Not an expert in the field, but from what I understand the idea is very contentious with sizeable camps on both sides, especially noticeable if you are talking to an Alzheimers scientist, or a immune system scientist.
There are dozens of us! Mostly because Nedergaard's lab(s) are like 50 people all by themselves.
I always find it interesting what people's perception of the size of academic subfields is. For most topics in the biological sciences (i.e. excluding cancer, HIV, malaria, AD, and other "whales") you can fit everyone that has directly worked on that topic in the last 5 years in a medium-sized auditorium. And many people work on multiple topics!
Very interesting article! However, the reduction of clearance rate (30%) is not a lot. It is possible the brain produces even less toxins while asleep. And the article also acknowledges there may be an increase in "bulk flow of fluid." All that said, this study was done on mice, so it's hard to draw conclusions.
Could it be possible that the coffee lobby is behind this 'counter'-study?, since a relatively simple inference from the OP has catastrophic consequences for the coffee business:
Deep sleep is necessary for the slow electrical waves that clear the brain of waste including amyloid proteins. (Excessive) coffee intake reduces the quality and quantity of deep sleep, thus leading to a build up of waste products including amyloid, resulting in cognitive declines such as Alzheimer's etc. Therefore, coffee intake (indirectly) causes Alzheimer's.
Admitting that last part is suicidal for the coffee business.
@dukeyukey, from these '_lot_ of studies', if we remove those that are directly or indirectly funded by the coffee lobby, are we left with the empty set ∅ ?
We have a _lot_ of studies and evidence that says coffee reduces overall mortality by quite a bit, and it holds for both caffeinated and decaf coffee. It seems like coffee specifically reduces the risk of Alzheimer's as well.
That result is almost certainly bullshit, at least for Alzheimer's. Or the effect is so minimal that it doesn't practically matter.
Why? Because Finland is the country that consumes the most coffee per capita in the world. Finland also has the highest amount of Alzheimer patients per capita. Correlation is not causation, but based on this, it should rather be suspected that coffee causes Alzheimer's rather than helps with it.
I know how much I am normally able to lift each exercise. So let's say 125 lbs shoulder press, I expect to be able to lift the weights 10 times the first set, 9 times the second, 8 the third set. If I can't lift the weights 10 times I failed early.
Basically failing to lift weights that you could lift say last week. There are other factors too of course like fatigue, food, etc. that can make you fail to lift the same weights.
"The team used mice that develop a form of Alzheimer's. They exposed these mice to bursts of sound and light that occurred 40 times a second.
The stimulation induced brain waves in the animals that occurred at the same, slow frequency.
Tests showed that the waves increased the flow of clean cerebrospinal fluid into the brain and the flow of dirty fluid out of the brain. They also showed that the fluid was carrying amyloid, the substance that builds up in the brains of Alzheimer's patients."
Does this mean we might be able to use something like TMS instead of sleeping?
And could a failure or reduced functioning in this system explain those people "allergic" to electromagnetic radiation?
Cleaning the brain is one function that is fulfilled during sleep, but it isn't the only function. Even if you can artificially induce this you would probably need to sleep for other things such as physical recovery(which intensifies during sleep). There may be a chance that it helps lessen the need for sleep or maybe even remove some of the deleterious effects of sleep deprivation
I volunteer to try it out. I have idiopathic hypersomnia and if I get even a few minutes short of what I’m supposed to it (seems to) hit me like when most people get a few hours short.
Seriously. Anyone in HN know how I could replicate this?
Re idiopathic hypersomnia: have you ruled out upper airway resistance syndrome (UARS)? Most standard sleep studies will miss it. It's often misdiagnosed as idiopathic hypersomnia or chronic fatigue syndrome.
The CPAP helped a great amount, but even with CPAP and meds (Solriamfetol for fatigue/sleep inertia, Daridorexant for insomnia) I'm not very energized.
"Go to bed" is useless advice. Some of us are unable to sleep longer than about 5 hours. Room darkening, white noise, complete silence, 8Sleep mattress pad, extended release melatonin, caffeine abstinence, going to bed later, going to bed earlier, nothing works. We just naturally wake up after 5 hours, no matter what, ready to go.
there’s always exceptions, but most people are capable of getting more, good sleep.
Not giving out generally useful advice just because an extremely small minority can’t use it is just silly. And giving it out is certainly useful to most people who hear it.
Just because you can’t use it, doesn’t mean someone shouldn’t give advice. There are other humans in existence.
This is a bad idea, because it would incentivize channeling even more people into the prison system in order to have test subjects.
Instead of more cures for diseases, we would get an equilibrium-finding economy of live human bodies, where most of the net gain is diverted to middlemen and administrative overhead. And don't forget the incomprehensible horror.
This is voluntary though. Sure the odds of more volunteering increases with the total number of bodies, but I don't think it'd be actually significant.
Sure. There isn't an inherent financial incentive here for the prison system (though an illegal one could easily develop, as it does with all else). It really boils down to the type of study and how much time gets exchanged: I'd assume the more dangerous something is, the more "time served" it's worth, for example. And of course there are all the usual caveats of determining a fair rate, ensuring informed consent, etc.
If 40 times a second is 40 Hz, than this frequency is pretty high for a deep sleep (in humans), 40Hz would mean some intense pattern recognition/focused attention.
Alzheimer seems worse to me. Although a daily recommended 1-1.5h dose of this might make me reconsider ;-) Whenever I do 30 minutes I can hear it in my ears for the next 10 minutes.
coinciding sure, but waste removal is highly unlikely to be the basis of learning. It is likely that 'updates' if you will are best performed during this maintenance period.
> So finding ways to help the brain clean itself — perhaps by inducing those slow electrical waves — might prevent a wide array of disorders.
Even before getting to the end this had me thinking of binaural beats. Back in college there was a beat that I would use whenever I was super tired and had a lot to do, and it'd help me refresh via a quick 20m nap (sometimes the nap itself wasn't even needed; just to let my mind be taken by the beat for the duration). If it's the case that a part of the effect is to trigger a "deep clean" (I've wondered on and off what's really happening), then this just may become a way to reduce said disorders...
IIRC they ware selling tracks that were supposed to make you smart or calm etc. I torrented the most expensive one which the legend said it costs 1000$ and makes you smart, didn't change a thing but maybe because I didn't pay for it :)
I remember those vividly. We were on a school trip, and some of the girls heard about it and wanted to try the Speed track (as in the drug). It certainly altered their consciousness, one of them even fainted. We tried to keep it a secret from the teacher, but it eventually got out, and I think all of us on that trip got confronted by the teacher during parent–teacher conferences.
