Welcome to Huberman Lab Essentials,
[music] where we revisit past episodes
for the most potent and actionable
science-based tools for mental health,
physical health, and performance.
I'm Andrew Huberman and I'm a professor
of neurobiology and opthalmology at
Stanford School of Medicine. And now for
my discussion with Dr. Gina Poe. Dr.
Gino Poe, welcome.
>> Thank you.
>> I've really been looking forward to this
conversation. I know that many people
are going to be excited to learn about
your work as it relates to sleep, as it
relates to problem solving, creativity,
and a number of other important topics.
To start things off, I would love for
you to educate us a bit about this thing
that we are all familiar with and yet
very few of us understand, which is
sleep. Could you describe the various
phases of sleep that exist, what
distinguish them, and perhaps frame this
within the context of what would a
perfect night's sleep look like?
>> All right. So sleep is really different
from wakefulness and in fact can't be
replaced by any state of wakefulness
that we've been able to come up with so
far. Our brain chemistry is completely
different and in the different stages of
sleep which there are is nonREM and REM
are the two major states of sleep. Those
two states are entirely different from
one another too. And even within nonREM
there are three states. Stage one, which
is what you slip into when you first
falling asleep. It's dozing. There's
kind of an interesting rhythm that goes
on in the brain. It's kind of a fast
gamma rhythm. And then there's stage
two, which is a really cool state. We
sort of used to ignore sleep researchers
because it was a transient state between
wakefulness and the deep stage three
slowwave sleep, which is the most
impressively different, which is when
big slow waves sweep through our brain.
And now we've realized that it cleans
our brain. Um, one of the things that
those big slow waves do is cleans our
brain and does other really important
things to restore us from a day of
wakefulness. And then REM sleep, which
is the most popular because that's where
we have the most active dreams. When you
wake up someone out of REM sleep,
they'll almost always report having
dreamed something really bizarre. That's
called REM sleep, rapid eye movement
sleep. So those are the four states of
sleep of human sleep. And we cycle
through them every 90 minutes or so. And
then we start over again. And we have
about five of those per night for a
perfect night's sleep. Four or five,
something like that. So a perfect
night's sleep is 7 and 1 half, 8 hours.
And
>> what about the sleep where we are
lightly asleep
>> and we might have a dream that has us
somehow thinking about movement or that
we jolt ourselves awake. That often
happens early in the night, right?
>> Yeah. That's the first stage, stage one
and stage two of sleep. And stage two
sleep is really cool because that has
something called sleep spindles and K
complexes. And what sleep spindles are
are a little of activity that's 10 to 15
hertz in frequency. It's a conversation
between the phalamus and the cortex. The
phalamus is the gateway to consciousness
and the neoortex, you know, processes
all our cognition. And if you wake up
out of that state, you will often report
a dream like a hallucination style
dream. It won't be a long dream report
like you have out of REM sleep, but it
will be some hallucination state.
>> Are they quite different than the
patterns of sleep and dreaming that
occur later in the night or toward
morning?
>> There is some evidence that the first 4
hours of sleep are very important for
memory processing. And in fact, if
you've learned something new that day or
have experienced a new sensory motor
experience, then your early sleep dreams
will incorporate that experience much
more than the later sleep dreams. Later
as that memory gets consolidated from
the early structures which are the
hippocampus deep in the temporal lobe to
the cortex in a distributed fashion that
memory seems to move from that
hippocampus to the cortex and also the
dreams that incorporate that memory also
move later in the night. So
>> there was a great study by Sedarto Rayo
who studied the consolidation of
memories from the hippocampus to the
cortex in a rat across the period of a
full day sleep because rats sleep in the
daytime. And he found that each
subsequent rim sleep period moved that
memory from the hippocampus to the f
first area that projects to it and then
the second area and then the third area.
and you can see the memory moving um
through the throughout the sleep.
>> There's a number of different hormones
associated with the different stages of
sleep. We know that melatonin is a
hormone
>> of night time
>> of nighttime that makes us sleepy. What
about growth hormone release? When does
that occur during sleep?
