"...the active clearance of the by-products of neural activity..."

November 11, 2014 11:13 AM

A recent study indicates that scientists may have found the first real mechanical reason we need to sleep.
posted by quin (56 comments total)

I wonder if they can do the same sort of imaging and research on daydreaming.

Related - are you a Night Owl or Albatross sleeper?
posted by Buttons Bellbottom at 11:16 AM on November 11, 2014 [3 favorites]

That was neat, thank you!
posted by Mrs. Pterodactyl at 11:21 AM on November 11, 2014

thank god we have learned this so that major corporations can invent drugs to provide the benefits of sleep without actually sleeping so we can work twenty-four hours per day
posted by mightygodking at 11:21 AM on November 11, 2014 [21 favorites]

thank god we have learned this so that major corporations can invent drugs to provide the benefits of sleep without actually sleeping so we can work twenty-four hours per day

Sleepocil^RX knits up the raveled sleeve of care!
posted by Mrs. Pterodactyl at 11:26 AM on November 11, 2014 [20 favorites]

Plus, it's an effective spot remover.
posted by moonmilk at 11:28 AM on November 11, 2014 [6 favorites]

Does "year-old" count as "recent" when positioning a news article?
posted by truex at 11:29 AM on November 11, 2014 [4 favorites]

Let's not let the fact that this could help develop treatments for Alzheimer's, Huntington's, Parkinson's, or any number of other neurodegenerative diseases get in the way of a good snark about working too hard.
posted by Justinian at 11:31 AM on November 11, 2014 [29 favorites]

thank god we have learned this so that major corporations can invent drugs to provide the benefits of sleep without actually sleeping so we can work twenty-four hours per day

I suspect you're kidding but I would actually appreciate this thanks.
posted by maxsparber at 11:34 AM on November 11, 2014 [15 favorites]

I have often wished for a parallel dimension where I could slip into it and get 8 hours of sleep and slip back in to reality with no time passed (no really! I think about these things!). But a power washer drug that let me sleep less would be good too.

silliness aside, I wonder if it will have any implication for sleep disorders, either mitigate the damage from chronic insomnia, or lead to new ways to induce sleep.

(I also want to see nice sleeping on a microscope.)
posted by [insert clever name here] at 11:38 AM on November 11, 2014 [3 favorites]

we can work twenty-four hours per day

This isn't necessarily evil if you truly enjoy what you do and/or are working for yourself, whether it's helping the less fortunate, writing a 500 page novel or fabricating an enormous sculpture, building a camouflaged log cabin over top of an abandoned mine shaft on federal land deep in the woods, or patiently MIG welding thousands of Damascus steel scimitars onto the arms of an asynchronous quantum-linked meat-metabolizing legion of robotic valkyries.
posted by CynicalKnight at 11:41 AM on November 11, 2014 [74 favorites]

thank god we have learned this so that major corporations can invent drugs to provide the benefits of sleep without actually sleeping so we can work twenty-four hours per day

I suspect you're kidding but I would actually appreciate this thanks.

Try Modafinil.
posted by leotrotsky at 11:42 AM on November 11, 2014 [1 favorite]

That's why I pop melatonin all day in my office and keep the door shut. Prime scrubbin' time.
posted by glaucon at 11:44 AM on November 11, 2014 [2 favorites]

I wonder if they can do the same sort of imaging and research on daydreaming.

The Brain's Default Network
posted by dephlogisticated at 11:49 AM on November 11, 2014

I could go for a nice brain rinse right about now.
posted by Foosnark at 12:01 PM on November 11, 2014 [3 favorites]

I could go for a nice brain rinse right about now.

Mentema? High Neuronic? Gah, it's so close I can almost taste it!
posted by Navelgazer at 12:04 PM on November 11, 2014 [7 favorites]

Youtube video by the researchers explaining the results.

Actual paper (paywall, free with registration).

This is a really fantastic result. The actual requirement for sleep in mammals has been a mystery for decades, even though much of the biochemical signalling pathways for wakefulness and sleep have been worked out.

