes actually occur very early on

in the disease process, so it could be a prodromal stage

of Parkinson's, and also in transgenic model of AD,

they're already showing a lot of circadian abnormalities

in this mouse.

So within dementia risk in particular,

Alzheimer's for instance,

there are kind of two clear features

that seem to be part of the pathology, right?

So there's beta-amyloid which accumulates in the brain,

and then there's kind of these tangles,

this tauopathies, right?

And so it sounds like sleep seems to be related

to the tauopathies.

What about kind of beta-amyloid?

Yes, in the transgenic mouse models of AD,

including those expressing

human mutant amyloid precursor protein,

APP type or both,

so that's kind of showing the sleep changes

in both of these pathologies.

Okay, so there is this bio-directional piece,

but I think perhaps the most exciting thing

that happened in the sleep field,

at least in my view,

has been understanding the role of sleep

and its clearance of beta-amyloid in the brain.

This idea that sleep is kind of the dishwasher of the brain,

it seems like, that you know A betta accumulates

as we kind of use energy,

and you know it's kind of a waste product,

and the idea that if you don't clear it out,

that it's going to build up and accumulate.

So the thing I'm most excited about sleep research

is, I think, first of all,

this complexity of the daytime/nighttime sleep,

what sleep is really doing to our body and to our brain,

and then is really from the epidemiologic

or public health perspective,

how we can best use sleep as a tool for the detection

and prevention of neurodegeneration in the long-term.

I'm excited about the future of sleep medicine.

I think there are incredible innovations that are happening

in the basic sciences, kind of really starting to understand

what are the clear biological processes

that underly some of these things

as they relate to disease risk,

and what is the true function of sleep,

kind of the why we sleep phenomenon, right?

So this was certainly a challenge today.

Everyone knew a little bit about sleep,

and I think that's great,

because sleep is incredibly important,

but there was also a lot of misinformation

around kind of how sleep works,

and people doing sleep behaviors

that may not be the most adaptive for them.

We're still uncovering new things every day

about how sleep works, but despite that,

all of us know that sleep is fundamental to our health,

and so I'm excited for sleep to kind of raise its profile

among other health behaviors

and get the investment and care that it needs.