>> So growth hormone release happens all
day long and all night long. But the
deep slow wave sleep that you get, the
very first sleep cycle is when you get a
big bolus of growth hormone release. and
in men and women equally. And if you
miss that first deep slow wave sleep
period, you also miss that big bolus of
growth hormone release. And you might
get ultimately across the day just as
much overall growth hormone release. But
andologists will tell you that big
bololises do different things than a
little bit eaked out over time. There's
also a big push to synthesize proteins.
So that's when the protein synthesis
part that builds memories for example in
our brain happens in that first cycle of
sleep. So you don't want to miss that
especially if you've learned something
really big and needs needs more synaptic
space to encode it.
>> How would somebody miss that first 90
minutes
>> depriving themselves? Yeah. So, so let's
say I normally go to sleep at 10:00 p.m.
>> and then from 10 to 11:30 would be this
first phase of sleep and that's when the
growth hormone big bololis of growth
hormone would be released. Does that
mean that if I go to sleep instead at
11:30 or midnight that I miss that first
phase of sleep? Why is it not the case
that I get that first phase of sleep
just simply starting later? Every cell
in our body has a clock and all of those
circadian clocks are synchronized and so
our cells are ready to respond to that
growth hormone release at a particular
time and if we miss it and it's a time
in relation to melatonin also. So if you
miss it, yeah, you might get some growth
hormone release, but it's occurring at a
time when that your clock has already
moved to the next phase. And so it's
it's just a clock thing. So what this
means is that we should have fairly
consistent bedtimes in addition to
fairly consistent wake times. Is that
right?
>> Exactly. And in fact, one of the best
markers of good neurological health when
we get older is consistent bedtimes.
>> What other things inhibit growth hormone
release or other components of this
first stage of sleep? Are there things
that I perhaps do in the preceding hours
or the preceding day like ingest
caffeine or alcohol that can make that
first stage of sleep less effective even
if I'm going to sleep at the same time?
>> Alcohol definitely will do that because
alcohol is a REM sleep suppressant and
it even suppresses some of that stage
two transition to REM with those sleep
spindles. And those sleep spindles, we
didn't talk about their function yet,
but they're really important for moving
memories to our cortex. It's a unique
time when our hippocampus the sort of
like the RAM of our brains writes it to
a hard disk which is the cortex and
there it's a unique time when they're
connected. So if you don't want to miss
that you don't want to miss REM sleep
when is also a part of the consolidation
process and alcohol before we go to
sleep will do that until we've
metabolized alcohol and put it out of
our bodies it will affect our sleep
badly. What about the second and third
90minute blocks of sleep? Is there
anything that makes those um unique?
What what is their signature? Besides
the fact that they come second and third
in the night,
>> there's more and more REM sleep the
later the night we get. There's also a
change in hormones. You know, the growth
hormone and melatonin levels are
starting to decline, but other hormones
are picking up. So, it is a really
different stage that you also don't want
to short change yourself on. And I think
that's the stage many studies are
showing that those are the times in
sleep when the most creativity can
happen. That's when our dreams can
incorporate and put together old and new
things together into a new way and our
schema are built during that time. So
that's when your computer of your brain
is opening folders and comparing
documents seeing if is there anything
the same? Are these two documents look
very much the same? that there's a
little bit of difference and it can it
can link those conceptually. So that
that's probably one of the origins of
creativity is finding things that are
related maybe just linked a little bit
and you can find that link and
strengthen it if it you know makes your
schema interesting and different.
>> Many people including myself tend to
wake up maybe once during the middle of
the night to use the restroom. I've
tried to drink less fluid before going
to sleep. I've heard also the impulse to
urinate is also dictated by how quickly
you drink fluid, not just the total
volume. So, I've switched to um sipping
fluids more slowly for my last beverage
of the day, which seems to help. Is
there any known detriment to this middle
of the night waking or should we
consider it a normal feature for some
people's sleep architecture?
