Essentials - Use Sleep to Enhance Learning, Memory & Emotional State | Dr. Gina Poe.

Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now for my discussion with Dr. Gina Poe. Dr. Gina Poe, welcome. Thank you. I've really been looking forward to this conversation. I know that many people are going to be excited to learn about your work as it relates to sleep, as it relates to problem solving, creativity, and a number of other important topics. To start things off, I would love for you to educate us a bit about this thing that we are all familiar with, and yet very few of us understand, which is sleep. Could you describe the various phases of sleep that exist? What distinguished them? And perhaps frame this within the context of what would a perfect night's sleep look like? All right, so sleep is really different from wakefulness, and in fact, can't be replaced by any state of wakefulness that we've been able to come up with so far. Our brain chemistry is completely different. And in the different stages of sleep, which there is non-REM and REM, are the two major states of sleep. Those two states are entirely different from one another too. And even within non-REM, there are three states. Stage one, which is what you slip into when you first falling asleep, it's dozing. There's kind of an interesting rhythm that goes on in the brain. It's kind of a fast gamma rhythm. And then there's stage two, which is a really cool state. We sort of used to ignore sleep researchers because it was a transient state between wakefulness and the deep stage three slow-wave sleep, which is the most impressively different, which is when big slow waves sweep through our brain, and now we realize that it cleans our brain. One of the things that those big slow waves do is cleans our brain and does other really important things to restore us from a day of wakefulness. And then REM sleep, which is the most popular because that's where we have the most active dreams. When you wake up someone out of REM sleep, they'll almost always report having dreamed something really bizarre. That's called REM sleep, rapid eye movement sleep. So those are the four states of sleep, of human sleep. And we cycle through them every 90 minutes or so. And then we start over again. And we have about five of those per night for a perfect night's sleep, four or five, something like that. So a perfect night's sleep is seven and a half, eight hours. And what about the sleep where we are lightly asleep and we might have a dream that has us somehow thinking about movement or that we jolt ourselves awake? That often happens early in the night, right? Yeah, that's the first stage, stage one and stage two of sleep. And stage two sleep is really cool because that has something called sleep spindles and K-complexes. And what sleep spindles are are a little bit of activity that's 10 to 15 Hertz in frequency. It's a conversation between the thalamus and the cortex. The thalamus is the gateway to consciousness and the neocortex processes all our cognition. And if you wake up out of that state, you will often report a dream, like a hallucination style dream. It won't be a long dream report like you have out of REM sleep, but it will be some hallucination state. Are they quite different than the patterns of sleep and dreaming that occur later in the night or toward morning? There is some evidence that the first four hours of sleep are very important for memory processing. And in fact, if you've learned something new that day or have experienced a new sensory motor experience, then your early sleep dreams will incorporate that experience much more than the later sleep dreams. Later as that memory gets consolidated from the early structures, which are the hippocampus deep in the temporal lobe to the cortex in a distributed fashion, that memory seems to move from that hippocampus to the cortex. And also the dreams that incorporate that memory also move later in the night. So there was a great study by Siddhartha Riveiro who studied the consolidation of memories from the hippocampus to the cortex in a rat across the period of a full day sleep because rats sleep in the daytime. And he found that each subsequent REM sleep period moved that memory from the hippocampus to the first area that projects to it and then the second area and then the third area. And you can see the memory moving throughout the sleep. There's a number of different hormones associated with the different stages of sleep. We know that melatonin is a hormone of nighttime that makes us sleepy. What about growth hormone release? When does that occur during sleep? So growth hormone release happens all day long and all night long, but the deep slow-wave sleep that you get the very first sleep cycle is when you get a big bolus of growth hormone release and in men and women equally. And if you miss that first deep slow-wave sleep period, you also miss that big bolus of growth hormone release. And you might get ultimately across the day just as much overall growth hormone release, but endocrinologists will tell you that big boluses do different things than a little bit eked out over time. There's also a big push to synthesize proteins. So that's when the protein synthesis part that builds memories, for example, in our brain happens in that first cycle of sleep. So you don't want to miss that, especially if you've learned something really big and needs more synaptic space to encode it. How would somebody miss that first 90 minutes? So let's say I normally go to sleep at 10 p.m. and then from 10 to 11.30 would be this first phase of sleep and that's when the big bolus of growth hormone would be released. Does that mean that if I go to sleep instead at 11.30 or midnight, that I miss that first phase of sleep? Why is it not the case that I get