Solving sleep: just a toe-dipping

by Capla6 min read30th Jun 201536 comments

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SleepNeuroscienceBiologyHuman Bodies
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[For the past few months I’ve been undertaking a mostly independent study of sleep, and looking to build a coherent model of what sleep does and find ways to optimize it. I’d like to write a series of posts outlining my findings and hypotheses. I’m not sure if this is the best venue for such a project, and I’d like to gauge community interest. This first post is a brief overview of one important aspect of sleep, with a few related points of recommendation, to provide some background knowledge.]

 

In the quest to become more effective and productive, sleep is an enormously important process to optimize. Most of us spend (or at least think we should spend) 7.5 to 8.5 hours in bed every night, a third of a 24 hour day. Not sleeping well and not sleeping sufficiently have known and large drawbacks, including decreased attention, greater irritability, depressed immune function, and generally weakened cognitive ability. If you’re looking for more time, either for subjective life-extension, or so that you can get more done in a day, taking steps to sleep most efficiently, so as to not spend more than the required amount of time in bed and to get the full benefit of the rest, is of high value.

Understanding the inner mechanisms of this process, can let us work around them. Sleep, baffling as it is (and it is extremely baffling), is not a black box. Knowing how it works, you can organize your behavior to accommodate the world as it is, just as taking advantage of the principles of aerodynamics, thrust, and lift, enables one to build an airplane.

The most important thing to know about sleep and wakefulness is that it is the result of a dual process: how alert a person feels is determined by two different and opposite functions. The first is termed  the homeostatic sleep drive (also, homeostatic drive, sleep load, sleep pressure, and process S), which is determined solely by how long it has been since an individual has last slept fully. The longer he/she’s been awake, the greater his/her sleep drive. It is the brain's biological need to sleep. Just as sufficient need for calories produces hunger, sufficient sleep-drive produces sleepiness. Sleeping decreases sleep drive, and sleep drive drops faster (when sleeping) then it rises (when awake).

Neuroscience is complicated, but it seems the chemical correlate of sleep drive is the build-up of adenosine in the basal forebrain and this is used as the brain’s internal measure of how badly one needs sleep.1 (Caffeine makes us feel alert by competing with adenosine for bonding sites and thereby inhibiting reuptake.)

This is only half the story, however. Adenosine levels are much higher (and sleep drive correspondingly lower) in the evening, when one has been awake for a while, than in the middle of the night, when one has just slept for several hours. If sleepiness were only determined by sleep drive, you would have a much more fragmented sleep: sleeping several times during the day, and waking up several times during the night. Instead, humans typically stay awake through the day, and sleep through the whole night. This is due to the second influence on wakefulness: the circadian alerting signal.

For most of human history, there was little that could be done at night. Darkness made it much more difficult to hunt or gather than it was during day. Given that the brain requires some fraction of the nychthemeron (meaning a 24-hour period) asleep, it is evolutionarily preferable to concentrate that fraction of of the nychthemeron in the nighttime, freeing the day to do other things. For this reason, there is also a cyclical component to one’s alertness: independent of how long it has been since an individual has slept, there will be times in the nychthemeron when he/she will feel more or less tired.   

Roughly, the circadian alerting signal (also known as process C) counters the sleep-drive, so that as sleep drive builds up during the day, alertness stays constant, and as sleep drive increases over the course of the night, the individual will stay asleep.

The alerting signal is synchronized to circadian rhythms, which are in turn attuned to light exposure. The circadian clock is set so that the alerting signal begins to increase again (after a night of sleep) at the time when the optic nerve is first exposed to light in the morning (or rather, when the the optic nerve has habitually been first exposed to light, since it takes up to a week to reset circadian rhythms), and increases with the sleep drive until about 14 hours later (from the point that the alerting signal started rising).

This is why if you pull an “all-nighter” you might find it difficult to fall asleep during the following day, even if you feel exhausted. Your sleep drive is high, but the alerting signal is triggering wakefulness, which makes it hard to fall asleep.

For unknown reasons, there is a dip in the circadian alerting about 8 hours after the beginning of the cycle. This is why people sometimes experience that “2:30 feeling.” This is also the time at which biphasic cultures typically have an afternoon siesta. This is useful to know, because this is the best time to take a nap if you want to make up sleep missed the night before.