>> Yeah, I think we shouldn't worry about
it. Actually, sleep is really incredibly
well homeostatically regulated. And so
really don't worry about how much you're
sleeping as long as you're not
intentionally depriving yourself of
sleep by doing something really
rewarding and exciting because even that
is stressful to your body and deprivives
you of a lot of the things we're talking
about. It's absolutely normal to wake up
at least once in the middle of the night
to go to the bathroom. And as long as
you can get back to sleep in a
reasonable amount of time or even if it
takes you an hour, don't worry about it.
as long as you have a lifestyle that
allows you to then make up that sleep
either the next morning or the next
night um or going to bed a little
earlier.
>> What is unique perhaps about the
architecture of dreams and sleep in the
let's say the last third of the night or
the or the second half of the night,
>> right? Yeah. In the second half of the
night, we have longer REM sleep periods
and those are considered the deepest
sleep. Even though slowwave sleep, big
slow wave is considered deep. It is
deep.
>> Yeah. They call slowwave sleep deep
sleep and REM sleep rapid eye. But now
you're telling me that REM sleep is
actually the deeper sleep.
>> The reason why you call slowwave sleep
deep sleep is because it's difficult to
arouse people out of that state. And
when you do arouse them out of that
state, they're most often confused and
just want to go back into sleep and can
go back pretty easily. If you arouse
someone out of REM sleep, they're more
likely to report something that was
really kind of almost like wakefulness.
It's it was so vivid. And maybe one of
the reasons why REM sleep is deeper is
especially in adults and older people
that deep slowwave sleep goes away. So
it's not as deep. It's not as big. The
slow waves aren't as large which is
probably problematic but we are not
sure. And so then REM sleep becomes the
deepest stage.
>> We are paralyzed during REM sleep.
Correct.
>> Yes. normally paralyzed and that's
really good because that's the time when
we're actively dreaming storyline dreams
and we could hurt ourselves. We're
actually really cut off from the outside
world in terms of responding to say this
table or window or a door and so
different from sleepwalking which is out
of slow sleep. Out of slow sleep that
sleepwalking is a mixture between sleep
and wakefulness. You can cook a full
meal, um, drive your car while you're in
deep, slow sleep. It's scary because you
never know what you're going to do. You
don't have voluntary voluntary control
over it. You have no conscious control
over it, but you can actually safely
navigate um some situations in
sleepwalking and actually have a
conversation. Although it may not make
much sense when you're sleeptalking, in
REM sleep, you're not processing the
outside world. and instead um when
you're acting out your dreams, you could
be doing things like walking through a
plate glass window or falling off of,
you know, down a stairs um things like
that. So, you really want your muscles
to be inactivated during REM sleep,
otherwise you will act out those dreams
and really hurt yourself or your bed
partner. So, as people start to approach
morning or the time when they normally
would wake up, I've heard that it's
important to, if possible, complete one
of these 90minute cycles prior to waking
up. That is, if you set your alarm for
halfway through one of these 90minute
cycles that come late in the night of
sleep that it can lead to um rather
groggy patterns of waking.
>> It's called sleep inertia. When we wake
up out of the wrong state, I liken it to
a washing machine cycle. This 90 minute
cycle is like a washing machine cycle.
And the first part is to add water,
right? Then your clothes are soaking
wet. You don't want to open the washing
machine and try and function, put them
on and wear them around while they're
soaking wet and full of soap. So you
have to wait until the cycle is through
before you can well actually
put it in the dryer, too. Um before you
want to wear them. So you can function.
It just takes a little while for those
clothes, that brain to dry out so you
can actually function well. But it's
better to wait through the whole cycle
is complete. So that's why you want to
set that 90 90 minute alarm clock. And
again, that's around 90 minutes because
the first stage of sleep, the first
cycle of sleep is actually a little
longer, more like 105, 110 minutes. But
then the second ones and third ones,
they get sort of shorter and shorter as
the night goes on. And in the last few
cycles, you're just doing the N2 REM
sleep cycle, which takes less time. And
if you wake up out of REM sleep, there's
usually no problem cognitively.
>> Are you a fan of of sleep trackers?
>> Yeah.
>> Yeah. Do you use one?
>> I have one on. I don't live my life by
them because the best ones right now are
about 70% effective at
>> staging your sleep. So 70% it's okay.