that first phase of sleep just simply starting later? Every cell in our body has a clock and all of those circadian clocks are synchronized. And so our cells are ready to respond to that growth hormone release at a particular time. And if we miss it, and it's a time in relation to melatonin also, so if you miss it, yeah, you might get some growth hormone release, but it's occurring at a time when your clock has already moved to the next phase. And so it's just a clock thing. So what this means is that we should have fairly consistent bedtimes in addition to fairly consistent wake times. Is that right? Exactly. And in fact, one of the best markers of good neurological health when we get older is consistent bedtimes. What other things inhibit growth hormone release or other components of this first stage of sleep? Are there things that I perhaps do in the preceding hours or the preceding day, like ingest caffeine or alcohol that can make that first stage of sleep less effective, even if I'm going to sleep at the same time? Alcohol definitely will do that because alcohol is a REM sleep suppressant and it even suppresses some of that stage two transition to REM with those sleep spindles. And those sleep spindles, we didn't talk about their function yet, but they're really important for moving memories to our cortex. It's a unique time when our hippocampus, the sort of like the RAM of our brains, writes it to a hard disk, which is the cortex. And it's a unique time when they're connected. So if you don't want to miss that, you don't want to miss REM sleep when it is also a part of a consolidation process. And alcohol before we go to sleep will do that. Until we've metabolized alcohol and put it out of our bodies, it will affect our sleep badly. What about the second and third 90 minute blocks of sleep? Is there anything that makes those unique? What is their signature besides the fact that they come second and third in the night? There's more and more REM sleep the later the night we get. There's also a change in hormones. You know, the growth hormone and melatonin levels are starting to decline, but other hormones are picking up. So it is a really different stage that you also don't want to shortchange yourself on. And I think that's the stage many studies are showing that those are the times in sleep when the most creativity can happen. That's when our dreams can incorporate and put together old and new things together into a new way. And our schema are built during that time. So that's when your computer of your brain is opening folders and comparing documents, seeing if there, is there anything the same? These two documents look very much the same, but there's a little bit of difference and it can link those conceptually so that that's probably one of the origins of creativity is finding things that are related, maybe just linked a little bit, and you can find that link and strengthen it if it makes your schema interesting and different. Many people, including myself, tend to wake up maybe once during the middle of the night to use the restroom. I've tried to drink less fluid before going to sleep. I've heard also the impulse to urinate is also dictated by how quickly you drink fluid, not just the total volume. So I've switched to sipping fluids more slowly for my last beverage of the day, which seems to help. Is there any known detriment to this middle of the night waking, or should we consider it a normal feature for some people's sleep architecture? I think we shouldn't worry about it, actually. Sleep is really incredibly well homeostatically regulated. And so really don't worry about how much you're sleeping as long as you're not intentionally depriving yourself of sleep by doing something really rewarding and exciting, because even that is stressful to your body and deprives you of a lot of the things we're talking about. It's absolutely normal to wake up at least once in the middle of the night to go to the bathroom. And as long as you can get back to sleep in a reasonable amount of time, or even if it takes you an hour, don't worry about it, as long as you have a lifestyle that allows you to then make up that sleep either the next morning or the next night, going to bed a little earlier. What is unique, perhaps, about the architecture of dreams and sleep in the, let's say, the last third of the night, or the second half of the night? Right, yeah, in the second half of the night, we have longer REM sleep periods, and those are considered the deepest sleep, even though slow-wave sleep, big slow-wave, is considered deep. It is deep, but actually- Yeah, they call slow-wave sleep deep sleep, and REM sleep, rapid, I mean, but now you're telling me that REM sleep is actually the deeper sleep? The reason why you call slow-wave sleep deep sleep is because it's difficult to arouse people out of that state, and when you do arouse them out of that state, they're most often confused and just want to go back into sleep and can go back pretty easily. If you arouse someone out of REM sleep, they're more likely to report something that was really kind of almost like wakefulness. It was so vivid, and maybe one of the reasons why REM sleep is deeper is especially in adults and older people that deep slow-wave sleep goes away, so it's not as deep, it's not as big. The slow-waves aren't as large, which is probably problematic, but we're not sure, and so then REM sleep becomes the deepest stage. We are paralyzed during REM sleep, correct? Yes, normally paralyzed, and that's really good because that's the time when we're actively dreaming storyline dreams and we could hurt ourselves. We're actually really cut off from the outside world in terms of responding to, say, this table or a window or a door, and so different from sleepwalking, which is out of