We were all like 14, so we had no idea what Speed actually was like. Seemed almost real for a minute there, but of course it's more akin to hypnosis than actual brain alteration.
Binaural beats is a phenomenon though, not a company, so no need to pay for anything ;). Of course there will be those creating tracks or generators with their "special sauce" and charging for it. Kinda like selling shell necklaces so you don't have to gather the shells and make one yourself.
How would audial waves affect the brain as electrical waves? I don't think that's possible. I'm figuring they'd need to directly take effect in the brain tissue itself to clean it.
Potentially via the ear in the same way that a microphone translates sound waves (vibrations in the air) into electrical signals. Just a guess. Seems like there must be signal-flow from from the ear to the brain that involves electricity and the recreation of the signal to be processed by the brain.
The beat frequency? Not really; I used an app called Gnaural (on Android, hasn't been updated in years), and just selected the "Power nap" profile. It'll be theta or delta though, maybe a combination.
Oh nice, thanks. I didn't think to check the source. Been thinking to update the app myself though as it's not installing on my current device, and I'd like to explore BBs more. I've also found "Energize", "Problem resolver", "Wakeup", "Rain shower" and "Babbling brook" to be useful. The rest by comparison are pretty meh, or maybe I just didn't find a task match.
I'm sure there are differences in their effectiveness.
Based on my limited knowledge the sound frequencies attempt to put the brain into theta or delta frequencies and does this by creating a ghost signal (left ear 100hz - right 106hz gives a 6hz theta wave).
Dreamachines work similarly (but mono) by creating a flickering light at set frequencies.
I'm sure tactile vibrations or pulses could have some effect also.
It’s pretty incredible that by showing the mice a light and music show, they were able to induce drainage of brain waste. That’s really exciting and I would love it if they could invent a hat to wear at night that accelerated the process while sleeping, effectively multiplying your time spent sleeping by some factor. It could be really effective for people with tough work schedules like doctors, truck drivers and pilots.
> It could be really effective for people with tough work schedules
If such a thing were invented it would effectively become mandatory, because anybody not willing to use it would be out-competed for work by people who were.
I don't know if that's true. Exercise, meditation, adderall, and spaced repetition learning all improve work performance for knowledge workers and those things are far from universally employed.
There's coffee/caffeine which is available at workplaces for employees who want to consume it.
If there are proven benefits without any known adverse effects, we can expect businesses to take the leap and try to make it available as long its legal, practical and cost effective.
> If such a thing were invented it would effectively become mandatory, because anybody not willing to use it would be out-competed for work by people who were.
I believe this dynamic is already happening to ADHD drugs.
This is entirely dependent on how people value free time vs money. The average person in the developed world would probably take the free time over more money. People already hate working 40 hours.
We've been working on this for about 4 years now at AffectableSleep.com - not 40hz, and not light. Phase-targeted auditory stimulation which has more than 10 years of research in humans.
Very interesting. Do you think this will ever turn into a device that regular people can buy? I've been an insomniac my entire life, and would be very interested in trying something in this space.
Yes, we are building a commercial experience, and I am also a lifelong chronic insomniac, which got me into this space.
HOWEVER, this is not an insomnia device. There are a bunch of "competing" devices that sound similar that promise to help you "fall asleep faster" often 70%+ faster, and looking at all the research they've done, it's BS.
Sorry, I wish I could solve our problem, but this isn't it.
However, as far as the getting the benefits of a full night sleep, this does help.
I've been speaking with a lot of insomniacs, and what I often bring up is "do you kinda like it"? We all know we "should" sleep, but I feel a large part of chronic insomnia isn't the "stress" that everyone assumes we have, but just that we enjoy being awake in the middle of the night, pondering, ruminating, etc.
Since the site owner is in this thread, FYI there's a minor typo on this page in the 'What does the stimulation sound like?' section; 'illicit' should be 'elicit'.
There is no information on what do they actually measure in every individual. Without some real-time feedback it seems somewhat not enough basis to deliver the treatment to the intended target. (But if they're hiring...)
What do you mean "there's no information on what do they actually measure in every individual"? We are measuring slow-waves, the synchronous firing of neurons which defines deep sleep. This is a real-time feedback system, with measured ERPs on a 5-second on, 5-second off stimulation protocol?
Happy to answer any questions, if I'm not understanding your statement correctly.
That's ok. There just seem to be no explicit mentioning of that, that individual differences in real-time will be taken into account, just some textbook style description.
Have you considered regulating skeletal muscle tone?
Ok, thanks for the feedback. I thought our "how it works" was pretty clear, but also simple for people to understand. It's a narrow path to wander.
By "regulating skeletal muscle tone" do you mean as an input? Or as a target?
We've mostly focused on neuro, though we did an experiment in Vagal stimulation, but you could never be sure what you were measuring, so we ditched that and focused on the area with the most research.
PTAS (the technical term for the stimulation) has considerable amount of research behind it with impactful results.
Always keen to learn more if there is something in muscle tone you think we should be looking at.
Make sure to check if it's legal in your jurisdiction before attempting to go and buy it.
Saying that from personal experience after I returned to Australia from the UK, and popped into a local pharmacist to grab some to try it out. The lady behind the counter and the customer next to her acted like I'd literally asked to buy heroin. (!)
It turns out Melatonin wasn't legal to buy at that time (a few years ago now), though the law has apparently been changed since.
I assume it's national not state based policy - I asked my pharmacist (in NSW) about this a few months back, evidently it's available to people over the age of 55 only.
You can get a prescription from a doctor if you have trouble sleeping. My sleep doctor prescribed me a sublingual suspension instead of the tablets (you measure it with an oral syringe and squirt it under your tongue), and to take it earlier than what is recommended. I do just 1mg, 2 hours before sleep and since starting my sleep has been far, far better than it ever has been in my life.
The sustained release tablets (like ‘Circadan’ or similar branding) I found were not good - I’d wake up groggy and generally didn’t get good sleep. They were just prescribed by a regular GP, and the sleep specialist I saw later on thinks it’s counter productive because they keep releasing longer than you want it to.
Yup, though for a cheaper option you can just buy it online (iherb stocks 3mg and 10mg tablets, f.e.). I have the 'Natrol' brand.