It's okay. But um take it with a grain
of salt is what I'm saying. tell us a
little bit more about the wash out that
occurs in the brain during sleep and
perhaps if there are any ways to ensure
that it happens or to ensure that it
doesn't happen and obviously we want
this to happen.
>> Yeah, we talked about the circadian
clock and how certain things happen at
certain times. Well, one of the things
that happens when we're awake and
talking to each other is that there's a
lot of plasticity. there's something
that I'm learning from you today and
you're learning from me and that changes
our synapses and it changes the way our
proteins are going to be folded and
changed during sleep. This process
actually uses a lot of ATP, the power um
structure, the fuel of the brain. It
unfolds also proteins while we're doing
this, while we're using them. And so
during that first part of the night, uh,
when we first fall asleep, in the first
20 minutes or so, we're building that
adenosine back into ATP. And that's, uh,
probably why power naps are called power
naps because we're actually rebuilding
the power. And then we're also cleaning
out through the deep slow waves of slow
wave sleep. We're cleaning out all those
misfolded proteins, unfolded proteins,
and other things that get broken down
and, you know, need to be rebuilt when
we're asleep because of its use during
wakefulness. So I liken that to, you
know, having a big party during
wakefulness and you need all those
partygoers to leave in order to do the
cleanup. What happens when a neuron is
firing is that it expands. The membrane
expands a little bit. It becomes more
translucent. That's how we know, one of
the ways we know that neurons expand
when they fire. And so every action
potential, the membrane expands a little
bit as sodium brings water into the
cell. And then when they're silent, they
contract. And so in during slow waves,
the cool thing is that the reason why
you can measure them is that all the
neurons at the same time, not all of
them, but a good portion of them are
firing at the same time and silent at
the same time. And so you think about
that as contracting and expanding all at
the same time. It's kind of like a
billagege pump of the brain. So that can
pump out. GIA are also really important
for this in terms of cleaning up debris
and transferring it to where it needs to
go. So, um, so I think of it actually as
a billagege pump cleaning out our brain.
>> Here you're talking about literally an
expansion and a contraction of the
neurons in unison
>> and pushing the fluid through
>> cleaning out any misfolded proteins or
debris that might occur
>> on the basis of these metabolic
pathways.
>> And the consequence of that is to to
what to leave the brain in a state of
more pristine action for the next day.
Is that right?
>> Yeah. You think of it again like a party
and if you don't clean up after that
party and you try and hold another one
the next day, it's going to get more
clogged. You know, it's people have a
harder time moving around and enjoying
themselves. And um if that builds up day
after day, you know, it's going to be
cognition that would be the partygoers
moving around becomes
hard.
>> And so this um build pump that you
describe is associated with the big slow
waves of slowwave sleep. So this is
going to occur more or less in the first
third of the night. Is that right?
>> That's right.
>> And is this similar to the case with
growth hormone where if you go to sleep
later than you would normally, you miss
the wash out. You It's not You don't
delay it. You miss You miss the wash
out.
>> That's right. That's right. So if you go
to sleep at 1 or 2 in the morning, your
sleep is still going to be dominated by
N2 and REM sleep, not by slow wave
sleep. So you need to you need to get
that first bit of sleep. Would a caveat
to that be if somebody normally goes to
sleep at 1 or 2 a.m. and wakes up at
10:00 a.m. if that's their normal sleep
cycle?
>> Yeah, it should be okay. Somebody would
want to do a sleep study with people who
do that normally and see if also the
melatonin release is later and the
corticostone rise that's happens
normally in the morning also happens
later. So if everything shifted good,
>> I'd love for you to tell us about this
incredible structure in the brain which
is the locus ceruius and hopefully tell
us a little bit about its relationship
to epinephrine aka adrenaline.
>> Yeah. So um the locus curillus is filled
with neurons that have in them
norepinephrine which is the brain's
version of epinephrine or adrenaline.
It's also called noradrenaline. And what
it does is it just like adrenaline in
the rest of our bodies, it helps prime
us to respond to our environment. So
when locus rules neurons fire and fire
in a burst, we can switch our attention
and they will fire in a burst if for
example a loud noise happens in the
middle of your concentrating on
something. It fires and it helps you
switch your attention to that thing and
then learn quickly from it. So it's
really important in a stress response.