Since sleep is such a costly and risky activity, if a few amino acid changes in an enzyme could get rid of the need for sleep, some species would have done it already. It makes much more sense that to get rid of sleep, you would have to overhaul the energy consumption machinery of the brain and the waste removal plumbing architecture simultaneously, which is much less likely to happen.

It also makes it very unlikely that simple genetic changes a la Beggars in Spain will happen anytime soon to make primates not require sleep.
posted by benzenedream at 12:09 PM on November 11, 2014 [18 favorites]

Side effects may include headache, itchiness, skin rash, permanent inability to distinguish reality from the dreaming state and spending the rest of your life pursued by terrifying nightmare hallucinations from the deepest of your unconscious fears, and dizziness. Ask your doctor if Sleepocil is right for you.
posted by strangely stunted trees at 12:13 PM on November 11, 2014 [16 favorites]

This is why I have to sleep so much! I think too hard! Thoughts fill my brain with toxins! Toxic, toxic toxins!
posted by Eyebrows McGee at 12:16 PM on November 11, 2014 [13 favorites]

Yup, now it's proven: those of use who sleep longer do better and may live longer.

IT'S NAP TIME, SISTER!!
posted by BlueHorse at 12:17 PM on November 11, 2014 [3 favorites]

I'd sleep even if I didn't have to, because sleep is awesome.
posted by The Card Cheat at 12:24 PM on November 11, 2014 [7 favorites]

I always followed Ray's line of reasoning, sleep is the only time I'm not actively destroying my body in some way
posted by The Whelk at 12:26 PM on November 11, 2014 [13 favorites]

Is that where you're a Viking?
posted by Foosnark at 12:28 PM on November 11, 2014 [2 favorites]

Naw. It's where I'm asleep.
posted by The Card Cheat at 12:36 PM on November 11, 2014

Try Modafinil.
posted by leotrotsky at 2:42 PM

Speaking as a daily user (100-200mg every morning) for 8.5 years: no.

Modafinil mitigates the cognitive detriment from sleep deprivation, it does nothing about the rest of your body's reaction to sleep dep. This is by design: after 48 hours, taking 200mg of Modafinil every 8 hours, the only part of you that doesn't feel like shit-beaten-with-hammers is your awareness-level, which is pretty much the only reason Wall Street hasn't seen a rash of deaths from young quantitative analysts abusing the hell out of it. In some ways it's worse than just pouring on the caffeine, because you're that much more aware of how absolutely horrible every part of your body feels.

Don't get me wrong, Modafinil's great if you're crunching as a programmer and need the extra focus and 5 IQ points for math-related tasks (it remains the only proven cognitive enhancer to pass the FDA, but this effect is limited to numerical tasks & memory), but you'll be feeling if anything more nausea than with caffeine after the first 24 hours.
posted by Ryvar at 12:42 PM on November 11, 2014 [8 favorites]

I could go for a nice brain rinse right about now.

Mentema? High Neuronic? Gah, it's so close I can almost taste it!

Try keeping your mouth closed while you wash your brain.
posted by Greg_Ace at 12:49 PM on November 11, 2014 [1 favorite]

Explains also while drunk sleep is poor sleep, since your brain is (maybe) flushing out the hooch instead of the thinky-exhaust.
posted by RobotVoodooPower at 1:02 PM on November 11, 2014 [6 favorites]

The Card Cheat: "I'd sleep even if I didn't have to, because sleep is awesome."

That's what Big Sleep wants you to think. Wake up, sleeple!
posted by Eyebrows McGee at 1:02 PM on November 11, 2014 [27 favorites]

I will be taking a glorious nap this afternoon. Rinse away.
(this is fascinating and hopefully encourages future public policy to make time for more sleep)
posted by Bacon Bit at 1:02 PM on November 11, 2014 [1 favorite]

It's to sober up, right?
posted by lumpenprole at 1:02 PM on November 11, 2014

Is that where you're a Viking?

