Dr. Gina Poe: Use Sleep to Enhance Learning, Memory & Emotional State

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.900 | I'm Andrew Huberman, and I'm a professor of neurobiology

00:00:11.720 | and ophthalmology at Stanford School of Medicine.

00:00:14.720 | Today, my guest is Dr. Gina Poe.

00:00:17.040 | Dr. Gina Poe is a professor in the Department

00:00:19.000 | of Integrative Biology and Physiology

00:00:21.280 | at the University of California, Los Angeles.

00:00:23.800 | Her laboratory and research focuses on the relationship

00:00:26.240 | between sleep and learning,

00:00:28.080 | in particular how specific patterns of brain activity

00:00:30.600 | that are present during specific phases of sleep

00:00:33.680 | impact our ability to learn and remember

00:00:36.500 | specific types of information.

00:00:38.280 | For instance, procedural information,

00:00:40.080 | that is how to perform specific cognitive or physical tasks,

00:00:43.840 | as well as encoding of emotional memories

00:00:46.160 | and discarding emotional memories.

00:00:48.540 | Indeed, her research focuses on how specific phases of sleep

00:00:51.640 | can act as its own form of trauma therapy,

00:00:54.020 | discarding the emotional tones of memories.

00:00:57.680 | In addition, her laboratory focuses on how specific phases

00:01:00.340 | of sleep impact things like the release of growth hormone.

00:01:04.000 | Growth hormone, of course, plays critical roles

00:01:05.960 | in metabolism and tissue repair,

00:01:07.480 | including brain tissue repair,

00:01:09.240 | and therefore has critical roles in vitality and longevity.

00:01:13.000 | Today, you will learn many things about the relationship

00:01:15.120 | between sleep, learning, emotionality, and growth hormone.

00:01:18.920 | One basic but very important takeaway

00:01:21.240 | that you'll learn about today, which was news to me,

00:01:23.680 | is that it's not just the duration

00:01:26.000 | and depth of your sleep that matter,

00:01:27.880 | but actually getting to sleep

00:01:29.220 | at relatively the same time each night

00:01:31.680 | ensures that you get adequate growth hormone release

00:01:34.240 | in the first hours of sleep.

00:01:35.940 | In fact, if you require, let's say,

00:01:38.480 | eight hours of sleep per night,

00:01:40.240 | but you go to sleep two hours later

00:01:42.320 | than your typical bedtime on any given night,

00:01:45.120 | you actually miss the window for growth hormone release.

00:01:48.520 | That's right, getting growth hormone release in sleep,

00:01:51.240 | which is absolutely critical

00:01:52.480 | to our immediate and long-term health,

00:01:54.560 | is not a prerequisite of getting sleep,

00:01:56.340 | even if we are getting enough sleep.

00:01:57.540 | As Dr. Poe explains, there are critical brain circuits

00:02:00.360 | and endocrine, that is hormone circuits,

00:02:02.080 | that regulate not just the duration and depth

00:02:04.620 | and quality and timing of sleep,

00:02:06.600 | but when we place our bow to sleep,

00:02:08.700 | that is when we go to sleep each night,

00:02:10.680 | plus or minus about a half hour or so,

00:02:12.920 | strongly dictates whether or not we will experience

00:02:15.200 | all the health promoting,

00:02:16.600 | including mind promoting benefits of sleep.

00:02:19.740 | Today's episode covers that

00:02:21.000 | and a lot more in substantial detail.

00:02:23.220 | You will learn, for instance,

00:02:24.280 | how to use sleep in order to optimize learning,

00:02:26.400 | as well as forgetting for those things

00:02:28.080 | that you would like to forget.

00:02:29.440 | So during today's episode,

00:02:30.520 | Dr. Gina Poe shares critical information

00:02:32.980 | about not just neuroscience,

00:02:34.240 | but physiology and the hormone systems of the brain and body

00:02:37.080 | that strongly inform mental health,

00:02:38.760 | physical health, and performance.

00:02:40.200 | So by the end of today's episode,

00:02:41.840 | you'll be far more informed about sleep and how it works,

00:02:44.880 | the different roles it performs,

00:02:46.400 | and you'll have several new actionable steps

00:02:48.240 | that you can take in order to improve

00:02:50.560 | your mental health, physical health, and performance.

00:02:53.120 | Before we begin, I'd like to emphasize that this podcast

00:02:55.800 | is separate from my teaching and research roles at Stanford.

00:02:58.560 | It is, however, part of my desire and effort

00:03:00.720 | to bring zero cost to consumer information about science

00:03:03.260 | and science-related tools to the general public.

00:03:05.840 | In keeping with that theme,

00:03:06.920 | I'd like to thank the sponsors of today's podcast.

00:03:09.720 | Our first sponsor is Element.

00:03:11.920 | Element is an electrolyte drink

00:03:13.520 | that has everything you need and nothing you don't.

00:03:15.680 | That means plenty of salt, magnesium, and potassium,

00:03:18.240 | the so-called electrolytes, and no sugar.

00:03:21.040 | The electrolytes are critical to the function

00:03:22.660 | of every cell in your body,

00:03:23.900 | in particular, the neurons, the nerve cells.

00:03:26.560 | So I've talked about before on this podcast,

00:03:28.480 | neurons, nerve cells, require adequate sodium and potassium,

00:03:32.760 | as well as magnesium, in order to fire action potentials,

00:03:35.460 | which are the electrical signals that allow neurons

00:03:37.400 | to do everything from generate focus and attention,

00:03:40.500 | allow you to learn and generate neuromuscular connection,

00:03:44.000 | and allow you to exercise or train

00:03:45.840 | or do any kind of skilled activity

00:03:47.460 | with a high degree of output.

00:03:48.760 | I take Element about two or three times per day,

00:03:51.280 | typically once in the morning and again after

00:03:53.420 | or during my bout of exercise each day,

00:03:56.100 | and sometimes an additional one

00:03:57.940 | if I've sat in a hot sauna and sweat a lot

00:03:59.680 | or if the weather is very hot.

00:04:01.140 | If you'd like to try Element, you can go to Drink Element,

00:04:03.660 | that's lmnt.com/huberman,

00:04:06.080 | to claim a free Element sample pack with your purchase.

00:04:08.400 | Again, that's Drink Element, lmnt.com/huberman,

00:04:11.800 | to claim a free sample pack.

00:04:13.400 | Today's episode is also brought to us by Helix Sleep.

00:04:16.040 | Helix Sleep makes mattresses and pillows

00:04:18.020 | that are the absolute highest quality.

00:04:20.480 | Now, sleep is the foundation of mental health,

00:04:22.720 | physical health, and performance.

00:04:23.920 | When we are sleeping well, all of those things excel.

00:04:27.080 | And when we are not sleeping well,

00:04:28.960 | all of those things suffer.

00:04:30.960 | Now, the surface that you sleep on,

00:04:32.300 | that is the mattress that you sleep on, is critical.

00:04:34.880 | And Helix understands that everybody

00:04:36.480 | has slightly different sleep needs.

00:04:38.400 | So if you were to go to the Helix site,

00:04:39.960 | which I invite you to do,

00:04:41.000 | and take their brief two-minute quiz,

00:04:42.940 | it will match your body type and sleep preferences

00:04:45.240 | to the perfect mattress for you.

00:04:46.440 | It will ask you questions, for instance,

00:04:48.880 | do you sleep on your back or your side or your stomach?

00:04:51.080 | Do you tend to run hot or cold during the night?

00:04:52.700 | Or maybe you don't know the answers to those questions.

00:04:54.760 | I went and took the sleep quiz at Helix,

00:04:57.000 | and it matched me to the so-called dusk mattress, D-U-S-K.

00:05:00.020 | I started sleeping on a dusk mattress over a year ago,

00:05:02.480 | and it's the best sleep that I've ever had.

00:05:04.200 | It's completely transformed the depth and duration

00:05:07.180 | and quality of my sleep in ways that make me feel

00:05:09.760 | far better during the daytime.

00:05:11.760 | If you're interested in upgrading your mattress,

00:05:13.380 | you can go to helixsleep.com/huberman,

00:05:15.840 | take their two-minute sleep quiz,

00:05:17.200 | and they'll match you to a customized mattress,

00:05:18.920 | and you'll get up to $350 off any mattress order

00:05:22.540 | and two free pillows.

00:05:24.000 | Again, if interested, go to helixsleep.com/huberman

00:05:27.000 | for up to $350 off and two free pillows.

00:05:29.940 | Today's episode is also brought to us by Eight Sleep.

00:05:32.700 | Eight Sleep makes smart mattress covers

00:05:34.360 | with cooling, heating, and sleep tracking capacity.

00:05:37.360 | Now, again, sleep is the foundation of mental health,

00:05:40.000 | physical health, and performance,

00:05:41.600 | but what many people don't realize

00:05:43.000 | is that in order to fall and stay asleep,

00:05:45.140 | your core body temperature has to drop

00:05:46.760 | by about one to three degrees.

00:05:48.720 | Conversely, in order to wake up each morning

00:05:50.920 | and feel refreshed,

00:05:52.120 | your body temperature actually has to increase

00:05:54.160 | by one to three degrees.

00:05:55.780 | Therefore, controlling the temperature

00:05:57.320 | of your sleeping environment is absolutely key.

00:05:59.880 | With Eight Sleep, that's very easy to do.

00:06:01.920 | Depending on whether or not you typically run too cold

00:06:04.240 | or too hot during the night,

00:06:05.560 | you can program your Eight Sleep mattress cover

00:06:07.740 | so that it's the optimal temperature,

00:06:09.400 | not just for you, but for each phase,

00:06:11.520 | the early, middle, and late phase of your sleep,

00:06:14.340 | and for waking up in the morning.

00:06:15.640 | In fact, you can even control the temperature

00:06:17.140 | of your Eight Sleep mattress cover

00:06:18.420 | differentially across the mattress

00:06:20.120 | if you're sleeping alongside somebody else.

00:06:22.120 | If you'd like to try Eight Sleep,

00:06:23.320 | you can go to eightsleep.com/huberman

00:06:25.600 | and check out their PodPro cover

00:06:27.020 | and save $150 at checkout.

00:06:29.160 | Eight Sleep currently ships in the USA, Canada, UK,

00:06:31.720 | and select countries in the EU and Australia.

00:06:33.920 | Again, that's eightsleep.com/huberman

00:06:36.680 | to save $150 at checkout.

00:06:38.760 | The Huberman Lab podcast is now partnered

00:06:40.520 | with Momentous Supplements.

00:06:41.760 | To find the supplements we discuss

00:06:43.080 | on the Huberman Lab podcast,

00:06:44.280 | you can go to Live Momentous, spelled O-U-S,

00:06:46.960 | livemomentous.com/huberman.

00:06:49.480 | And I should just mention that the library

00:06:50.860 | of those supplements is constantly expanding.

00:06:53.040 | Again, that's livemomentous.com/huberman.

00:06:56.160 | And now for my discussion with Dr. Gina Poe.

00:06:58.960 | Dr. Gina Poe, welcome.

00:07:00.880 | - Thank you.

00:07:01.780 | - I've really been looking forward to this conversation

00:07:04.360 | because I'm familiar with your work,

00:07:06.300 | and I know that many people are going to be excited

00:07:09.000 | to learn about your work as it relates to sleep,

00:07:12.200 | as it relates to problem solving, creativity,

00:07:14.840 | addiction and craving, relapse,

00:07:17.840 | and a number of other important topics.

00:07:19.720 | So to start things off, I would love for you

00:07:22.560 | to educate us a bit about this thing

00:07:24.620 | that we are all familiar with,

00:07:26.120 | and yet very few of us understand, which is sleep.

00:07:29.680 | And if you would, could you describe the various phases

00:07:33.580 | of sleep that exist, what distinguished them,

00:07:36.400 | and perhaps frame this within the context

00:07:39.040 | of what would a perfect night's sleep look like?

00:07:41.720 | - Okay.

00:07:42.560 | - How long would it last, more or less?

00:07:44.740 | And what would the biology look like?

00:07:47.560 | What is a perfect night's sleep?

00:07:49.640 | - Oh yeah, that's a great question.

00:07:51.300 | All right, so sleep is really different from wakefulness,

00:07:54.360 | and in fact, can't be replaced by any state of wakefulness

00:07:58.240 | that we've been able to come up with so far.

00:08:01.160 | Our brain chemistry is completely different,

00:08:03.560 | and in the different stages of sleep,

00:08:05.320 | which there is non-REM and REM

00:08:07.440 | are the two major states of sleep,

00:08:09.200 | and every animal we've studied so far

00:08:11.020 | seems to have both of those states.

00:08:13.600 | Anyway, those two states are entirely different

00:08:15.980 | from one another, too.

00:08:16.960 | And even within non-REM, there are three states.

00:08:19.920 | Stage one, which is what you slip into

00:08:21.920 | when you're first falling asleep, it's dozing.

00:08:24.840 | There's kind of an interesting rhythm

00:08:26.340 | that goes on in the brain.

00:08:27.280 | It's kind of a fast gamma rhythm.

00:08:29.160 | And then there's stage two, which is a really cool state.

00:08:32.760 | We sort of used to ignore sleep researchers

00:08:35.760 | because it was a transient state between wakefulness

00:08:38.520 | and the deep stage three, slow wave sleep,

00:08:40.760 | which is the most impressively different.

00:08:43.000 | And then, and between that and REM sleep.

00:08:46.100 | So stage two, I'll talk a little bit more about,

00:08:48.600 | and then the deep slow wave sleep state,

00:08:50.620 | which is when big slow waves sweep through our brain,

00:08:53.320 | and now we realize that it cleans our brain.

00:08:56.480 | One of the things that those big slow waves do

00:08:58.160 | is cleans our brain and does other really important things

00:09:01.060 | to restore us from a day of wakefulness.

00:09:04.960 | And then REM sleep, which is the most popular

00:09:07.240 | because that's where we have the most active dreams

00:09:09.940 | and when you wake up someone out of REM sleep,

00:09:13.760 | they'll almost always report having dreamed

00:09:15.960 | something really bizarre.

00:09:17.600 | That's called REM sleep, rapid eye movement sleep.

00:09:19.920 | So those are the four states of sleep, of human sleep.

00:09:22.920 | And we cycle through them every 90 minutes or so.

00:09:26.720 | When we go to sleep, say 10, 10, 30, 11 o'clock,

00:09:30.480 | our first REM sleep period comes about 105 minutes

00:09:34.600 | after we fall asleep and lasts about 20 minutes.

00:09:38.440 | Actually, it comes about 95 minutes

00:09:41.760 | and lasts 10 or 15 minutes.

00:09:43.820 | And then we start over again.

00:09:47.140 | And we have about five of those per night

00:09:48.920 | for a perfect night's sleep,

00:09:50.360 | four or five, something like that.

00:09:51.980 | So a perfect night's sleep is seven and a half, eight hours.

00:09:55.860 | There was a really great study that put people

00:09:58.780 | in a semi darkened room with nothing but the bed

00:10:01.920 | for 12 hours every day for a month.

00:10:04.140 | And what people did initially is,

00:10:05.880 | because we're in a sleep deprived nation,

00:10:08.220 | is that they slept a lot more than usual,

00:10:10.720 | like 10 or 11 hours of the 12.

00:10:13.300 | And then they leveled off after a week or two

00:10:16.680 | to about eight hours and 15 minutes of sleep.

00:10:18.940 | So you actually can't oversleep.

00:10:20.940 | I mean, they had nothing else to do but sleep

00:10:23.440 | and they would round off to, on average,

00:10:25.360 | eight hours and 15 minutes a night.

00:10:27.140 | And then they spend the rest of the time

00:10:28.500 | twiddling their thumbs, humming tunes, daydreaming.

00:10:32.140 | - I want to get back to the contour of a perfect night's sleep

00:10:34.200 | but I'm intrigued by this idea that people can't oversleep.

00:10:37.500 | I'm often asked whether or not we can get too much sleep

00:10:40.820 | and whether or not sleeping too long, excuse me,

00:10:43.220 | can make us groggy the next day.

00:10:45.580 | Is there anything to that?

00:10:46.960 | And how does one determine how long they should sleep

00:10:51.900 | on average? - On average, yeah.

00:10:53.540 | Well, that's interesting because different people

00:10:56.740 | seem to need different amounts of sleep

00:10:59.000 | but we don't really even know exactly what sleep is for.

00:11:02.420 | So what they need is, you know, kind of,

00:11:06.420 | it's, you know, murky.

00:11:08.680 | So we do know a lot of things that sleep does now for us

00:11:14.660 | but we don't know how long those things take.

00:11:16.980 | So how long we need to sleep is also just a big question mark

00:11:21.380 | but some people don't feel rested

00:11:23.100 | until they've slept nine hours.

00:11:24.820 | Some people don't feel rested after three or four and a half.

00:11:28.940 | But most people, if they consistently deprive themselves

00:11:33.040 | of sleep so that they're only sleeping four,

00:11:34.780 | four and a half hours a night,

00:11:36.420 | build up a cognitive deficit that just builds up over time.

00:11:41.220 | The more nights you have with sleep deprivation,

00:11:44.700 | the more cognitive deficit you have.

00:11:46.720 | And so you need sleep, again, to sleep more to recover.

00:11:51.180 | Now, the question you had about--

00:11:53.020 | - Can you overs-- - Can you oversleep?

00:11:55.900 | - Can you sleep to the point where it's too much?

00:11:58.220 | You know, that we, growing up when I was in high school,

00:12:02.300 | my girlfriend's dad had this belief that no one

00:12:05.100 | should sleep in past 6 a.m.

00:12:07.220 | So he would wake all the,

00:12:09.400 | there were two children in that home,

00:12:10.460 | he would wake up the kids in that house.

00:12:12.260 | He had this thing against oversleeping

00:12:13.900 | regardless of when people went to sleep.

00:12:16.100 | And I always thought that was an interesting mentality.

00:12:18.780 | - Yeah, it's not terrible, actually,

00:12:20.820 | because what that will do is it'll put you,

00:12:23.380 | make you sleep the next night to get to bed on time.

00:12:26.660 | So it'll build up your homeostatic need

00:12:29.420 | if you wake up too early.

00:12:30.620 | But, so I don't think you can oversleep,

00:12:34.100 | but people who sleep a lot,

00:12:35.580 | like people who sleep over nine hours,

00:12:37.500 | it's probably indicative of some other problem,

00:12:40.020 | because in fact, if you have a lot of different conditions,

00:12:44.940 | it will cause you to sleep a lot more,

00:12:46.420 | probably because what it does is it interferes

00:12:48.380 | with your efficient sleep, the efficiency of your sleep.

00:12:51.160 | So if you find yourself sleeping consistently

00:12:54.380 | nine hours plus every night,

00:12:56.940 | then you might want to consult a doctor

00:12:58.500 | about maybe what else it might be.

00:13:00.680 | It could be cancer, it could be sleep apnea,

00:13:05.180 | that just affects a lot of people.

00:13:07.100 | It could be that your sleep is super inefficient

00:13:09.100 | because you're snoring a lot more than you know,

00:13:11.460 | or you're waking up a lot more than you know every night.

00:13:14.380 | So you might want to sleep steady

00:13:16.420 | just to see how your sleep is

00:13:19.180 | and then see what else might be causing you to sleep so much.

00:13:22.300 | - And that wouldn't be if somebody is sleeping

00:13:24.700 | nine or 10 hours every once in a while.

00:13:27.240 | You mean if they're consistently sleeping

00:13:28.940 | for more than nine hours?

00:13:30.460 | - If they feel like they need it

00:13:31.700 | in order to function cognitively the next day,

00:13:34.860 | it might be that your sleep is just not efficient

00:13:37.260 | and you might want to look into why that's the case.

00:13:40.780 | - Interesting.

00:13:41.820 | Forgive me for the anecdote, but I can't resist.

00:13:43.580 | Years ago, I went to an acupuncturist

00:13:45.940 | and he gave me these red pills

00:13:49.100 | of which I don't know what they contained.

00:13:52.240 | But I took them because he told me

00:13:53.900 | they would help with my sleep.

00:13:55.460 | And I would fall asleep about 30 minutes after taking them.

00:13:58.880 | And I would have incredibly, excuse me, vivid dreams.

00:14:03.000 | And I'd wake up four or five hours

00:14:05.480 | after having gone to sleep feeling completely rested.

00:14:08.300 | Something that I've never really experienced

00:14:10.800 | on a consistent basis.

00:14:12.040 | I want to do mass spec on these pills.

00:14:13.840 | I still have no idea what was in them whatsoever.

00:14:16.140 | - I want to do mass spec on these pills too.

00:14:17.320 | - Exactly.

00:14:18.160 | Some people thought that perhaps they had GHB,

00:14:20.680 | gamma hydroxybutyrate, which is by the way, an illegal drug.

