The Mysterious World of REM Sleep. Podcast with John Peever

As the stage in which people dream each night, rapid eye movement (REM) sleep can bring euphoria, terror, and even genuine harm in some instances.

On transition into REM sleep, your body enters a fascinating state. True to its name, REM sleep results in characteristic, swift, saccadic eye movements. But many other features of REM sleep are noteworthy. During REM sleep, activity in some brain regions is even higher than during wakefulness, so it’s little surprise that it is from this sleep stage that you naturally arise each day. This state has therefore been dubbed the “gateway to waking”. But while your brain is highly active in REM sleep, your muscles (other than your heart and respiratory muscles) are actually paralyzed. For this reason, REM sleep is sometimes known as “paradoxical sleep”.

Your body cycles through different stages of sleep each night, predictably moving from light sleep to deep sleep to REM sleep every 90 minutes or so. However, how much time you spend in each stage shifts across the night, and REM sleep makes up an increasing proportion of sleep as the night progresses. Interestingly, the nature of REM sleep itself changes subtly across the night too.

But why is this so?

And what exactly is REM sleep actually for?

This brings us to the topic of the latest episode of humanOS Radio.

In this show, I speak with Professor John Peever, Director of the Centre for Biology Timing and Cognition at the University of Toronto. Professor Peever’s research focuses on how the brain regulates wakefulness and sleep, and our discussion focuses on REM sleep. Professor Peever recently coauthored a terrific review of the scientific literature on REM sleep (1).

Professor Peever strongly supports the National Sleep Foundation’s maxim that sleep is “just as important as diet and exercise, only easier”. Yet it seems that not all mammals have REM sleep. If some animals seemingly thrive without REM sleep, is it really essential?

People have long speculated that REM sleep is critical to certain processes, one of which is learning. Historically, scientists have not been able to prevent REM sleep in very precise ways. Recent progress in the use of certain techniques has produced solutions to this problem, however.

One of these techniques is optogenetics, a method in which scientists use light to control the electrical activity in specific neurons that have been genetically modified to have ion channels that are sensitive to light. Using this technique, Antoine Adamantidis and his colleagues at McGill University in Montreal starved only a small network of cells of REM sleep in a brain structure named the medial septum in mice (2). The researchers found that REM sleep loss impairs animals’ learning – they fared worse in a widely used test of memory that involves exploration of familiar and novel objects.

Other studies have shown that pharmacological suppression of REM sleep doesn’t really impair learning, however, and many people routinely take drugs that potently suppress REM sleep, with few apparent ill effects. (These drugs include two categories of compounds used to treat depression, namely monoamine oxidase inhibitors and tricyclic antidepressants.) Other drugs (like LSD) prolong time spent in REM sleep, but it’s difficult to determine the effects of this increase in isolation of other effects in humans.

During normal REM sleep, activity in motor neurons (the nerves that relay signals to muscles to produce force) is suppressed, leading to paralysis (muscle atonia) so that you don’t carry out your dreams, since doing so could be risky! Some people, however, do not experience this loss of muscle activity and act out their dreams. This condition is called REM sleep behavior disorder, and the majority of people with this pathology go on to develop crippling neurodegenerative diseases, such as Parkinson’s. In contrast to REM sleep behavior disorder, the neural circuits that produce muscle atonia are active at inappropriate times during bouts of cataplexy in narcolepsy, and these poor people collapse, against their own volition.

Many questions related to these sleep disorders remain unanswered. Considering REM sleep behavior disorder, is it that the cells that cause muscle paralysis are damaged? Or is suppression of muscle activity during REM sleep important for brain health? If so, this might explain the increased risk of diseases of the nervous system in these patients.

In this episode, Professor Peever sheds light on these questions. He also discusses whether REM sleep behavior disorder prevalence differs between men and women, the social consequences of REM sleep disorders, whether there is an optimum amount of REM sleep, tips to get better sleep, and his thoughts on apps that supposedly wake you from your slumber during REM sleep.

Tune in below for more!