The liquid form sounds like an interesting option. I haven't experimented much with timing - instructions suggest 20-30 minutes prior to bed, which I've been following for my very occasional usage.
My teenage son's paediatrician has no issues with my buying melatonin from iHerb vs the liquid on prescription, as the latter is obscenely expensive and wasn't covered by the PBS last time I checked.
I think testosterone should be legalized. There are hundreds of black market websites that sell it to US customers and its usage is actually very common. Better to take the cryptocurrency, scams, counterfeits off the market.
I feel this will be very subjective of course. The biggest thing I have found I can do for a full rest (not length but quality) is no screens at all after 8pm and no lights except candle light after 930pm, coupled with reading by candle light. Melatonin does help me occasionally but it's hit or miss. Reading instead of watching or listening seems to be the biggest help. I guess different parts of my brain fires during that activity than normal.
> no screens at all after 8pm and no lights except candle light after 930pm
I swear by blue-blocking glasses for this reason, especially when driving at night since the advent of obnoxiously bright LED (but I repeat myself) head and tail lights on every car. These are my current pair, no affiliation: https://www.amazon.com/gp/product/B07CXYT17C/
I have a much darker, cheaper pair that's great for before bedtime, but would be far too dangerous for night driving. I'll have to try these some time and see how they compare.
I am imagining a household transforming into Amish roleplay by 9:30 PM.
I’ve achieved a similar-but-less-impactful effect by putting Zwave dimmer switches where I could, and setting the turn-on brightness to be lower during a “wind-down” house mode.
Switching my smart lights to red works pretty well for me, although from the street it definitely looks like something unholy is happening in the apartment.
I did the same thing for a while, and found it weirdly hard to replace with electricity. Most options are too bright, almost none are incandescent.
If I try it again I’ll have to build my own battery powered lanterns with ultra-low-wattage incandescent bulbs (don’t want the spiky spectrum of LED for this purpose) to get them dim enough and in a useful form factor.
I could read and get around just fine by two beeswax candles (and after getting used to that, full room lighting seemed insane, it’s so bright) but most things you can buy are at least 5x that bright. Even most plug in night lights are brighter than two beeswax tapers.
I have Kasa Smartbulbs (KL110) for bedside and couch-side lamps. They claim 2700K, and while I don’t have a way to measure that, they feel pretty similar to incandescents. They’re also extremely dimmable, which was my main reason for getting them. At the lowest setting, they claim 10 lumens, which is roughly equivalent to a candle. Two of them in the living room at a low-moderate brightness are plenty for evening relaxation.
I’m looking at getting Philips Hue bulbs. They’re expensive but look promising. I cannot stand the eco friendly bright white lightbulbs these days. Nothing against saving energy it’s just not for me.
I take magnesium (Mg) at bed time. I believe it helps reduce muscle cramping, improving my sleep.
TIL There are many compounds avail OTC. The most common Mg-citrate upsets my tummy. After trying a few variataions, I settled on Mg-glycinate, which is also reasonably priced (vs say Mg-orotate).
YMMV. Please consult your doc. Adverse effects, drug interactions, etc.
Best, of course, is a nice hot bath with epsom salt. But that's not always practical.
Or, you know, fix the issues that prevent you from sleeping instead of messing with hormones. If you really need to sleep, take some GABA. Otherwise, work on it and maybe take magnesium.
Read this book few years back, that dreams are a way of different regions of the brain to defend territory. So the neurons in the visual processing region stop receiving input signal when one sleeps. Those neurons can then be used by neighboring regions for whatever. To prevent that takeover pseudo signals are created to keep them busy. Can't remember the name of the book, but it was a pretty cool theory.
EDIT: found the book - Livewired by David Eagleman
It may sound a little woo woo, but I definitely feels this. After duration of difficult mental work (often difficult reading) I can feel my ability to focus slipping and eyes getting heavy. If I can successfully take a short deep nap (sometimes less than 15 minutes) all that is flushed away and I can focus again. Weird analogy, but a the relief is similar to emptying a full bladder. Related, not napping in these circumstances seems like it would be very unhealthy and damaging.
I wish I could take naps like that. I’m lucky that I don’t have trouble falling asleep at night but once the sun is up it’s like my brain just refuses to shut off. Once every week or two I’m able to pull off a nap in the late mornings.
I’ll try that! Driving tired scares me. It’s tough when you’re driving through Nebraska for example and places to stop are so spaced out. All of a sudden the sleepiness just hits you and you’re cooked unless you pull over on the side of the highway, which is what you’re supposed to do. How do glucose spikes play into that?
I hope your Nebraska highways have some exits/side roads you can pull into. I’ll do that sometimes, or find a town and park a gas station somewhere.
Glucose spike is referring to the thanksgiving dinner effect where you get tired and need a nap after eating. Feeling tired after lunch. Etc.
It can happen after almost any meal, even while well rested, etc.
There’s ways to reduce the spikes but afaik once you get the spike, nap is the best solution.
Coffee can help for some type of tiredness, but sometimes it’s not enough.
I’ll do 15-20 min nap increments. Sometimes one nap isn’t enough, I need to rest longer. Thankfully, I can always tell when the one nap is insufficient before getting on the highway again.
Wouldn’t it be better then to just eat small snacks through your the day on a road trip vs pulling over for an entire meal? That way you can modulate the spikes and keep them to a minimum.
Yep because at the office it will be multiple hours of fighting having to sleep and literally getting nothing done while trying to not appear totally unconscious
You’re not far off the mark. Many jobs/skills that require intense mental concentration report practitioners needing a rest period or having an upper limit to performance.
A notable example I remember are the United Nations’ live interpreters. They can only interpret a live conversation for only about 45 minutes before they have to switch off with a new interpreter because the error rate just exponentially goes up due to mental fatigue.
Not weird to me — I feel it too. And I always described it as feeling like a wave of ... release, passing over my mind. It feels wonderful and I wake with a clarity as though a weight were lifted from my mind.
It might also just be energy stores filling up again. Its like running, if you take a short break you can often get going at a good pace again, not just because you get your breath back but also energy resverse replensih
My dad would say he wished the day was about 30 hours. He liked to work long stretches, 10-12 hours, and then unwind for a few hours and sleep for 12 hours. Unfortunately just didn't work well with the real world.
yes, we've known for two centuries that a couple of hours of extra sleep can help us undo the effects of days and days of sleep deprivation. This is one of the strongest argument against this brain clearance non-sense. If we can get this done in 15 minutes, why sleep 8 hours a day?
solo sailors (amongst others) do this; 30-90mins of sleep each time, but they cat nap all the time, not just once a day.