slow-wave sleep, and out of slow-wave sleep, that sleepwalking is a mixture between sleep and wakefulness. You can cook a full meal, drive your car while you're in deep slow-wave sleep. It's scary because you never know what you're going to do. You don't have voluntary control over it. You have no conscious control over it, but you can actually safely navigate some situations in sleepwalking and actually have a conversation, although it may not make much sense when you're sleep-talking. In REM sleep, you're not processing the outside world, and instead, when you're acting out your dreams, you could be doing things like walking through a plate-glass window or falling off of, you know, down the stairs, things like that. So you really want your muscles to be inactivated during REM sleep. Otherwise, you will act out those dreams and really hurt yourself or your bed partner. So as people start to approach morning or the time when they normally would wake up, I've heard that it's important to, if possible, complete one of these 90-minute cycles prior to waking up. That is, if you set your alarm for halfway through one of these 90-minute cycles that come late in the night of sleep, that it can lead to rather groggy patterns of waking. It's called sleep inertia. When we wake up out of the wrong state, I liken it to a washing machine cycle. This 90-minute cycle is like a washing machine cycle, and the first part is to add water, right? Then your clothes are soaking wet. You don't want to open the washing machine and try and function, put them on and wear them around while they're soaking wet and full of soap. So you'd have to wait until the cycle is through before you can, well, actually, let's put it in the dryer too, before you want to wear them. So you can function, it just takes a little while for those clothes, that brain to dry out so you can actually function well, but it's better to wait through the whole cycle is complete. So that's why you want to set that 90-minute alarm clock. And again, that's around 90 minutes because the first stage of sleep, the first cycle of sleep is actually a little longer, more like 105, 110 minutes, but then the second ones and third ones, they get sort of shorter and shorter as the night goes on. And in the last few cycles, you're just doing the N2 REM sleep cycle, which takes less time. And if you wake up out of REM sleep, there's usually no problem cognitively. Are you a fan of sleep trackers? Yeah. Do you use one? I have one on. I don't live my life by them because the best ones right now are about 70% effective at staging your sleep. So 70%, it's okay. It's okay, but take it with a grain of salt is what I'm saying. Tell us a little bit more about the washout that occurs in the brain during sleep and perhaps if there are any ways to ensure that it happens or to ensure that it doesn't happen. And obviously we want this to happen. Yeah. We talked about the circadian clock and how certain things happen at certain times. Well, one of the things that happens when we're awake and talking to each other is that there's a lot of plasticity. There's something that I'm learning from you today and you're learning from me. And that changes our synapses and it changes the way our proteins are going to be folded and changed during sleep. This process actually uses a lot of ATP, the power structure, the fuel of the brain. It unfolds also proteins while we're doing this, while we're using them. And so during that first part of the night, when we first fall asleep in the first 20 minutes or so, we're building that adenosine back into ATP. And that's probably why power naps are called power naps because we're actually rebuilding the power. And then we're also cleaning out through the deep slow waves of sleep, we're cleaning out all those misfolded proteins, unfolded proteins, and other things that get broken down and need to be rebuilt when we're asleep because of its use during wakefulness. So I liken that to having a big party during wakefulness and you need all those party goers to leave in order to do the cleanup. What happens when a neuron is firing is that it expands. The membrane expands a little bit, becomes more translucent. That's how we know, one of the ways we know that neurons expand when they fire. And so every action potential, the membrane expands a little bit as sodium brings water into the cell. And then when they're silent, they contract. And so during slow waves, the cool thing is that the reason why you can measure them is that all the neurons at the same time, not all of them, but a good portion of them are firing at the same time and silent at the same time. And so you think about that as contracting and expanding all at the same time. It's kind of like a bilge pump of the brain. So that can pump out. Glia are also really important for this in terms of cleaning up debris and transferring it to where it needs to go. So I think of it actually as a bilge pump, cleaning out our brain. Here you're talking about literally an expansion and a contraction of the neurons in unison and pushing the fluid through, cleaning out any misfolded proteins or debris that might occur on the basis of these metabolic pathways. And the consequence of that is to what? To leave the brain in a state of more pristine action for the next day, is that right? Yeah, you think of it, again, like a party. And if you don't clean up after that party and you try and hold another one the next day, it's gonna get more clogged. People have a harder time moving around and enjoying themselves. And if that builds up day after day, it's gonna be cognition, that would be the party goers moving around, becomes hard. And so this bilge pump that you describe is associated with the big slow waves of slow wave sleep. So this is gonna occur more or less