On Soundcloud, iTunes, Google Play, Stitcher, and YouTube.

Dan prepared for and conducted the interview, Greg wrote the first draft of this blog post, Dan edited the draft, and Professor Peever continues to do the hard work!

Was this interesting and helpful? You can help support the work of the humanOS team by making a donation. If you do, thank you so much – we really appreciate your support! And no worries if you can’t chip in, the important thing is that you benefited from listening today.

John Peever - 00:06: Some of the early examples of what's going on in REM sleep were actually written or drawn actually on the caves in France.

Kendall Kendrick - 00:13: HumanOS, learn, master, achieve.

Dan Pardi - 00:28: John Peever, welcome to humanOS Radio.

John Peever - 00:31: Thanks for having me Dan.

Dan Pardi - 00:33: Tell us about what you do?

John Peever - 00:34: I'm a Professor at the University of Toronto in Canada and what our lab does is to try and figure out how the brain gets you to go to sleep and gets you to wake up and in particular, what our research is focused on is really understanding dreaming sleep. What parts of the brain initiate dreaming sleep and what does dreaming sleep actually do for the brain and the body.

Dan Pardi - 01:00: Let's talk about the process of sleep initiation and then what type of stages do we go through in the sleep process.

John Peever - 01:08: There are really two types of sleep. I think most people intuitively understand that there are two types of sleep. There's what we call deep sleep, which is that phase in the sleep cycle, where you fall asleep and you sort of drift off in never land, don't really remember much about what happens from the time that you were awake to the time you went to sleep. But then after about 90 minutes, at least in people, they enter into this amazingly curious state of dreaming sleep or rapid eye movement or REM sleep, in which, they tend to have very, very vivid, surreal dreams. Most people will be familiar with Salvador Dali's strange paintings of clocks melting over rocks and that's the type of strange imagery that happens during dreaming or REM sleep.

01:56: Humans and most mammals actually go through that very standard cycle of sleep where you drift into that deep sleep and then you go into dreaming sleep, and then you go back into deep sleep and then you go back to the dreaming sleep. There's this oscillation of those two types of sleep in most mammals. Scientists actually define REM sleep in a very quantitative way, that the brain, once it goes from that deep phase into REM, changes the patterns of activity in the cells and if you measure all the brain activity on the surface of the brain, REM sleep has some really amazing, what we call, brain wave signature that's very different than that phase of deep sleep.

02:34: REM sleep is also characterized by as the name rapid eye movement and implies, eyes darting back and forth. One of the other really amazing features is that even though the brain, during REM sleep is almost as active and can be more active than when you're alert and awake, you have this paralysis of the muscles of the body, except for the breathing muscles and the heart, most of the body's muscles are actually forced into a state of muscle paralysis. It's that signature of rapid eye movements, very characteristic signatures and brain wave activity in the muscle paralysis accompanied by the dreaming that scientists used to, in human and many animals, characterize REM sleep.

03:16: Now, not all animals actually experience REM sleep. So for example dolphins and whales seem to have parts of what human REM sleep look like but not all of them and so, most terrestrial mammals have REM sleep but sea mammals, particularly, dolphins and whales, they don't seem to have REM sleep.

Dan Pardi - 03:35: So it can look different in different animals and then, are there different types of REM sleep even in humans? Or is it just one phase that always looks the same?

John Peever - 03:42: No, REM sleep is actually pretty different across the night. At the beginning of the night, the first time that you enter into REM sleep, it's a really short period. Then as the night progresses and you get closer to the morning, every time you enter into a period of REM sleep, those periods get longer. There's lots of evidence to suggest that even the signatures of REM sleep that I mentioned like how quiet your muscles are and the type of dreaming and brain activity, they can `actually change as well across the night. So, REM sleep, although it's in the broadest sense, pretty much the same, it seems to evolve across the night.

Dan Pardi - 04:19: What are some of the theoretical purposes of this type of sleep?