However, research shows that long term learning etc, as well as critical decision making, are impaired.
My anecdata of 1; I prefer 6-7 hours of sleep, but during some expeditions, I'd be lucky to get 2-3 hours before a summit attempt of 12-18 hours (leave at 1-2am, return to high camp by 3-4pm, pack up and head down to a lower level for safety). For safety, I make sure to practice all the skills required (rope, carabiner and knot handling) so these are "routine", and not require more cognitive effort to "figure out".
A funny story during an expedition: a friend couldn't lift his foot whilst we were all preparing for some ice traverse - it was stuck for some reason, we all stood around wondering why, and we finally realised I was standing on one of his crampon straps. I swear it took us 10mins to figure this out, a result of sleep deprivation, high elevation, being swathed in layers of clothing, and general fatigue.
It would be an amazing gift to be able to sleep even only half the time every day.
That said, I have had the unsettling thought that the brain is never really “off” during your lifetime. With computers you can restart them, but your brain keeps going, even when you’re sleeping. So I think we should be nice to our brains.
It would be an amazing gift to you, but it would not make sense from the evolutionary point of view. Take an animal of your choice (e.g. a cat or a dog or a mouse) and give them through magic the ability to sleep only 1 hour a day or nothing for the rest of their life. Do you think they would have an evolutionary advantage? Quite the opposite. they would end up burning more energy for nothing, having to look for more food and eventually endanger themselves to predation wondering, rather than cozy up in their nest sleeping.
Perhaps decrease of waste with sleep is exponential, not linear. After days of sleep deprivation, waste concentration is very high, so initial clearance rate is very high as well. As is clears, concentration decrease, so concentration rate also decreases.
I do regular full night's sleep. But when my brain is particularly spent, a short nap is nearly unavoidable. Afterward, I wake up on my own (no alarm) and can resume work immediately. No grogginess.
The article is literally about how we've known about the glymphatic system but not what its mechanisms actually are, and this is precisely about now figuring out the mechanisms.
Surprisingly, the glymphatic system was only discovered a decade ago. The new part is this 40hz light and sound, which has only be done in mice so far.
Guess this is a similar mechanism to why brainfog is gone afer a powernap?
Lets hope that with enough research one can induce it for the people in need some day.
you may also check out the quite logical and convincing "Visceral Theory of Sleep":
> The visceral hypothesis suggests that during sleep, the central nervous system, particularly the cerebral cortex, switches from analyzing exteroceptive information to analyzing signals arriving from interoceptors distributed throughout all the systems of the body
This also fits well with the theory that lack of deep sleep increases the risk of alzheimers and dementia:
https://www.medicalnewstoday.com/articles/not-getting-enough...
Just a few weeks ago this appeared somewhere on HN
https://www.sciencealert.com/study-finds-sleep-may-not-flush...
Not an expert in the field, but from what I understand the idea is very contentious with sizeable camps on both sides, especially noticeable if you are talking to an Alzheimers scientist, or a immune system scientist.
> sizeable camps on both sides
There are dozens of us! Mostly because Nedergaard's lab(s) are like 50 people all by themselves.
I always find it interesting what people's perception of the size of academic subfields is. For most topics in the biological sciences (i.e. excluding cancer, HIV, malaria, AD, and other "whales") you can fit everyone that has directly worked on that topic in the last 5 years in a medium-sized auditorium. And many people work on multiple topics!
Very interesting article! However, the reduction of clearance rate (30%) is not a lot. It is possible the brain produces even less toxins while asleep. And the article also acknowledges there may be an increase in "bulk flow of fluid." All that said, this study was done on mice, so it's hard to draw conclusions.
@clumsysmurf, nice catch!
Could it be possible that the coffee lobby is behind this 'counter'-study?, since a relatively simple inference from the OP has catastrophic consequences for the coffee business:
Deep sleep is necessary for the slow electrical waves that clear the brain of waste including amyloid proteins. (Excessive) coffee intake reduces the quality and quantity of deep sleep, thus leading to a build up of waste products including amyloid, resulting in cognitive declines such as Alzheimer's etc. Therefore, coffee intake (indirectly) causes Alzheimer's.
Admitting that last part is suicidal for the coffee business.
@dukeyukey, from these '_lot_ of studies', if we remove those that are directly or indirectly funded by the coffee lobby, are we left with the empty set ∅ ?
Do you think I would have posted that if what you say is true?
We have a _lot_ of studies and evidence that says coffee reduces overall mortality by quite a bit, and it holds for both caffeinated and decaf coffee. It seems like coffee specifically reduces the risk of Alzheimer's as well.
That result is almost certainly bullshit, at least for Alzheimer's. Or the effect is so minimal that it doesn't practically matter.
Why? Because Finland is the country that consumes the most coffee per capita in the world. Finland also has the highest amount of Alzheimer patients per capita. Correlation is not causation, but based on this, it should rather be suspected that coffee causes Alzheimer's rather than helps with it.
Could Finland's high incidence of Alz also have to do with its high latitude and Finlanders' lack of Vitamin D?
I've read that exercise negates all of this...
I've found out (the hard way) that chronic lack of sleep leads to not having enough energy for intense workouts... (walking is ok though)
Failing lifts is strongly correlated with a bad night's sleep.
Source: skimming various forums and personal experience et al, 2024.
I do not understand what 'failing lifts' is in this context?
I know how much I am normally able to lift each exercise. So let's say 125 lbs shoulder press, I expect to be able to lift the weights 10 times the first set, 9 times the second, 8 the third set. If I can't lift the weights 10 times I failed early.
I can only assume it means failing to lift a weight in the context of gym exercise.
Basically failing to lift weights that you could lift say last week. There are other factors too of course like fatigue, food, etc. that can make you fail to lift the same weights.
Ahh but working out makes you sleep better. The workouts dont even need to be intense!
> exercise negates all of this...
That would be logical taking in mind this article
In what way? It can make up for a lack of sleep?
"The team used mice that develop a form of Alzheimer's. They exposed these mice to bursts of sound and light that occurred 40 times a second.
The stimulation induced brain waves in the animals that occurred at the same, slow frequency.