 

http://bonytobombshell.com/wp-content/uploads/2015/05/energy-levels-sleep-drive-alert-chart-1-bony-bombshell.jpg

 

The neurochemistry of the circadian alerting signal is more complex than that of the sleep drive, but one of the key chemicals of process C is melatonin, which is secreted by the pineal gland about 12 hours after the start of the circadian cycle (two hours before habitual bedtime). It is mildly sleep-inducing.

This is why taking melatonin tablets before is recommended by gwern and others. I second this recommendation. Though not FDA-approved, there seem to be little in the way of negative side effects and they make it much easier to fall asleep.

The natural release of melatonin is inhibited by light, and in particular blue light (which is why it is beneficial applications to red-shift the light of their computer screens, like flux or reds.shift, or wear red-tinted goggles, before bed). By limiting light exposure in the late evening you allow natural melatonin secretion, which both stimulates sleep and prevents the circadian clock from shifting (which would make it even more difficult to fall asleep the following night). Recent studies have shown bright screens ant night do demonstrably disrupt sleep.2

The thing that interests me about this fact that alertness is controlled by both process S and process C, is that it may be possible to modulate each of those processes independently. It would be enormously useful to be able to “turn off” the circadian alerting signal on demand, so that a person can fall asleep at any time off the day, to make up sleep loss whenever is convenient. Instead of accommodating circadian rhythms when scheduling, we could adjust the circadian effect to better fit our lives. When you know you’ll need to be awake all night, for instance, you could turn off the alerting signal around midday and sleep until your sleep drive is reset. In fact, is suspect that those people who are able to live successfully on a polyphasic sleep schedule get the benefits by retraining the circadian influence. In the coming posts, I want to outline a few of the possibilities and (significant) problems in that direction. 

1 Blanco-Centurion, C., Xu, M., Murillo-Rodriguez, E., Gerashchenko, D., Shiromani, A., Salin-Pascual, Shiromani, P. (2006). Adenosine and Sleep Homeostasis in the Basal Forebrain. Journal of Neuroscience, 8092-8100.    

2National Sleep Foundation. (2011, March 7). Annual Sleep in America Poll Exploring Connections with Communications Technology Use and Sleep. Retrieved August 17, 2011, from http://www.sleepfoundation.org/article/press-release/annual-sleep-america-poll- exploring-connections-communications-technology-use-.

 

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36 comments, sorted by Highlighting new comments since Today at 1:24 PM
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For those interested, Coursera currently has a course running on this topic, which goes into a lot of detail about sleep from both neurobiological and clinical perspectives. They also recommend the textbook 'Brain Control of Wakefulness and Sleep' by Steriade and McCarley.

I'm definitely interested in subsequent posts on sleep, so please continue posting. I don't want to practice polyphasic sleep or super-optimize sleep anyway, rather just generally improve the quality of sleep, because I sleep much and still wake up feeling like crap.

I kindly ask you, however, to change the font to defaults and break paragraphs with 2 lines instead of indentation, it makes it much more readable.

Didn't see the original, but it looks good now.

Regarding sleeping a lot and waking up tired: Is it possibly some degree of sleep apnea? As of a few months ago I had this problem.

Then I tried those breathing strips (despite my skepticism) that help prevent snoring. If I snore now it's at a much lower volume. The quality of sleep is vastly improved for me too. I generally wake refreshed after ~7 hours. The difference is like, ahem, night and day.

Never heard of sleep apnea and nasal strips before, thanks! I'll try them out. Sleep quality can be influenced by lots of factors, one of them is depression and anxiety. For example, on Bipolar II disorder Wikipedia page it states that type I bipolars sleep less, while type II bipolars sleep much more. Another example is that many depression scales such as Beck Depression Inventory actually consider lack of sleep or oversleeping as one symptom of depression among others. So, counter-intuitively, some people, who have sleep problems, might benefit from reading Feeling Good :).

As a narcoleptic, I am always suspicious of extreme polyphasic sleep claims. Biphasic seems to be natural, but anything like the uberman schedule seems to conflict with what I know about narcolepsy.