John Peever - 04:23: I think REM sleep is one of those amazing phases in the human and animal life span that if you could imagine a purpose for REM sleep, someone has proposed ... You know, we sort of go back into some of the earliest sort of examples of what's going on in REM sleep were actually written or drawn actually on the caves in France. So one of the other things I didn't mention is that in men, they typically have, or in healthy men, they have an erection during REM sleep. One of the very earliest examples of REM sleep in history is actually a cave drawing in the Western part of France showing that there are men with erections in little bubbles, almost like cartoon bubbles above their head-

Dan Pardi - 05:04: Oh, wow.

John Peever - 05:05: Depicting [inaudible 00:05:05]. I think that was their way of understanding what REM sleep might be doing and so in early history, a lot of different cultures thought that your mind was leaving your bodies and tele transporting to another realm and as crazy as that might seem, there are actually some sleep scientists, the most famous of all of them, being [inaudible 00:05:23], who actually thought that wasn't necessarily a crazy idea that it was time for the brain to sort of disconnect from reality and maybe even the body.

Dan Pardi - 05:31: If somebody is not getting adequate amounts of REM sleep, what are some things that we see as a consequence?

John Peever - 05:38: So this has been one of the real sticking points for hardcore scientists is how do you actually figure out what REM sleep is doing for the brain and the body. One of the real problems and this might be really fine-grained but how do you actually figure out how to figure out what REM sleep is doing and what has classically been done is to just basically take REM sleep away, sort of starve the brain and body of REM sleep. But a lot of scientists have really questioned the validity of that.

06:04: One of the most recent and amazing studies is by a colleague of mine in Switzerland, Antoine Adamantidis, where, what he decided to do was to prevent just one element of REM sleep and look at how that impacts learning and why he did that was there's a very characteristic, as I mentioned before, signature and brain activity that happens in REM sleep. He basically starved a very tiny group of cells in the brain of that activity and what he found is when he did that, it didn't disrupt sleep, it didn't wake the animals up, it didn't do anything to it perturbiously but what he found is the animals didn't learn as well once he did that. He really sort of discovered that one of the signatures in REM sleep that are very characteristic brain activity seems to help you learn better.

Dan Pardi - 06:46: In my conversation with Professor Luis de Lecea at Stanford, we talked about the techniques that are now being used to selectively inhibit the function of certain neurons in a live animal. Is this the optogenetic inhibition of GABA cells in the medial septum that was able to derive this finding?

John Peever - 07:05: Yeah, so one of the really amazing things in neuroscience is the ability to study cells in the brain and what they do for normal behavior. The study I was referring to by Dr. Adamantidis, he was able to basically silence very specific group of cells in the region of the brain called the medial septum that generate this characteristic brain activity in REM sleep and showed that when you silence their activity, you don't change how much REM sleep a mouse has, you the particular brain activity that happens in REM, these mice weren't able to learn as well. So, optogenetics is really a powerful way of doing that. It's just you're able to use light to turn cells on and off in the brain then study how those cells contribute to a behavior. In this case, REM sleep behavior.

Dan Pardi - 07:53: Has he been able to activate GABA cells in the medial septum during REM sleep to see if you could actually enhance learning?

John Peever - 08:00: They've not published anything about that yet but I'm guessing that that is what their plan is, is to basically fortify those brain signatures in REM sleep and see if you can learn better and, presumably, seeing if you can make it happen while you're awake and even learn better than when you're just sleeping.

Dan Pardi - 08:19: So the mice spent the same amount of time in REM sleep. From a electroencephalographic recording, you couldn't tell that there was any difference but by the manipulation of the type of waves that were occurring during sleep, it website actually changing whether it was functional or not.

John Peever - 08:34: Yeah, so they did a whole bunch of really [inaudible 00:08:37] deep stage of sleep, where they're not normally active or it's called non-REM sleep or slow-wave sleep and they [inaudible 00:08:45] it seems that just preventing those cells from working just during REM sleep, is what's important for perturbing behavior. There's been a really long-standing hypothesis by many but not all in the science community that REM sleep is really important for a specific type of motor [inaudible 00:09:02] and that's what Dr. Adamantidis was able to show.