00:14:23.360 | It can kill you.

00:14:24.200 | It's not something you want to take.

00:14:25.800 | - No, that's not good.

00:14:26.700 | - But anyway, if ever someone can figure out

00:14:29.080 | what the red pills were, I'll be very-

00:14:31.180 | - That's really great.

00:14:32.020 | - And this is not a red pill of the other sort red pill.

00:14:34.420 | This is just the red sleep pills.

00:14:36.240 | - Interesting.

00:14:37.080 | I mean, it could have been even a placebo effect

00:14:39.400 | because placebo is extremely strong.

00:14:42.020 | - Although I don't know,

00:14:43.240 | there was really something to these red pills.

00:14:45.240 | So shout out to the acupuncturists and the Eastern medicine.

00:14:50.680 | But to return to this idea of the architecture

00:14:54.680 | of a perfect night's sleep.

00:14:55.960 | So you said we fall asleep, the first 90 minutes of sleep,

00:15:00.440 | REM sleep, rapid eye movement sleep,

00:15:03.300 | will arrive at about 95 minutes in.

00:15:05.540 | Does that mean that the rest of that 90 minutes

00:15:09.060 | is consumed with slow wave sleep?

00:15:11.400 | - Yeah, non-REM sleep.

00:15:12.560 | - Okay, and what about the sleep where we are lightly asleep

00:15:16.760 | and we might have a dream that has us

00:15:19.600 | somehow thinking about movement

00:15:20.960 | or that we jolt ourselves awake?

00:15:22.480 | That often happens early in the night, right?

00:15:24.240 | - Yeah, that's the first stage,

00:15:26.360 | stage one and stage two of sleep.

00:15:28.360 | And stage two of sleep is really cool

00:15:30.740 | because that has something called sleep spindles

00:15:34.700 | and K complexes.

00:15:35.880 | And what sleep spindles are,

00:15:37.120 | are a little of activity that's 10 to 15 Hertz in frequency.

00:15:42.120 | It's a conversation between the thalamus and the cortex.

00:15:47.080 | The thalamus is the gateway to consciousness

00:15:49.840 | and the neocortex processes all our cognition.

00:15:53.280 | And so it's these spindles, they're called sleep spindles.

00:15:58.280 | And if you wake up out of that state,

00:16:01.520 | you will often report a dream,

00:16:03.240 | like a hallucination style dream.

00:16:05.520 | It won't be a long dream report

00:16:07.760 | like you have out of REM sleep,

00:16:09.200 | but it will be some hallucination state.

00:16:11.820 | And during, while we're falling asleep,

00:16:13.700 | one of the reasons we call it falling asleep

00:16:15.520 | is because in stage one and stage two,

00:16:17.400 | our muscles are relaxing.

00:16:19.320 | And if there's part of our brain that's conscious enough

00:16:22.560 | to sort of recognize that relaxation,

00:16:24.880 | we'll feel like we're falling and we'll jerk awake.

00:16:28.040 | So often that hallucination,

00:16:30.240 | it's called hypnagogic hallucination,

00:16:32.300 | will feel like it'll include some falling aspect

00:16:35.980 | that we'll wake up out of.

00:16:37.520 | - That's really interesting to me.

00:16:39.520 | I've long felt that sensation

00:16:42.920 | of almost like dropping back into my head,

00:16:46.060 | so much so that if I elevate my feet just slightly

00:16:48.760 | and I tilt my head back just slightly

00:16:51.000 | in order to go to sleep,

00:16:51.840 | I find that I fall asleep much faster.

00:16:54.240 | But it does feel as if I'm going to fall,

00:16:55.560 | like almost going to do a backward somersault.

00:16:57.560 | I actually really like the sensation

00:16:59.560 | and usually because it proceeds falling deeply asleep.

00:17:01.840 | - Yeah, that's really interesting.

00:17:03.720 | Somebody has to do a study of elevated feet.

00:17:07.000 | - Yeah, there's a little bit on body position and sleep

00:17:11.000 | and some of the washout that we'll talk about.

00:17:12.540 | So early in the night,

00:17:13.700 | you've got these lighter stages of sleep,

00:17:16.840 | less rapid eye movement sleep.

00:17:19.040 | What can we say about the dreams that occur

00:17:20.960 | during the say first and second 90 minute cycles of sleep?

00:17:25.960 | Are they quite different than the patterns of sleep

00:17:29.640 | and dreaming that occur later in the night

00:17:31.480 | or toward morning?

00:17:32.460 | - Well, okay, that's an interesting question.

00:17:34.840 | There's a lot of facets to it.

00:17:37.000 | There is some evidence that the first four hours of sleep

00:17:41.080 | are very important for memory processing.

00:17:44.400 | And in fact, if you've learned something new that day

00:17:49.400 | or have experienced a new sensory motor experience,

00:17:54.920 | then your early sleep dreams

00:17:58.140 | will incorporate that experience

00:17:59.700 | much more than the later sleep dreams.

00:18:02.240 | Later as that memory gets consolidated

00:18:04.320 | from the early structures,

00:18:06.920 | which are the hippocampus deep in the temporal lobe

00:18:09.200 | to the cortex in a distributed fashion,

00:18:12.680 | that memory seems to move from that hippocampus

00:18:16.400 | to the cortex and also the dreams

00:18:18.600 | that incorporate that memory also move later in the night.

00:18:21.660 | So nobody knows why,

00:18:24.440 | but there was a great study by Sidarto Ribeiro

00:18:29.280 | who studied the consolidation of memories

00:18:32.200 | from the hippocampus to the cortex in a rat

00:18:35.720 | across the period of a full day's sleep

00:18:39.640 | because rats sleep in the daytime.

00:18:41.280 | And he found that each subsequent REM sleep period

00:18:45.360 | moved that memory from the hippocampus

00:18:47.980 | to the first area that projects to it

00:18:50.960 | and then the second area and then the third area.

00:18:53.320 | And you can see the memory moving

00:18:55.880 | throughout the sleep period.

00:18:58.760 | - Very cool, I have to read that study.

00:19:01.340 | So there's a number of different hormones

00:19:04.800 | associated with the different stages of sleep.

00:19:07.080 | We know that melatonin is a hormone--

00:19:09.280 | - Of nighttime.

00:19:10.120 | - Of nighttime that makes us sleepy.

00:19:12.800 | What about growth hormone release?

00:19:14.200 | When does that occur during sleep?

00:19:15.680 | - So growth hormone release happens all day long

00:19:18.160 | and all night long,

00:19:19.080 | but the deep slow wave sleep that you get,

00:19:21.780 | the very first sleep cycle

00:19:25.040 | is when you get a big bolus of growth hormone release

00:19:28.120 | and in men and women equally.

00:19:31.040 | And if you miss that first deep slow wave sleep period,

00:19:34.840 | you also miss that big bolus of growth hormone release.

00:19:38.400 | And you might get ultimately across the day

00:19:41.260 | just as much overall growth hormone release,

00:19:44.260 | but androchronologists will tell you

00:19:45.760 | that big boluses do different things

00:19:48.360 | than a little bit eked out over time.

00:19:50.500 | So that is when we know there's also a big push

00:19:55.500 | to synthesize proteins.

00:19:58.960 | So that's when the protein synthesis part

00:20:02.360 | that builds memories, for example, in our brain

00:20:05.160 | happens in that first cycle of sleep.

00:20:08.120 | So you don't want to miss that,

00:20:09.600 | especially if you've learned something really big

00:20:11.640 | and needs more synaptic space to encode it.

00:20:15.280 | - How would somebody miss that first 90 minutes?

00:20:17.960 | - Sleep deriving themselves.

00:20:19.080 | Yeah, so you can--

00:20:19.920 | - So let's say I normally go to sleep at 10 p.m.

00:20:23.020 | and then from 10 to 1130 would be this first phase of sleep

00:20:27.800 | and that's when the big bolus of growth hormone

00:20:30.520 | would be released.

00:20:31.480 | Does that mean that if I go to sleep instead

00:20:33.800 | at 1130 or midnight that I miss that first phase of sleep?

00:20:37.200 | Why is it not the case that I get that first phase of sleep

00:20:40.440 | just simply starting later?

00:20:41.840 | - It is a beautiful clock that we have in our body

00:20:45.200 | that knows when things should happen.

00:20:46.920 | And it's every cell in our body has a clock

00:20:49.520 | and all of those clocks are normally synchronized

00:20:52.720 | and the circadian clocks are synchronized.

00:20:55.980 | And so our cells are ready to respond

00:21:00.680 | to that growth hormone release at a particular time.

00:21:03.240 | And if we miss it,

00:21:04.320 | and it's a time in relation to melatonin also.

00:21:07.560 | So if you miss it, yeah,

00:21:09.240 | you might get some growth hormone release,

00:21:11.400 | but it's occurring at a time

00:21:12.680 | when your clock has already moved to the next phase.

00:21:15.900 | And so it's just a clock thing.

00:21:18.820 | - Yeah, I don't think we can overstate the importance

00:21:21.480 | of what you just described.

00:21:22.580 | And to be honest, despite knowing a bit

00:21:24.740 | about the sleep research in circadian biology,

00:21:26.980 | this is the very first time that I've ever heard this,

00:21:30.720 | that if you normally go to sleep at a particular time

00:21:33.840 | and growth hormone is released in that first phase of sleep,

00:21:36.280 | that you can't simply initiate your sleep bout later

00:21:38.960 | and expect to capture that first phase of sleep.

00:21:42.560 | That's incredible and I think important.

00:21:44.560 | And as many listeners are probably realizing,

00:21:48.480 | also highly actionable.

00:21:49.600 | So what this means is that we should have

00:21:50.920 | fairly consistent bedtimes

00:21:52.480 | in addition to fairly consistent wake times.

00:21:54.640 | Is that right? - Yes, exactly.

00:21:55.900 | And in fact, one of the best markers

00:21:58.800 | of good neurological health when we get older

00:22:01.760 | is consistent bedtimes.

00:22:03.780 | - Wow, okay.

00:22:05.860 | I don't want to backtrack,

00:22:08.380 | but I did write down something that I think is important

00:22:11.500 | for me to resolve or for you to resolve.

00:22:14.460 | So I'm going to ask this.

00:22:15.920 | People that sleep nine hours or more,

00:22:17.980 | perhaps that reflecting an issue,

00:22:20.500 | some underlying issue, perhaps,

00:22:22.560 | is being a teenager or an adolescent

00:22:25.600 | and undergoing a stage of development

00:22:28.400 | where there's a lot of bodily and brain growth

00:22:30.360 | and exception to that.

00:22:31.200 | Because I don't recall sleeping a ton when I was a teenager.

00:22:35.260 | I had a ton of energy,

00:22:36.640 | but I know a few teenagers and they sleep a lot.

00:22:41.240 | Like they'll just sleep and sleep and sleep and sleep.

00:22:43.000 | Should we let them sleep and sleep and sleep?

00:22:44.840 | - Yes, let them sleep.

00:22:45.680 | - Okay, so that's the one exception.

00:22:47.000 | What about us? - Just like babies.

00:22:48.960 | When you're developing something in your brain

00:22:51.600 | or the rest of your body,

00:22:52.920 | you really need sleep to help organize that.

00:22:56.040 | I mean, sleep is doing really hard work

00:22:57.920 | in organizing our brains and making it develop right.

00:23:01.360 | And if we deprive ourselves of sleep,

00:23:03.900 | we will actually also, just like I said,

00:23:06.400 | we have a daily clock.

00:23:08.320 | We also have a developmental clock

00:23:09.960 | and we can miss a developmental window

00:23:12.640 | if we don't let ourselves sleep extra like we need to.

00:23:16.640 | - What other things inhibit growth hormone release

00:23:19.160 | or other components of this first stage of sleep?

00:23:21.360 | In other words, if I go to sleep religiously

00:23:23.680 | every night at 10 p.m.,

00:23:25.720 | are there things that I perhaps do in the preceding hours

00:23:29.080 | or the preceding day, like ingest caffeine or alcohol

00:23:32.480 | that can make that first stage of sleep less effective,

00:23:35.120 | even if I'm going to sleep at the same time?

00:23:37.000 | - Alcohol definitely will do that

00:23:38.740 | because alcohol is a REM sleep suppressant

00:23:41.120 | and it even suppresses some of that stage two

00:23:43.280 | transition to REM with those sleep spindles.

00:23:45.520 | And those sleep spindles,

00:23:46.400 | we didn't talk about their function yet,

00:23:48.080 | but they're really important for moving memories

00:23:51.680 | to our cortex.

00:23:52.600 | It's a unique time when our hippocampus,

00:23:55.800 | sort of like the RAM of our brains,

00:23:59.020 | writes it to a hard disk, which is the cortex.

00:24:02.300 | And it's a unique time when they're connected.

00:24:04.960 | So if you don't want to miss that,

00:24:06.700 | you don't want to miss REM sleep

00:24:07.900 | when it's also a part of the consolidation process

00:24:11.200 | and schema changing process.

00:24:14.320 | And alcohol before we go to sleep, we'll do that.

00:24:18.040 | Until we've metabolized alcohol and put it out of our bodies,

00:24:22.060 | it will affect our sleep badly.

00:24:24.660 | - So probably fair to say no ingestion of alcohol

00:24:28.840 | within the four to six hours preceding sleep,

00:24:32.160 | given the half life, or at all would be better,

00:24:35.320 | but I know some people refuse to go that way.

00:24:37.520 | - Maybe a little bit is okay.

00:24:39.480 | I don't know what the dose response is,

00:24:41.700 | but there are studies out there you can look at.

00:24:44.780 | - Great. - Yeah.

00:24:46.380 | - So we're still in the first stage of sleep

00:24:48.220 | and I apologize for slowing us down,

00:24:49.760 | but it sounds like it's an incredibly important

00:24:53.000 | first phase of sleep.

00:24:54.500 | What about the second and third 90 minute blocks of sleep?

00:24:57.540 | Is there anything that makes those unique?

00:25:00.600 | What is their signature besides the fact

00:25:03.200 | that they come second and third in the night?

00:25:04.940 | - There's more and more REM sleep the later the night we get.

00:25:08.960 | There's also a change in hormones.

00:25:11.300 | You know, the growth hormone and melatonin levels

00:25:15.360 | are starting to decline, but other hormones are picking up.

00:25:18.760 | So it is a really different stage

00:25:21.680 | that you also don't want to shortchange yourself on.

00:25:24.660 | And I think that's the stage many studies are showing

00:25:27.600 | that those are the times in sleep

00:25:29.680 | when the most creativity can happen.

00:25:32.080 | That's when our dreams can incorporate

00:25:34.320 | and put together old and new things together into a new way.

00:25:38.880 | And our schema are built during that time.

00:25:42.460 | So yeah, we can change our minds best

00:25:46.420 | during those phases of sleep.

00:25:48.420 | - Could you elaborate a little bit more on schema?

00:25:51.480 | I don't think anyone on this podcast

00:25:52.920 | has ever discussed schema.

00:25:54.420 | I'm a little bit familiar with schema

00:25:56.340 | from my courses on psychology, but it's been a while.

00:25:59.340 | So maybe if you could just refresh mine

00:26:00.840 | and everyone else's memory.

00:26:01.680 | - Well, it's still a concept.

00:26:03.860 | - Sure, but how do you define schema, right?

00:26:07.140 | I think of schema as like we have a schema of Christmas,

00:26:12.140 | right, we have all kinds of ideas that we sew together

00:26:17.740 | and call Christmas, a holiday season

00:26:20.420 | in the Northern hemisphere, it's cold.

00:26:22.620 | We have Santa Claus and reindeer and jingle bells

00:26:26.660 | and even things that are false

00:26:29.500 | but we normally associate with Christmas presents,

00:26:32.300 | family gathering, when it is, all of this stuff

00:26:35.540 | is sewn together into one, there's a thread linking them all

00:26:38.960 | and we can just give ourselves a list of words

00:26:42.020 | and none of them contain the word Christmas

00:26:45.740 | and then ask people later, give them another list of words

00:26:50.180 | and include the word Christmas and they'll say,

00:26:51.940 | "Oh yeah, that word was there."

00:26:53.740 | Because in their minds, they brought up that word Christmas

00:26:56.700 | because it's part of that whole schema.

00:26:58.740 | So that's what, it's sort of a related,

00:27:01.420 | a lot of related concepts, I guess.

00:27:04.100 | - Can I think about it sort of like on the desktop

00:27:06.260 | of my computer would scare some people

00:27:08.740 | but it's just a ton of folders.

00:27:10.660 | But each of the folder names mean something very clear

00:27:13.100 | and specific to me and inside of those folders

00:27:15.780 | are collections of things that make sense

00:27:18.000 | in terms of how they're batched.

00:27:19.180 | Is that one way to think about it?

00:27:20.020 | - Exactly, no, that's a great way to think of it

00:27:21.740 | and when you're in REM sleep in the later parts of the night

00:27:25.320 | and that transition to REM, that's when your computer

00:27:29.300 | of your brain is opening folders and comparing documents,

00:27:32.740 | seeing if there, is there anything the same,

00:27:35.020 | these two documents look very much the same

00:27:37.100 | but there's a little bit of difference

00:27:38.940 | and it can link those conceptually

00:27:41.780 | so that that's probably one of the origins of creativity

00:27:44.660 | is finding things that are related,

00:27:47.300 | maybe just linked a little bit

00:27:49.300 | and you can find that link and strengthen it

00:27:51.640 | if it makes your schema interesting and different, yeah.

00:27:56.420 | - Very interesting.

00:27:58.060 | Many people, including myself, tend to wake up

00:28:01.500 | maybe once during the middle of the night

00:28:02.900 | to use the restroom.

00:28:03.780 | I've tried to drink less fluid before going to sleep.

00:28:06.260 | I've heard also that the impulse to urinate,

00:28:11.260 | forgive the topic, but a lot of people deal with this.

00:28:13.820 | So the impulse to urinate is also dictated

00:28:15.780 | by how quickly you drink fluid, not just the total volume.

00:28:18.520 | So I've switched to sipping fluids more slowly

00:28:20.840 | for my last beverage of the day, which seems to help

00:28:23.660 | but the point here is that I think a lot of people wake up

00:28:25.900 | once in the middle of the night,

00:28:26.740 | oftentimes to use the restroom

00:28:28.160 | but oftentimes just around 3 a.m.

00:28:30.540 | and might be up for a few minutes,

00:28:32.500 | hopefully not on their phone or viewing any bright light,

00:28:34.780 | which can cause more wakefulness,

00:28:36.420 | but then go back to sleep.

00:28:38.360 | Is there any known detriment

00:28:41.060 | to this middle of the night waking

00:28:42.780 | or should we consider it a normal feature

00:28:44.820 | for some people's sleep architecture?

00:28:46.740 | - Yeah, I think we shouldn't worry about it actually.

00:28:49.300 | I think sleep is really incredibly

00:28:51.940 | well homeostatically regulated

00:28:53.900 | and so really don't worry about how much you're sleeping

00:28:57.160 | as long as you're not intentionally depriving yourself of sleep

00:29:00.120 | by doing something really rewarding and exciting

00:29:02.380 | because even that is stressful to your body

00:29:04.800 | and deprives you of a lot of things we're talking about.

00:29:07.540 | So don't worry about it.

00:29:09.260 | It's absolutely normal to wake up

00:29:12.580 | at least once in the middle of the night

00:29:13.920 | to go to the bathroom

00:29:15.260 | and as long as you can get back to sleep

00:29:17.260 | in a reasonable amount of time,

00:29:18.860 | or even if it takes you an hour,

00:29:21.700 | don't worry about it as long as you have a lifestyle

00:29:24.340 | that allows you to then make up that sleep

00:29:26.960 | either the next morning or the next night

00:29:30.020 | or going to bed a little earlier.

00:29:31.640 | - So if I understand correctly,

00:29:32.660 | there's a little bit of asymmetry to sleep

00:29:34.520 | that catching that first phase of sleep,

00:29:37.120 | it's like you either get it or you don't

00:29:38.760 | and you have to get it by going to sleep

00:29:40.480 | essentially the same time each night,

00:29:42.800 | maybe plus or minus 15 minutes or so.

00:29:45.380 | But then if I wake up in the middle of the night

00:29:47.300 | and go back to sleep, I can not catch up

00:29:49.760 | but I can gather all the sleep that I would have gotten

00:29:52.540 | had I just slept the whole way through the night.

00:29:54.160 | Is that right? - Yeah, yeah, yeah.

00:29:55.680 | And we don't know actually the answer

00:29:57.860 | to whether or not the sleep in the middle

00:29:59.760 | between that early sleep and the late sleep

00:30:02.140 | is in fact different for another reason.

00:30:04.960 | And whether depriving yourself of sleep

00:30:07.080 | from say one to 2.30 in the morning

00:30:09.240 | is bad in a different way, we don't know.