Well it's where I'm a CynicalKnight.
posted by resurrexit at 1:03 PM on November 11, 2014 [1 favorite]

This isn't necessarily evil if you truly enjoy what you do and/or are working for yourself, whether it's helping the less fortunate, writing a 500 page novel or fabricating an enormous sculpture, building a camouflaged log cabin over top of an abandoned mine shaft on federal land deep in the woods, or patiently MIG welding thousands of Damascus steel scimitars onto the arms of an asynchronous quantum-linked meat-metabolizing legion of robotic valkyries.

This will crush NETFLIX.
posted by srboisvert at 1:39 PM on November 11, 2014 [2 favorites]

thank god we have learned this so that major corporations can invent drugs to provide the benefits of sleep without actually sleeping so we can work twenty-four hours per day

You shouldn't trust Big Pharma. We've long known that they have been injecting us with medicines that cause bad feelings, hemachromachromatomatosis, bowel Tourette's, and nougat intolerances. You may be interested to learn of a new product that I and my team of holistic medicinists have been working on ever since we read these findings. Using a combination of cutting edge science and homeopathically-proven dosages of non-essential oils we have developed CORTEX DRAIN. All you need to do is buy one of our 1ml bottles, and take fifty-seven drops of CORTEX DRAIN every half hour. That pressure you feel building up behind your eyeballs? That's CORTEX DRAIN hard at work, flushing out your brain tubes (sp?) and neural roadpaths of accumulated toxics and poisonthoughts.

CORTEX DRAIN helps you to lead the busy lifestyle you've convinced yourself you need to lead and constantly tell others that you are leading. Dribble CORTEX DRAIN in your bullshit smoothies or on your bullshit lunchtime salads that you have at 3 in the afternoon even though you could have just as easily eaten at 12 or 1 and just want to be seen eating lunch at 3 by other annoying fuckheads, Jesus.
posted by turbid dahlia at 1:48 PM on November 11, 2014 [8 favorites]

I predict that when and if they announce a "cure" for the need to sleep, they'll have been giving it to soldiers without their consent for years prior.
posted by tommasz at 2:12 PM on November 11, 2014 [2 favorites]

Charles Czeisler

There's a name I haven't heard in a few years. He's done some excellent work and advocacy regarding circadian rhythm disorders like DSPS (delayed sleep phase syndrome/disorder, which is what I have) and N24. Brilliant man. This is fascinating stuff, thanks!

Screw Modafinil (tried it, didn't like the accompanying headaches), or the eponymous drug in Ned Beauman's book Glow, which any William Gibson fan should read, by the way. No way is anyone taking my lucid dreams away from me. My time spent asleep is absolutely fucking amazing.
posted by quiet earth at 2:12 PM on November 11, 2014

Colored toxic proteins? I thought the Mountain Dew thread was yesterday?
posted by Hamusutaa at 2:18 PM on November 11, 2014 [3 favorites]

Since sleep is such a costly and risky activity, if a few amino acid changes in an enzyme could get rid of the need for sleep, some species would have done it already.

The great thing about a sleep-accelertor, unlike most other brain enhancers, is that there are arguably pretty good reasons why nature might not have already invented it even if it was easy to do. A common evolutionary rationale for sleep these days is that, all else being equal, nature would prefer we spend 100% of the time safely asleep except for a brief bout of reproduction every now and then. We're active because we need to eat and defend ourselves, but inasmuch as an animal has a good supply of food and a reasonably safe spot, there's no good reason to be awake at all. In particular, most of us mammals are evolved to be either nocturnal or diurnal (or crepuscular), and being awake during the time we're not specialized for would only have given us more opportunity to get into trouble. So there could well be some simple switches nature has declined to flip for our own evolutionary safety that are just waiting to be discovered.
posted by chortly at 2:35 PM on November 11, 2014 [4 favorites]

Or is it the compulsive need to find lost gods of Kadath and help the dream cats keep the machinations of the zoogs at bay?
posted by mfoight at 2:38 PM on November 11, 2014 [2 favorites]

Navelgazer: "I could go for a nice brain rinse right about now.

Mentema? High Neuronic? Gah, it's so close I can almost taste it!"