Dan Pardi - 09:05: Is it associated or thought to be associated with other types of learning as well?

John Peever - 09:08: Like I said before, if there's been an idea that what REM sleep does, it's been proposed and some of them are crazy but certainly REM sleep had been thoughtfully involved in various types of learning. The evidence to support that is actually quite equivocal. What I mean by that, it's not clear in certain circumstances. If you look at people who are taking a particular class and drug, it actually prevents all expression of REM sleep but those people seem to learn just as well as people who have REM sleep. I think a lot of caution needs to be cast on what REM sleep does. I think one of the problems is that we think it just does one thing, and it's pretty clear from looking at the literature and certainly from other work, that REM sleep has many different functions.

Dan Pardi - 09:54: People that are depressed, take anti-depressants, those can have a profound impact on suppressing REM. Yet there doesn't seem to be an impairment in learning. That would challenge the idea that REM sleep is fundamental to learning.

John Peever - 10:05: Yeah, I think that's one of the things that we need to be really cautious as researchers is that you often read in newspaper articles and even in scientific literature that sleep is required for certain types of learning. I think that's just a clear factual misunderstanding. Sleep's clearly facilitates certain types of learning but it's not required for it.

Dan Pardi - 10:28: So far, we've described that this is a unique state, where you have a highly active brain and the body is paralyzed. That's one of the cardinal classic features of REM sleep is this REM sleep associated to atonia or muscle expression. Let's talk a little bit about the mechanisms there because it's been hard to figure out and it's pretty interesting how it works. I know this can get really deep in the weeds here but generally speaking, what is taking place during REM that causes the body to go into paralysis?

John Peever - 10:55: There is one group of cells in the brain, called motor neurons and they're the cells in the brain that actually tell your muscles to contract or not contract and so what my group and others have shown is that the signals that go to those motor neurons are basically shut off during REM sleep so that they can't activate the muscles and when they can't activate the muscles, you have REM sleep paralysis. Those are very specific series of chemical processes going on in the brain that only happen in REM sleep that make sure those cells are remaining inactive so that your muscles also remain inactive.

Dan Pardi - 11:30: Are there any pathological situations, where this connection between the typical atonia or muscle loss during REM becomes aberrant in some way?

John Peever - 11:40: I personally think this one of the biggest and most important elements in understanding REM sleep and what it does for the brain and body. The reason I say that is that there's a group of people who have what's called, REM sleep behavior disorder and those individuals don't have that normal loss muscle tone and they move around and they appear to act out their dreams. Face value that a lot of people think that's cute and funny and some people think it's embarrassing that they're moving around and acting out their dreams, but the really amazing thing from clinical perspective is that the vast majority of those individuals, 80 to 90% of them go onto develop a very particular type of neurodegenerative disorder and the most common one is Parkinson's disease.

12:26: All these people, virtually all of them, develop Parkinson's disease or some other degenerative process such as a form of dementia. It seems really remarkable that when you lose the normal ability to shut your muscles off in REM sleep, that you develop this type of neurodegeneration. I think that's a way of the body telling you that when REM sleep muscle paralysis is lost, something terribly wrong goes on in the brain.

Dan Pardi - 12:52: Originally, I thought, is this REM sleep behavior disorder, is the pathology behind that, have common overlap in terms of the pathology with dementia but it sounds like it might be the fact that the suppression of motor activity is important in some way for the brain as physiology that's being suppressed or altered that is causing the downstream problems with dementia.

John Peever - 13:13: Yeah, so I think that's a really excellent point. I think there are two ways to think of it. Either one, the cells that cause your muscles to shut off in REM sleep are damaged and that's why you don't have the normal loss of muscle tone during REM sleep, and you act out your dreams. Or two, and I think this is the far more provocative idea is that the suppression of muscle activity during REM sleep is actually really important for the brain. We found, actually, recently that the muscle activity during REM sleep seems to be extremely instructive for the brain in order to terminate REM sleep and then wake up. I think, either of those possibilities is still an open question. Is it that the cells that cause you to go into REM sleep in your muscles stay quiet. Is that they're dying or is it that the loss of muscle paralysis during REM sleep ,then wreaks havoc with the brain, and you develop a form neurodegenerative disorder.