Tests showed that the waves increased the flow of clean cerebrospinal fluid into the brain and the flow of dirty fluid out of the brain. They also showed that the fluid was carrying amyloid, the substance that builds up in the brains of Alzheimer's patients."
Does this mean we might be able to use something like TMS instead of sleeping?
And could a failure or reduced functioning in this system explain those people "allergic" to electromagnetic radiation?
Cleaning the brain is one function that is fulfilled during sleep, but it isn't the only function. Even if you can artificially induce this you would probably need to sleep for other things such as physical recovery(which intensifies during sleep). There may be a chance that it helps lessen the need for sleep or maybe even remove some of the deleterious effects of sleep deprivation
I volunteer to try it out. I have idiopathic hypersomnia and if I get even a few minutes short of what I’m supposed to it (seems to) hit me like when most people get a few hours short.
Seriously. Anyone in HN know how I could replicate this?
Re idiopathic hypersomnia: have you ruled out upper airway resistance syndrome (UARS)? Most standard sleep studies will miss it. It's often misdiagnosed as idiopathic hypersomnia or chronic fatigue syndrome.
FWIW, I have both IH and sleep apnea.
The CPAP helped a great amount, but even with CPAP and meds (Solriamfetol for fatigue/sleep inertia, Daridorexant for insomnia) I'm not very energized.
I'll look into it, although my issues seem to have started after a brain injury back when I was 12, so it's doubtful.
Here: https://en.wikipedia.org/wiki/Dreamachine (from 1959). There's a link at the bottom for one that will run in your browser.
Expose yourself to lights and sounds turning on and off at 40hz?
Here's a good rule of thumb: any time you try to undo a billion years of evolution, there will probably be unintended side effects. Go to bed.
New daily/weekly schedule based on tracking animals to exhaustion:
1) Walk for a day or two, with naps during afternoon heat. 2) Eat absolutely enormous meal. 3) Sleeeep. 4) Repeat.
"Go to bed" is useless advice. Some of us are unable to sleep longer than about 5 hours. Room darkening, white noise, complete silence, 8Sleep mattress pad, extended release melatonin, caffeine abstinence, going to bed later, going to bed earlier, nothing works. We just naturally wake up after 5 hours, no matter what, ready to go.
there’s always exceptions, but most people are capable of getting more, good sleep.
Not giving out generally useful advice just because an extremely small minority can’t use it is just silly. And giving it out is certainly useful to most people who hear it.
Just because you can’t use it, doesn’t mean someone shouldn’t give advice. There are other humans in existence.
Yea… um, also… I like sleeping. I find it a nice change of pace compared to the rest of my day.
mice models are notoriously known for being bad to predict anything related to the actual disease pathways
“Humanized mice”… yea, still mice though.
I’m kind of not joking that I think asking for medical study volunteers from prison populations in exchange for time served would put us way ahead.
Or instead of the death penalty, we try some things out that maybe might not work.
We would have cured for colds, cancers, and hair loss in a few years of human testing.
This is a bad idea, because it would incentivize channeling even more people into the prison system in order to have test subjects.
Instead of more cures for diseases, we would get an equilibrium-finding economy of live human bodies, where most of the net gain is diverted to middlemen and administrative overhead. And don't forget the incomprehensible horror.
Didn't this already happen repeatedly in US history? Legislation was passed preventing human testing in the early 90s
This is voluntary though. Sure the odds of more volunteering increases with the total number of bodies, but I don't think it'd be actually significant.
“in exchange for time served”
Sure. There isn't an inherent financial incentive here for the prison system (though an illegal one could easily develop, as it does with all else). It really boils down to the type of study and how much time gets exchanged: I'd assume the more dangerous something is, the more "time served" it's worth, for example. And of course there are all the usual caveats of determining a fair rate, ensuring informed consent, etc.
Truly monstrous idea. It alarms me that you can't immediately identify several massive problems with this idea
What I like it that you don’t think this is already being done, just probably not in the US a lot.
Why do you like that?
If 40 times a second is 40 Hz, than this frequency is pretty high for a deep sleep (in humans), 40Hz would mean some intense pattern recognition/focused attention.
"Does this mean we might be able to use something like TMS instead of sleeping?"
The trillionaires will greatly benefit from our new 20 hour work days.
https://www.youtube.com/watch?v=UVne_84qZkA
That noise gave me cancer. Thank you.
You might be confusing medicine with pleasure.
I hope the patient's suffering is worthwhile.
Alzheimer seems worse to me. Although a daily recommended 1-1.5h dose of this might make me reconsider ;-) Whenever I do 30 minutes I can hear it in my ears for the next 10 minutes.
Sleep is about more than waste removal. You cant really learn new things without sleeping on it.
That's making an assumption that the two aren't actually entirely linked phenomena.
coinciding sure, but waste removal is highly unlikely to be the basis of learning. It is likely that 'updates' if you will are best performed during this maintenance period.
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> So finding ways to help the brain clean itself — perhaps by inducing those slow electrical waves — might prevent a wide array of disorders.
Even before getting to the end this had me thinking of binaural beats. Back in college there was a beat that I would use whenever I was super tired and had a lot to do, and it'd help me refresh via a quick 20m nap (sometimes the nap itself wasn't even needed; just to let my mind be taken by the beat for the duration). If it's the case that a part of the effect is to trigger a "deep clean" (I've wondered on and off what's really happening), then this just may become a way to reduce said disorders...
IIRC they ware selling tracks that were supposed to make you smart or calm etc. I torrented the most expensive one which the legend said it costs 1000$ and makes you smart, didn't change a thing but maybe because I didn't pay for it :)
I remember those vividly. We were on a school trip, and some of the girls heard about it and wanted to try the Speed track (as in the drug). It certainly altered their consciousness, one of them even fainted. We tried to keep it a secret from the teacher, but it eventually got out, and I think all of us on that trip got confronted by the teacher during parent–teacher conferences.
We were all like 14, so we had no idea what Speed actually was like. Seemed almost real for a minute there, but of course it's more akin to hypnosis than actual brain alteration.
I remember trying a bunch of these in middle school as well. They really just gave me a headache.
Binaural beats is a phenomenon though, not a company, so no need to pay for anything ;). Of course there will be those creating tracks or generators with their "special sauce" and charging for it. Kinda like selling shell necklaces so you don't have to gather the shells and make one yourself.
You saved 1k$ and that looks quite smart to me. So... success?