I believe you're looking for Shamanic Colonic...
posted by symbioid at 2:42 PM on November 11, 2014

I really wish his parents had spelled it "Czarles Czeisler"
posted by DoctorFedora at 2:42 PM on November 11, 2014

or patiently MIG welding thousands of Damascus steel scimitars onto the arms of an asynchronous quantum-linked meat-metabolizing legion of robotic valkyries.

kickstarter link plz
posted by Mayor West at 2:46 PM on November 11, 2014 [3 favorites]

Try Modafinil.

It really doesn't work that well long-term, though, at least in my experience. I have Unknown Sleep Disorder Of Some Kind (getting a diagnosis next week, thank all the gods), and it's good for some stuff but it wears off how well it works over time, at least for me (taking it daily). It's not a sleep replacement by any means.

I hope this research turns up some good stuff, because it could really help people like me.
posted by NoraReed at 2:49 PM on November 11, 2014 [1 favorite]

I finished my diss on Modafinil and on day 4 I saw / hallucinated / felt the presence of a fucking angel. Hovering next to my stove in the kitchen. I got an A.
posted by yoHighness at 2:51 PM on November 11, 2014 [9 favorites]

(Not a cute baroque baby angel, more one of those flaming sword wrath of god types, both deadly and utterly innocent.)
posted by yoHighness at 2:53 PM on November 11, 2014 [8 favorites]

I predict that when and if they announce a "cure" for the need to sleep, they'll have been giving it to soldiers without their consent for years prior.
posted by tommasz

During Desert Storm B-2 bomber pilots were routinely given Modafinil for the 19 hour Florida->Baghdad round trip (B-2s generally aren't based outside the continental US). This was done with the pilots' express knowledge, however.

From a discussion a few years ago with a childhood friend who washed out in the final week of Army Ranger qualification tests (major medical issue at the tail end of the 6-week hell course): in general a big part of soldiering is learning to manage and when necessary overcome your body's sleep cycles - sometimes stimulants or sleep-blockers are used, but ideally a soldier in the special forces should be able to fight effectively and make correct decisions for 72 hours without. As any bodybuilder can tell you, the rate-limiting factor for muscle growth is repair time, and therefore sleep deprivation is enormously detrimental to the muscle mass gains essential for lugging 100lbs. of equipment through training exercises.

My point is: while "consent" might be too strong a word (as it doesn't necessarily map to a soldier's decision-making process), giving sleep-blockers of any kind to soldiers without their knowledge would generally be highly counter-productive both in terms of physical impact and developing their ability to manage sleep.
posted by Ryvar at 2:58 PM on November 11, 2014 [2 favorites]

it's good for some stuff but it wears off how well it works over time, at least for me (taking it daily). It's not a sleep replacement by any means.

If your schedule permits, I highly recommend reducing dosage to as low as you can safely go (ie 50mg) on weekends. That plus taking August off nearly every year has kept it effective for daily usage, for the aforementioned 8.5 years.

(Obviously everybody is different - in my case I'm just countering the 15-hours-per-day sleep requirement side effect from a different drug)
posted by Ryvar at 3:05 PM on November 11, 2014 [1 favorite]

The time I'm asleep is a fabulous vacation.
posted by yoga at 4:16 PM on November 11, 2014

I actually took a year off and found it still only tends to work for a few hours for me; I generally take at least a day or two off on weekends. I'm on armodafanil, though, so maybe that one builds a tolerance faster, I dunno.
posted by NoraReed at 4:43 PM on November 11, 2014

I'm a second year grad student with a specialty in Behavioral Sleep Medicine and experience working in sleep research and I loved seeing all the energy you guys have in your comments about sleep and had to comment on some:

thank god we have learned this so that major corporations can invent drugs to provide the benefits of sleep without actually sleeping so we can work twenty-four hours per day

To some extent we already work while sleep. Some dream researchers have long speculated and have some supporting research that dreams are a way of practicing things for the future. In effect a pre-processor for life.

That's why I pop melatonin all day in my office and keep the door shut.