Dan Pardi - 14:06: If there's an acute risk of people acting out our dreams, there's theories that the reason we go into paralysis is so we don't hurt ourselves by running into a tree while we're asleep and this might be a pocketful but I've heard that there have even been people that have been acquitted of murder for attacking their bed partner, who they thought were attacking them in their dream but they were shown to have REM sleep behavior disorder and they were acquitted.

John Peever 14:27: Yeah, there's a lot of stories like that actually evolving. There's an entire field of law now that involves sleep experts basically explaining why people have done some really unusual and often violent things during their sleep. There's been recent cases where someone beat their partner up. There's a case where someone rapes their partner and the individual is found to actually have REM sleep behavior disorder or other types of sleep disorders in which these behaviors actually become apparent. So, some pretty crazy things can happen when you're sleeping because you're not aware of what you're doing. Are you really, legally culpable for those action?

Dan Pardi - 15:09: So there's acute risk for hurting yourself or others and then pretty high percentage that it'll lead to neurodegeneration of some form that causes dementia in some way. Now, talk about men and women. Does this occur equally in both genders?

John Peever - 15:22: That's an open-ended question, I think. At the moment, it seems that men are much more affected by this REM sleep disorder and it's really fascinating from a sex difference between men and women is that, women who do have REM sleep beahvior disorder, their dreams tend to be much more gentle and their movements therefore are much milder than men. So one of the conundrums is that maybe men and women have the same rate REM sleep disorder. It's just that the way women act out their dreams is much gentler than men and so they're underdiagnosed. But at present, it seems that men are much more afflicted with REM sleep behavior disorder than women but I think caution needs to be given to that, given that women's dreams are so much milder. They may not land up getting to the hospital or to see the doctor to be diagnosed with that disorder.

Dan Pardi - 16:16: Are the rates of downstream Dementia equivalent in men and women?

John Peever - 16:20: There are so many forms of Dementia and Parkinson's disease that I just don't think there's a way to answer it in a retrospective way, simply because there are different types of Dementia and different types of Parkinson's and they develop at different rates and overall, they're pretty equal in men and women, when you look at the global picture, in terms of the sheer percentages.

Dan Pardi - 16:42: Are there any other interesting conditions where this lack or disruption of the atonia show up in the world?

John Peever - 16:50: There's the complete opposite to this, where you lose REM sleep paralysis while you're in REM sleep but there's a complete polar opposite which is where REM sleep paralysis or atonia occurs while you're awake. That's been one of our other major focuses of research is looking at when your muscles simply go paralyzed or become extremely weak when you're awake and that condition is known as cataplexy and it's a symptom of a sleep disorder called narcolepsy.

17:19: Someone who experiences an episode of cataplexy, they all of a sudden seem to lose muscle tone in their face and in their neck and then the loss of muscle tone sort of goes from the top of the head towards the feet. These people just sort of slump over and they're unable to move. But what's really amazing is that they're totally awake and aware of what's going on. They just can't move their bodies in response. One of the things that's really quite unfortunate is those events of cataplexy are typically triggered by very emotionally coded events with the most common one being laughter.

17:57: Someone who has narcolepsy and has cataplexy, if someone were to crack a really funny joke, that joke would trigger a highly excited emotion and then precipitating cataplexy. Joke leads to loss of muscle tone to someone lying on the floor, unable to move but they're completely aware of what's going on.

Dan Pardi - 18:17: Think about how somebody who has narcolepsy and cataplexy would therefore want to modify their life to try to suppress the emotions if they don't enter into cataplexy. A sad aspect of that condition.