The primary symptom or possibly the primary cause of narcolepsy is skipping straight from light sleep to REM within minutes of falling asleep. When I was tested, I entered REM between 3 and 7 minutes of falling asleep. Sleep cycles are fractured and slow wave sleep is reduced or skipped entirely.

By contrast, a normal person enters REM after usually more than an hour, stopping along the way in three different phases of sleep. The deepest stage, slow wave sleep, is where quite a lot of brain repair occurs. Glial cells are restored, free radicals are cleared out, glucose is stored in the brain. Growth hormones repair tissue damage.

Many of the claims of ubermen proponents seem to rest on entering REM almost immediately after staring a nap. Much like a narcoleptic. Stage four is arguably more important for mental health, but this stage is not mentioned by proponents that I have seen. Furthermore, some of the symptoms of narcolepsy seem to match the experiences of polyphasic sleepers, particularly the general awakeness/non-grogginess which is occasional unexpected and uncontrollably strong daytime sleepiness.

Background: The idea of less sleep super appeals to me because I need so much. Before I was diagnosed I tried Uberman but it didn't seem to reduce my daily hours of sleep needed, and in retrospect it obviously could never have done that for me. But my natural sleep cycle is super polyphasic, 3 or 4 naps a day and reduced sleep at night. Unfortunately, my body wants is 10+ hours regardless of whether its in one chunk or spaced out throughout the day, and spacing seems irrelevant since I rarely have SWS regardless.

I'm polyphasic on Everyman 3 since about March 2011 (Jan and Feb spent unsuccessfully trying to make Uberman work). According to my aging Zeo I get approximately the same REM and SWS as I did on 7.4hrs of monophasic sleep before I adapted. Nearly all of the SWS is in my 3hr core. On Uberman I never achieved enough SWS in my naps to get me through. The adaptation was ridiculously hard - both for how very unpleasant it was and for having to get through that while sleep deprived.

I could believe that a 3 hour core could contain a lot of SWS, making it definitely better than Uberman. In those little naps, it's easy to jump into REM and hard to jump into SWS. I was under the impression that 3 hours is still less SWS than the minimum to prevent sleep deprivation symptoms, but I also am endlessly impressed by the capacity of the human brain to adapt to any symptom. Did you do any cognitive functioning tests before/after switching to Everyman?

Also consider how different humans are. Even the recommended sleep ranges have a spread of almost x2 between min and max.

infographic that is too large to inline

Oh dear. Can we please not post very large very bright low-information-density infographics right into threads?

sorry. didn't find a way to rescale and forgot.

I agree with your skepticism. The polyphasic community claims that they are able to make drastic reduction in sleep time because they go straight into REMs when taking a nap. This conflicts with a lot of my understanding.

It is my suspicion that they are mistaken about that, and that actually, if a person has acclimated to polyphasic, he/she isn't going into REM at all and that this is where gains come from.

The polyphasic community claims that they are able to make drastic reduction in sleep time because they go straight into REMs when taking a nap.

Who do you mean with "the polyphasic community" exactly? Who's actually doing polyphasic sleep and claiming such a thing (e.g. hasn't read Stampi)?

There's the polypahsic society. They are more-or-less the representatives of consensus among polyphonic folks. (I think. Perhaps I'm misrepresenting them?)

Stampi is not very helpful for figuring out what polyphasic people are doing while they sleep. So far, I've yet to find a single paper that features a polysomnographic evaluation of someone doing uberman or everyman, much less one that does a basic evaluation of whether someone who has been polyphonic (long term) is exhibiting clinical symptoms of sleep deprivation. Both of those, but particularly the polysomnograph, would be very informative.

I've read some of the Polyphasic Society's website, and they make a different argument. Unfortunately it doesn't seem the website exists any longer (or now it's at a different location?), but the Internet Archive has the page I read. You can see that they claim something a little more sophisticated than that they go straight into REM (with the implication that REM is all you need, etc.). Likely, they do this because the REM claims are false for multiple reasons. I discussed this with ChristianKI on LessWrong a year ago. Beyond the REM claims, their newer claims are contradicted by the research in Stampi's book (see the link in the previous sentence for justification).