in the first third of the night, is that right? That's right. And is this similar to the case with growth hormone where if you go to sleep later than you would normally, you miss the washout. It's not, you don't delay it, you miss the washout. That's right, so if you go to sleep at one or two in the morning, your sleep is still gonna be dominated by N2 and REM sleep, not by slow wave sleep. So you need to get that first bit of sleep. Would a caveat to that be, if somebody normally goes to sleep at one or 2 a.m. and wakes up at 10 a.m., if that's their normal sleep cycle? Yeah, it should be okay. Somebody would wanna do a sleep study with people who do that normally and see if also the melatonin releases later and the corticosterone rise that happens normally in the morning also happens later. So if everything shifted, good. I'd love for you to tell us about this incredible structure in the brain, which is the locus coeruleus, and hopefully tell us a little bit about its relationship to epinephrine, aka adrenaline. Yeah, so the locus coeruleus is filled with neurons that have in them norepinephrine, which is the brain's version of epinephrine or adrenaline. It's also called noradrenaline. And what it does is it, just like adrenaline in the rest of our bodies, it helps prime us to respond to our environment. So when locus coeruleus neurons fire and fire in a burst, we can switch our attention, and they will fire in a burst if, for example, a loud noise happens in the middle of your concentrating on something. It fires, and it helps you switch your attention to that thing and then learn quickly from it. So it's really important in a stress response. It helps us do quick one-trial learning. But just tonic levels are signature of wakefulness and alertness. So too much is panic with a locus coeruleus activity. A burst is switching attention, and then tonic levels are sustained constant attention. And then when we go to sleep, the locus coeruleus slows and goes from about, on average, two Hertz to about one Hertz, one cycle per second tonically. And then when we go into REM sleep, it's the only time when it shuts off completely. And it appears that that complete silence is really, really important for a number of things. And the main thing that I think it's important for is the ability to erase and break down synapses that are no longer working for us. So they encode things that are false now, or they are encoding things that we learned in the novelty encoding pathway of our brain that have now been consolidated to other pathways. And so we need to now erase them from the novelty encoding pathway. And that is really, really important for being able to continue to learn things all of our lives. So like erasing that REM or that, I don't know, what do you call those discs that you stick in the computers? Thumb drives. Yeah, erasing your thumb drives. That thumb drive is what you carry around all day long. And then during sleep, you write that thumb drive to the cortex, to the long-term memory structures, and you need to refresh that thumb drive. And that's what happens during REM sleep when the locus realis is off. And so if we're not able to do that, we fill up that REM really quickly, or that thumb drive really quickly, and we're not able to learn new things. Even memories that are years past, if you're never able to downscale that novelty encoding structure and purge it from that traumatic memory, it will stay fresh and new and then become maladaptive. What approaches are you aware of that can turn down the output of locus coeruleus during these phases of sleep and allow late stages of sleep each night to have their maximum positive effect? Is there anything that I can do besides avoiding serotonergic or neuroadrenergic compounds? Well, I would also avoid anything just prior to going to sleep that might excite those systems. So a lot of novelty, stress-inducing video games. Try and enter sleep with as much calm as you can. So maybe deep breathing exercises. That's a beautiful way to calm your sympathetic fight-or-flight system is deep breathing. And if there's a way you can make your sympathetic nervous system calm down before you go to sleep, might free for you meditation or deep breathing exercises. It might be for some a warm bath or a comforting book. Nothing too exciting, but also nothing too boring perhaps. Just something right in the middle which makes you feel happy and calm is what you should do. And if you instead go to sleep while you're anxious or hyped up, then your sleep could become maladaptive. I'd love for you to share with us a little bit more about the spindles that have come up a few times. The density of our sleep spindles, the number that we produce per minute is well correlated with our intelligence in the first place and that no matter what your intelligence is and no matter what your sleep spindle density is, if you learn something during the day and increase your sleep spindle density, it's really almost perfectly correlated with our ability to consolidate that information and incorporate it into the schema that we already have in our brain. So if you try and learn something new, even if your sleep spindle density at baseline is great, if you don't increase your sleep spindles that night, you're not gonna use sleep to really incorporate it. One of the things we now know through some great studies by Julie Seep and Anita Luthi is that sleep spindles are accompanied by an incredible plasticity out in the distal dendrites, the listening branches of our neurons that listen to other cortical areas. So there are proximal dendrites in our neurons that listen to the external world and are conducted through the thalamus and then there are distal dendrites which listen to an internal conversation that's happening in our