00:30:12.320 | - Well, I suppose I am the experiment in that case

00:30:14.400 | because I do tend to wake up once per night

00:30:16.280 | and I've sort of come to recognize it

00:30:19.020 | as part of my normal sleep architecture.

00:30:20.840 | I don't obsess over it.

00:30:22.040 | I do notice that when I go back to sleep

00:30:24.000 | and especially toward morning,

00:30:26.260 | that my sleep is incredibly deep.

00:30:28.240 | My dreams are incredibly vivid.

00:30:30.740 | I don't always remember them,

00:30:31.960 | but what is unique perhaps about the architecture of dreams

00:30:36.380 | and sleep in the, let's say the last third of the night

00:30:39.500 | or the second half of the night?

00:30:41.200 | - Right, yeah, in the second half of the night,

00:30:42.480 | we have longer REM sleep periods

00:30:45.000 | and those are considered the deepest sleep

00:30:48.240 | even though slow wave sleep,

00:30:50.360 | big slow wave is considered deep, it is deep.

00:30:53.200 | - Yeah, they call slow wave sleep deep sleep

00:30:55.020 | and REM sleep rapid, I mean,

00:30:56.260 | but now you're telling me that REM sleep

00:30:57.720 | is actually the deepest. - The deepest.

00:30:59.240 | - Okay, there needs to be a new nomenclature

00:31:01.160 | of sleep researchers. - Yeah, I know,

00:31:02.000 | you really shouldn't call it deep or not deep.

00:31:03.560 | - No, no, please.

00:31:04.640 | - The reason why you call slow wave sleep deep sleep

00:31:06.600 | is because it's difficult to arouse people out of that state

00:31:10.600 | and when you do arouse them out of that state,

00:31:12.880 | they're most often confused

00:31:15.000 | and just want to go back into sleep

00:31:16.600 | and can go back pretty easily.

00:31:19.040 | If you arouse someone out of REM sleep,

00:31:21.000 | they're more likely to report something

00:31:22.360 | that was really kind of almost like wakefulness.

00:31:24.640 | It was so vivid, but in fact,

00:31:27.360 | if you give someone a non-threatening kind of stimulation,

00:31:32.360 | like somebody dropping keys or a ping

00:31:37.420 | or something like that, instead of waking,

00:31:39.440 | that same volume will wake someone up out of non-REM sleep,

00:31:44.160 | but out of REM sleep and instead lengthen the amount of time

00:31:47.640 | or make it even more dense,

00:31:49.680 | your rapid eye movements more dense

00:31:51.200 | and often people will incorporate that sound

00:31:53.560 | into their dreams.

00:31:55.120 | So the body and brain are somehow conscious of the sound

00:32:00.120 | and I've heard also smells

00:32:01.680 | can even make it into our dreams in REM sleep,

00:32:05.120 | but that it doesn't arouse us from sleep.

00:32:07.480 | - It doesn't arouse us as often, yeah.

00:32:09.840 | And maybe one of the reasons why REM sleep is deeper

00:32:12.960 | is especially in adults and older people

00:32:15.360 | that deep slow wave sleep goes away.

00:32:17.440 | So it's not as deep, it's not as big,

00:32:20.280 | the slow waves aren't as large,

00:32:21.960 | which is probably problematic, but we're not sure.

00:32:24.720 | And so then REM sleep becomes the deepest stage.

00:32:28.720 | Actually in children, it's kind of a toss up

00:32:31.960 | because it's really hard to wake them up

00:32:33.980 | out of that deep slow wave sleep.

00:32:35.400 | And in fact, fire alarms don't wake them up,

00:32:39.760 | even really loud fire alarms out of that state of sleep.

00:32:43.300 | So that's why they're trying to change fire alarms

00:32:46.620 | so that instead of something

00:32:49.960 | that the kids don't associate with anything,

00:32:52.040 | like the, whatever they don't associate with,

00:32:55.120 | it says their name or something else

00:32:57.200 | that may be less loud, but more salient to them

00:33:01.920 | and will wake them up.

00:33:02.840 | - I don't know, having carried sleeping children

00:33:04.840 | in from the car, I don't know that I want children

00:33:07.000 | to start waking up from sleep

00:33:08.200 | 'cause that's one of the best things when you get home

00:33:10.120 | and the kids are asleep in the backseat,

00:33:11.760 | you can literally throw them over your shoulder,

00:33:13.920 | gently of course, and put them to sleep

00:33:16.040 | and they are completely out.

00:33:18.120 | - Yeah, it's wonderful.

00:33:19.340 | - It is wonderful.

00:33:20.440 | One of nature's gifts.

00:33:22.440 | I'd like to take a quick break

00:33:23.960 | and acknowledge one of our sponsors, Athletic Greens.

00:33:26.860 | Athletic Greens, now called AG1,

00:33:29.320 | is a vitamin mineral probiotic drink

00:33:31.680 | that covers all of your foundational nutritional needs.

00:33:34.580 | I've been taking Athletic Greens since 2012,

00:33:37.260 | so I'm delighted that they're sponsoring the podcast.

00:33:39.480 | The reason I started taking Athletic Greens

00:33:41.080 | and the reason I still take Athletic Greens

00:33:43.160 | once or usually twice a day is that it gets me

00:33:46.280 | the probiotics that I need for gut health.

00:33:48.760 | Our gut is very important, it's populated by gut microbiota

00:33:52.400 | that communicate with the brain, the immune system,

00:33:54.160 | and basically all the biological systems of our body

00:33:56.560 | to strongly impact our immediate and long-term health.

00:34:00.200 | And those probiotics in Athletic Greens are optimal

00:34:03.220 | and vital for microbiota health.

00:34:05.880 | In addition, Athletic Greens contains

00:34:07.440 | a number of adaptogens, vitamins, and minerals

00:34:09.360 | that make sure that all of my foundational

00:34:11.240 | nutritional needs are met and it tastes great.

00:34:14.680 | If you'd like to try Athletic Greens,

00:34:16.140 | you can go to athleticgreens.com/huberman

00:34:19.540 | and they'll give you five free travel packs

00:34:21.520 | that make it really easy to mix up Athletic Greens

00:34:23.840 | while you're on the road, in the car,

00:34:25.120 | on the plane, et cetera.

00:34:26.420 | And they'll give you a year's supply of vitamin D3K2.

00:34:29.820 | Again, that's athleticgreens.com/huberman

00:34:32.500 | to get the five free travel packs

00:34:33.880 | and the year's supply of vitamin D3K2.

00:34:36.860 | So this enhanced volume or proportion

00:34:41.340 | of rapid eye movement sleep in the second half of the night

00:34:44.420 | relates to more elaborate dreams.

00:34:47.160 | We are paralyzed during REM sleep, correct?

00:34:49.520 | - Yes, normally paralyzed and that's really good

00:34:52.600 | because that's the time when we're actively dreaming

00:34:55.560 | storyline dreams and we could hurt ourselves.

00:34:59.340 | We're actually really cut off from the outside world

00:35:02.920 | in terms of, you know, responding to say this table

00:35:07.560 | or a window or a door.

00:35:09.360 | And so different from sleepwalking,

00:35:12.520 | which is out of slow wave sleep, out of slow wave sleep,

00:35:14.880 | that sleepwalking is a mixture

00:35:16.620 | between sleep and wakefulness.

00:35:18.000 | So you actually will respond to the door.

00:35:19.740 | You can cook a full meal,

00:35:22.240 | drive your car while you're in deep slow wave sleep.

00:35:24.680 | It's scary because you never know what you're going to do.

00:35:27.300 | You don't have voluntary control over it.

00:35:30.180 | You have no conscious control over it,

00:35:31.880 | but you can actually safely navigate some situations

00:35:36.520 | in sleepwalking and actually have a conversation.

00:35:40.040 | Although it may not make much sense

00:35:41.680 | when you're sleep talking.

00:35:43.200 | In REM sleep, you're not processing the outside world.

00:35:47.120 | And instead, when you're acting out your dreams,

00:35:50.280 | you could be doing things like walking

00:35:52.280 | through a plate glass window or falling off of,

00:35:55.680 | you know, down the stairs, things like that.

00:35:58.240 | So you really want your muscles to be inactivated

00:36:02.620 | during REM sleep.

00:36:03.640 | Otherwise you will act out those dreams

00:36:05.660 | and really hurt yourself or your bed partner.

00:36:08.980 | - What about sleep talking?

00:36:10.700 | Or talking in sleep?

00:36:12.700 | I don't know how many relationships

00:36:14.020 | have been saved by sleep talking,

00:36:16.280 | but I'm guessing a few have been destroyed.

00:36:18.860 | And I'm guessing that talking in sleep could have meaning

00:36:22.680 | or perhaps has no meaning just as dreams

00:36:25.020 | could have meaning or no meaning, as we recall them.

00:36:27.500 | - Yeah, do not take sleep talking seriously.

00:36:30.500 | No matter what people say,

00:36:31.980 | it doesn't necessarily reflect truth.

00:36:34.020 | So it's not like you're being more truthful

00:36:36.320 | when you're sleep talking.

00:36:37.520 | - You just saved a number of relationships.

00:36:39.180 | [laughing]

00:36:41.060 | - I'm not directing this at anyone in particular,

00:36:42.860 | but I guarantee you just did, noted.

00:36:46.640 | So as people start to approach morning

00:36:50.980 | or the time when they normally would wake up,

00:36:53.180 | I've heard that it's important to, if possible,

00:36:57.780 | complete one of these 90 minute cycles prior to waking up.

00:37:01.180 | That is, if you set your alarm for halfway through

00:37:04.220 | one of these 90 minute cycles that come late

00:37:06.380 | in the night of sleep, that it can lead

00:37:09.740 | to rather groggy patterns of waking.

00:37:12.960 | So I'll just ask you directly, do you use an alarm clock?

00:37:17.540 | - I do not.

00:37:18.760 | Thankfully, I'm in a line of work

00:37:20.540 | that doesn't require me normally

00:37:21.980 | to do anything at any particular time.

00:37:24.540 | I do it when I do it, unless I have to catch a plane

00:37:27.220 | and then I always set my alarm just in case.

00:37:29.180 | - Well, as a fellow academic, I can tell you

00:37:31.200 | there are plenty of punishing features

00:37:32.560 | about being an academic scientist

00:37:34.220 | that offset the fact that you don't have

00:37:37.060 | to use an alarm clock, but it is nice

00:37:38.420 | that you can often set your own schedule.

00:37:40.620 | So would you recommend that, if possible,

00:37:42.620 | that people not use an alarm clock?

00:37:44.260 | - Yeah, absolutely.

00:37:45.700 | If you can just listen to your body

00:37:47.260 | and wake up when you need to wake up, that would be great.

00:37:50.100 | But one of the reasons why we have such a grogginess,

00:37:55.020 | it's called sleep inertia, when we wake up

00:37:56.760 | out of the wrong state, which is deep slow wave sleep,

00:38:00.460 | is because I liken it to like a washing machine

00:38:04.140 | cycle, this 90 minute cycle is like a washing machine cycle.

00:38:07.220 | And the first part is to add water, right?

00:38:10.860 | And then your clothes are soaking wet.

00:38:13.440 | You don't wanna open the washing machine

00:38:14.940 | and try and function, put them on and wear them around

00:38:18.620 | while they're soaking wet and full of soap.

00:38:20.220 | So you have to wait until the cycle is through

00:38:23.260 | before you can, well, actually, let's put it

00:38:26.580 | in the dryer too, before you wanna wear them.

00:38:30.220 | So yeah, you can function.

00:38:34.000 | It just takes a little while for those clothes,

00:38:36.700 | that brain to dry out so you can actually function well,

00:38:40.060 | but it's better to wait through the whole cycle is complete.

00:38:43.560 | And so that's why you want to set that 90 minute alarm clock.

00:38:48.560 | And again, that's around 90 minutes

00:38:51.720 | because the first stage of sleep,

00:38:54.060 | the first cycle of sleep is actually a little longer,

00:38:57.260 | more like 105, 110 minutes,

00:38:59.740 | but then the second ones and third ones,

00:39:01.500 | they get sort of shorter and shorter as the night goes on.

00:39:04.320 | And in the last few cycles,

00:39:05.940 | you're just doing the end to REM sleep cycle,

00:39:09.700 | which takes less time.

00:39:10.800 | And if you wake up out of REM sleep,

00:39:12.200 | it's usually no problem cognitively.

00:39:14.720 | You're good to go.

00:39:16.720 | - Are you a fan of sleep trackers?

00:39:19.460 | - Sure, yeah.

00:39:21.540 | - Do you use one?

00:39:22.380 | - I have one on, I don't take,

00:39:25.200 | I don't live my life by them

00:39:29.560 | because they are, the best ones right now

00:39:31.920 | are about 70% effective at staging your sleep.

00:39:35.440 | So 70%, it's okay, it's okay.

00:39:38.360 | But take it with a grain of salt is what I'm saying.

00:39:41.320 | - Yeah, I've tried various ones

00:39:42.480 | and I compare the mattress based one to,

00:39:45.000 | actually wear it on my ankle instead of my wrist.

00:39:46.800 | But, and I do find it informative,

00:39:49.000 | but a colleague of mine at Stanford, Ali Crum,

00:39:52.360 | who works on mindset and belief effects,

00:39:54.360 | talked to me about a study they did

00:39:56.480 | where people often will bias their sense

00:40:00.200 | of daytime wakefulness based on their sleep score

00:40:02.640 | more than their subjective score.

00:40:05.420 | In other words, if they were told

00:40:06.480 | they got a poor night's sleep,

00:40:07.400 | even if they got a great night's sleep,

00:40:08.880 | and this was of course measured in the sleep lab,

00:40:11.200 | so they were able to compare,

00:40:12.800 | people report feeling more groggy.

00:40:15.040 | And the opposite is also true,

00:40:16.640 | that if it says 100% or 90% on your sleep score,

00:40:19.400 | then people go, oh, I feel great,

00:40:20.360 | even though they might not have slept well.

00:40:21.920 | So this speaks to the, I don't want to say placebo effect,

00:40:24.360 | but the sort of belief effects

00:40:25.320 | that are woven in with a score.

00:40:26.960 | So it seems to me that combining subjective

00:40:30.720 | and objective data is probably best.

00:40:32.800 | - And I do believe that you should trust your own physiology

00:40:37.200 | and the way that your body is telling you to feel,

00:40:40.720 | because in fact, it used to be that people with insomnia

00:40:45.160 | were often not believed,

00:40:47.000 | because you put them in a sleep lab

00:40:49.020 | and they look like they slept great,

00:40:50.320 | and you wake them up in the morning,

00:40:51.520 | they say, oh, I didn't sleep very well at all.

00:40:53.640 | And that's because probably we just came out with a paper

00:40:56.720 | that shows that subcortical structures

00:40:59.640 | can be in a completely different sleep state

00:41:01.760 | than cortical structures,

00:41:02.880 | which is what we measure in the sleep lab,

00:41:05.640 | what the cortex is doing.

00:41:07.480 | So it might be that people who say,

00:41:09.520 | I did not sleep all night long,

00:41:11.200 | even though the cortex is saying,

00:41:12.760 | oh no, you had great sleep,

00:41:14.600 | was because they're monitoring their subcortical,

00:41:19.080 | hypothalamus, hippocampus, thalamus.

00:41:22.480 | Other structures that the sleep lab just can't access

00:41:27.400 | unless you have depth electrodes,

00:41:29.080 | which nobody really wants.

00:41:30.600 | - Right, because that requires holes in the skull and wires.

00:41:34.400 | Wow, so does that mean that the last 50 plus years

00:41:37.160 | of sleep science, it's potentially flawed in some way

00:41:41.520 | because they're only recording from,

00:41:43.580 | I guess this would be the analogy would be,

00:41:45.120 | it's like recording from the surface of the ocean

00:41:48.320 | as opposed to the depth of the ocean.

00:41:50.160 | - Right, and trying to ascertain the life moving down deep

00:41:54.280 | and the depth of the ocean.

00:41:55.120 | - Brace yourselves colleagues

00:41:56.760 | at Stanford Sleep Lab and elsewhere,

00:41:58.600 | but please just tell us,

00:41:59.560 | 'cause I think scientists want to know the truth.

00:42:02.160 | - Yeah, I mean, it's not for nothing

00:42:04.000 | that you want to know what the cortex is doing.

00:42:06.520 | I mean, the cortex is really important for a lot of things,

00:42:09.160 | but it doesn't necessarily tell you

00:42:11.060 | what a lot of other really important parts of the brain

00:42:13.800 | are doing in terms of sleep.

00:42:16.040 | And, but there's hope because in fact, it would be great.

00:42:21.040 | I think that's possible from the paper.

00:42:23.760 | If you look at it, it's in PNAS this year,

00:42:26.600 | that you could detect subtle changes in the cortical EEG

00:42:31.600 | that might be able to tell you

00:42:33.360 | what the subcortical structures are doing.

00:42:36.040 | Things like the absolute power in that sleep spindle band,

00:42:40.420 | that sigma band would change if the hippocampus

00:42:45.040 | is in REM sleep and cortex is in that sleep spindle state

00:42:48.320 | and vice versa.

00:42:49.920 | So there is some hope that we can gain

00:42:53.780 | from people with depth electrodes

00:42:55.920 | or animals with depth electrodes

00:42:58.200 | that we could backwards machine learn

00:43:01.700 | what the cortex might be able to tell us

00:43:04.860 | about subcortical structures from the cortical EEG, so.

00:43:08.560 | - Interesting, this is going to be a stimulant.

00:43:10.640 | Yeah, stay tuned.

00:43:11.640 | This is going to be a stimulus

00:43:12.600 | for development of new technology,

00:43:14.120 | which is always going to assist in scientific discovery.

00:43:18.100 | There's one more thing I wanted to ask about

00:43:22.000 | the architecture of the night's sleep

00:43:24.420 | in terms of early part of the night.

00:43:26.420 | Earlier, you mentioned the washout of debris

00:43:30.120 | and the so-called glymphatic system,

00:43:32.680 | I think is what you're referring to.

00:43:33.840 | Could you tell us a little bit more about the washout

00:43:36.240 | that occurs in the brain during sleep,

00:43:37.920 | what that is and what roles it's thought to serve,

00:43:41.840 | and perhaps if there are any ways to ensure

00:43:44.080 | that it happens or to ensure that it doesn't happen,

00:43:46.760 | and obviously we want this to happen.

00:43:48.280 | - Yeah, yeah.

00:43:49.120 | All right, great question.

00:43:52.000 | We talked about the circadian clock

00:43:53.800 | and how certain things happen at certain times.

00:43:56.200 | Well, one of the things that happens when we're awake

00:43:58.420 | and talking to each other is that

00:44:01.320 | there's a lot of plasticity.

00:44:03.000 | There's something that I'm learning from you today

00:44:05.320 | and you're learning from me, and that changes our synapses

00:44:09.060 | and it changes the way our proteins are going to be folded

00:44:13.200 | and changed during sleep.

00:44:15.480 | It unfolds.

00:44:17.340 | This process actually uses a lot of ATP,

00:44:19.920 | the power structure, the fuel of the brain,

00:44:23.980 | and it unfolds also proteins while we're doing this,

00:44:28.060 | while we're using them.

00:44:29.660 | And so during that first part of the night,

00:44:32.380 | when we first fall asleep in the first 20 minutes or so,

00:44:35.480 | we're building that adenosine back into ATP,

00:44:39.600 | and that's probably why power knobs are called power knobs

00:44:42.920 | because we're actually rebuilding the power.

00:44:46.000 | And then we're also cleaning out

00:44:50.160 | through the deep slow waves of slow wave sleep,

00:44:52.120 | we're cleaning out all those misfolded proteins,

00:44:54.840 | unfolded proteins, and other things that get broken down

00:44:59.440 | and need to be rebuilt when we're asleep

00:45:04.440 | because of its use during wakefulness.

00:45:07.720 | So I liken that to having a big party during wakefulness

00:45:11.740 | and you need all those party goers to leave

00:45:13.840 | in order to do the cleanup.

00:45:15.160 | And so what I think the mechanism is,

00:45:17.400 | and this is still something to be tested,

00:45:19.100 | is actually slow waves themselves,

00:45:21.520 | which is bad news for us as we get older

00:45:23.540 | and those slow waves get smaller

00:45:25.460 | and slow asleep goes away.

00:45:27.680 | So what happens when a neuron is firing

00:45:33.160 | is that it expands, the membrane expands a little bit,

00:45:36.000 | it becomes more translucent.

00:45:37.400 | That's how we know, one of the ways we know

00:45:39.200 | that neurons expand when they fire.

00:45:41.740 | And so every action potential,

00:45:43.540 | the membrane expands a little bit

00:45:45.420 | as sodium brings water into their cell.