The reason you don't see studies about polyphasic schedules like Uberman and Everyman is probably because sleep researchers consider the idea to be so far-fetched that it's not worth doing a study. I have seen some polyphasic sleep proponents use Zeo, however. Look at the Polyphasic Society link I gave in the previous paragraph for an example.

That was a wonderfully clear introduction! I'd definitely want to see more posts on sleep since I think it's one of the most important, if not the most important aspect of optimizing cognitive performance.

I second Mirzhan_Irkegulov's disinterest in polyphasic sleep though, at least until several lower hanging fruits have been picked. Polyphasic sleep is likely to be excessively difficult to maintain by most people, even if it were a viable alternative. Since sleep is enormously important as you stated and likely interesting as it is to many people, your posts will have a greater positive impact if you explore the less niche venues first.

Most people in society follow the same sleeping patterns so I can't see why disabling circadian control at will would be extremely useful unless you do shift work or have to socialize at nights. Could expand on that? I think it's much easier to not get sleep deprived in the first place. Problems of shift work are increasingly mitigated by the internet as work is computerized and thus can be done by people on the sunny side of the planet while you sleep.

Suggestions for subtopics based on my personal interest

  • alcohol, nicotine, caffeine
  • exercise and its timing, nutrition and its timing
  • chronological age
  • optimizing artificial lighting and the bedroom
  • z-drugs and their dangers
  • melatonin, mirtazapine, mianserin, quetiapine
  • stress, depression, anxiety
  • effects of antidepressants on sleep structure

If you need help with article paywalls PM me and I'll see what I can do.

Another interesting topic would be the effect of body temperature on sleep latency and/or quality (or possibly temperature of selected body parts--there is some buzz about the so-called "cooling cap" for insomnia lately, for example).

To me it seems a big breakthrough for being able to trim sleep time down substantially would be some technology that allowed a person to pass through the lighter stages of NREM sleep more quickly so that you could spend the majority of sleep time in slow wave.

I am curious to what extent the info in this post is common knowledge. Are these things familiar to people?

I knew about melatonin and red/blue light from reading people in this community. I also had a vague understanding that circadian rhythms controlled falling asleep and were based on light, but I don't think I'd seen things spelled out as clearly as they are here. Thank you for putting this together and I do look forward to the rest of your series.

See this post and discussion from 5 years ago. I saw someone wearing red goggles at an LW meetup years ago.

EDIT: Even if this has been discussed before, I still read and enjoyed your post, and it contained new info. I think sleep optimization is important - somebody should be keeping me informed of any new research. ;)

First a plug for the best Sleep text by far, "Principles and Practice of Sleep Medicine", by Kryger, Roth, and Dement. If you don't have this, you need it.

To turn off the circadian alerting, it would suffice to suppress cortisol.

I would think that there is plenty of low hanging fruit to exploit before that though. After well known sleep hygiene measures have been addressed, and pathologies excluded, the largest remaining drain on sleep quality is maladaptive emotional processing. See Barry Krakow's "Sound Sleep, Sound Mind" for lots of detail on this. This book is rather unusual in making a big deal of the link between poor emotional processing and poor sleep quality, but dude is a very highly regarded sleep specialist who had been running a top-notch sleep clinic for many, many years, and not to be pooh-poohed lightly.

Thanks, i'm going to buy this.

This is why taking melatonin tablets before is recommended by gwern and others. I second this recommendation. Though not FDA-approved, there seem to be little in the way of negative side effects and they make it much easier to fall asleep.

(This paragraph is retracted. See jacob_cannell's post below.) Melatonin is marginally useful on occasion, but overrated. People who take melatonin for a long period of time likely don't get much benefit from it. The longest duration study I've seen on melatonin suggested the benefits did not last a year for over 90% of participants. To be fair, the study participants had delayed sleep phase disorder (DSPD), so perhaps the response is different for normal people. But I consider that unlikely given that both normals and people with DSPD take melatonin to shift their circadian rhythm and fall asleep at a more appropriate time.

My opinion is that sleep hygiene is far more useful than any drug or supplement. I'm a particular fan of the so-called "Bootzin technique", which basically makes falling asleep quickly at an appropriate time and place a habit. Also, if you suspect you might have a sleep disorder like sleep apnea or narcolepsy, it would be best to get that checked out.

