Scientists uncover how the brain washes itself during sleep

Relevant comic, "The Science News Cycle"

https://phdcomics.com/comics.php?f=1174

Nonlinear (and inverting!) response curves for drug dosimetry that's population and person specific. Especially when there's a temporal delay. Trying to explain grapefruit to my elderly parents is like pulling teeth.

Another sign "big Carob" has taken over the health industry, pushing its "kids, it's healthier" lie. Chocolate, Wine and Cheese are the three vital food groups.

  > I have to tell my parents to stop reading 

I'm livid about this because this erodes public trust in science. Worse, people don't see that connection...

I don't understand how major news publications can't be bothered to actually reach out to authors. Or how universities themselves will do that and embellish work. I get that it's "only a little" embellishment, but it's not a slippery slope considering how often we see that compound (and how it is an excuse rather than acting in good faith). The truth is that the public does not understand the difference in the confidence levels of scientists for things like "anthropomorphic climate change" vs "drinking wine and eating chocolate is healthy for you." To them, it's just "scientists" who are some conglomerate. It is so pervasive that I can talk to my parents about something things I have domain expertise and written papers on and they believe scientists are making tons of money over this while I was struggling with student debt. I have to explain when I worked at a national lab isn't full of rich people[0]. There's a lot of easier ways to make money... And my parents, each, made more than any of the scientists I knew...

[0] People I know that have jumped ship and moved from lab to industry 2x-3x their salary (these are people with PhDs btw).

https://www.levels.fyi/companies/oak-ridge-national-laborato...

https://www.levels.fyi/companies/lawrence-livermore-national...

[Side note]: I wish we were able to be more honest in papers too. But I have lots of issues with the review system and the biggest is probably that no one wants to actually make any meaningful changes despite constant failure in the process and widespread frustration.

This hasn't been my experience at all in medicine and science. I perhaps have more exposure to both science and medicine than most because I have an MD-PhD. Perhaps at the medical student level there is truth to this, but the physicians who are conducting clinical research are often at academic centers where they go specifically for the opportunity to do research. Academic centers almost universally pay much less than private hospitals. In my area, physicians make double salary in private practice over academia.

And this all ignores that the authors are PhD scientists. So I'm confused how this is categorized as "medical field" in the first place. I found that the ability to memorize is essentially useless in PhD level biological science (I studied immunology, so I can't necessarily speak to other fields), and it is all systems level conceptualizing.

I think this is a team with many talented people who came together to do their best. But I'm sure I'm naive. There seems to have been a lot of new interest and debate about what is happening in the glymphatics sphere.

I don't really believe that. The real issue is that basic science in medicine is hard. You can't test a human in ways that might cause harm, which really limits how much investigation we can do. Ethics and morals also restrict what can be done to animals to investigate the basics on them too, though admittedly a lot of the time things just don't carry over anyway.

That being said, I think the rise of "evidence-based" medicine is also causing issues. It gets used as a cop-out to avoid thinking about the mechanics of what is actually happening in an injury. While this is certainly a good things for treatments where A or B superiority is uncertain, there's a lot of cases where I think an RCT just doesn't really make sense.

A pet example:

I broke my ankle recently, and this dug into the literature and common practice. A significant number of people will get end-stage arthritis a few years after "simple" ankle fractures and often the doctors have no idea why. At the same time, an important part of ankle anatomy is often left unfixed (the deltoid ligament) because a few studies back in the 80s found it wasn't necessary to fix it. The bone that serves an equivalent purpose IS fixed (if broken) though. Mechanically, they restrict the ankle joint and prevent it moving in certain directions.

When presented with biomechanical reasons for fixing it, and concurrent common poor outcomes for some patients, I've seen the response from surgeons thusly - "it's not supported by evidence" presumably because there isn't an RCT demonstrating definitive superiority.

So much of medicine and treatment is literally just hearsay and whatever your surgeon happened to read last week. As a whole the standard is rising, but so much research is so disjoint, disorganised and inconsistent that doctors often have no definitive guidance. It's probably more of a problem in some fields (like ortho) than others, but its still surprising when you see it yourself.