How would audial waves affect the brain as electrical waves? I don't think that's possible. I'm figuring they'd need to directly take effect in the brain tissue itself to clean it.
Potentially via the ear in the same way that a microphone translates sound waves (vibrations in the air) into electrical signals. Just a guess. Seems like there must be signal-flow from from the ear to the brain that involves electricity and the recreation of the signal to be processed by the brain.
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could you find the exact one?
The beat frequency? Not really; I used an app called Gnaural (on Android, hasn't been updated in years), and just selected the "Power nap" profile. It'll be theta or delta though, maybe a combination.
Looking at the beatfreq values in the XML source of the preset [1], it's indeed combination of 4 to 11 Hz beats (mostly theta) and 2 Hz (delta).
[1] https://sourceforge.net/projects/gnaural/files/Presets/Minds...
Oh nice, thanks. I didn't think to check the source. Been thinking to update the app myself though as it's not installing on my current device, and I'd like to explore BBs more. I've also found "Energize", "Problem resolver", "Wakeup", "Rain shower" and "Babbling brook" to be useful. The rest by comparison are pretty meh, or maybe I just didn't find a task match.
There are lots of them on YouTube now. I listen to one most nights. Just search for “sleep” and “binaural beats.
I'm sure there are differences in their effectiveness.
Based on my limited knowledge the sound frequencies attempt to put the brain into theta or delta frequencies and does this by creating a ghost signal (left ear 100hz - right 106hz gives a 6hz theta wave).
Dreamachines work similarly (but mono) by creating a flickering light at set frequencies.
I'm sure tactile vibrations or pulses could have some effect also.
I made this a few years ago after getting into Hemi Sync tapes to test out what different tones feel like.
https://numtel.github.io/binaural-playground/
It’s pretty incredible that by showing the mice a light and music show, they were able to induce drainage of brain waste. That’s really exciting and I would love it if they could invent a hat to wear at night that accelerated the process while sleeping, effectively multiplying your time spent sleeping by some factor. It could be really effective for people with tough work schedules like doctors, truck drivers and pilots.
> It could be really effective for people with tough work schedules
If such a thing were invented it would effectively become mandatory, because anybody not willing to use it would be out-competed for work by people who were.
Yes, but early adopters would either move up in socioeconomic status, or develop new horrors beyond comprehension
Either way, sign me up!
Yep, I’ll take more effective sleep any day
So modern society and many of its ills.
I don't know if that's true. Exercise, meditation, adderall, and spaced repetition learning all improve work performance for knowledge workers and those things are far from universally employed.
There's coffee/caffeine which is available at workplaces for employees who want to consume it.
If there are proven benefits without any known adverse effects, we can expect businesses to take the leap and try to make it available as long its legal, practical and cost effective.
> If such a thing were invented it would effectively become mandatory, because anybody not willing to use it would be out-competed for work by people who were.
I believe this dynamic is already happening to ADHD drugs.
This is entirely dependent on how people value free time vs money. The average person in the developed world would probably take the free time over more money. People already hate working 40 hours.
We've been working on this for about 4 years now at AffectableSleep.com - not 40hz, and not light. Phase-targeted auditory stimulation which has more than 10 years of research in humans.
Very interesting. Do you think this will ever turn into a device that regular people can buy? I've been an insomniac my entire life, and would be very interested in trying something in this space.
Yes, we are building a commercial experience, and I am also a lifelong chronic insomniac, which got me into this space.
HOWEVER, this is not an insomnia device. There are a bunch of "competing" devices that sound similar that promise to help you "fall asleep faster" often 70%+ faster, and looking at all the research they've done, it's BS.
Sorry, I wish I could solve our problem, but this isn't it. However, as far as the getting the benefits of a full night sleep, this does help.
I've been speaking with a lot of insomniacs, and what I often bring up is "do you kinda like it"? We all know we "should" sleep, but I feel a large part of chronic insomnia isn't the "stress" that everyone assumes we have, but just that we enjoy being awake in the middle of the night, pondering, ruminating, etc.
I wonder what people think of the research this is based on https://www.affectablesleep.com/science
Since the site owner is in this thread, FYI there's a minor typo on this page in the 'What does the stimulation sound like?' section; 'illicit' should be 'elicit'.
Thanks so much! Will fix.
There is no information on what do they actually measure in every individual. Without some real-time feedback it seems somewhat not enough basis to deliver the treatment to the intended target. (But if they're hiring...)
P.S. The website design is also imho a bit wacky.
What do you mean "there's no information on what do they actually measure in every individual"? We are measuring slow-waves, the synchronous firing of neurons which defines deep sleep. This is a real-time feedback system, with measured ERPs on a 5-second on, 5-second off stimulation protocol?
Happy to answer any questions, if I'm not understanding your statement correctly.
That's ok. There just seem to be no explicit mentioning of that, that individual differences in real-time will be taken into account, just some textbook style description. Have you considered regulating skeletal muscle tone?
Ok, thanks for the feedback. I thought our "how it works" was pretty clear, but also simple for people to understand. It's a narrow path to wander.
By "regulating skeletal muscle tone" do you mean as an input? Or as a target?
We've mostly focused on neuro, though we did an experiment in Vagal stimulation, but you could never be sure what you were measuring, so we ditched that and focused on the area with the most research.
PTAS (the technical term for the stimulation) has considerable amount of research behind it with impactful results.
Always keen to learn more if there is something in muscle tone you think we should be looking at.
Very cool. I’ll take a look!!
Random fun theory. I wonder if there’s any connection to light shows at EDM concerts inducing specific effects
There might already be something available in the form of binaural beats. Not a hat, but a pair of earphones and a BB app or audio track...
If you haven’t already, try taking melatonin before bed. I found my sleep to decrease in length but I wake more rested.
Make sure to check if it's legal in your jurisdiction before attempting to go and buy it.
Saying that from personal experience after I returned to Australia from the UK, and popped into a local pharmacist to grab some to try it out. The lady behind the counter and the customer next to her acted like I'd literally asked to buy heroin. (!)
It turns out Melatonin wasn't legal to buy at that time (a few years ago now), though the law has apparently been changed since.
I assume it's national not state based policy - I asked my pharmacist (in NSW) about this a few months back, evidently it's available to people over the age of 55 only.
You can get a prescription from a doctor if you have trouble sleeping. My sleep doctor prescribed me a sublingual suspension instead of the tablets (you measure it with an oral syringe and squirt it under your tongue), and to take it earlier than what is recommended. I do just 1mg, 2 hours before sleep and since starting my sleep has been far, far better than it ever has been in my life.