It helps us do quick one trial learning.
But just tonic levels are signature of
wakefulness and alertness. So too much
is panic with the locusillis activity. A
burst is switching attention. And then
tonic levels are sustained constant
attention. And then when we go to sleep
the locus slows and come goes from about
on average um two hertz to about one
hertz one cycle per second tonically and
then when we go into REM sleep it's the
only time when it shuts off completely
and it appears that that complete
silence is really really important for a
number of things and the main thing that
I think it's important for is the
ability to erase and break down synapses
that are no longer working for us. So
they encode things that are false now or
they are encoding things that we um
learned in the novelty encoding pathway
in of our of our brain that have now
been consolidated to other pathways and
so we need to now erase them from the
novelty encoding pathway and that is
really really important for being able
to continue to learn things all of our
lives. So like erasing that RAM um or
that I don't know what do you call those
discs that you stick into computers that
>> oh thumb drives thumb drives erasing
your thumb drive. So that thumb drive is
what you carry around all day long and
then during sleep you write that thumb
drive to the cortex to the long-term
memory structures and you need to
refresh that thumb drive and that's what
happens during REM sleep when the locus
realis is off and so if we're not able
to do that we fill up that RAM um really
quickly or that thumb drive really
quickly and we're not able to learn new
things even memories that are years past
if you're never able to downscale that
novelty encoding structure and purge it
from that traumatic memory, it will stay
fresh and new and then become
maladaptive.
>> What approaches are you aware of that
can um turn down the output of locus
ceruius during these phases of sleep and
allow late stages of sleep each night to
have their maximum positive effect.
>> Is there anything that I can do besides
avoiding um serotonin or noradinergic
compounds? Well, I would also avoid
anything just prior to going to sleep
that might excite those systems. So, a
lot of novelty, stress inducing video
games. Try and enter sleep with as much
calm as you can. So, maybe deep
breathing exercises. That's a beautiful
way to calm your sympathetic fight
orflight system is deep breathing. And
if there's a way you can make your
sympathetic nervous system calm down
before you go to sleep, might free for
you meditation or deep breathing
exercises. Might be for some a warm bath
or a comforting book. Nothing too
exciting, but also nothing too boring
perhaps. Just something right in the
middle which makes you feel happy and
calm is what you should do. And if you
instead go to sleep while you're anxious
or hyped up, then your sleep could
become maladaptive.
>> I'd love for you to share with us a
little bit more about um these spindles
that have come up a few times.
>> The density of our sleep spindles, the
number that we produce per minute is
well correlated with our intelligence in
the first place. And that no matter what
your intelligence is and no matter what
your sleep spindle density is, if you
learn something during the day and
increase your sleep spindle density,
it's really almost perfectly correlated
with our ability to consolidate that
information and and incorporate it into
the schema that we already have in our
brain. So if you try and learn something
new, even if your sleep spindle density
at baseline is great, if you don't
increase your sleep spindles that night,
you're not going to, you know, use sleep
to really incorporate it. One of the
things we now know through some great
studies by Julie Seep and Anita Luthie
is that sleep spindles are accompanied
by an incredible
plasticity out in the distal dendrites,
the listening branches of our neurons
that listen to other cortical areas. So
there are proximal dendrites in our
neurons that listen to the external
world and are conducted through the
phalamus and then there are distal
dendrites which listen to an internal
kind of you know conversation that's h
happening in our brains. It's kind of
you know our internal state really and
during sleep spindles that's when those
distal dendrites are able to best learn
from other cortical areas and from the
hippocampus. It is during sleep spindles
that the hippocampus and the cortex are
best connected and when that plast
incredible plasticity can happen. So
when I talk about schema, that's a
cortical cortical thing. There's big
surges of calcium into those distal
dendrites and where plasticity happens
in just huge amounts during that sleep
spindle stage of sleep which is N2
stage. There's another excitatory event
that comes all the way from the brain
stem and projects everywhere in our
cortex which is called PGO waves which
we should generalize to P waves because
they come from the ponds and go to the
phalamus and then the cortex happens all
over the brains and that is where
glutamate which is a major excitatory
neurotransmitter involved in learning
and plasticity is being released in big
amounts also in those distal dendrites.