00:45:48.420 | And then when they're silent, they contract.

00:45:51.340 | And so during slow waves, the cool thing is that

00:45:54.420 | the reason why you can measure them

00:45:56.020 | is that all the neurons at the same time,

00:45:58.340 | not all of them, but a good portion of them,

00:46:00.860 | are firing at the same time and silent at the same time.

00:46:03.600 | And so you think about that as contracting

00:46:06.380 | and expanding all at the same time,

00:46:08.740 | it's kind of like a bilge pump of the brain.

00:46:10.900 | So that can pump out,

00:46:12.460 | glia are also really important for this

00:46:15.560 | in terms of cleaning up debris

00:46:18.320 | and transferring it to where it needs to go.

00:46:20.800 | So I think of it actually as a bilge pump,

00:46:24.540 | cleaning out our brain.

00:46:27.100 | - Interesting, I've heard about the glymphatic system

00:46:29.060 | and the glymphatic washout.

00:46:30.260 | I've never thought about the mechanical aspects of it before.

00:46:33.340 | I always thought that for some reason,

00:46:35.920 | that now it's obvious to me

00:46:37.140 | there had to be something mechanical,

00:46:39.380 | but only now that you've educated me about this.

00:46:42.020 | I thought that for some reason,

00:46:43.060 | the cerebral spinal fluid just starts washing through,

00:46:46.060 | but here you're talking about literally an expansion

00:46:48.660 | and a contraction of the neurons in unison

00:46:51.220 | and pushing the fluid through,

00:46:53.620 | cleaning out any misfolded proteins

00:46:55.540 | or debris that might occur

00:46:57.580 | on the basis of these metabolic pathways.

00:47:00.060 | And the consequence of that is to what?

00:47:02.980 | To leave the brain in a state of

00:47:04.900 | more pristine action for the next day, is that right?

00:47:09.900 | - Yeah, you think of it again like a party.

00:47:12.940 | And if you don't clean up after that party

00:47:14.860 | and you try and hold another one the next day,

00:47:16.940 | it's going to get more clogged.

00:47:19.320 | People have a harder time moving around

00:47:21.140 | and enjoying themselves.

00:47:22.780 | And if that builds up day after day,

00:47:25.740 | it's going to be cognition

00:47:27.380 | that would be the party goers moving around becomes hard.

00:47:33.780 | - And so this bilge pump that you described

00:47:36.260 | is associated with the big slow waves of deep,

00:47:40.880 | well, of slow wave sleep.

00:47:43.300 | So this is going to occur more or less

00:47:44.640 | in the first third of the night, is that right?

00:47:46.740 | - That's right.

00:47:47.660 | - And are there things that inhibit this process

00:47:51.060 | and are there things that facilitate this process?

00:47:53.940 | - Yeah, so, well, one thing to inhibit is not to get it.

00:47:58.940 | But--

00:48:00.660 | - Right, and here too, sorry to interrupt,

00:48:02.780 | but, and is this similar to the case with growth hormone

00:48:06.020 | where if you go to sleep later than you would normally,

00:48:09.140 | you miss the washout.

00:48:10.380 | - You just miss it, yeah.

00:48:11.220 | - It's not, you don't delay it, you miss the washout.

00:48:14.140 | - That's right, that's right.

00:48:15.140 | So if you go to sleep at one or two in the morning,

00:48:18.240 | your sleep is still going to be dominated

00:48:19.860 | by N2 and REM sleep, not by slow wave sleep.

00:48:23.260 | So you need to get that first bit of sleep.

00:48:27.140 | - Would a caveat be if somebody normally goes to sleep

00:48:30.300 | at one or two a.m. and wakes up at 10 a.m.

00:48:33.580 | If that's their normal sleep cycle.

00:48:35.300 | - Yeah, that should be okay.

00:48:37.860 | It should be okay.

00:48:39.260 | You would probably want to do,

00:48:42.340 | somebody would want to do a sleep study

00:48:44.200 | with people who do that normally

00:48:45.700 | and see if also the melatonin release is later

00:48:48.500 | and the corticosterone rise that happens normally

00:48:51.940 | in the morning also happens later.

00:48:54.180 | So if everything shifted, good.

00:48:57.060 | - Okay, yeah, there are a few studies I've come across

00:49:00.900 | that really do argue for the fact

00:49:03.400 | that waking up circa sunrise, that doesn't mean at sunrise,

00:49:07.760 | but within an hour or two, maybe three hours of sunrise

00:49:10.500 | and going to sleep within four hours after sunset or so

00:49:15.500 | is actually better for the health of all human beings

00:49:20.860 | than is being a night owl.

00:49:21.960 | And the night owl, there's almost like a night owl posse

00:49:25.020 | out there, especially on social media.

00:49:26.720 | They get very upset when you say

00:49:28.720 | that you should see morning sunlight,

00:49:30.420 | that after 10 a.m. you kind of miss the boat.

00:49:33.640 | They get very upset because I think there are about 20

00:49:36.940 | or 30% of people perhaps who really feel

00:49:40.080 | like they function better staying up late

00:49:41.980 | and waking up late and they function much less well

00:49:44.900 | waking up early and going to bed early.

00:49:46.700 | But the data on health metrics suggests

00:49:49.640 | that sorry night owls, that they are wrong.

00:49:52.480 | - Yeah, sorry me 'cause I'm a night owl.

00:49:54.380 | - Oh boy, okay.

00:49:55.260 | - Well then I'm apologizing directly.

00:49:56.720 | And here, I'm not a really early morning person.

00:49:59.160 | I'm kind of more typical.

00:50:00.160 | If I wake up naturally around 6.30,

00:50:02.680 | somewhere between 6.30 and 7.30 a.m.,

00:50:04.600 | go to sleep somewhere between 10 and 11 p.m.

00:50:09.500 | These are averages.

00:50:10.580 | But I do notice that when I force myself

00:50:13.680 | to get up a little earlier and go to sleep a little earlier,

00:50:18.200 | that my mood and alertness and just overall productivity

00:50:22.200 | is much higher.

00:50:23.360 | And there could be other variables there too.

00:50:24.600 | - Yeah, you're absolutely right.

00:50:25.520 | I'm a night owl.

00:50:26.620 | I love staying up late at night,

00:50:28.300 | doing, you know, writing grants, writing papers,

00:50:31.180 | watching movies, whatever it is, I love it.

00:50:34.140 | But I like you and like every human being on earth,

00:50:38.560 | do better if I go to bed earlier and wake up earlier.

00:50:42.120 | So one good thing for night owls is to have a child.

00:50:45.840 | Because they will wake you up.

00:50:47.760 | Their circadian rhythms are so strong.

00:50:50.760 | They will wake up.

00:50:51.600 | And even if you deprive them of sleep

00:50:53.200 | in the first half of the night,

00:50:54.960 | they will still wake up like clockwork

00:50:57.040 | because their circadian rhythms are so strong at 6 a.m.

00:50:59.960 | And so what you've,

00:51:00.960 | you haven't done anything good for your kid.

00:51:03.280 | You haven't moved their cycle to later

00:51:05.160 | and be more in line with yours.

00:51:06.700 | In fact, you've just sleep deprived them

00:51:08.440 | and made them miss a window

00:51:09.520 | and made them cranky the next day

00:51:11.000 | and made your life more miserable.

00:51:12.440 | So go to bed soon after your kids go to bed

00:51:15.660 | and wake up with them.

00:51:16.520 | That's the way to do it.

00:51:17.640 | - Great, the child alarm clock.

00:51:18.960 | Another reason to have children.

00:51:20.320 | - Yes.

00:51:21.280 | - I got a dog, a puppy, and then that became a dog

00:51:24.720 | specifically, well, for many reasons.

00:51:27.640 | But one reason was I wanted to be one of those

00:51:29.120 | early morning, 5.30 a.m. every morning.

00:51:32.240 | But I ended up getting a bulldog

00:51:33.680 | that would literally sleep 16 hours if he could.

00:51:36.880 | A nuclear bomb could go off and he wouldn't wake up.

00:51:40.080 | But what I started to learn was that

00:51:42.000 | bulldogs actually have sleep apnea.

00:51:44.200 | As far as I know, they're the only species

00:51:46.720 | that has a genetically,

00:51:49.640 | they're essentially an inbred sleep defect.

00:51:52.480 | And so I actually don't encourage people to get bulldogs

00:51:54.880 | because it's kind of a cruel breed.

00:51:56.380 | They suffer a lot in that body that they're born into.

00:51:58.880 | Anyway, a dog can accomplish some of this,

00:52:02.020 | but get the breed of dog that is going to wake up early.

00:52:06.320 | So in other words, don't get a bulldog or a mastiff.

00:52:08.280 | - Well, interestingly, all predatory animals

00:52:12.920 | like dogs and cats and lions and us,

00:52:16.600 | well, more dogs, cats, and lions than us

00:52:19.600 | will can sleep, you know, 16 hours a day.

00:52:23.120 | Ferrets are predatory.

00:52:24.560 | They can sleep. - I had a pet ferret.

00:52:26.520 | And sadly, I also used to work on ferrets,

00:52:28.920 | publish a number of papers, delightful animals.

00:52:31.280 | - Yeah, and great because you can study development.

00:52:34.400 | It's really cool because they're born very altricial

00:52:37.840 | like we are with brains that are not very well developed.

00:52:40.760 | And so you can see what happens through development

00:52:43.640 | and how important these different phases of development

00:52:46.640 | really are.

00:52:47.800 | But yes, yeah, maybe we're not as much predators as we think

00:52:52.800 | because in fact, our sleep is somewhere between the prey

00:52:57.720 | and the predators in terms of the amount of sleep

00:53:00.820 | that we usually need at night.

00:53:02.800 | But those predators can sleep 16 hours napping all day long

00:53:07.160 | and they're more crepuscular perhaps like their prey are.

00:53:10.920 | - So dawn and dusk active?

00:53:12.760 | - Yeah, dawn and dusk active.

00:53:14.620 | Yeah, but anyway, yes, children and dogs.

00:53:20.080 | Actually, there was a poll done

00:53:21.960 | by the National Sleep Foundation

00:53:23.920 | to see what the number one thing is

00:53:25.360 | that wakes people up at night.

00:53:26.800 | And number two is going to the bathroom.

00:53:29.640 | Number three is children because, you know,

00:53:32.820 | when your children are young,

00:53:33.660 | but that only lasts a few years

00:53:35.080 | that they'll wake you up when they're babies.

00:53:38.160 | But the number one thing is pets

00:53:40.120 | and pets needing to go out or cats wanting to curl up

00:53:44.000 | with you or whatever it is,

00:53:45.980 | pets needs will wake you up more in the middle of the night

00:53:48.220 | than anything else.

00:53:49.440 | - Another reason to not get a nocturnal pet.

00:53:52.360 | People who get hamsters pretty quickly realize

00:53:54.920 | that they are nocturnal

00:53:56.000 | and they want to run on their wheel and around.

00:53:57.440 | - Yeah, you got to put them in the living room

00:53:58.680 | away from where you sleep.

00:54:00.040 | - I vote fish tank, folks.

00:54:02.320 | Freshwater fish tank.

00:54:03.520 | There are all sorts of reasons to not get a saltwater tank.

00:54:05.240 | Freshwater fish tank or a child.

00:54:09.760 | - I appreciate that vote.

00:54:10.820 | And I appreciate you mentioning ferrets.

00:54:12.380 | And by the way, folks, they are carnivores.

00:54:14.100 | They are not rodents.

00:54:15.060 | And they have very elaborate brain structures.

00:54:18.560 | They're very smart.

00:54:19.780 | In the same family as the honey badgers

00:54:22.680 | and the other mustelids.

00:54:23.800 | Anyway, I shouldn't geek out too much on the mustelids

00:54:27.160 | or else I'll take the remainder of all our time.

00:54:29.600 | I'd love for you to tell us about REM sleep

00:54:34.200 | and the sleep later in the night

00:54:35.780 | as it relates to dreams and emotionality.

00:54:38.240 | And this is probably the appropriate time

00:54:40.740 | for you to introduce us to this incredible structure

00:54:43.380 | in the brain, which is the locus coeruleus.

00:54:46.640 | A difficult structure to spell,

00:54:49.220 | but a beautifully named structure.

00:54:52.280 | I find locus coeruleus to be just fascinating.

00:54:56.200 | And I know a small fraction of what it does

00:54:59.520 | and I'm hoping you're going to educate me and our audience

00:55:02.220 | about more about what it does.

00:55:04.120 | And hopefully tell us a little bit about its relationship

00:55:06.400 | to epinephrine, AKA adrenaline.

00:55:09.280 | - Yeah, I'm so glad you brought this up

00:55:11.880 | because I can totally geek out on the locus coeruleus.

00:55:14.480 | - Please do.

00:55:15.320 | - Locus meaning spot or place and coeruleus meaning blue.

00:55:18.560 | So you could just call it the blue spot.

00:55:20.640 | That's the easiest.

00:55:21.460 | Every animal with a brain has a blue spot.

00:55:25.280 | And yeah, and I mean every other animal with a brain

00:55:29.340 | because of course there are animals with nervous systems

00:55:32.980 | that are not centralized like jellyfish.

00:55:36.100 | But anyway, we're digressing there.

00:55:39.140 | So the locus coeruleus is filled with neurons

00:55:41.820 | that have in them norepinephrine,

00:55:43.660 | which is the brain's version of epinephrine or adrenaline.

00:55:47.260 | It's also called noradrenaline.

00:55:49.100 | And what it does is it,

00:55:50.860 | just like adrenaline in the rest of our bodies,

00:55:52.680 | it helps prime us to respond to our environment.

00:55:56.680 | So when locus coeruleus neurons fire and fire in a burst,

00:56:01.520 | we can switch our attention and they will fire in a burst

00:56:04.800 | if, for example, a loud noise happens

00:56:07.280 | in the middle of your concentrating on something.

00:56:09.400 | So you can, it helps, it fires,

00:56:11.560 | and it helps you switch your attention to that thing

00:56:13.880 | and then learn quickly from it.

00:56:15.560 | So it's really important in a stress response.

00:56:18.080 | It helps us do quick one-trial learning.

00:56:21.320 | And then a tonic activity during the day

00:56:24.600 | when you're just doing normal,

00:56:27.200 | going about your normal concentration kind of activities

00:56:31.200 | is really good for sustained attention.

00:56:34.880 | It works with the cholinergic system of our basal forebrain,

00:56:39.200 | which is really important for learning and memory also

00:56:41.640 | to help us learn about things and put things together.

00:56:46.220 | But just tonic levels are signature

00:56:50.160 | of wakefulness and alertness.

00:56:52.320 | So too much is panic with a locus coeruleus activity.

00:56:56.440 | A burst is switching attention,

00:56:59.120 | and then tonic levels are sustained constant attention.

00:57:03.200 | And then when we go to sleep, the locus coeruleus slows

00:57:06.440 | and goes from about, on average, two hertz

00:57:10.400 | to about one hertz, one cycle per second tonically.

00:57:15.400 | And then when we go into REM sleep,

00:57:17.000 | it's the only time when it shuts off completely.

00:57:19.360 | And it appears that that complete silence

00:57:23.180 | is really, really important for a number of things.

00:57:26.240 | And the main thing that I think it's important for

00:57:29.420 | is the ability to erase and break down synapses

00:57:33.880 | that are no longer working for us.

00:57:35.320 | So they encode things that are false now,

00:57:38.400 | or they are encoding things that we learned

00:57:42.440 | in the novelty encoding pathway of our brain

00:57:46.760 | that have now been consolidated to other pathways.

00:57:49.520 | And so we need to now erase them

00:57:51.000 | from the novelty encoding pathway.

00:57:52.640 | And that is really, really important

00:57:54.680 | for being able to continue to learn things all of our lives.

00:57:59.000 | So like erasing that REM, or that,

00:58:02.200 | I don't know, what do you call those disks

00:58:03.840 | that you stick into computers?

00:58:05.880 | - Hard drive, no, thumb drives.

00:58:07.880 | - Thumb drives, yeah, erasing your thumb drives.

00:58:10.240 | That thumb drive is what you carry around all day long.

00:58:13.200 | And then during sleep, you write that thumb drive

00:58:16.080 | to the cortex, to the long-term memory structures,

00:58:18.560 | and you need to refresh that thumb drive.

00:58:20.800 | And that's what happens during REM sleep

00:58:22.860 | when the locus coeruleus is off,

00:58:24.040 | because whenever it's on and neuroadrenaline is there,

00:58:26.800 | it helps us to put things together.

00:58:28.880 | It helps us to learn and strengthen synapses,

00:58:31.040 | but it does not allow us to actually weaken synapses

00:58:34.620 | that are also a really important part

00:58:36.520 | for life, a important part of lifelong learning.

00:58:39.340 | Yeah, there's so much more I could say about that.

00:58:43.000 | - Yeah, locus coeruleus sounds fascinating.

00:58:45.240 | So it's connected to the basal forebrain cholinergic system.

00:58:48.280 | The neurons in locus coeruleus, if I'm not mistaken,

00:58:52.840 | release norepinephrine, perhaps epinephrine as well?

00:58:57.840 | - Well, no, the brain's version of epinephrine

00:59:01.280 | is norepinephrine.

00:59:02.600 | The other thing it also,

00:59:04.760 | the precursor to norepinephrine is dopamine.

00:59:07.560 | And so the source of dopamine in the hippocampus

00:59:11.160 | seems to be the locus coeruleus,

00:59:12.560 | and it's still a mystery as under what conditions

00:59:15.600 | the locus coeruleus also releases dopamine,

00:59:17.880 | but it's really important when we're learning something new

00:59:21.200 | to also release dopamine or to at least activate

00:59:23.960 | the dopaminergic receptors in our hippocampus.

00:59:26.640 | So yeah, so dopamine, norepinephrine,

00:59:29.880 | and then there's also galanin,

00:59:33.320 | which is important for releasing when we're stressed,

00:59:36.680 | and it helps also without rapid learning.

00:59:40.160 | It works in concert with norepinephrine

00:59:42.400 | and in doing what it needs to do to strengthen synapses

00:59:45.360 | so that we learn really quickly.

00:59:47.560 | - I love that there are multiple molecules involved

00:59:52.120 | because that signals us to a principle,

00:59:54.680 | which is that even if people can't remember all the names,

00:59:59.020 | that rarely in biology is something handled

01:00:02.440 | by just one molecule or pathway,

01:00:04.040 | that redundancy is the rule

01:00:06.160 | because signaling attention to specific events

01:00:10.280 | is so important.

01:00:11.320 | So I'm going to use that as a just so story.

01:00:14.080 | I always say, I wasn't consulted at the design phase,

01:00:17.120 | but it makes sense to me as to why redundancy

01:00:19.120 | would exist in the system.

01:00:19.960 | - Absolutely.

01:00:20.800 | And in fact, when we form hypotheses about the brain,

01:00:23.600 | we're always wrong.

01:00:25.860 | And the reason why we're always wrong

01:00:27.240 | is because it's more complicated than we'd like to think.

01:00:30.080 | And because in our brains, when we're forming hypotheses,

01:00:32.720 | it's we fail to account for all of the factors

01:00:35.900 | that are involved, the glia, the neuropeptides,

01:00:38.920 | the neurotransmitters, the physical structure of synapses.

01:00:42.960 | And so when I was going through grad school 35 years ago,

01:00:47.600 | we, the dogma was that every neuron

01:00:50.640 | contains one neurotransmitter

01:00:51.960 | and releases one neurotransmitter.

01:00:53.320 | And you had excitatory neurotransmitters

01:00:55.160 | and inhibitory neurotransmitters

01:00:56.640 | and neuromodulatory neurotransmitters,

01:00:58.640 | but that's as complicated as it's got.

01:01:00.440 | And then we started talking about neuropeptides

01:01:03.060 | and people said, oh no, please don't complicate it.

01:01:06.040 | And then we started talking about how neurons

01:01:07.920 | contain both neuropeptides and neurotransmitters

01:01:10.200 | and maybe more than one neurotransmitter.

01:01:11.480 | - And maybe even hormones too.

01:01:12.720 | - Hormones and oh Lord, it's just so complicated,

01:01:16.320 | but I gotta admit that's why it works, right?

01:01:19.080 | And every time the brain teaches us something new

01:01:21.240 | about itself that we didn't hypothesize,

01:01:23.400 | we say, oh, of course that wouldn't work

01:01:25.840 | if the way I hypothesized it with it.

01:01:28.320 | We actually need redundancy.

01:01:29.720 | We need all of these systems to work together.

01:01:32.380 | - Yeah, it's daunting sometimes,

01:01:35.120 | but it also ensures many careers in science

01:01:38.120 | and neuroscience in particular.

01:01:39.800 | So note that aspiring scientists,

01:01:43.600 | there's plenty of room for discovery.