John Peever - 18:29: I think a lot of times, it's really amazing that in movies and in social media, narcolepsy and cataplexy is almost made fun of because these people simply can't move and they ... Someone tells a joke and they fall on the floor. I've talked to a lot of people, who have cataplexy. It's really an emotionally very difficult feature of their disorder because they avoid social context in which funny things or scary things are happening for fear of having an episode of cataplexy. It's really embarrassing for these people or at least they seem to think it's embarrassing that in the middle of the mall, they're lying on the floor, unable to move.

19:05: A lot of people have told me that why it's embarrassing is that other people who don't understand what's going on, think that they're drunk or that there's something wrong with them and it's a bonafide condition. That they're sort of faking it if you will. People with and really avoid parties and any type of thing, in which funny things or scary things are happening for fear of having cataplexy in public.

Dan Pardi - 19:29: The comorbidity of depression in people with narcolepsy and cataplexy is rather high and you can look at it as a nature nurture question. Ourselves the depression a fundamental part of the alterations in the neuro circuitry that are taking place in people that have cataplexy or that have narcolepsy or is it actually sort of a nurture experience, where if you're turning away from emotional experiences in life, then that part of them is unfulfilled.

John Peever - 19:53: So chicken and eggs scenario. Are you depressed because you have narcolepsy? Or are you depressed because what causes narcolepsy also make you depressed? I think that it's really likely that there are both elements going in this condition.

20:08: There's evidence that if you take away the cells in the brain that cause narcolepsy, that there's also elements of depression associated. But it's equally as clear that people who have narcolepsy are depressed because their life isn't as good as it was before they developed narcolepsy. They're limited in how they can socialize. They're limited in what jobs they can do. I think you've got kind of two elements going on where the depression is part of the disorder itself but the depression is also a side effect of the disorder because they realize that life isn't quite the same as it was before they developed narcolepsy.

Dan Pardi - 20:48: Let's talk about drugs or substances or things that have shown to increase REM sleep or things that suppress it. So it's about some of the things that actually will suppress REM. Some pharmacological agents that cause us to get less REM sleep.

John Peever - 21:00: There's a variety of different classes of drugs that seem to be really good at suppressing REM sleep. Some of them are tricyclic antidepressants, and some of them are called monoamine oxidase inhibitors. Each of those drugs is used for different medical purposes but what's really amazing is that it suppresses all the measurable or outward symptoms of REM sleep in people and in animals and those drugs seem to be really good at suppressing cataplexy, which we were just talking about and what I mentioned was that it seems that cataplexy may be the pathological turning on, if you will, of those brain circuits that cause muscle paralysis, except in cataplexy, it happens when you're awake. One idea that scientists and clinicians have had is that the drugs that suppress REM sleep are really good at suppressing cataplexy and maybe they're suppressing cataplexy by suppressing the parts of the brain that generate REM sleep paralysis.

Dan Pardi - 22:02: We know that some drugs will increase REM sleep, like M2 agonists, [Resparity 00:22:06] and Prazosin, even LSD. What do you think about increasing REM sleep pharmacologically?

John Peever - 22:11: That's a great question, because I think there's so much attention focused on the fact that more REM sleep could be good for the body, for the brain and in specific, for learning. But I think, some real caution needs to be given to trying to increase REM sleep when we really don't know if that's a good idea. A simple analogy here is in the context of eating. Eating more sounds like a great idea and everyone loves to do it but the problem is that the nasty side effect is getting fat. One of my concerns from a scientific point of view is that sounds all good to have more sleep, is too much sleep, in particular too much REM sleep really a good thing. There's some really nice evidence out there that sleep in general, that people, who sleep too long, actually have some negative health outcomes such as not living as long.

23:12: I think a lot of caution needs to be given in the angle of trying to increase REM sleep because we really don't know if it's a good of bad thing at this point in time.

Dan Pardi - 23:20: What do you know about the lifestyle healthy REM connection?