> the medical field selects hard for people who can memorize information, to the exclusion of people who can understand systems.

sounds similar to the problem with tech coding interviews. ive refactored the backend orchestration software of a SaaS company's primary app and saved 24tb of RAM, while getting 300% faster spinup times for the key part of the customer app, but i bomb interviews because i panic and mix up O(n) for algorithms and forget to add obvious recursion base cases. i know i can practice that stuff and pass, its just frustrating to see folks that have zero concept of distributed systems getting hired because they succeed at this hazing ritual.

but with that said, i suppose no industry or job will ever be free from "no true scottsman" gate-keeping from tenured professionals. hiring someone that potentially knows more than you puts your own job security at risk.

This is pretty true for MDs, but I don't know how true it is for PhDs.

The classic meme is that MDs love organic chemistry, but they hate biochemistry [1], because one is about memorization and the other is...less so, anyway.

But then again, neuroscientists do tend to love their big books of disjointed facts, so maybe it's more like medicine than I realize. I remember the one class I took on neuroscience was incredibly frustrating because of the wild extrapolations they were making from limited, low-quality data [2], that made it almost impossible to form a coherent theory of anything.

[1] ...except for the Krebs cycle! Gotta memorize that thing or we'll never be able to fix broken legs!

[2] "ooh, the fMRI on two people turned slightly pink! significant result!"

Also note that the medical field selects hard for people who can memorize information, to the exclusion of people who can understand systems

It's not impossible for people who are good in memorization to also be good in understanding systems.

Those people, in turn, are the ones doing this research.

Although common, it's not quite so that only people with a pure medical background do neuroscience.

All in all, having met quite some people in the field, the things you're hinting at never occurred to mee as an actual problem. My guess is because the people who actually have issues get weeded out very soon. Like: before even finishing their PhD. It's not an easy field.

  > Also note that the medical field selects hard for people who can memorize information, to the exclusion of people who can understand systems. 

I understand testing knowledge and intelligence is an intractable problem, but I my main wish is that this would simply be acknowledged. That things like tests are _guidelines_ rather than _answers_. I believe that if we don't acknowledge the fuzziness of our measurements we become overconfident in them and simply perpetuate Goodhart's Law. There's an irony in that to be more accurate, you need to embrace the noise of the system. Noise being due to either limitations in measurements (i.e. not perfectly aligned. All measurements are proxies. This is "measurement uncertainty") or due to the stochastic nature of what you're testing. Rejecting the noise only makes you less accurate, not more.

I agree that the selection for memorization is high, and I've worked with many neuroscientists who cared more about biological "stamp collecting" than understanding systems.

But in my experience neuroscientists have to have a solid level of systems thinking to succeed in the field. There are too many factors, related disciplines (from physics to sociology), and levels of analysis to be closed off.

Luckily, those two different traits are learnable, so I'd guess as the field advance and mature, this will change?

Honestly 'our knowledge of [X] is largely mechanistic and without a sense of the larger picture' is weirdly applicable to most scientific fields once they escaped the 'natural philosophy' designation.

Another nuance that most people don't understand is that there are different levels of "badness."

There's a difference between "cigarettes cause cancer" and "phones cause cancer". The former is very definitely true, confirmed by many studies, and the health impact is very significant. The latter is probably untrue (there are studies that go both ways, but the vast majority say "no cancer"). Even if there's any impact, it's extremely minimal when compared to cigarettes.

People can't distinguish between those two levels of "causes cancer" in a headline.

Worse than Origin of Life researchers?

Patents?

So how evolution works is that a feature needs to have an evolutionary advantage, but the specimen must also not die. So there are two adversarial pressures here, carefully balancing each other in a mammal species that already has one of the highest birth mortality rates of both mother and child. If heads were any larger, it would create a proportional amount of negative evolutionary pressure by both direct and indirect death (of the mother) at birth.

Interestingly, there seem to be some indications showing that human interventions by modern technology already show clear evolutionary trends: https://pmc.ncbi.nlm.nih.gov/articles/PMC5338417/

Humans might eventually evolve to not even being able to be born naturally anymore at some point.

Beneficial kinda just means "leads to more procreation" right?