01:01:46.280 | - Do you want me to talk about norepinephrine

01:01:48.280 | and emotion and stress?

01:01:49.760 | - Yes, well, what I'd love for you to tell us about

01:01:52.920 | is what role this lack of norepinephrine release

01:01:57.680 | during rapid eye movement sleep is thought to achieve.

01:02:02.040 | And maybe you could also review some of your work

01:02:05.160 | describing conditions under which norepinephrine invades.

01:02:08.920 | - Yeah, invades sleep.

01:02:10.200 | - Rapid eye movement sleep and other patterns of sleep

01:02:12.720 | and how that can be detrimental.

01:02:14.040 | - Yeah, so a lot of this is hypothetical,

01:02:16.520 | but based on a lot of good evidence

01:02:18.360 | that we're sewing together into a schema

01:02:20.640 | from which these hypotheses come,

01:02:22.200 | so a model schema from which the hypotheses come.

01:02:25.580 | But one thing that happens to people

01:02:27.680 | with post-traumatic stress disorder

01:02:30.060 | is that there is a lot of evidence

01:02:32.400 | that the locus surrealis doesn't stop firing in REM sleep.

01:02:36.060 | So whereas their levels of norepinephrine

01:02:39.580 | might be similar to people without PTSD during the day

01:02:44.180 | and even during the first part of the night,

01:02:46.960 | during the wee hours of the morning

01:02:48.940 | and when you measure norepinephrine levels

01:02:51.140 | from metabolites in the blood or the cerebral spinal fluid,

01:02:55.460 | you see that people with PTSD,

01:02:57.380 | it's during the wee hours of the morning

01:02:59.020 | when you have the most REM sleep

01:03:00.180 | that their norepinephrine levels differentiate most

01:03:03.700 | from those that don't have PTSD.

01:03:06.180 | And so that's evidence that the locus surrealis

01:03:08.560 | is not shutting down during REM sleep like it should.

01:03:11.740 | Other evidence is heart rate variability.

01:03:13.940 | When our locus surrealis is firing,

01:03:16.360 | our heart rates are generally a little higher

01:03:19.600 | and they don't vary as much as they do

01:03:22.140 | when the locus surrealis is not firing.

01:03:25.220 | So during slow wave sleep,

01:03:26.580 | normally we have this big juicy variability in heart rate

01:03:29.380 | with every breath in and breath out

01:03:31.220 | because our noradrenergic levels, our norepinephrine levels

01:03:34.500 | are lower during REM sleep that goes away entirely

01:03:37.520 | and our heart rate is dominated by parasympathetic

01:03:41.540 | rather than sympathetic activity

01:03:46.980 | and also what our brain is driving,

01:03:49.060 | what we're dreaming about.

01:03:50.260 | For example, if we're dreaming,

01:03:51.380 | we're running, our heart rates will go up.

01:03:53.300 | But norepinephrine levels still should be low or off.

01:03:57.660 | So people with PTSD that noradrenergics,

01:04:01.580 | we're studying these in rats too,

01:04:03.420 | is it true that our locus surrealis doesn't shut off

01:04:06.960 | when we have post-traumatic stress disorder

01:04:09.320 | and the preliminary evidence is yes,

01:04:11.420 | it's true that it doesn't shut off.

01:04:13.380 | So what that would do is norepinephrine would act

01:04:17.340 | at synapses to prevent that weakening that you really need,

01:04:21.380 | for example, of novelty encoding structures.

01:04:23.860 | And it keeps memories in that novelty encoding structure

01:04:27.900 | even once it's consolidated to the rest of the brain.

01:04:30.980 | So in the hippocampus, which is important

01:04:33.180 | for remembering things throughout our lives

01:04:36.400 | and it's that thumb drive,

01:04:38.720 | we need it to be erased so that we can learn new things

01:04:44.820 | once it's been consolidated to the hard drive of our cortex.

01:04:50.100 | And so if we're not able to do that,

01:04:52.820 | we fill up that REM really quickly

01:04:56.180 | or that thumb drive really quickly

01:04:57.620 | and we're not able to learn new things.

01:04:59.820 | So for example, after a trauma,

01:05:01.940 | I talked to all the locus surrealists

01:05:03.260 | responding in stressful situations.

01:05:05.300 | That's great, it's very adaptive,

01:05:07.100 | but then you need it to stop.

01:05:08.420 | Once you've learned what you need to learn from it

01:05:10.700 | and you wanna go to sleep,

01:05:11.820 | you need the locus surrealist to calm down

01:05:13.860 | and during REM sleep, you want it to stop

01:05:15.660 | because then when you've consolidated

01:05:17.940 | that traumatic memory to the cortex,

01:05:19.460 | you need to erase it from the novelty encoding structures.

01:05:22.420 | For example, in the hippocampus.

01:05:24.020 | So that then when you're in the context of safety,

01:05:26.600 | you can learn those new things, those new contexts

01:05:30.100 | and stop responding to those same stimuli

01:05:35.100 | as though you're in that original situation.

01:05:38.220 | So if you're not able to erase that thumb drive,

01:05:41.760 | you will always feel like that trauma happened

01:05:45.300 | that same day, like earlier that same day

01:05:48.340 | and respond as you would to an early, a recent trauma,

01:05:53.340 | which is with beating heart and all of that.

01:05:56.660 | So even memories that are years past,

01:06:00.960 | if you're never able to downscale that novelty

01:06:04.180 | encoding structure and you purge it

01:06:06.100 | from that traumatic memory, it will stay fresh and new

01:06:10.380 | and then become maladaptive.

01:06:13.480 | - I'd like to just take a brief moment

01:06:15.060 | and thank one of our podcast sponsors,

01:06:16.880 | which is InsideTracker.

01:06:18.120 | InsideTracker is a personalized nutrition platform

01:06:20.800 | that analyzes data from your blood and DNA

01:06:23.380 | to help you better understand your body

01:06:24.940 | and help you reach your health goals.

01:06:26.820 | I've long been a believer in getting regular blood work done

01:06:29.100 | for the simple reason that blood work is the only way

01:06:32.080 | that you can monitor the markers, such as hormone markers,

01:06:34.420 | lipids, metabolic factors, et cetera,

01:06:36.560 | that impact your immediate and long-term health.

01:06:39.280 | One major challenge with blood work, however,

01:06:41.400 | is that most of the time it does not come back

01:06:44.000 | with any information about what to do

01:06:45.620 | in order to move the values for hormones,

01:06:47.860 | metabolic factors, lipids, et cetera,

01:06:49.740 | into the ranges that you want.

01:06:51.160 | With InsideTracker, changing those values

01:06:53.620 | becomes very straightforward

01:06:54.780 | because it has a personalized dashboard that you can use

01:06:57.720 | to address the nutrition-based, behavior-based,

01:07:00.760 | supplement-based approaches that you can use

01:07:03.500 | in order to move those values into the ranges

01:07:05.640 | that are optimal for you, your vitality,

01:07:07.540 | and your longevity.

01:07:08.660 | InsideTracker now includes a measurement

01:07:10.400 | of apolipoprotein B, so-called ApoB in their ultimate plan.

01:07:14.060 | ApoB is a key marker of cardiovascular health,

01:07:16.720 | and therefore there's extreme value

01:07:18.460 | to knowing your ApoB levels.

01:07:20.480 | If you'd like to try InsideTracker,

01:07:21.880 | you can go to insidetracker.com/huberman

01:07:24.600 | to get 20% off any of InsideTracker's plans.

01:07:26.920 | Again, that's insidetracker.com/huberman to get 20% off.

01:07:31.560 | - What approaches are you aware of

01:07:33.920 | that can turn down the output of locus coeruleus

01:07:38.200 | during these phases of sleep?

01:07:40.520 | And for that matter, what things can cause ramping up

01:07:44.180 | of locus coeruleus during this phase of sleep?

01:07:46.480 | We've had a couple of podcast episodes, solo episodes,

01:07:50.500 | and with guests talking about trauma.

01:07:52.060 | We had Dr. Paul Conte, who's a Stanford-trained,

01:07:54.500 | Harvard-trained psychiatrist who talked a lot about trauma,

01:07:57.540 | wrote an excellent book on trauma.

01:07:58.900 | And certainly sleep was emphasized as a key thing,

01:08:03.580 | like get enough sleep.

01:08:04.480 | But here you're saying even if somebody with trauma

01:08:06.220 | gets enough sleep,

01:08:07.340 | if locus coeruleus is hyperactive during sleep,

01:08:10.420 | those traumas are going to persist.

01:08:11.580 | And most of the trauma treatments that I'm aware of

01:08:13.640 | are everything ranging from cognitive behavioral therapy,

01:08:16.940 | talk therapy, drug therapy, EMDR, hypnosis.

01:08:19.740 | Nowadays, there's a lot of interest and attention

01:08:22.860 | on clinical studies on exploring psychedelics,

01:08:26.880 | high-dose psilocybin, and MDMA.

01:08:29.180 | So it's a vast landscape, none of which, as far as I know,

01:08:32.580 | is really focused on sleep specifically.

01:08:34.740 | - No, they're not.

01:08:35.580 | And they should be,

01:08:36.860 | because actually psychedelics is a sleep-like state,

01:08:40.460 | and it's a REM sleep-like state.

01:08:42.540 | Although, of course, there are some major differences.

01:08:45.140 | So yeah, so much to talk about here.

01:08:49.100 | So antidepressants are often

01:08:52.620 | neurodenergic or serotonergic reuptake inhibitors.

01:08:55.740 | So they leave norepinephrine, actually,

01:08:58.200 | out there in the synapses.

01:08:59.580 | And what that does is it inhibits REM sleep.

01:09:03.200 | And if you're able to get REM sleep,

01:09:04.900 | it would probably be REM sleep with some

01:09:07.020 | neurodenergic activity.

01:09:08.100 | So actually, I think, anyway, I'm not a physician,

01:09:11.360 | that antidepressants are counter-indicated.

01:09:14.580 | You don't want to take them if you've experienced a trauma

01:09:18.100 | and you're experiencing PTSD, because if anything,

01:09:21.040 | it's going to make it worse or at least prevent

01:09:23.260 | the type of adaptive REM sleep that you really need

01:09:26.020 | in order to resolve those emotions and move on.

01:09:29.480 | - Is that statement specific to antidepressants

01:09:32.840 | that tickle the noradrenergic pathway?

01:09:35.160 | So the one that comes to mind is brupipryon,

01:09:39.760 | which is, I think the brand name is Wellbutrin.

01:09:42.820 | It's a dopaminergic and noradrenergic agonist.

01:09:46.060 | So that's the net effect, as opposed to the

01:09:48.300 | Prozaxoloft variety, which are SSRIs.

01:09:50.940 | - Yes, yes, but SSRIs themselves also are problematic

01:09:55.720 | because we didn't talk about it yet,

01:09:57.120 | but the dorsal raphe nucleus, which produces serotonin,

01:10:00.540 | which the specific serotonin reuptake inhibitors

01:10:05.160 | block from being reuptaken,

01:10:07.660 | leaves too much serotonin out there.

01:10:10.140 | And what serotonin also is another neuro-drenergic,

01:10:13.660 | I'm sorry, another neurotransmitter

01:10:15.760 | that's down-regulated during REM sleep,

01:10:18.240 | that's specifically off during REM sleep.

01:10:20.560 | And what serotonin does is it weights all of our cognition

01:10:25.560 | to being able to recognize novelty again.

01:10:29.240 | So it sort of weights our brain away

01:10:32.800 | from a sense of familiarity and toward novelty.

01:10:36.320 | And it might be one reason why

01:10:38.720 | it's an effective antidepressant,

01:10:41.480 | because it makes the world feel fresh and new again, right?

01:10:44.720 | But when you have too much,

01:10:50.880 | you're holding a novel traumatic memory

01:10:53.960 | in your novelty encoding structure too strongly already,

01:10:59.200 | you don't want to, again, weight things toward novelty.

01:11:02.280 | You need that absence of serotonin also

01:11:05.000 | to help you get that sense of familiarity

01:11:08.040 | and to start erasing the novelty encoding structures.

01:11:11.040 | So you need both to be absent.

01:11:12.720 | - It's really interesting.

01:11:14.240 | We hear a lot about serotonin

01:11:16.040 | and it's not often discussed

01:11:18.520 | in terms of its features related to novelty enough, I think.

01:11:22.380 | And what you just described,

01:11:24.320 | and accuse me to something that Dr. Paul Conte and others

01:11:27.140 | have said in terms of trauma,

01:11:28.720 | and here I'm paraphrasing,

01:11:29.980 | so my apologies to them for not getting this exactly right,

01:11:32.400 | that an effective treatment for trauma

01:11:36.040 | does not erase the traumatic memory,

01:11:38.240 | but it causes a transition

01:11:40.520 | of what once was disturbing and invasive and maladaptive

01:11:45.520 | to eventually just become kind of a boring old story

01:11:50.720 | that has kind of a fuzzy texture to it,

01:11:53.040 | as opposed to this kind of sharp, high friction texture

01:11:57.060 | that invades our thinking

01:11:59.040 | and obviously our sleeping states as well.

01:12:01.600 | So again, and I appreciate the disclaimer,

01:12:05.500 | the caveats around not being a clinician, et cetera,

01:12:08.260 | but I do think that there's a lot of interest now

01:12:10.060 | in whether or not antidepressants

01:12:11.840 | are effective for trauma or not.

01:12:13.260 | And I think these aspects of neuromodulation

01:12:16.380 | as they relate to, let's call it erasing traumas

01:12:19.800 | or changing the emotional load of traumas during sleep

01:12:23.140 | is something important to take note.

01:12:24.480 | We also have a lot of clinicians that listen to this podcast,

01:12:26.640 | so they should also take note, please.

01:12:29.400 | So if I want to reduce the amount of norepinephrine

01:12:34.400 | released from locus coeruleus

01:12:36.640 | during rapid eye movement sleep

01:12:38.880 | to eliminate the troubling or maybe even traumatic memories

01:12:42.680 | and allow late stages of sleep each night

01:12:47.580 | to have their maximum positive effect,

01:12:50.660 | is there anything that I can do besides avoiding traumas,

01:12:55.080 | avoiding serotonergic or noradrenergic compounds?

01:12:58.600 | - Well, I would also avoid anything

01:13:00.840 | just prior to going to sleep

01:13:02.160 | that might excite those systems.

01:13:04.560 | So a lot of novelty, a lot of exciting,

01:13:08.760 | stress-inducing video games.

01:13:12.720 | Try and enter sleep with as much calm as you can.

01:13:17.720 | So maybe deep breathing exercises.

01:13:20.080 | That's a beautiful way to calm your sympathetic

01:13:23.860 | fight or flight system, this deep breathing.

01:13:26.280 | And we haven't been able to test this with rats

01:13:29.420 | because we can't ask them to do a deep breathing exercise.

01:13:32.420 | (laughs)

01:13:33.620 | There might be a way we can do that,

01:13:35.140 | but I haven't found out or figured it out yet.

01:13:37.560 | But if there's a way you can make your sympathetic system,

01:13:42.680 | nervous system calm down before you go to sleep,

01:13:45.760 | might free for you meditation

01:13:47.480 | or deep breathing exercises might be for some,

01:13:49.960 | a warm bath or a comforting book.

01:13:52.560 | Nothing too exciting, but also nothing too boring perhaps.

01:13:57.560 | Just something right in the middle

01:13:59.300 | which makes you feel happy and calm is what you should do.

01:14:03.300 | And if you instead go to sleep while you're anxious

01:14:06.600 | or you're hyped up, then your sleep could become maladaptive.

01:14:11.600 | Another thing that happens in rats

01:14:15.020 | that we have yet to know if it happens in women

01:14:18.380 | is that female rats have three phases of their estrous cycle

01:14:23.380 | that their locus realus doesn't seem to calm down

01:14:26.520 | during REM sleep as much.

01:14:27.820 | And we don't know why, but during the high estrogen phases

01:14:32.120 | of their estrous cycle, the locus realus shuts down

01:14:36.060 | just like it does in male rats.

01:14:37.440 | But in the other three phases, it doesn't.

01:14:39.780 | So one thing that might work, and in fact,

01:14:43.780 | there are a few studies that show it,

01:14:45.620 | it could work really well is giving women

01:14:50.620 | after a trauma event something that contains estrogen

01:14:55.340 | because estrogen somehow is protective against PTSD.

01:14:59.540 | And they know that through a retrospective studies

01:15:02.420 | where they gave women an emergency room,

01:15:05.260 | either a pill with estrogen or without,

01:15:07.620 | and those that had a pill with estrogen in it

01:15:09.980 | were much less likely to get PTSD from that trauma

01:15:12.940 | as measured a year later than those

01:15:14.580 | that had the pill without.

01:15:15.900 | So there's some really good studies by Bronwyn Graham.

01:15:20.900 | She's out of Australia to really hone in

01:15:24.380 | on how much estrogen do you need.

01:15:26.460 | And also testosterone, just so you know,

01:15:28.820 | gets converted to estrogen in the brain.

01:15:30.920 | So testosterone also can be protective

01:15:33.300 | because it gets converted to estrogen.

01:15:35.740 | But there's something about estrogen

01:15:37.100 | that's really helpful and protective

01:15:39.120 | from the high locus realus firing.

01:15:43.880 | And this is again, preliminary data

01:15:45.580 | that we don't have full, we don't have all the answers yet,

01:15:48.780 | and we are looking into it actively right now,

01:15:52.280 | but it's really important.

01:15:53.680 | The other thing about women is that we are

01:15:55.760 | two to four times more susceptible

01:15:57.780 | to anxiety-related mental health disorders,

01:16:00.440 | including post-traumatic stress disorder.

01:16:02.780 | So if we could figure out what's happening

01:16:05.280 | to the locus realus during sleep in women,

01:16:07.440 | and then figure out a way to normalize that

01:16:12.340 | so the locus realus is silent when it needs to be silent,

01:16:14.920 | I think we could go a long way in helping women

01:16:18.300 | be more resilient to stress-related disorders.

01:16:22.720 | - What are some other sex differences

01:16:25.160 | as they relate to sleep?

01:16:26.580 | - Yeah, yeah, that's a really good question.

01:16:29.140 | There have been very few studies, unfortunately,

01:16:33.960 | of women in sleep, women in estrous cycle

01:16:37.880 | or menstrual cycle in sleep.

01:16:39.760 | And, but what we have found,

01:16:42.640 | which actually largely replicated the study in 1960,

01:16:46.680 | is that women or females rather at high estrogen,

01:16:52.460 | high hormonal phases of their estrous cycle

01:16:55.480 | or menstrual cycle sleep a lot less,

01:16:58.340 | but that sleep is more efficient.

01:17:00.380 | So that sleep is more dense in those sleep spindles,

01:17:04.220 | which I haven't gone into what they might do

01:17:05.880 | except this connection between the hippocampus and cortex,

01:17:09.480 | but those sleep spindles are more dense

01:17:11.320 | and more coherent across the brain areas.

01:17:14.100 | The theta cycle, which is five to 10 hertz

01:17:17.160 | in the hippocampus, important for one year learning

01:17:19.760 | and also important during REM sleep,

01:17:21.500 | is also bigger and juicier during the high hormonal phases.

01:17:25.960 | So even though there's less sleep,

01:17:27.480 | it's more efficient and better.

01:17:29.160 | But, so all of that efficiency seems to be reduced

01:17:35.240 | in those other hormonal phases.

01:17:38.740 | So even though you might sleep a little more,

01:17:42.060 | you might need more sleep, in fact,

01:17:44.620 | in order to accomplish the same thing that you can get

01:17:47.620 | with that short, very efficient sleep of high hormonal phases.

01:17:52.620 | - Very interesting.

01:17:54.460 | I think there is a growing trend,

01:17:57.420 | at least among NIH funded grants to require that,

01:18:02.420 | as they refer to it in the grants,

01:18:05.100 | a biological sex as a variable.

01:18:07.060 | And here we're talking about sex, the verb,

01:18:10.340 | although I'm sure there's studies about that too,

01:18:12.020 | but biological sex is a variable

01:18:13.460 | because there is a dearth of studies exploring

01:18:16.060 | sex differences in most everything.

01:18:19.620 | There are all sorts of reasons for that,

01:18:21.260 | but more importantly, fortunately, the trend is shifting.

01:18:24.700 | - Yeah, and even when you study males versus females,

01:18:29.060 | a lot of people just include females in their studies,

01:18:32.820 | but then don't track the estrous cycle

01:18:35.540 | or menstrual cycle, and hormones have huge effects

01:18:39.500 | on our behavior.

01:18:40.340 | I mean, just think of when you said sex,

01:18:42.380 | before our hormones come in, we're not interested in it.

01:18:46.060 | And suddenly, that's kind of a main driver of behaviors.