John Peever - 23:24: I don't think there's any really solid scientific evidence to suggest that there is an optimum amount of REM sleep. I say that about optimum amounts of REM sleep because people who don't have very much REM sleep because they're taking various drugs, they seem to be totally normal and healthy. It cast doubt on the validity of how much REM sleep you need. Do you even need REM sleep to be a healthy individual. To go back to the much more important question of sleep in general as close to REM sleep, it's crystal clear that an optimal amount of sleep is important for an overall healthy lifestyle. The National Sleep Foundation has a phenomenal quote that I absolutely adore and I use all the time when I do public speaking events is, "Sleep, just as important as diet and exercise, only easier."

24:13: I think what I really want to end with is there are some really simple, easy to do things that allow you to get a good night of sleep.

Dan Pardi - 24:20: Please.

John Peever - 24:21: That is keeping a very regular routine calming down at the end of a night. Don't look at your computer. Don't get yourself revved up before bed. Don't eat too much before you go to bed. Don't drink coffee. Don't smoke cigarettes. Don't drink alcohol before going to bed and those are all real simple tools that people can use to help optimize a good night of sleep. They're not a cure all. But in the average Joe or Jane, they're helpful in getting a decent night of sleep.

Dan Pardi - 24:48: REM has been called the gateway to waking. You've published some work looking at that phenomenon specifically and there are now apps that will try to predict an optimal time to wake up based off of what stage of sleep they're detecting you're in. Do you think it's a good idea or should you just try to sleep another 20 minutes and will that additional sleep be better than waking up a little bit earlier but from theoretically, a better stage?

John Peever - 25:13: I think waking up at the right time in sleep is really important. It should be intuitive that every person who is listening to this, if you ever fall asleep on a Saturday afternoon, you've drifted into deep sleep and then you wake up out of that deep sleep because your kids run in or your partner runs in and they wake you up and you have no idea where you are, you might not even understand what day it is. You're disoriented. It can be quite frightening. But when you wake up out of REM sleep, your body is prepared to wake up and why that is, is because every time an animal and every time a human finishes an episode of REM sleep, it terminates with waking up.

25:53: I think the tools and apps that you're talking about, that can sort of tune or optimize when to turn the alarm on. If they can do that at the end of a puritive REM sleep, that is really quite beneficial because our research and others have really shown that the brain and body are designed to wake up at the end of REM sleep. That's just not the case at the end of deep sleep or non-REM sleep, where the body can wake up sluggish or it might even be preparing to move into REM sleep.

26:26: One of the things that we're really curious on is, is it that REM sleep is important to recuperate what happened while you were awake or is REM sleep actually stage in the sleep cycle that's preparing you to wake up. I think this is one of the big questions in what is sleep doing for the brain and body and one of the things that we're working on is really trying to understand is, is REM sleep really preparing you to wake up as opposed to keeping you asleep.

Dan Pardi - 26:52: Do you have any idea about, from what stage you wake from, does that have an effect on your wake quality that lasts an hour? Or might it last the entire day?

John Peever - 27:03: Yeah. I don't really know of any data. I'm sure it's there. I'm just not familiar with it. Whether if you wake up out of deep sleep and bearing in mind there are different types of deep sleep. Whether that impacts for a significant period time, your mood and the quality of your wakefulness, but certainly again, from a highly intuitive point of view, if you wake up out of the deepest stage of sleep or slow-wave sleep, it's really ugly. You're tired, you're sluggish, you have what we call, sleep inertia. But when you wake up at a REM sleep, you're pretty geared. You're jacked. You're ready to go.

27:36: There's some really beautiful old studies from Adrian Morrison at the University of Pennsylvania, showing that, even in animals, the type of wakefulness that follows REM sleep is very different than the type of wakefulness that follows waking up from deep sleep.

Dan Pardi - 27:52: Well, that's a great point to end on. Thank you for your time and your work on the field to help us understand that neuro circuitry better and also to hopefully prevent some of the pathological conditions that can happen.

John Peever - 28:02: It's my pleasure.

Kendall Kendrick - 28:06: Thanks for listening and come visit us soon at humanos.me.