So if bigger brains meant people reproducing more, our brains would get bigger to the point that most births are cesarean or something.

I do wonder what happens when we eventually evolve to a point where we can't survive without more and more advanced technology.

A lot of people who would have died off before reproducing 200 years ago now don't, which is of course incredible for us. But what are effects of that 100/1000 years down the line?

Presumably we'll have plenty of more immediately pressing issues over that time frame.

Why are your competitors and predators asleep?

At night it is harder to see food. It is harder to see predators, some of whom are in fact nocturnal. It is harder to notice visual cues and gestures from allies/kin. It is harder to navigate, both due to difficulty seeing distant landmarks and nearby obstructions, so you are more likely to get lost and/or injured. It is colder so your body has to spend more calories to keep you warm.

There are adaptations that can improve nocturnal capabilities, but these typically come with tradeoffs that make diurnal life harder. Evolution is a series of many baby steps - either you need to adapt to not sleeping while you're still at a disadvantage at night, or you need to adapt to being awake at night while you still need to sleep. Neither path seems like it would have been advantageous to our ancestors.

Well we can't see can we

The polyphasic sleep experiments

Get an LLM to dream, and to use the time effectively to purge those hallucinations, and reinforce the "valid and true" memories, and you might have something there ?

Or when my early-riser wife talks to me about anything before I've had my coffee.

I did it for a couple of years and it was getting worse. It got better with rest and walking.

Yeah, I also suspected a vicious cycle of stress/cortisol causing poor sleep, which leads to more cortisol and poor recovery.

It did get better when I stopped cycling, as much as I loved it. I'm now walking instead and feeling much better. I intend to increase volume over time and once my VO2Max is back to my baseline then I may introduce cycling with an eye on going easy and eating enough before/during/after exercise.

Thanks for the advice, it is good to hear that it worked on other people.

I still do this sometimes, but I occasionally unintentionally torture myself by programming pretty late and then trying to fall asleep 15m later. I'll sleep, it's not restful at all. There needs to be some period to let brain activity decrease before falling asleep.

Yes. I think that should be the commonly spread advice instead of the blue/red light thing

> Ambien is a scary drug to rely on as it can create dependency and also masks underlying issues that are causing not inability to sleep.

That just sounds like you think every sleeping-pill is scary, as that's true for literally all of them.

Sleeping pills are mostly effective together with other types of therapy to address the underlying causes, just like most "temporary solutions". They're supposed to be used as "We'll try to figure out what's wrong, but in the meantime, so you can feel relatively human, here is a temporary crutch", not as a long-term solution.

Carbohydrates have been a big part of what I’ve needed to figure out in order to reach sleep again after an unusually tough period.

Carbohydrate metabolism has histamine intimately involved in it; Histamine – as per its inflammatory role – is basically used by the body to open tissue to receive blood glucose.

As it happens, histamine is also a neurotransmitter! An excitatory alertness neurotransmitter!

Both these aspects have been extant as scientific knowledge on record for some significant time, but are only really becoming known-known as of recent.

I have ADHD. I take lisdexamfetamine. Upon starting medication at 39.5 years of age, I quickly noticed that I had to be really careful with coffee, and especially to not at all touch any sweet foods or desserts around evening or so. Or I would wake up at 5:30 AM. (Exactly and precisely 5:30. Reliably. It’s sort of fascinating.)

As it turns out, amphetamine releases histamine! And! Caffeine inhibits the enzymatic breakdown of histamine! And sugar causes histamine to be released.

You're talking about "older drugs" like Chlordiazepoxide like they don't have any drawbacks or the drawbacks are less heavy compared to other more modern drugs. I'll give you that everyone is different, and doctors should evaluate what works for each patient, but I don't think it's ever as simple as "older drugs == better, newer drugs == worse".

My understanding is that magnesium blood tests are not reliable. Since magnesium is a natural element found in foods such as spinach, nuts, seeds, and whole grains, you know it is safe. Try a supplement and if it helps with muscle stiffness or sleep then you have a magnesium deficiency.

The glymphatic system

https://en.wikipedia.org/wiki/Glymphatic_system