Also, while we're on the topic of sleep control, there are a number of mathematical models of sleep which you might find useful. I have no idea how accurate these models are, or if they offer any hints about controlling sleep beyond what's obvious. Here's a review paper about what seems to be the most popular model. SuperMemo, the spaced repetition memory software, has a module which uses something like this model.

The longest duration study I've seen on melatonin suggested the benefits did not last a year for over 90% of participants.

This sounded interesting to me so I followed your link to the study. I think you may have seriously misinterpreted it. They treated the subjects with 5mg nightly melatonin for 6 weeks. After the treatment ended, they followed up over a year later. 91.5% reported a relapse to previous sleeping patterns after stopping melatonin treatment.

I'm not sure how you could conclude "people who take melatonin for a long period of time don't get much benefit from it" based on that study.

You are absolutely correct. Thank you. It appears I misread the abstract, which is worrisome, but I'm glad to have been corrected. I added a note to the original post retracting that statement. I also tracked down another post where I made the same claim and retracted the claim there. I'll have to read things more carefully*.

I am now not aware of any studies which looked at the long term effects of melatonin supplementation. I would not be surprised at all if oral melatonin lost effectiveness over time, though I recall gwern saying he did not see evidence of a tolerance effect. I also think people claim many positive things about melatonin that don't seem to check out (negative things, too, in my case). In particular, I don't see solid reasons to believe melatonin improves sleep quality. It seems to basically only shift the circadian cycle, which can be useful in circadian rhythm disorders and insomnia. I don't have my papers available right now, but I can pull up a few on melatonin's effect on sleep architecture if you are interested. (I'll probably do this anyway just to make sure I read them correctly after the mistake you highlighted!)

* To be honest, when I was reading studies about sleep a year-ish ago, I was very tired. My motivation was understanding why I might be so tired during the day. I should not be surprised if I was sloppy through this process. I decided I'm a long sleeper, and I've been considerably better since trying to get as much a sleep as possible.

I've been taking melatonin for about ... 5 years, so if you DO have some evidence for any long term effects, that is of course something I'm interested in.

I suspect that there is some genetic variation in the circadian system such that melatonin isn't one size fits all. In particular I have a pretty long sleep onset. Before melatonin, my estimate of my own sleep estimate was about 30 minutes to an hour. With melatonin it's usually less than 30 minutes, although I've adjusted my dose down to 2 mg or so trying to get the minimum that works.

For me the benefit seems to be more than the 30 minutes saved, my sleep also becomes somewhat more effective.

Can I get a little clarification? Are people up-voting because they like the content of this post or because they like the prospect of later posts on sleep?

I was unsure of whether to put this up, since I thought it didn't have much in the way of novel insight, just background knowledge.

Both.

It may not have been original, but it was new (or at least unfamiliar) to me.

Small typo:

bright screens ant night

Unless I'm misreading, I think the following two lines contradict each other. Does more adenosine correspond to higher or lower levels of sleep drive?

it seems the chemical correlate of sleep drive is the build-up of adenosine in the basal forebrain and this is used as the brain’s internal measure of how badly one needs sleep.

Adenosine levels are much higher (and sleep drive correspondingly lower) in the evening

It's a mistake, it should say higher.

The link in source 2 appears to be broken:

2National Sleep Foundation. (2011, March 7). Annual Sleep in America Poll Exploring Connections with Communications Technology Use and Sleep. Retrieved August 17, 2011, from http://www.sleepfoundation.org/article/press-release/annual-sleep-america-poll- exploring-connections-communications-technology-use-.

Hmm...Let me check that out.

For unknown reasons, there is a dip in the circadian alerting about 8 hours after the beginning of the cycle. This is why people sometimes experience that “2:30 feeling.”

Hunh. That makes sense. I didn't realize that I was why I feel tired in the afternoon. I thought it was because of eating lunch just before.

Lunch could still be an important factor, postprandial somnolence is a well-known phenomenon. There might be a phenomenological difference between that and sleepiness, though. We often do not properly distinguish between sleepiness and fatigue.