The sustained release tablets (like ‘Circadan’ or similar branding) I found were not good - I’d wake up groggy and generally didn’t get good sleep. They were just prescribed by a regular GP, and the sleep specialist I saw later on thinks it’s counter productive because they keep releasing longer than you want it to.
Yup, though for a cheaper option you can just buy it online (iherb stocks 3mg and 10mg tablets, f.e.). I have the 'Natrol' brand.
The liquid form sounds like an interesting option. I haven't experimented much with timing - instructions suggest 20-30 minutes prior to bed, which I've been following for my very occasional usage.
My teenage son's paediatrician has no issues with my buying melatonin from iHerb vs the liquid on prescription, as the latter is obscenely expensive and wasn't covered by the PBS last time I checked.
Their 3mg tablets work great for the both of us.
It's so weird to think that a naturally occurring hormone which is safely available in one first world country would be so restricted in another.
It's not so weird to me, I don't know much about melatonin but testosterone (probably the most popular steroid) is also just a natural hormone
I think testosterone should be legalized. There are hundreds of black market websites that sell it to US customers and its usage is actually very common. Better to take the cryptocurrency, scams, counterfeits off the market.
Thyroid hormone is prescription only, and for good reason. Hormone overdose can be dangerous.
I feel this will be very subjective of course. The biggest thing I have found I can do for a full rest (not length but quality) is no screens at all after 8pm and no lights except candle light after 930pm, coupled with reading by candle light. Melatonin does help me occasionally but it's hit or miss. Reading instead of watching or listening seems to be the biggest help. I guess different parts of my brain fires during that activity than normal.
> no screens at all after 8pm and no lights except candle light after 930pm
I swear by blue-blocking glasses for this reason, especially when driving at night since the advent of obnoxiously bright LED (but I repeat myself) head and tail lights on every car. These are my current pair, no affiliation: https://www.amazon.com/gp/product/B07CXYT17C/
I have a much darker, cheaper pair that's great for before bedtime, but would be far too dangerous for night driving. I'll have to try these some time and see how they compare.
> …no lights except candle light after 930pm…
I am imagining a household transforming into Amish roleplay by 9:30 PM.
I’ve achieved a similar-but-less-impactful effect by putting Zwave dimmer switches where I could, and setting the turn-on brightness to be lower during a “wind-down” house mode.
Switching my smart lights to red works pretty well for me, although from the street it definitely looks like something unholy is happening in the apartment.
Yes I intend on getting smart lights. They’re expensive but I’m sure they’re worth it.
Or you’re running a brothel!
FYI, candle light probably makes your air worse.
I did the same thing for a while, and found it weirdly hard to replace with electricity. Most options are too bright, almost none are incandescent.
If I try it again I’ll have to build my own battery powered lanterns with ultra-low-wattage incandescent bulbs (don’t want the spiky spectrum of LED for this purpose) to get them dim enough and in a useful form factor.
I could read and get around just fine by two beeswax candles (and after getting used to that, full room lighting seemed insane, it’s so bright) but most things you can buy are at least 5x that bright. Even most plug in night lights are brighter than two beeswax tapers.
I have Kasa Smartbulbs (KL110) for bedside and couch-side lamps. They claim 2700K, and while I don’t have a way to measure that, they feel pretty similar to incandescents. They’re also extremely dimmable, which was my main reason for getting them. At the lowest setting, they claim 10 lumens, which is roughly equivalent to a candle. Two of them in the living room at a low-moderate brightness are plenty for evening relaxation.
I’m looking at getting Philips Hue bulbs. They’re expensive but look promising. I cannot stand the eco friendly bright white lightbulbs these days. Nothing against saving energy it’s just not for me.
Why not just get regular orange led light with a dimmer?
those orange salt lamps have a similar spectrum to candles
Vitamin D3 might also help.
Magnesium as well.
Yes and:
I take magnesium (Mg) at bed time. I believe it helps reduce muscle cramping, improving my sleep.
TIL There are many compounds avail OTC. The most common Mg-citrate upsets my tummy. After trying a few variataions, I settled on Mg-glycinate, which is also reasonably priced (vs say Mg-orotate).
YMMV. Please consult your doc. Adverse effects, drug interactions, etc.
Best, of course, is a nice hot bath with epsom salt. But that's not always practical.
I’m a huge fan of magnesium in tea before bed
I'd like to try this. Recommendations? (My quick search's results were roobios, white tea, etc.) TIA.
Well I prefer celestial seasonings sleepytime tea and CALM brand magnesium
Not the parent, but I love some fresh mint tea with honey.
I need to get back into taking that. Good idea!
Or, you know, fix the issues that prevent you from sleeping instead of messing with hormones. If you really need to sleep, take some GABA. Otherwise, work on it and maybe take magnesium.
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> during sleep, slow electrical waves push the fluid around cells from deep in the brain to its surface.
Is that what dreams are? Electrical waves and fluid knocking on our brain cells?
Read this book few years back, that dreams are a way of different regions of the brain to defend territory. So the neurons in the visual processing region stop receiving input signal when one sleeps. Those neurons can then be used by neighboring regions for whatever. To prevent that takeover pseudo signals are created to keep them busy. Can't remember the name of the book, but it was a pretty cool theory.
EDIT: found the book - Livewired by David Eagleman
Dreams occur during REM sleep.
No.
I was going to say onto the Internet as a joke.
Glad you didn't!
Since it’s a fluid, what about the effect of head angle during sleep?
It may sound a little woo woo, but I definitely feels this. After duration of difficult mental work (often difficult reading) I can feel my ability to focus slipping and eyes getting heavy. If I can successfully take a short deep nap (sometimes less than 15 minutes) all that is flushed away and I can focus again. Weird analogy, but a the relief is similar to emptying a full bladder. Related, not napping in these circumstances seems like it would be very unhealthy and damaging.
I wish I could take naps like that. I’m lucky that I don’t have trouble falling asleep at night but once the sun is up it’s like my brain just refuses to shut off. Once every week or two I’m able to pull off a nap in the late mornings.
It’s not necessary to actually fall asleep. Just set a timer and relax.
For me it’s only a semi-conscious pre sleep state, but it helps significantly.
Do this if you get tired while driving too. It’s a life saving practice!