Pwaves and spindles work together to
cause plasticity and sew our schema
together which could be the origins for
insight and creativity. Now when P waves
were first discovered, it was thought to
be random because this small area that
generates P waves all over the brain
projects all over the phalamus and
causes P waves all over. And you don't
measure P waves all over the brain at
the same time. In fact, it's just seems
sporadic and random. And Pwaves also
happening even more during REM sleep,
rapid eye movement sleep. So that's why
people think that REM dreams are so
random is because these P waves are
random and they could generate dreams
because they're an internal source of
excitation that kind of replaces the
outside world during our dream state.
And so these Pwaves, if they are random,
could be the underlying reason why
creativity can happen there is because
we're randomly activating, co-activating
different things in our brain that we
can then sew together. Um, but it might
not be as random as we think. So that's
a caveat there.
>> So locus ceruius is suppressed. So we
can't release norepinephrine. We can't
act out our dreams. This almost starts
to sound like a little bit of a built-in
um while sleeping trauma therapy. Mh.
>> So please if there's anything about
locust ceruius and and dreams and that
can help people basically extinguish
traumas or traumatic features to to real
life events and we definitely want to
know about them.
>> Yeah. Yeah. Well, I think one of the
things that people thought might help
after a trauma like a school shooting or
whatever you know car accident is to
talk about it and in but in fact that
ended up being counterproductive. And I
think one of the reasons why it was
counterproductive is because it didn't
take you them back down. It brought them
up and continued to reactivate the
emotions of it, but then didn't
emphasize the safety fact that it's over
or help them work through how they might
avoid it again in the future to calm the
sympathetic nervous system down again
before they went to sleep. And and in
any none of these studies has sleep ever
been considered, but to me that's the
key part is bringing down your
sympathetic nervous system before you go
to sleep so that your sleep can be
adaptive, your locus can shut off like
it normally does or should do and then
able to erase the novelty of it. The
other thing that I just mentioned a
minute ago was that the emotional system
is highly activated in REM sleep. And
that's definitely true. And that might
seem counterproductive in terms of, you
know, the nightmares and and how to help
REM sleep be a therapeutic thing rather
than reinforcing the emotionality of the
trauma. And I think the key to that
again is the absence of norepinephrine.
So even though the emotional system is
in high gear, without norepinephrine,
you can actually divorce those highly
activated emotions from the cognitive
parts of the memory that you have just
written out in that N2 stage of sleep
when the sleep spindles are going. So
you've just now consolidated the
information that you'll need to survive
and to you know to make that adaptive
and now you need to divorce from that
schema and from that semantic parts of
memory the emotional part because
whenever you remember something it's
fine if you remember the being emotional
at the time but you don't want to bring
back and sew into that memory all of the
same emotional systems. You don't want
to bring back, you know, the heart rate
changes and the sweating and and all of
that. You want to be able to remember
all the parts of it and even remember
that you were traumatized and that you
did cry and that you did have, you know,
your heart was racing. But when you're
talking about it years later, you don't
want to have to relive all that.
Otherwise, who who would ever want to
recall a traumatic memory because you're
basically putting yourself through the
same trauma, which is what people with
PTSD have. They don't want to recall
this traumatic memory because it's
reliving it like it's just happening
again. So that's what we're thinking is
that the emotional parts are not able to
be divorced because the norphan system
is not downscaled during REM sleep. And
so that REM sleep serves to instead
reinforce and in fact amplify the
emotions because your your emotional
system is up. Look, Serilla says, "Hi,
re- sewing in every night the
emotionality of those memories and with
the memory itself."
>> I must say, you've taught us a
tremendous amount in um in a relatively
short amount of time about the
architecture of sleep, the different
phases, such a wealth of information,
and much of it that's actionable for
people. So, I want to say thank you for
taking the time to sit down and have
this conversation that so many people
are sure to benefit from. I know I speak
for everybody when I say thank you so
much. [music]
>> Thank you so much.