Doing this would really screw up a persons system. Potential issues include gynecomastia, poor insulin tolerance, and a number of other issues related to the fact that melatonin isn't a sedative, its a chronobiotic, and therefor affects much more than just when you want to go to sleep.

Try Modafinil.

Wall Street is already on to this. But note that the guy in this article states he stopped modafinil use and has substituted exercise and a good nights sleep.

I will be taking a glorious nap this afternoon. Rinse away.
(this is fascinating and hopefully encourages future public policy to make time for more sleep)

This, sleep extension, can also be bad for you and can actually cause insomnia.

Explains also while drunk sleep is poor sleep

Drunk sleepers also tend to have a high number of wake after sleep onset events (WASO) and really inefficient sleep.

Yup, now it's proven: those of use who sleep longer do better and may live longer.

See my above comment, not enough sleep is bad, too much sleep is also bad.

Speaking as a daily user...

Modafinil has some great uses. Having worked shift and been a student I can attest to them. I'm very suspicious about it actually being a nootropic though, especially given that we haven't had a theory about how it works up until recently, and the current theories are all hotly being debated.

I predict that when and if they announce a "cure" for the need to sleep, they'll have been giving it to soldiers without their consent for years prior.

Dr. Gulio Tononi at the University of Wisconsin at Madison has made some strong arguments for why this would be a very bad idea even if we fixed the problem of waste products. Google Tononi SHY hypothesis for an idea why. Also keep in mind that their are people who don't sleep, at least for a little while, they have whats called fatal familial insomnia, and yes its terminal.

I finished my diss on Modafinil and on day 4 I saw / hallucinated / felt the presence of a fucking angel. Hovering next to my stove in the kitchen. I got an A.

Psychosis is not an uncommon after effect of extended sleep deprivation.

The great thing about a sleep-accelertor...

Again see the SHY hypothesis by Tononi. It's still in the early phases, but if it's correct it could also explain why we sleep and why it's not just to reduce the energy we spend/keep us out of trouble.
posted by Jernau at 5:43 PM on November 11, 2014 [8 favorites]

RobotVoodooPower: Explains also while drunk sleep is poor sleep, since your brain is (maybe) flushing out the hooch instead of the thinky-exhaust.

This could also explain the reason it's easy to get "wet brain" if you're drinking moderately to heavily for days and days. Too busy filtering out all that crap to ever get rid of the thinky-exhaust.
posted by emptythought at 5:45 PM on November 11, 2014

I hope this research turns up some good stuff, because it could really help people like me.

Best wishes with your diagnosis NoraReed.
posted by Jernau at 6:11 PM on November 11, 2014

I'm on armodafanil, though, so maybe that one builds a tolerance faster, I dunno.

Modafinil (and even moreso Armodafinil) has a crazy-long half-life, so if you're a daily user you hit a certain baseline minimum amount in your bloodstream just before taking it every morning. Armodafinil has a 20-25% longer half-life and corresponding 37% higher CMax, so a weekend may just not be enough to really drop that baseline. So, totally naive random-internet-person guess is you're never really letting your body flush it out.

Also, the minute differences in the pharmacodynamics suggest Armodafinil is just never going to quite kick you in the teeth the way Modafinil does - the two enantiometers (Modafinil is R and S, Armodafinil is R-only) interact with dopamine receptors differently.

Good luck with your testing, though - I know how frustrating it can be when nobody has solid answers for why that sort of thing is occurring.

Modafinil has some great uses. Having worked shift and been a student I can attest to them. I'm very suspicious about it actually being a nootropic though, especially given that we haven't had a theory about how it works up until recently, and the current theories are all hotly being debated.

I'm just a random Internet person as far as this stuff goes (and, as a 16-years-lapsed cog sci student I'm certain you can kick my ass on this topic), but I can't help but notice the review you linked to is dated June 2007 and includes nothing from that year, and all the papers Wikipedia cites regarding current best-guesses on the mechanism behind the nootropic effect (greater neuronal coupling resulting in enhanced gamma band rhythmicity) are dated July 2007 or later.