(And no, driving tired isn’t always due to bad nights sleep. Glucose spikes can be dangerous even if you sleep well at night.)
I’ll try that! Driving tired scares me. It’s tough when you’re driving through Nebraska for example and places to stop are so spaced out. All of a sudden the sleepiness just hits you and you’re cooked unless you pull over on the side of the highway, which is what you’re supposed to do. How do glucose spikes play into that?
It’s very scary.
I hope your Nebraska highways have some exits/side roads you can pull into. I’ll do that sometimes, or find a town and park a gas station somewhere.
Glucose spike is referring to the thanksgiving dinner effect where you get tired and need a nap after eating. Feeling tired after lunch. Etc.
It can happen after almost any meal, even while well rested, etc.
There’s ways to reduce the spikes but afaik once you get the spike, nap is the best solution.
Coffee can help for some type of tiredness, but sometimes it’s not enough.
I’ll do 15-20 min nap increments. Sometimes one nap isn’t enough, I need to rest longer. Thankfully, I can always tell when the one nap is insufficient before getting on the highway again.
Wouldn’t it be better then to just eat small snacks through your the day on a road trip vs pulling over for an entire meal? That way you can modulate the spikes and keep them to a minimum.
Yep.
I love to nap after a brain draining moment. I’m revitalized and ready to go. One of the major WFH benefits.
Yep because at the office it will be multiple hours of fighting having to sleep and literally getting nothing done while trying to not appear totally unconscious
yep, i cant stand in office work
You’re not far off the mark. Many jobs/skills that require intense mental concentration report practitioners needing a rest period or having an upper limit to performance.
A notable example I remember are the United Nations’ live interpreters. They can only interpret a live conversation for only about 45 minutes before they have to switch off with a new interpreter because the error rate just exponentially goes up due to mental fatigue.
Not weird to me — I feel it too. And I always described it as feeling like a wave of ... release, passing over my mind. It feels wonderful and I wake with a clarity as though a weight were lifted from my mind.
I wonder if they will study the waste buildup of various polyphasic sleep cycles like Everyman.
It might also just be energy stores filling up again. Its like running, if you take a short break you can often get going at a good pace again, not just because you get your breath back but also energy resverse replensih
Which makes the "false doctor" voice of my ego say "hmm.. could be pre-diabetes."
My dad would say he wished the day was about 30 hours. He liked to work long stretches, 10-12 hours, and then unwind for a few hours and sleep for 12 hours. Unfortunately just didn't work well with the real world.
Earth, anyway.
yes, we've known for two centuries that a couple of hours of extra sleep can help us undo the effects of days and days of sleep deprivation. This is one of the strongest argument against this brain clearance non-sense. If we can get this done in 15 minutes, why sleep 8 hours a day?
solo sailors (amongst others) do this; 30-90mins of sleep each time, but they cat nap all the time, not just once a day.
However, research shows that long term learning etc, as well as critical decision making, are impaired.
My anecdata of 1; I prefer 6-7 hours of sleep, but during some expeditions, I'd be lucky to get 2-3 hours before a summit attempt of 12-18 hours (leave at 1-2am, return to high camp by 3-4pm, pack up and head down to a lower level for safety). For safety, I make sure to practice all the skills required (rope, carabiner and knot handling) so these are "routine", and not require more cognitive effort to "figure out".
A funny story during an expedition: a friend couldn't lift his foot whilst we were all preparing for some ice traverse - it was stuck for some reason, we all stood around wondering why, and we finally realised I was standing on one of his crampon straps. I swear it took us 10mins to figure this out, a result of sleep deprivation, high elevation, being swathed in layers of clothing, and general fatigue.
It would be an amazing gift to be able to sleep even only half the time every day.
That said, I have had the unsettling thought that the brain is never really “off” during your lifetime. With computers you can restart them, but your brain keeps going, even when you’re sleeping. So I think we should be nice to our brains.
It would be an amazing gift to you, but it would not make sense from the evolutionary point of view. Take an animal of your choice (e.g. a cat or a dog or a mouse) and give them through magic the ability to sleep only 1 hour a day or nothing for the rest of their life. Do you think they would have an evolutionary advantage? Quite the opposite. they would end up burning more energy for nothing, having to look for more food and eventually endanger themselves to predation wondering, rather than cozy up in their nest sleeping.
Read more about Intel ME ;)
Perhaps decrease of waste with sleep is exponential, not linear. After days of sleep deprivation, waste concentration is very high, so initial clearance rate is very high as well. As is clears, concentration decrease, so concentration rate also decreases.
Where are you getting 15 minutes from?
That might be enough to recharge you to a normal level after something particularly taxing.
It's not enough to restore you completely, and certainly not after an entire day's worth of activity.
And there's so much more to sleep that you're missing, like consolidating memories, muscular coordination habits and patterns, etc.
I do regular full night's sleep. But when my brain is particularly spent, a short nap is nearly unavoidable. Afterward, I wake up on my own (no alarm) and can resume work immediately. No grogginess.
If it were possible, not harmful, I imagine we would already be doing it. Ain't evolution grand?
A little confusing, I thought we've known about the glymphatic system for a while now
What's confusing?
The article is literally about how we've known about the glymphatic system but not what its mechanisms actually are, and this is precisely about now figuring out the mechanisms.
The title. Now we know where it goes, but we knew that already. This article is from this month
Surprisingly, the glymphatic system was only discovered a decade ago. The new part is this 40hz light and sound, which has only be done in mice so far.
A decade is a very long time in a field as young as neuroscience
Guess this is a similar mechanism to why brainfog is gone afer a powernap? Lets hope that with enough research one can induce it for the people in need some day.
I thought exercise was the key to flushing proteins out of the brain?
Yeah, I was expecting mention of exercise too.
So is this similar to the idea behind 40hz binaural beats?
40hz is kinda off the scale, and is for very high concentration, so even though it matches off-hand that's a point to consider.
This study was done on mice, so the equivalent frequency for humans (if it exists) is likely lower.
No, they used pulses (ta-ta-ta-ta-ta 40 times a second) not continuous waves.
you may also check out the quite logical and convincing "Visceral Theory of Sleep":
> The visceral hypothesis suggests that during sleep, the central nervous system, particularly the cerebral cortex, switches from analyzing exteroceptive information to analyzing signals arriving from interoceptors distributed throughout all the systems of the body
This is huge
I wonder how red light on the brain is mixed in with this
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