brains. It's kind of our internal state, really. And during sleep spindles, that's when those distal dendrites are able to best learn from other cortical areas and from the hippocampus. It is during sleep spindles that the hippocampus and the cortex are best connected and when that incredible plasticity can happen. So when I talk about schema, that's a cortical, cortical thing. There's big surges of calcium into those distal dendrites and where plasticity happens in just huge amounts. During that sleep spindle stage of sleep, which is N2 stage, there's another excitatory event that comes all the way from the brainstem and projects everywhere in our cortex, which is called PGO waves, which we should generalize to P waves because they come from the pons and go to the thalamus and then the cortex happens all over the brain and that is where glutamate, which is a major excitatory neurotransmitter involved in learning and plasticity is being released in big amounts also in those distal dendrites. So P waves and spindles work together to cause plasticity and so our schema together, which could be the origins for insight and creativity. Now, when P waves were first discovered, it was thought to be random because this small area that generates P waves all over the brain projects all over the thalamus and causes P waves all over and you don't measure P waves all over the brain at the same time. In fact, it's just seems sporadic and random and P waves also happening even more during REM sleep, rapid eye movement sleep. So that's why people think that REM dreams are so random is because these P waves are random and they could generate dreams because they're an internal source of excitation that kind of replaces the outside world. During our dream state. And so these P waves, if they are random, could be the underlying reason why creativity can happen there is because we're randomly activating, co-activating different things in our brain that we can then sew together. But it might not be as random as we think. So that's a caveat there. So locus coeruleus is suppressed. So we can't release norepinephrine. We can't act out our dreams. This almost starts to sound like a little bit of a built-in while sleeping trauma therapy. So please, if there's anything about locus coeruleus and dreams that can help people basically extinguish traumas or traumatic features to real life events, we definitely want to know about them. Yeah, yeah. Well, I think one of the things that people thought might help after a trauma like a school shooting or whatever, you know, car accident is to talk about it. But in fact, that ended up being counterproductive. And I think one of the reasons why it was counterproductive is because it didn't take them back down. It brought them up and continued to reactivate the emotions of it, but then didn't emphasize the safety effect that it's over or help them work through how they might avoid it again in the future to calm the sympathetic nervous system down again before they went to sleep. And none of these studies has sleep ever been considered. But to me, that's the key part is bringing down your sympathetic nervous system before you go to sleep so that your sleep can be adaptive. Your locus coeruleus can shut off like it normally does or should do, and then able to erase the novelty of it. The other thing that I just mentioned a minute ago was that the emotional system is highly activated in REM sleep, and that's definitely true. And that might seem counterproductive in terms of, you know, the nightmares and how to help REM sleep be a therapeutic thing rather than reinforcing the emotionality of the trauma. And I think the key to that again is the absence of norepinephrine. So even though the emotional system is in high gear, without norepinephrine, you can actually divorce those highly activated emotions from the cognitive parts of the memory that you have just written out in that N2 stage of sleep when the sleep spindles are going. So you've just now consolidated the information that you'll need to survive and to, you know, to make that adaptive. And now you need to divorce from that schema and from that semantic parts of memory, the emotional part. Because whenever you remember something, it's fine if you remember being emotional at the time, but you don't wanna bring back and so into that memory all of the same emotional systems. You don't wanna bring back, you know, the heart rate changes and the sweating and all of that. You wanna be able to remember all the parts of it and even remember that you were traumatized and that you did cry and that you did have, you know, your heart was racing. But when you're talking about it years later, you don't wanna have to relive all that. Otherwise, who would ever want to recall a traumatic memory because you're basically putting yourself through the same trauma, which is what people with PTSD have. They don't want to recall this traumatic memory because it's reliving it like it's just happening again. So that's what we're thinking is that the emotional parts are not able to be divorced because the norepinephrine system is not downscaled during REM sleep. And so that REM sleep serves to instead reinforce and in fact, amplify the emotions because your emotional system is up, locus aureolus is high, re-sewing in every night the emotionality of those memories and with the memory itself. I must say, you've taught us a tremendous amount in a relatively short amount of time about the architecture of sleep, the different phases, such a wealth of information and much of it that's actionable for people. So I wanna say thank you for taking the time to sit down and have this conversation that so many people are sure to benefit from. I know I speak for everybody when I say, thank you so much. Thank you so much.