01:18:49.940 | Hormones can definitely change who we are and what we do.

01:18:53.460 | So we should be studying hormones, not just sex.

01:18:56.820 | - I always say that puberty is perhaps

01:18:58.980 | the most massive transformation and rate of aging

01:19:02.100 | that any of us go through in a short amount of time.

01:19:04.100 | An individual, their cognition changes,

01:19:05.940 | their worldview changes, and that's largely hormonal-driven,

01:19:08.740 | and obviously, neural architecture has changed too.

01:19:12.100 | I'm very happy that you mentioned trying to get

01:19:15.540 | into calmer states prior to sleep and some ways to do that.

01:19:19.460 | I'm a big fan, and I've talked a lot before

01:19:21.140 | on this podcast about things like yoga nidra,

01:19:23.700 | which is a non-movement-based practice,

01:19:26.180 | sometimes called non-sleep deep rest,

01:19:28.100 | where people actually take some time each day

01:19:30.100 | to practice how to go into a more parasympathetic,

01:19:32.820 | aka relaxed state, deliberately,

01:19:34.740 | because it's a bit of a skill.

01:19:36.420 | Yeah, and there's some good data, really,

01:19:39.300 | mostly out of a laboratory in Scandinavia,

01:19:41.140 | showing huge increases in nigrostriatal dopamine

01:19:46.020 | when people basically engage in a practice

01:19:49.700 | of deliberate non-movement,

01:19:52.740 | and that the brain actually enters states

01:19:54.500 | of a very shallow sleep, so sort of nap-ish,

01:19:58.580 | but the idea is to actually stay awake but motionless,

01:20:00.980 | and it does seem to restore a certain number of features

01:20:03.700 | of neurochemistry, but perhaps more importantly,

01:20:06.100 | it teaches people to relax,

01:20:08.820 | which is something that most people are not very good at.

01:20:12.020 | But in any event, and people who listen to this podcast

01:20:15.700 | have heard me say this over and over again,

01:20:17.140 | so I sound like a broken record,

01:20:18.340 | but this practice, as a zero-cost practice

01:20:20.580 | that doesn't require any pharmacology,

01:20:22.900 | does seem to really enhance people's ability

01:20:25.380 | to fall asleep more quickly and to fall back asleep

01:20:28.340 | if they wake up in the middle of the night.

01:20:29.700 | So in any event, another plug for NSDR, yoga nidra.

01:20:32.820 | - Well, I just also want to add to that,

01:20:35.620 | that's one of the reasons why insomnia is so insidious

01:20:38.340 | is because when people feel like they haven't gotten

01:20:40.580 | enough sleep and they aren't getting enough sleep

01:20:42.100 | and they become anxious about getting enough sleep,

01:20:43.780 | and then you're anxious before going to sleep,

01:20:46.100 | like I'm not going to fall asleep,

01:20:47.060 | it's going to be 45 minutes in,

01:20:48.340 | and then that's a positive feedback loop.

01:20:50.500 | So you need to break that loop, say, okay,

01:20:53.380 | my body's going to get as much sleep as it needs,

01:20:55.540 | I needn't worry about it,

01:20:56.580 | and then practice this relaxation to say,

01:21:00.020 | hey, it's all okay, it's going to be all right,

01:21:03.700 | and then concentrate on things that relax you,

01:21:06.660 | whether it's concentrating or not concentrating,

01:21:09.780 | whatever it is.

01:21:10.500 | You mentioned yoga nidra,

01:21:14.740 | and that reminded me of transcendental meditation,

01:21:19.860 | which is something that also hasn't been studied well,

01:21:22.420 | largely because we can't ask non-human animals to do it.

01:21:25.700 | And so we don't know what's happening

01:21:28.020 | with our neurochemistry and our brain activity

01:21:31.300 | in a deep and meaningful way.

01:21:35.460 | But one thing that has been shown

01:21:37.860 | and those that can do it really well

01:21:39.380 | is that that theta activity that I said happens

01:21:42.420 | when you're learning something or when you're in REM sleep,

01:21:45.780 | it's well established and increases

01:21:50.580 | during the transcendental meditation.

01:21:52.500 | So it might be that some states of meditation

01:21:56.260 | could in some ways replace or mimic some functions of,

01:22:01.460 | for example, REM sleep.

01:22:02.740 | But again, we don't know if all the neurochemistry is right

01:22:06.100 | to do, for example, the thing that I was talking about,

01:22:08.100 | which is erasing the novelty and coding structures of the brain.

01:22:11.460 | That needs an absence of norepinephrine and serotonin,

01:22:14.980 | which we don't know if that goes away

01:22:16.980 | with transcendental meditation.

01:22:19.220 | We just don't know the answer to that yet.

01:22:21.620 | - Yeah, the studies on yoga nidra and sleep replacement

01:22:24.900 | are kind of interesting.

01:22:25.860 | It does seem to be the case that nothing

01:22:29.300 | can really replace sleep except sleep,

01:22:31.300 | but that if one is sleep deprived

01:22:33.060 | or is having trouble falling back asleep,

01:22:34.820 | that these things like, and I hear it's,

01:22:39.220 | I acknowledge this is essentially like yoga nidra,

01:22:41.540 | but we now call it non-sleep deep breast or NSDR

01:22:44.100 | because oftentimes names like yoga nidra act

01:22:47.060 | as a kind of a barrier for what would otherwise be people

01:22:50.500 | willing to try a practice.

01:22:51.780 | It sounds mystical, it sounds like flying carpets

01:22:54.980 | and, you know, it sounds like you have to go to Esalen,

01:22:57.300 | by the way, Esalen's a beautiful place,

01:22:59.220 | but it sounds like you have to go there

01:23:00.420 | or live in the West Coast to believe in this stuff,

01:23:02.900 | but it's simply not the case.

01:23:04.100 | These are practices that are really just self-directed

01:23:08.020 | relaxation as a practice that allows people to get better

01:23:12.020 | and better at directing their brain states

01:23:14.500 | towards more relaxation.

01:23:16.020 | And most people have an asymmetry.

01:23:17.620 | Like for instance, most people can force themselves

01:23:19.780 | to stay up later, but they have a hard time

01:23:22.820 | going to sleep earlier.

01:23:24.020 | And that just speaks to the asymmetry

01:23:25.620 | that's probably adaptive and survival-based,

01:23:28.100 | that we can ramp ourselves up far more easily

01:23:30.820 | than we can tend to calm ourselves down.

01:23:32.420 | - Yeah, yeah, and actually, you know,

01:23:33.940 | to appeal to other Christians like me,

01:23:36.260 | prayer can be a wonderful way to calm yourself down

01:23:40.820 | because through prayer, you're giving your cares to God

01:23:45.540 | and saying, you know, and then you are relaxed, more relaxed.

01:23:50.340 | And I just want to say that because the same reason

01:23:53.540 | that yoga might put some people off,

01:23:55.220 | it might put some people off to talk about prayer,

01:23:59.380 | but it's the same process of being able to relax.

01:24:04.580 | And yeah.

01:24:06.740 | - And get outside our own experience a little bit.

01:24:08.420 | - Get outside our own experience, yeah.

01:24:09.540 | - Yeah.

01:24:10.340 | - Back out, get a worldview that might actually

01:24:12.740 | also help us to relax.

01:24:14.500 | - Well, you might be surprised at how many clinicians

01:24:17.860 | and scientists who've come on this podcast

01:24:19.540 | have mentioned things like prayer from various perspectives,

01:24:23.220 | Christianity, Judaism, Muslim traditions, and others,

01:24:26.260 | that as a parallel to all of these things.

01:24:29.220 | And I think what it speaks to is the fact that ultimately

01:24:32.260 | the biological architectures that we're all contending with

01:24:35.540 | are going to be identical, right?

01:24:36.900 | And so different ways to tap into them

01:24:38.660 | and ones that are congruent with people's beliefs,

01:24:42.340 | I think are great.

01:24:44.500 | - Yeah, because anything non-congruent with your beliefs

01:24:47.380 | is also stressful.

01:24:48.420 | - Right, and feels forced.

01:24:49.460 | And that's why this idea of calling it non-sleep deep rest

01:24:52.420 | in addition to yoga nidra was not to detract from the naming

01:24:55.620 | or the history around yoga nidra,

01:24:57.380 | but I was finding that it was a barrier.

01:24:59.380 | Likewise, yoga nidra tends to include things like intentions,

01:25:03.380 | whereas NSDR scripts, and by the way,

01:25:05.140 | we will provide links to some NSDR and yoga nidra scripts,

01:25:07.700 | but NSDR has no intentions.

01:25:09.940 | It's simply a body scan deep relaxation base.

01:25:12.660 | So it's sort of the scientific version of all of this stuff.

01:25:15.060 | And actually we study it in the laboratory

01:25:17.140 | and some of the brain states that people go into,

01:25:19.380 | but that's a discussion for another time.

01:25:21.060 | - Well, another thing, this is hard not to,

01:25:23.140 | my mother used to tell me when I said we could play,

01:25:25.380 | I can't go to sleep.

01:25:26.180 | She'd say, well, you know, start with your toes and relax.

01:25:29.940 | So you would clench your muscles around your toes

01:25:32.820 | and you relax them and do that all the way from your toes

01:25:35.860 | all the way to your head.

01:25:36.580 | And I don't know where she got this.

01:25:37.860 | It might've been her own common sense,

01:25:39.620 | or she might've gotten it from this NPR show.

01:25:43.540 | It's called "The Mind Can Keep You Well."

01:25:45.460 | She used to listen to.

01:25:46.820 | But that's another intentional relaxation

01:25:49.540 | that focuses on the body rather than

01:25:52.980 | on your own mental processes, but.

01:25:55.620 | - I do a little bit of work with the military

01:25:58.020 | and there's a method within certain communities

01:26:00.900 | of special operations in the US military,

01:26:02.820 | where if they can't sleep

01:26:04.820 | or they're having challenges sleeping,

01:26:06.580 | they will deliberately try and relax their facial muscles

01:26:10.420 | in particular, like sort of drape the facial muscles

01:26:13.460 | and use long or exhale-emphasized breathing,

01:26:17.380 | does seem to increase the probability

01:26:20.340 | of transitioning back into sleep.

01:26:22.100 | And those are hallmarks of yoga nidra,

01:26:24.980 | non-sleep deep breaths, body scans.

01:26:27.460 | And so I think all of these things converge

01:26:29.140 | on a common theme, you know, as neurobiologists,

01:26:31.460 | we can say all of the things that we are describing,

01:26:34.500 | certainly move the needle away

01:26:37.140 | from locus coeruleus activation.

01:26:38.900 | And we haven't done the experiment to really look at that,

01:26:41.220 | but it seems all these things are counter

01:26:43.380 | to noradrenaline release.

01:26:44.820 | - Right, another one is yawning.

01:26:47.140 | Yawning in itself is that kind of sort of tensing

01:26:50.580 | of all the muscles in your face and then relaxing them.

01:26:53.940 | So it might be why we yawn.

01:26:55.860 | We don't know why we yawn yet,

01:26:57.140 | but it might also be really great.

01:27:00.260 | Actually animals yawn too, you know.

01:27:02.180 | - No, my bulldog was a perpetual,

01:27:04.900 | if he wasn't sleeping, he was yawning.

01:27:06.420 | - And it would be interesting to see what yawning does

01:27:09.940 | to the locus coeruleus.

01:27:10.820 | Does that also come and switch the locus coeruleus activity?

01:27:13.940 | Because it's interesting that facial nerve,

01:27:17.140 | like trigeminal nerve, you know, through the vagus connects

01:27:20.820 | indirectly to the locus coeruleus

01:27:23.700 | and has a powerful effect on that.

01:27:25.220 | - Interesting, a common, I think friend of ours

01:27:27.700 | and direct colleague of yours, Jack Feldman was a guest

01:27:30.580 | on this podcast telling us about all the amazing structures

01:27:33.460 | he and others have discovered in respiration and breathing.

01:27:36.660 | Sounds like we have a collaboration brewing

01:27:38.500 | that the three of us should definitely carry out.

01:27:41.060 | I'd love for you to share with us a little bit more

01:27:43.940 | about the spindles that have come up a few times.

01:27:46.660 | And I don't know if it's relevant to this,

01:27:48.980 | so if it's not, let's separate it out.

01:27:51.380 | But I'd love for you to tell us a little bit

01:27:53.780 | about the role of sleep in problem solving and creativity.

01:27:57.620 | And if spindles are involved,

01:27:58.820 | and I'll consider myself lucky for batching them

01:28:00.820 | in the same question, and if they're not involved,

01:28:02.580 | simply feel free to separate them out.

01:28:04.340 | - I think they could be involved.

01:28:06.180 | And the reason why I think they could be involved,

01:28:07.780 | 'cause we now know a lot more about spindles.

01:28:09.780 | First of all, the first thing that we knew,

01:28:11.780 | first of all, we ignored them.

01:28:13.460 | Then we thought they had something to do

01:28:14.900 | with keeping us asleep, and that was their function

01:28:16.980 | is when an external stimulus came,

01:28:18.820 | they would keep us asleep because they would arise.

01:28:20.980 | But now we know that the density of our sleep spindles,

01:28:23.940 | the number that we produce per minute

01:28:26.500 | is well correlated with our intelligence in the first place,

01:28:29.460 | and that no matter what your intelligence is,

01:28:31.540 | and no matter what your sleep spindle density is,

01:28:34.500 | if you learn something during the day

01:28:36.660 | and increase your sleep spindle density,

01:28:38.900 | it's really almost perfectly correlated

01:28:41.540 | with our ability to consolidate that information

01:28:43.860 | and incorporate it into the schema

01:28:46.340 | that we already have in our brain.

01:28:47.780 | So if you try and learn something new,

01:28:50.260 | even if your sleep spindle density at baseline is great,

01:28:53.140 | if you don't increase your sleep spindles that night,

01:28:55.780 | you're not gonna use sleep to really incorporate it.

01:28:59.540 | Interestingly, sleep spindles are poor

01:29:02.740 | in those with schizophrenia.

01:29:04.180 | It's one of the characteristic signatures of sleep

01:29:08.100 | is that sleep spindles are very few and far between,

01:29:10.340 | which might mean that people with schizophrenia

01:29:14.980 | might not be able to incorporate new information

01:29:17.380 | into already existing schema,

01:29:19.140 | and instead it sort of flaps in the breeze out there

01:29:22.340 | and can be accessed erroneously at times when you,

01:29:25.780 | you know, you don't want it to be involved.

01:29:28.020 | So I digress.

01:29:30.580 | So sleep spindles and creativity.

01:29:32.100 | So one of the things we now know

01:29:33.940 | through some great studies by Julie Seep and Anita Luthy

01:29:36.900 | is that sleep spindles are accompanied

01:29:40.180 | by an incredible plasticity out in the distal dendrites,

01:29:44.900 | the listening branches of our neurons

01:29:47.620 | that listen to other cortical areas.

01:29:50.580 | So there are proximal dendrites in our neurons

01:29:53.220 | that listen to the external world

01:29:56.020 | and are conducted through the thalamus.

01:29:58.180 | And then there are distal dendrites,

01:29:59.540 | which listen to an internal kind of, you know,

01:30:02.340 | conversation that's happening in our brains.

01:30:05.220 | It's kind of, you know, our internal state really.

01:30:08.340 | And during sleep spindles,

01:30:09.620 | that's when those distal dendrites are able to best learn

01:30:14.500 | from other cortical areas and from the hippocampus.

01:30:17.380 | It is during sleep spindles at the hippocampus

01:30:20.100 | and the cortex are best connected.

01:30:22.500 | And when that incredible plasticity can happen.

01:30:25.860 | When I talk about schema,

01:30:27.220 | that's a cortical cortical thing.

01:30:28.660 | That's when, you know, the image of Santa Claus

01:30:31.220 | and presents, you know, comes together.

01:30:33.140 | It's not through some external thing.

01:30:34.820 | Once we learn those things together,

01:30:36.820 | it's our cortex that encodes that

01:30:38.900 | and brings those images back up together.

01:30:41.140 | And that's during sleep spindles when that's happening.

01:30:44.500 | When there's big surges of calcium

01:30:48.100 | into those distal dendrites

01:30:50.500 | and where plasticity happens in just huge amounts.

01:30:54.740 | During that sleep spindle stage of sleep,

01:30:57.780 | which is N2 stage,

01:30:59.460 | there's also another excitatory event

01:31:02.900 | that comes all the way from the brainstem

01:31:04.580 | and projects everywhere in our cortex,

01:31:07.140 | which is called P-Geo waves.

01:31:08.820 | P for pons,

01:31:11.220 | G for geniculate nucleus of the thalamus,

01:31:13.460 | which is where they're first discovered,

01:31:15.220 | and O for occipital area,

01:31:17.140 | which is our visual area,

01:31:18.180 | which is again where they're first discovered.

01:31:20.500 | But in fact, it's now been shown that P-Geo waves,

01:31:23.460 | which we should generalize to P waves

01:31:25.460 | because they come from the pons and go to the thalamus

01:31:27.620 | and then this cortex happens all over the brains.

01:31:30.500 | And that is where glutamate,

01:31:33.140 | which is a major excitatory neurotransmitter

01:31:35.860 | involved in learning and plasticity

01:31:37.620 | is being released in big amounts

01:31:39.860 | also in those distal dendrites.

01:31:41.380 | So P waves and spindles work together to cause plasticity.

01:31:45.460 | And so our schema together,

01:31:46.820 | which could be the origins for insight and creativity.

01:31:50.980 | Now, when P-Geo waves or P waves are first discovered,

01:31:53.700 | it was thought to be random

01:31:57.060 | because this small area that generates P waves

01:31:59.940 | all over the brain projects all over the thalamus

01:32:05.060 | and causes P waves all over.

01:32:06.340 | And you don't measure P waves

01:32:08.820 | all over the brain at the same time.

01:32:10.260 | In fact, it just seems sporadic and random.

01:32:13.220 | So that's probably,

01:32:14.260 | and P waves are also happening even more during REM sleep,

01:32:18.180 | rapid eye movement sleep.

01:32:19.300 | So that's why people think that REM dreams are so random

01:32:25.620 | is because these P waves are random

01:32:27.700 | and they could generate dreams

01:32:30.260 | because they're an internal source of excitation

01:32:34.500 | that kind of replaces the outside world

01:32:37.140 | during our dream state.

01:32:38.660 | And so these P waves, if they are random,

01:32:41.300 | could function or could be the underlying reason

01:32:45.140 | why REM sleep dreams are random.

01:32:47.620 | And it might also be why creativity can happen there

01:32:51.940 | is because we're randomly activating,

01:32:54.500 | coactivating different things in our brain

01:32:56.660 | that we can then sew together.

01:32:58.420 | But it might not be as random as we think.

01:33:00.980 | So that's a caveat there.

01:33:02.660 | - Well, I just learned a lot from you

01:33:04.260 | because I teach brainstem to medical students

01:33:07.780 | and I talk about the pons.

01:33:10.100 | And the pons is like this dense collection

01:33:11.700 | of all these different nuclei involved

01:33:13.460 | in a bunch of different things.

01:33:14.740 | And it's close by a bunch of interesting things.

01:33:17.300 | And it's still kind of a mysterious brain area.

01:33:20.340 | But when I learned about PGO waves,

01:33:22.340 | I thought pons, geniculate, occipital,

01:33:24.420 | because occipital is most commonly associated

01:33:26.580 | with visual cortex.

01:33:27.540 | I thought it was the origin

01:33:30.020 | of the visual component of dreams.

01:33:32.420 | - It probably is.

01:33:33.140 | - I'm very happy to learn that they should be called P waves

01:33:37.060 | because they include lots of different areas of the brain.

01:33:39.540 | And it makes really good sense to me

01:33:41.620 | why the kind of pseudo randomness of dreams,

01:33:45.780 | especially these late night or an early morning,

01:33:48.020 | later in sleep, I should say,

01:33:50.820 | and early morning dreams seem to be cobbled together

01:33:54.180 | from kind of disparate experiences.

01:33:56.420 | You walk through a door and suddenly

01:33:58.820 | it's a completely different context and landscape.

01:34:00.900 | - Yes, beautiful.

01:34:02.180 | - Yeah, I like this idea a lot.

01:34:04.580 | It makes intuitive sense.

01:34:05.940 | It makes biological sense.

01:34:07.140 | It also gives me something to talk about

01:34:08.740 | to the medical students next quarter

01:34:10.100 | when I talk about pons.

01:34:11.060 | - You want to talk about where in the pons,

01:34:12.660 | it's right below the locus coeruleus.

01:34:14.740 | It's called the subceruleus.

01:34:16.180 | They're glutamatergic.

01:34:17.540 | It's also called SLD, sub lateral dorsal nucleus.