In particular, this one. Table 3 of which tabulates results from dozens of studies on human adults which establish the positive impact on digit span pretty universally. This matches my own experiences, which include the "magical" feeling of somehow always being able to rattle off the 8-digit ID numbers for the top 10 highest-priority bugs in our database at any given moment, and noting things like the scoring pattern for a Ping-pong game I'm playing is the exact same as last Tuesday's game in reverse. I was 99.99th percentile in standardized math tests before Modafinil - and something palpably different afterward.
posted by Ryvar at 6:33 PM on November 11, 2014

I'd need to look at some of the specific articles it references, Muller et all (2004) being one that I think your looking at.

The problem I have with Modafinil as a nootropic is that it's entirely possible Modafinil's primary action could be on the orexin (hypocretin2) system. The result would possibly cascade through to the other systems (dopamine etc) and all it would be doing is suppressing sleep. In other words, without excruciatingly careful controls on participants for sleep, it could just be that Modafinil puts parts of your mind in the position of being well rested. This plus a placibo effect could result in some people (who may have extended poor sleep) mistakenly believing its made them smarter rather than just being at an optimal point in their daily cycle. Does it really count as a Nootropic if it just puts you at your best? Perhaps the expected release of an orexin antagonist, Suvorexant, will shed some light on this.

On the bright side, the article you sited Ryvar sums up my problem with Modafinil quite well.

"The range of off-label uses for modafinil nevertheless appears to be outpacing the growth of this empirical literature, despite a lack of clear consensus about the precise neurochemical mechanism of action of this agent, inadequate clinical experience and a dearth of empirical data addressing the long-term use of this agent."
posted by Jernau at 7:05 PM on November 11, 2014

Note on the orexin system: it's still pretty poorly understood. I know orexin knockout mice still get the effects of modafinil, but that doesn't mean the gene being knocked out is the only one that uses orexin. We just don't know.
posted by Jernau at 7:14 PM on November 11, 2014 [1 favorite]

Nice, I was JUST about to say orexin-null mice actually show greater response, yeah.

My personal, entirely subjective experience is that there's a (for me) 130mg saturation point beyond which Modafinil ceases to act as a mere VLPO-blocking wakefulness agent, and starts acting closer to an SSRI. Specifically, it feels *exactly* like ramping on/off Citalopram.
posted by Ryvar at 7:25 PM on November 11, 2014 [1 favorite]

Just throwing the idea out there but given that we know different combinations of genes respond differently to Modafinil, it's possible that some people genetically or behaviorally have a higher homeostatic sleep state (their best isn't really their best).

In other words, optimal sleep is never reached even with good sleep cycles. In this case Modafinil would allow them to reach a new peak that was previously not possible. Of course it's also possible they simple don't have optimal sleep already, and Modafinil just temporarily gets them to a that point.

I'd really love to work on it someday. I'm currently interested in seeing about building on Michael Perlis (2004) work with Cognitive Behavioral Therapy for insomnia +/- Modafinil and it's effects on compliance with CBT-i. I can easily see that kind of work providing a route to some answers to these questions, after all if you can get people to optimal sleep, then you have something to compare Modafinil with.
posted by Jernau at 7:34 PM on November 11, 2014 [4 favorites]

chortly: We're active because we need to eat and defend ourselves, but inasmuch as an animal has a good supply of food and a reasonably safe spot, there's no good reason to be awake at all.

I am constantly reminded of this by the cats and dogs that have been in my life. Being carnivores, they don't have to spend much time eating to amass enough calories (my dog manages it in about 15 minutes every 2-3 days, on a raw diet - by his choice, he won't eat more often!). Being neutered, no need to waste energy hunting other's genitals. Being safe, no need to spend hours building dens or exhaustively tracking herd movements (although they'll spend time casually imitating this, at 1% of the energy outlay). The rest of their day is: poop, pee, get petted, sleep. 99% the latter. Sometimes multi-tasking the latter two activities.

Herbivores eat food that is generally much less energy-dense, and CAN NOT FORGET that they are prey (housecat-or-larger predators rarely are), so that fills a lot of time.
posted by IAmBroom at 12:11 PM on November 12, 2014