01:34:22.100 | - So note to any aspiring neurobiologist,

01:34:26.820 | there's a vast landscape of yet to be undiscovered structure

01:34:31.060 | and functions in the pons.

01:34:32.100 | You want to work on something

01:34:33.380 | that is sure to reveal something novel?

01:34:35.060 | Work on the pons because it's in every textbook.

01:34:37.380 | It's a clinically very important structure.

01:34:40.260 | Sadly, gliomas and other cancers of the brain

01:34:45.380 | can sometimes, can often surface in the pons,

01:34:48.180 | but we still know very little about it.

01:34:50.180 | I read a paper this last year,

01:34:53.940 | and I think it was covered in a bit of popular press,

01:34:56.580 | that during rapid eye movement sleep,

01:34:59.220 | people can solve problems or respond to external stimuli.

01:35:04.580 | Like for instance, they would give them math problems.

01:35:06.580 | They'd whisper in their ear while they were in REM sleep,

01:35:08.980 | you know, what's two plus two?

01:35:10.340 | And people would say, even though they were paralyzed,

01:35:12.260 | apparently they could still move their mouth

01:35:13.780 | because they'd say four or something like that.

01:35:16.740 | Or they'd say, you know, what's your name?

01:35:18.260 | And people could respond.

01:35:19.220 | And so that in REM sleep, perhaps people,

01:35:21.140 | some elements of cognition are still active.

01:35:25.620 | - I'm glad you brought that up.

01:35:27.300 | - What do you think?

01:35:28.100 | And I don't know the authors of that study.

01:35:29.780 | And listen, if ever I say something wrong,

01:35:33.460 | it's great on this podcast

01:35:35.060 | because someone will tell us in the YouTube comments.

01:35:37.220 | It's one of the great uses of YouTube comments,

01:35:39.540 | but I'd love to know your thoughts on that study.

01:35:41.860 | I mean, is that just kind of an odd feature

01:35:46.340 | or does this have meaning?

01:35:48.020 | Should we actually care about this result?

01:35:49.540 | - There's no just about it.

01:35:51.140 | It's really actually intriguing and interesting

01:35:53.700 | and might relate to this paper that I talked about

01:35:56.260 | where we said different areas of the brain

01:35:58.260 | can be in different states at the same time.

01:36:00.420 | So lucid dreaming is another thing we can't ask animals to do

01:36:04.340 | or can't ask them if they've done it,

01:36:05.940 | but we can certainly ask humans to do it

01:36:09.460 | and some people can do it really well.

01:36:11.460 | And it would be really interesting to see

01:36:13.460 | in those people who could lucid dream really well,

01:36:15.780 | whether they spend more or less time

01:36:18.100 | in this asymmetrical state

01:36:21.140 | where one area of the brain is in one state

01:36:22.980 | and another area of the brain is in another.

01:36:24.820 | And it might be that those people can respond to questions

01:36:28.580 | during REM sleep.

01:36:29.860 | Best are those that have the most asymmetry or dissimilarity

01:36:34.980 | or dissociation between subcortical and cortical structures.

01:36:38.500 | Or it might be that they're the ones with the most symmetry.

01:36:40.740 | We don't know.

01:36:41.300 | I do worry a little bit about lucid dreaming

01:36:45.060 | because it's a fad.

01:36:46.420 | People are really excited about it.

01:36:47.780 | And to be able to remember one's dreams is fun often

01:36:51.140 | unless they're nightmares.

01:36:52.180 | But it's really interesting.

01:36:53.940 | Or to be able to direct one's dreams

01:36:55.540 | if they are a nightmare is really wonderful power to have

01:36:59.060 | to be able to redirect a nightmare

01:37:01.380 | that has been repeated to something else

01:37:03.220 | and then kick yourself out of that repetitive nightmare

01:37:06.340 | is really nice.

01:37:07.140 | But I worry a little bit about because we know so little

01:37:12.260 | about what's actually going on in the brain.

01:37:14.420 | And if this lucid dreaming state is preventing us from,

01:37:18.980 | for example, from the locus realus from calming down

01:37:21.300 | or the serotonergic system from silencing like it should.

01:37:24.900 | And maybe what we're doing during this state is, yeah,

01:37:28.180 | we're activating the learning and memory structures,

01:37:30.740 | but in a way that's maladaptive in terms of the erasure

01:37:34.580 | that we need to do.

01:37:35.540 | So maybe one of the reasons why most people don't remember

01:37:38.660 | most of their dreams is for good reason.

01:37:40.820 | Your hippocampus is in a state where it's not writing

01:37:43.620 | new memories.

01:37:44.340 | In fact, it's writing out the memories it learned

01:37:47.380 | during the day to the cortex.

01:37:49.060 | And it's immune from incoming new information.

01:37:52.820 | So maybe lucid dreaming is bad because you're activating

01:37:58.420 | the hippocampus in a way that's writing new memories.

01:38:01.140 | And it might be really maladaptive for things like PTSD.

01:38:05.140 | On the other hand, let me just argue myself right out

01:38:08.340 | of this.

01:38:08.840 | When I used to have a repeated nightmare when I was a kid,

01:38:12.180 | my mother, who's so wise, would tell me, well, listen,

01:38:16.180 | just next time you're in that dream, say, hey, I'm in a dream

01:38:21.380 | and then change something about it.

01:38:22.980 | So she and I rehearsed what the horrible dream that was.

01:38:26.340 | It was a big monster running after me.

01:38:28.500 | And my legs were like mud.

01:38:29.860 | And I couldn't run away.

01:38:30.820 | And it was just terrifying.

01:38:32.340 | And that was a dream I would have time and time again.

01:38:35.540 | She said, OK, next time, what are you going to do?

01:38:37.860 | And that monster comes after you.

01:38:39.460 | I thought, I'm going to run away.

01:38:40.500 | No, that's what you do every time.

01:38:42.260 | And it's always the same outcome.

01:38:43.700 | You can't run.

01:38:44.420 | So let's do something different.

01:38:45.860 | Like, what could you do that's different?

01:38:47.700 | So I came up with, well, I could turn around and punch it.

01:38:50.980 | And the nose, yeah, that's great.

01:38:52.740 | So the next time I had that dream,

01:38:55.460 | I did recognize this is that same old dream,

01:38:58.500 | which means that there's part of my brain that's

01:39:00.340 | conscious enough to know that I'm in a dreaming state.

01:39:04.260 | And then I didn't have the courage in my dream

01:39:06.900 | because I was still terrified to punch or touch

01:39:09.380 | the monster in any way.

01:39:10.820 | But I did have the courage to turn around and look

01:39:13.140 | it in the eye and say, no, that was enough.

01:39:15.620 | I said, no.

01:39:16.580 | And that was enough to knock me out of that rut of that dream

01:39:20.260 | so that I never had it again.

01:39:22.260 | I never had that same dream again.

01:39:24.580 | And in fact, it gave me peace about dreaming

01:39:27.060 | because I knew that if ever there

01:39:29.380 | was a nightmare that was just too scary,

01:39:31.300 | I could probably do something to change it

01:39:34.020 | and knock myself out of it.

01:39:35.780 | So even though I don't recommend lucid dreaming

01:39:38.500 | on a normal day-to-day basis, if it's enough that can knock you

01:39:43.380 | out of a rut, one thing that happens with people with PTSD

01:39:47.300 | is they have the same repeated horrible nightmare, which

01:39:50.580 | is often a reliving of the day's trauma that they had.

01:39:55.220 | So maybe lucid dreaming can be used on occasion

01:39:58.900 | to be a powerful tool because there's so much plasticity that

01:40:04.100 | happens during REM sleep to knock you out

01:40:06.580 | of that rut of reliving that event and just change it.

01:40:10.740 | And you could probably practice that during wakefulness,

01:40:15.140 | rehearse the event that happened that was so traumatic,

01:40:18.420 | and then just introduce a new element like now I'm safe.

01:40:23.940 | Now the sound that was associated

01:40:26.420 | with that really traumatic thing,

01:40:27.700 | I should now associate with something else.

01:40:30.340 | And next time I have that dream, I'm going to change it.

01:40:32.660 | So that sound is now this new thing

01:40:34.980 | that should be associated with safety.

01:40:37.140 | And that might be enough, maybe, I hope,

01:40:39.460 | to knock you out of that repeated nightmare

01:40:43.380 | and maybe even start you on the path to recovery.

01:40:45.460 | Because if you can calm down about those nightmare

01:40:48.180 | states of sleep, then maybe your locus surrealis,

01:40:50.900 | which is involved in stress, can also relax.

01:40:53.540 | And you can do the erasure parts that need to be done.

01:40:56.100 | I love it.

01:40:57.860 | I seem to recall a paper--

01:40:59.860 | and I'll have to find the reference and send it to you.

01:41:03.220 | We will also put in the show note captions--

01:41:05.300 | that described a protocol that essentially matches this idea.

01:41:10.500 | And I think what they had people do

01:41:12.180 | was either cue themselves to a particular smell

01:41:14.420 | or tone in wakefulness, then to try and recall

01:41:18.340 | a recurring nightmare.

01:41:19.460 | Then during the night's sleep, they

01:41:22.260 | had the tone playing in the background,

01:41:23.780 | which would then cue them to the wakeful state.

01:41:25.860 | They're still asleep, mind you, but in the pseudo-lucid

01:41:28.180 | or lucid state.

01:41:29.460 | And then try and change some variable, as you're describing.

01:41:33.060 | Some either look the predator in the eyes

01:41:35.780 | or do something different.

01:41:36.820 | And then in the waking state, take a little bit of time

01:41:40.420 | to try and script out a different narrative altogether.

01:41:44.340 | And it took several nights, as I recall, or more,

01:41:46.820 | but that they were able to escape this recurring nightmare.

01:41:49.220 | Yeah, it was like a week or something.

01:41:50.580 | Oh, so you're familiar with the study.

01:41:52.020 | Yeah, it's a beautiful study.

01:41:53.220 | I loved it.

01:41:53.940 | Yeah, we will put a reference to that.

01:41:56.020 | I need to revisit that study.

01:41:58.100 | It was pretty recent, but I need to dive into it again,

01:42:01.140 | because I think I didn't go as deep into it as I should have.

01:42:03.780 | No, no, but the one thing that you-- well,

01:42:06.740 | you said many right things.

01:42:07.780 | But one of the things you said is

01:42:09.140 | that they were able to cue the dreamer when they knew,

01:42:13.380 | and they were going to REM sleep,

01:42:14.980 | and then they played the sound or had the odor.

01:42:17.780 | Now, when you're normally asleep alone in your bed,

01:42:20.100 | you're not going to be able to cue yourself.

01:42:21.860 | But it might be that rehearsal enough before you go to sleep

01:42:25.780 | is enough to help cue you to that repeated nightmare,

01:42:29.700 | remembering what the nightmare is,

01:42:31.540 | and then figuring out how to cue yourself

01:42:34.580 | to do something different.

01:42:35.860 | For years, I had the same recurring nightmare.

01:42:38.740 | Yeah.

01:42:39.220 | Over and over and over again.

01:42:41.140 | And it was so salient and so clear.

01:42:42.820 | And I'm not going to share what it is,

01:42:44.020 | because it's not that it's that disturbing.

01:42:46.100 | It was just-- I think it was the emotional load of it

01:42:49.300 | and just how salient certain features were.

01:42:51.860 | Like one person who was a real-life person

01:42:55.300 | had a particular clothing on.

01:42:59.300 | And it's like, and that just served as this cue.

01:43:00.980 | And I don't know if I ever did any direct work

01:43:03.060 | to try and deal with it.

01:43:04.020 | But now it almost seems silly to describe it.

01:43:06.260 | Oh, yeah.

01:43:06.740 | Well, dreams are usually silly to describe.

01:43:08.660 | Yeah, it was pretty silly.

01:43:09.620 | But it was a pretty violent dream.

01:43:11.380 | Yeah, and your emotional system is so geared up

01:43:15.140 | during REM sleep, which is another thing

01:43:16.900 | we could talk about.

01:43:17.700 | Yeah, please.

01:43:19.060 | I would love to-- yeah, so locus coeruleus

01:43:21.700 | is ideally suppressed.

01:43:23.300 | So we can't really snore epinephrine.

01:43:25.060 | We can't act out our dreams.

01:43:26.420 | During these very emotionally laden thoughts and storylines

01:43:33.140 | during sleep, this almost starts to sound

01:43:35.540 | like a little bit of a built-in while sleeping trauma therapy.

01:43:40.980 | Because most trauma therapies involve

01:43:42.580 | trying to get people into states of--

01:43:44.020 | counter to what most people think you actually

01:43:47.300 | want to get close to the trauma in terms of the narrative,

01:43:49.940 | but try and suppress the emotional activity of it.

01:43:52.740 | Or I guess that's the motivation for ketamine-based therapies

01:43:56.100 | for trauma.

01:43:57.060 | Or I've also heard-- and this is still perplexing to me--

01:43:59.860 | that other waking-based trauma therapies involve taking people

01:44:03.620 | the other way, making it very cathartic,

01:44:05.060 | take them to the peak of the emotional response,

01:44:07.300 | but then allow that to finally cycle down

01:44:09.700 | into a more relaxed response.

01:44:11.540 | So please, if there's anything about locus coeruleus

01:44:16.260 | and dreams that can help people basically

01:44:20.180 | extinguish traumas or traumatic features to real-life events,

01:44:23.940 | we definitely want to know about them.

01:44:25.060 | Yeah, yeah.

01:44:25.700 | Well, I think one of the things that people

01:44:28.980 | thought might help after a trauma,

01:44:31.140 | like a school shooting or whatever,

01:44:33.300 | you know, car accident is to talk about it.

01:44:35.300 | But in fact, that ended up being counterproductive.

01:44:39.060 | And I think one of the reasons why it was counterproductive

01:44:41.380 | is because it didn't take them back down.

01:44:44.100 | It brought them up and continued to reactivate

01:44:47.700 | the emotions of it, but then didn't emphasize the safety

01:44:52.340 | effect that it's over or help them work through how they

01:44:56.740 | might avoid it again in the future

01:44:58.420 | to calm the sympathetic nervous system down again

01:45:02.180 | before they went to sleep.

01:45:03.460 | And none of these studies has sleep ever been considered.

01:45:06.740 | But to me, that's the key part is bringing down

01:45:10.500 | your sympathetic nervous system before you go to sleep

01:45:12.900 | so that your sleep can be adaptive,

01:45:14.980 | your locus coeruleus can shut off like it normally does

01:45:17.780 | or should do, and then able to erase the novelty of it.

01:45:23.220 | The other thing that I just mentioned a minute ago

01:45:27.060 | is that the emotional system is highly activated in REM sleep.

01:45:30.260 | And that's definitely true.

01:45:31.780 | And that might seem counterproductive

01:45:33.860 | in terms of the nightmares and how to help REM sleep

01:45:39.220 | be a therapeutic thing rather than reinforcing

01:45:45.860 | the emotionality of the trauma.

01:45:47.940 | And I think the key to that, again,

01:45:50.100 | is the absence of norepinephrine.

01:45:52.100 | So even though the emotional system is in high gear,

01:45:56.900 | without norepinephrine, you can actually divorce

01:46:03.300 | those highly activated emotions from the cognitive parts

01:46:08.900 | of the memory that you have just written out

01:46:11.060 | in that NT stage of sleep when the sleep spindles are going.

01:46:15.300 | So you've just now consolidated the information

01:46:19.540 | that you'll need to survive and to make that adaptive.

01:46:23.380 | And now you need to divorce from that schema

01:46:27.300 | and from that semantic parts of memory the emotional part.

01:46:31.220 | Because whenever you remember something,

01:46:33.060 | it's fine if you remember being emotional at the time,

01:46:37.780 | but you don't want to bring back and sew into that memory

01:46:41.220 | all of the same emotional systems.

01:46:42.740 | You don't want to bring back the heart rate changes

01:46:46.020 | and the sweating and all of that.

01:46:48.500 | You want to be able to remember all the parts of it

01:46:50.980 | and even remember that you were traumatized

01:46:53.220 | and that you did cry and that you did have,

01:46:55.540 | you know, your heart was racing.

01:46:57.700 | But when you're talking about it years later,

01:47:00.580 | you don't want to have to relive all that.

01:47:02.100 | Otherwise, who would ever want to recall a traumatic memory

01:47:06.180 | because you're basically putting yourself

01:47:07.540 | through the same trauma,

01:47:08.420 | which is what people with PTSD have.

01:47:10.740 | They don't want to recall this traumatic memory

01:47:13.300 | because it's reliving it like it's just happening again.

01:47:16.820 | So that's what we're thinking is that the emotional parts

01:47:21.220 | are not able to be divorced

01:47:24.420 | because the neurocerenorphine system

01:47:26.580 | is not downscaled during REM sleep.

01:47:28.660 | And so that REM sleep serves to instead reinforce

01:47:33.140 | and in fact amplify the emotions

01:47:35.140 | because your emotional system is up,

01:47:37.940 | locus surrealis is high, re-sewing in every night

01:47:42.500 | the emotionality of those memories

01:47:44.420 | and with the memory itself.

01:47:46.580 | You've told us a lot about locus surrealis

01:47:50.260 | and norepinephrine from locus surrealis.

01:47:52.020 | Is there any role for norepinephrine, epinephrine,

01:47:56.740 | and cortisol released from the adrenals?

01:47:58.660 | My understanding is that norepinephrine and epinephrine

01:48:04.100 | will not cross the blood-brain barrier,

01:48:06.020 | which is probably why we have a brain-based

01:48:08.500 | noradrenergic system, locus surrealis and other neurons.

01:48:12.660 | Actually, that's a question I should ask you.

01:48:14.660 | Are there other sites in the brain where norepinephrine

01:48:16.660 | is released from or is it just locus surrealis?

01:48:19.220 | So there are seven, nine different adrenergic,

01:48:23.780 | yes, there's nine different adrenergic structures.

01:48:26.900 | I'm sorry, I didn't ask, but it just occurred to me

01:48:29.220 | that in some cases like with Rafe,

01:48:31.940 | there are other sources of serotonergic drive in the brain,

01:48:35.860 | but Rafe is like the main site.

01:48:38.340 | That's the one that goes to the cortex

01:48:40.020 | and the locus surrealis is also the one

01:48:42.740 | that goes to the cortex.

01:48:44.100 | But there are other adrenergic sources,

01:48:45.860 | some from the brainstem that descend

01:48:48.500 | and help us to ignore pain, for example,

01:48:51.380 | when we're stressed and needing to run away from the tiger.

01:48:55.140 | We don't want to be thinking, oh, my ankle hurts.

01:48:57.380 | You want to just be able to ignore it

01:48:58.740 | and go do what you need to do.

01:49:00.020 | Yeah, so there are lots of other noradrenergic nuclei,

01:49:05.700 | but the locus surrealis is the main one

01:49:07.460 | that projects all over the brain.

01:49:09.060 | Actually, the only place it doesn't project

01:49:10.820 | is the dorsal striatum.

01:49:12.340 | You talked about ventral striatum and addiction.

01:49:14.820 | The dorsal striatum is the only place

01:49:16.740 | the locus surrealis doesn't project to

01:49:19.060 | and that's involved in procedural learning, motor learning.

01:49:22.580 | The kinds of learning that take over

01:49:25.060 | when your hippocampus, for example, is compromised,

01:49:28.020 | bilateral if you don't have a good hippocampus,

01:49:29.940 | you can still do procedural learning and it's great.

01:49:32.820 | It's a redundant system.

01:49:33.940 | And so if your locus surrealis is not working,

01:49:37.780 | if you don't have it anymore,

01:49:39.220 | you can still do, if you don't have a good hippocampus,

01:49:41.940 | you can still do learning

01:49:43.060 | through this dorsal striatum structure.

01:49:44.980 | So it might be for those kinds of learning functions,

01:49:48.980 | sleep deprivation where you never let

01:49:52.580 | the locus surrealis stop firing is okay

01:49:55.620 | because it doesn't have any receptors

01:49:58.020 | for norepinephrine anyway.

01:49:59.380 | So yeah.

01:50:00.900 | And what about bodily, like adrenals?

01:50:03.780 | Yes, adrenals, yeah.

01:50:05.380 | You know, I often remind people

01:50:07.060 | there's no such thing as adrenal burnout per se,

01:50:09.460 | that adrenals don't actually burn out.

01:50:12.260 | But some people have adrenal insufficiency syndrome.

01:50:16.020 | Other people have adrenals that are just chronically

01:50:18.980 | cranking out epinephrine, norepinephrine,

01:50:22.260 | and cortisol at the wrong times in particular.

01:50:25.380 | Yeah, yeah.

01:50:26.020 | So those are great questions

01:50:29.940 | and I think the answers to them have yet to be discovered,

01:50:33.220 | the connections between our periphery

01:50:35.140 | and our central nervous system.

01:50:36.580 | But we know that there are beautiful connections

01:50:38.980 | and its untapped source of being able to manipulate

01:50:42.980 | our brains is to work through our bodies.

01:50:45.620 | And so, adrenals do great things.

01:50:49.140 | They constrict our blood vessels,

01:50:50.900 | causing higher blood pressure,

01:50:52.580 | which help blood rush out to all the extremities

01:50:55.700 | that need blood, you know, our muscles, for example,

01:50:59.060 | for running away from the lion or the tiger or whatever.

01:51:03.060 | Or meeting a grand deadline.

01:51:04.660 | Or meeting a grand deadline.

01:51:05.940 | Or catching a train.

01:51:06.980 | Or catching a train, yeah.

01:51:08.900 | The adrenals help our hearts bump faster.

01:51:11.300 | Our muscles get perfused with the blood it needs.

01:51:15.300 | It diverts blood and everything away

01:51:18.420 | from our parasympathetic system, which is rest and digest.

01:51:22.580 | We don't really need to digest that croissant

01:51:24.820 | when we're running for a train.

01:51:26.020 | We can do that later.

01:51:26.980 | So it's doing really important things.

01:51:31.380 | What we don't know, because it doesn't cross

01:51:33.300 | the blood-brain barrier, is how that affects the brain

01:51:36.020 | and whether our, if we can independently activate

01:51:39.860 | our adrenals, when a time when our brain thinks

01:51:44.420 | that we should be fine and calm and asleep,

01:51:46.580 | how our brain detects that.

01:51:49.380 | Is it a feedback through, our heart is racing,

01:51:52.500 | and then our brain stem says, what's going on?

01:51:54.740 | My heart is racing.

01:51:55.620 | And then wakes us up.

01:51:57.060 | And then our hearts were racing together

01:51:58.980 | with our brain racing.

01:52:00.260 | We just don't know the answers to these questions yet.

01:52:04.020 | There are some good studies, old studies,

01:52:06.500 | but we need a lot more.

01:52:09.060 | - Very well.

01:52:10.340 | Another nod to the fact that there's lots of great work

01:52:13.060 | ongoing and still to do.

01:52:14.900 | I'd love for you to tell us about some of the work

01:52:17.300 | that you're doing more recently on the relationship

01:52:19.380 | between sleep and opiate use, withdrawal,

01:52:24.740 | relapse, and craving, just addiction generally.

01:52:29.060 | I get a lot of questions about people trying

01:52:32.660 | to come off benzodiazepines or people's challenges

01:52:36.740 | with benzodiazepine and other types of addiction.

01:52:39.380 | Yeah, what is the role of sleep in addiction

01:52:43.300 | and recovery from addiction and opiates in particular?

01:52:46.020 | - Yeah, well, this is a very young area.

01:52:48.980 | And in fact, my laboratory has just started.

01:52:51.140 | I have a graduate student who's been in my lab

01:52:53.860 | for just one year.

01:52:54.740 | She's done amazing work already,

01:52:57.220 | but completely groundbreaking work.

01:52:59.460 | And what she has discovered already,

01:53:01.620 | we don't have the paper out yet,

01:53:02.980 | but we're working on it,

01:53:04.740 | is that when animals withdraw from opiates

01:53:09.620 | and this has been sort of replicated in other ways

01:53:12.340 | with other types of things, our sleep is disturbed.

01:53:16.260 | Our sleep is terribly disturbed.

01:53:17.860 | And the amount of sleep disturbance

01:53:19.860 | predicts relapse behaviors.

01:53:21.700 | And you might think, well, of course,

01:53:24.100 | you're going to relapse if you can't sleep

01:53:25.940 | because opiates calm you down.

01:53:27.300 | Well, one of the reasons why opiates calm you down

01:53:29.220 | is because the locus coeruleus, again,

01:53:31.460 | blue spot is covered with opiate receptors

01:53:34.500 | that are normally really responsive

01:53:36.980 | to our endogenous opiates.

01:53:38.820 | And so what happens when we're pleased, for example,

01:53:43.860 | or laughing or whatever, our endogenous opiates

01:53:46.500 | activate those receptors in the locus coeruleus

01:53:49.780 | and calm it down.

01:53:50.820 | And it actually suppresses locus coeruleus activity,

01:53:54.980 | makes us happy and relaxed.

01:53:56.820 | One of the reasons why opiates are so addictive

01:53:59.460 | is because it also calms us down and makes us relaxed.

01:54:03.060 | But the problem with exogenous opiates

01:54:06.500 | is that they really strongly bind these receptors

01:54:10.500 | on our locus coeruleus.

01:54:11.860 | And if you take exogenous opiates again and again,

01:54:15.220 | like you're recovering from surgery, for example,

01:54:17.140 | and take these pain medications,

01:54:19.060 | is that our locus coeruleus struggles

01:54:20.900 | to do what it's supposed to do, which is keep us awake

01:54:23.780 | and learning and concentrating on things.

01:54:26.180 | So it will downregulate.

01:54:27.780 | It will internalize these receptors

01:54:29.860 | that are normally only occupied by endogenous opiates.

01:54:33.140 | And it will do this, it will change our genes

01:54:36.020 | that are associated with producing these receptors.

01:54:38.740 | So you actually have very many fewer receptors.

01:54:41.140 | So the locus coeruleus, at least during wakefulness,

01:54:43.540 | can fire and help us to do these things,

01:54:45.860 | like learn about our environment.

01:54:48.100 | And so if you long-term reduce

01:54:50.340 | the number of receptors out there,

01:54:51.860 | then when you withdraw the exogenous opiates,

01:54:54.980 | there is not enough of your endogenous opiates

01:54:57.620 | to be able to occupy those few receptors that are there.

01:55:02.660 | And our locus coeruleus has nothing to calm it down anymore,

01:55:05.220 | no pacifier.

01:55:06.500 | And it just fires and fires and fires.

01:55:08.660 | And that phasic and tonic high activity stresses us out

01:55:14.340 | because it's normally associated with stress.

01:55:16.980 | And so any exogenous stressor that adds to that

01:55:20.020 | and also activates our locus coeruleus,

01:55:22.340 | there's nothing to calm it down again.

01:55:24.340 | And so it just keeps firing.

01:55:26.180 | It disturbs our sleep.

01:55:27.380 | And that's why maybe sleep disturbance

01:55:30.660 | is an indicator of a hyperactive locus coeruleus

01:55:35.700 | and such a good predictor of relapse behaviors

01:55:40.260 | because nobody likes to live in that high stress state.

01:55:43.860 | And they will do anything to get back to normal.

01:55:47.940 | So the problem with taking these drugs

01:55:52.500 | is that it leaves you relaxed and happy.

01:55:59.540 | But then when you come off of it,

01:56:00.660 | you're worse than when you were at baseline.

01:56:04.100 | You take it again.

01:56:04.900 | It only brings you up this far

01:56:07.300 | because you have fewer receptors.

01:56:08.820 | When you come off it,

01:56:09.700 | you're down even more depressed and anxious.

01:56:13.140 | And depressed is a word I use loosely.

01:56:16.100 | And that's not what I should say.

01:56:17.380 | Certainly central nervous system depression.

01:56:19.380 | I mean, sleepier, less motivated, lower mood.

01:56:23.140 | Yeah.

01:56:23.460 | I mean, our locus coeruleus is actually,

01:56:25.300 | it's the anxiety kind of depression,

01:56:28.180 | actually the anxiety related depression.

01:56:29.940 | So yeah.

01:56:32.180 | So we don't know yet what,

01:56:34.820 | and there's some good research going on right now,

01:56:36.580 | what could restore our own endogenous receptors

01:56:40.580 | so that our own endogenous opiates

01:56:42.260 | can properly calm our locus coeruleus.

01:56:45.780 | Once that they have been tamped down by exogenous opiates,

01:56:49.460 | but that would be really one way

01:56:51.220 | that you can access the sleep disturbance.

01:56:53.940 | So we talked about sleep and the importance of sleep

01:56:56.420 | in terms of learning and memory,

01:56:57.620 | the importance of the structure

01:56:58.820 | of the 90 minute cycle for all of that.

01:57:01.620 | So you can imagine if your sleep is disturbed

01:57:03.700 | by too much locus coeruleus activity,

01:57:05.460 | the structure and the function of those sleep spindles

01:57:10.740 | and that theta during REM sleep

01:57:12.260 | and the lack of norepinephrine,

01:57:14.820 | all of those structures,

01:57:16.900 | all those functions for learning something new,

01:57:20.900 | like a new behavior that doesn't involve the drugs

01:57:24.820 | becomes compromised.

01:57:26.740 | And so that's something that Tania Lugos

01:57:28.980 | in collaboration with Pamela Kennedy at UCLA

01:57:32.420 | that we're looking at,

01:57:33.540 | how is learning and memory affected

01:57:35.380 | by the sleep disturbance?

01:57:36.580 | If there a way we can,

01:57:37.700 | in animals that have coming off of opiates,

01:57:40.820 | can we restore their sleeps to normal

01:57:43.140 | so that then they are less likely

01:57:45.220 | to do relapse kinds of behaviors.

01:57:48.500 | - Fascinating.

01:57:50.500 | And I will certainly have to have you back on

01:57:53.620 | to tell us the results of those studies.

01:57:55.300 | Meanwhile, I think for anyone

01:57:56.740 | who's trying to come off opiates,

01:57:58.900 | exogenous opiates and restore these systems,

01:58:01.780 | what I'm hearing is that it's going to take some time,

01:58:05.060 | but that any and all things that people can do

01:58:07.380 | to buffer their healthy normal sleep architecture,

01:58:10.740 | like morning and daytime sunlight,

01:58:12.660 | limiting bright light exposure,

01:58:14.020 | lowering the temperature at night,

01:58:15.380 | a number of things that we've talked about

01:58:16.500 | in this podcast. - Calming yourself,

01:58:17.780 | deep breathing exercises, exercises, meditation,

01:58:20.260 | whatever it is that helps you calm yourself

01:58:22.100 | before sleep, yeah.

01:58:22.900 | - Right, would facilitate not just sleep,

01:58:25.380 | but perhaps even accelerate the recovery

01:58:28.500 | and shorten this period of withdrawal,

01:58:30.820 | which from the questions I get

01:58:32.740 | and from what I hear can be absolutely brutal.

01:58:36.420 | - Yeah, oh, I can imagine.

01:58:38.340 | I had to take opiates for,

01:58:40.900 | I only took it for three days after giving birth

01:58:43.300 | to my first son, I think, second son, one of them.

01:58:47.220 | And I just said after three days, this is enough.

01:58:51.380 | I'm just going to try Tylenol.

01:58:53.060 | And so I weaned myself, not weaned.

01:58:56.260 | I just did a sudden sharp cutoff.

01:58:58.260 | And even though I felt,

01:58:59.780 | I didn't get the high of opiates

01:59:02.500 | when I was taking the Tylenol codeine.

01:59:06.180 | When I went off it, boy,

01:59:08.900 | it was like PMS times 100.

01:59:10.980 | I was so anxious and upset at little things

01:59:15.060 | and thankfully only lasted a few hours.

01:59:16.820 | But if I had taken it for a week or two weeks,

01:59:19.300 | who knows if my endogenous opiate receptors

01:59:22.820 | would have been permanently down-regulated

01:59:24.740 | and I would have been an addict, an addict.

01:59:28.100 | I would have been addicted.

01:59:29.060 | I shouldn't say an addict.

01:59:30.340 | There's negative connotations.

01:59:31.700 | It's just a very physiological state.

01:59:33.540 | So no judgments at all associated with it.

01:59:37.140 | So yeah, they're powerful, powerful painkillers,

01:59:41.140 | but can also alter your entire brain and rewire it.

01:59:44.340 | - Well, all the more reason why I and many others

01:59:47.940 | are grateful that you're doing this work

01:59:49.300 | to figure out ways that people can recover

01:59:51.460 | more quickly and more thoroughly.

01:59:54.020 | I must say you've taught us a tremendous amount

01:59:58.340 | in a relatively short amount of time

02:00:00.980 | about the architecture of sleep, the different phases,

02:00:04.340 | the relationship between sleep and dreaming

02:00:06.340 | and this incredible structure, locus coeruleus.

02:00:08.420 | And I'm so happy we also got into the ponds

02:00:10.340 | that just delights me because we rarely talk

02:00:13.220 | about the ponds on this podcast,

02:00:14.580 | but it's such an interesting structure.

02:00:15.940 | Sex differences that are important in creativity

02:00:19.620 | and problem solving and trauma, sleep spindles,

02:00:22.580 | just such a wealth of information

02:00:24.900 | and much of it that's actionable for people.

02:00:27.380 | So first of all, I want to say thank you

02:00:29.220 | for taking the time to sit down

02:00:30.420 | and have this conversation that so many people

02:00:32.580 | are sure to benefit from.

02:00:33.860 | I also want to thank you for doing the work you do,

02:00:35.860 | even though I'm a fellow neurobiologist.

02:00:37.860 | I think that it's not often that we take a step back

02:00:42.900 | and realize that it's really the work

02:00:44.820 | of hard thinking, hard, strongly motivated PIs,

02:00:52.660 | it stands for principal investigator by the way,

02:00:54.660 | PIs like yourself, graduate students and postdocs

02:00:57.060 | that really drive the discovery forward

02:00:58.740 | and that lead to these new therapeutics.

02:01:00.340 | Physicians are wonderful.

02:01:02.100 | Clinicians are absolutely wonderful,

02:01:03.860 | but clinicians don't develop new treatments.

02:01:05.780 | They only implement the ones that researchers discover.

02:01:08.660 | So thank you for being a brain explorer

02:01:11.140 | with a focus on growing the good in the world.

02:01:15.620 | I know I speak for everybody when I say thank you so much.

02:01:19.780 | - Thank you so much, Andrew.

02:01:21.540 | Thank you for being an amazing interviewer.

02:01:23.540 | You brought a lot out of me in a coherent fashion

02:01:26.580 | that normally I can't do when I'm speaking in public.

02:01:28.820 | - I don't know about that.

02:01:29.940 | I've heard your lectures and they're superb.

02:01:31.540 | We'll direct people to some of the other ones.

02:01:33.060 | - Well, thank you.

02:01:34.100 | And I also want to put a plug in for graduate students

02:01:36.500 | in general and the key and amazing role

02:01:39.220 | that they play in research.

02:01:40.500 | I'm a PI, as you said.

02:01:43.540 | I used to be a graduate student and a postdoc trainee myself

02:01:46.820 | doing all of this on the ground hands-on experimentation.

02:01:50.260 | It's so hard to do.

02:01:51.540 | It's so hard to do right.

02:01:52.740 | It's so hard to think through all of that.

02:01:54.580 | Now I'm a PI, I get to be an idea person and just say,

02:01:57.940 | hey, why don't you do this?

02:01:58.980 | And hey, what do you think about that?

02:02:01.060 | And they, of course, intellectually contribute so much

02:02:04.660 | to these planned experiments,

02:02:08.260 | but they also do the really hard work.

02:02:10.340 | And so I just want to say thank you, graduate students.

02:02:14.180 | Thank you to my graduate students

02:02:15.460 | and all graduate students out there.

02:02:16.900 | Thank you, postdocs.

02:02:17.740 | - We're all underpaid and to the major institutions,

02:02:21.220 | Stanford, UCLA, and all other major institutions,

02:02:23.460 | pay them more, please.

02:02:25.060 | We need them and they need to have a standard of living.

02:02:27.620 | I'm not afraid to say that despite my primary employer.

02:02:30.900 | Pay them more, they need it, they deserve it.

02:02:32.660 | - They deserve it, absolutely.

02:02:34.100 | - Great, well, we will absolutely have you back again

02:02:37.220 | if you'll be willing.

02:02:38.980 | And meanwhile, we will direct people

02:02:41.060 | to where they can learn more about you

02:02:42.900 | and your exciting work.

02:02:43.860 | And once again, thanks so much.

02:02:45.300 | - Thank you so much.

02:02:46.260 | - Thank you for joining me today for my discussion

02:02:48.580 | about sleep, mental health, physical health, and performance

02:02:51.380 | with Dr. Gina Poe.

02:02:52.900 | I hope you found it to be as informative

02:02:54.820 | and as actionable as I did.

02:02:56.260 | In fact, I'm already implementing the regularity of bedtime

02:02:59.620 | plus or minus half an hour

02:03:01.140 | in order to get that growth hormone release.

02:03:03.140 | And I can already see both my sleep scores improving

02:03:05.620 | and my feelings of daytime vigor and focus

02:03:08.580 | and other markers of sleep health improving as well.

02:03:11.380 | If you're learning from and or enjoying this podcast,

02:03:13.700 | please subscribe to our YouTube channel.

02:03:15.300 | That's a terrific zero cost way to support us.

02:03:18.020 | In addition, please subscribe to the podcast

02:03:19.940 | on both Spotify and Apple.

02:03:21.380 | And on both Spotify and Apple,

02:03:22.820 | you can also leave us up to a five-star review.

02:03:25.380 | If you have questions for us or comments or suggestions

02:03:27.380 | about guests you'd like me to include on the podcast,

02:03:29.460 | please put those in the comment section on YouTube.

02:03:31.540 | I do read all the comments.

02:03:33.460 | In addition, please check out the sponsors mentioned

02:03:35.700 | at the beginning and throughout today's episode.

02:03:37.700 | That's the best way to support this podcast.

02:03:40.100 | On the Huberman Lab Podcast, we often discuss supplements.

02:03:42.980 | While supplements aren't necessary for everybody,

02:03:45.300 | many people derive tremendous benefit from them

02:03:47.300 | for things like enhancing the quality and duration of sleep,

02:03:49.940 | for enhancing focus, and for hormone support.

02:03:52.580 | The Huberman Lab Podcast is proud to announce

02:03:54.580 | that we've partnered with Momentous Supplements.

02:03:56.820 | We've done that for several reasons.

02:03:58.020 | First of all, Momentous Supplements

02:03:59.700 | are of the very highest quality.

02:04:01.220 | Second of all, they mainly focus

02:04:02.980 | on single ingredient formulations,

02:04:04.820 | which is absolutely key if you want to develop

02:04:06.900 | a supplement regimen that's most biologically

02:04:09.540 | and cost-effective.

02:04:10.500 | It, for instance, allows you to alternate dosages

02:04:12.660 | across days to change the dosages of individual ingredients,

02:04:15.780 | so on and so forth.

02:04:17.060 | In addition, Momentous Supplements ship internationally,

02:04:19.780 | which we know is important because many of you reside

02:04:21.940 | outside of the United States.

02:04:23.540 | If you'd like to see the supplements discussed

02:04:25.060 | on the Huberman Lab Podcast, please go to Live Momentous,

02:04:27.700 | spelled O-U-S, so that's livemomentous.com/huberman,

02:04:31.460 | and you can get a 20% discount on any of those supplements.

02:04:34.180 | Again, it's livemomentous.com/huberman.

02:04:37.140 | The Huberman Lab Podcast has a zero-cost newsletter

02:04:40.260 | that includes summaries of podcast episodes and toolkits,

02:04:43.540 | so checklists of actionable tools that you can use

02:04:46.260 | for all aspects of mental health, physical health,

02:04:48.260 | and performance.

02:04:49.300 | You can access this completely zero cost

02:04:51.300 | by going to HubermanLab.com, go to the menu,

02:04:53.620 | and scroll down to newsletter.

02:04:55.140 | Just put it in your email.

02:04:56.260 | We do not share your email with anybody,

02:04:58.500 | and you will get our monthly newsletter.

02:04:59.860 | And there are also some examples of previous newsletters

02:05:02.500 | also there at HubermanLab.com.

02:05:04.580 | If you're not already following me on social media,

02:05:06.660 | it is Huberman Lab on all platforms,

02:05:08.740 | Instagram, Twitter, Facebook, and LinkedIn.

02:05:11.860 | And at all of those places, I cover science

02:05:13.780 | and science-related tools, some of which overlap

02:05:15.940 | with the content of the Huberman Lab Podcast,

02:05:17.780 | but much of which is distinct

02:05:19.060 | from the Huberman Lab Podcast content.

02:05:20.820 | Again, that's Huberman Lab on all social media platforms.

02:05:23.860 | Thank you again for joining me for today's discussion

02:05:25.780 | with Dr. Gina Poe, all about sleep and its relationship

02:05:29.380 | to mental health, physical health, and performance.

02:05:31.780 | And last, but certainly not least,

02:05:33.940 | thank you for your interest in science.

02:05:35.620 | [upbeat music]

02:05:38.200 | (upbeat music)

Dr. Gina Poe: Use Sleep to Enhance Learning, Memory & Emotional State | Huberman Lab Podcast

Chapters