The brain's waste clearing lymphatic system shown in people for first time
110 comments
·October 25, 2024PaulKeeble
ClearAndPresent
Paul's animation wasn't playing at an even rate for me, for some reason, so I created two video versions (8Hz and 12Hz) with the 16 second on/off period, starting with an off period, running for 254 seconds, as per the paper. These versions end with an an additional off period, as a 'cool down' from the flicker.
Framerate of 24Hz differs from the 120Hz as presented in the paper, but here there is no 40Hz flicker attempt so it shouldn't be an issue.
Compression may affect the edges of the lines, but downloads are enabled.
8Hz version - https://vimeo.com/1023278230/8ad6db6234
12Hz version - https://vimeo.com/1023275135/378186db55
lagniappe
I stared at the 8hz one, for the entire duration, and I feel a calm afterward, however I'm not sure if this is because I stopped doing/thinking for a few minutes with measured breathing or if it is me noticing the difference now that there's a lack of stimuli after the video ends.
What measurements or tests can I do to judge whether something is happening, or has happened after watching the videos?
criddell
The idea that watching a video triggers some waste clearing mechanism is pretty wild.
Makes me think of Neal Stephenson's Snow Crash where a datafile can be a narcotic or mind virus. Maybe that's not such a crazy idea?
diggan
> The idea that watching a video triggers some waste clearing mechanism is pretty wild.
It kind of makes sense. We can look at images of food and get a physical reaction like hunger, or look at macabre images and feel disgust, or stare at animations for one minute and then be affected for many minutes afterwards when we look away.
It doesn't surprise me we're still discovering new mechanisms for triggering physical reactions in our bodies.
Edit: I do agree it's pretty wild regardless :) Especially wild if we're finally discovering mechanisms that have useful effects, not just "fun" effects like visual distortion.
fasa99
Not wild at all. think of brain cancer (AKA GBM AKA glioblastoms multiforme).
The more you think, the more blood to the brain, the faster the cancer grows.
Think about it.
datavirtue
You can also watch a video that will add waste to your brain.
tripper_27
Wow! So a visual effect similar to some psychadelic hallucinations is associated with brain cleaning!
Also, I've been at concerts where the light show guy seems to have reverse-engineered the filters our brains use to process raw signal into "images", and could use the lights to create just the raw primitives.
A few hours of that and it was like I was learning to see all over again, a tune-up/calibration of my visual system.
DonHopkins
It's like the Brown Noise for your brain!
e40
What are you supposed to look at? The center red dot?
sharpshadow
Would be interesting to find out if there could be an desired effect of this in conjunction with binaural beats.
Workaccount2
What is the difference or use cases for 8Hz vs. 12Hz?
ClearAndPresent
My understanding from the paper is there is no difference between 4, 8, 12, and 40Hz frequencies on the neurobiologcial effects, but I found the 8Hz a bit less comfortable than the 12, so I uploaded both.
null
joelignaatius
[dead]
khafra
This is some amazing work; and it also raises my belief that a Langford Basilisk is neurologically possible by about 25%
reverius42
Thanks for introducing me to the concept! Just read the short story I assume you are referring to: https://www.infinityplus.co.uk/stories/blit.htm
Karellen
Looks like it, according to Wikipedia: https://en.wiktionary.org/wiki/Langford%27s_basilisk
Just read the story, thought it was very reminiscent of one of the plot points in Neal Stephenson's Snow Crash (1992) - until I noticed the publication date of 1988, 4 years earlier!
rozab
I hadn't heard of this one before, it's also similar to the crucifix glitch in Peter Watts' Blindsight
shagie
https://www.nature.com/articles/44964 is also a fun read on the BLIT.
I also recommend Different Kinds of Darkness.
https://www.lightspeedmagazine.com/fiction/different-kinds-o...
haccount
It's possible.
But only for the brains of people with severe or undertreated epilepsy of carefully selected varieties. You can trigger a potentially fatal seizure by showing them an appropriately stimulating image. Which likely was a known concept to the author of the story.
For the rest of us the negative feedback along the optical axis puts a stop to such shenanigans.
altruios
https://en.wikipedia.org/wiki/McCollough_effect is evidence to the contrary. This seems to rewire something outside the optical pathway. The effect can last for months. Works on almost all brains, no epilepsy required...
candiddevmike
GenAI images sometimes do this to me. Not anything scary per say, but some of the faults make my brain feel weird as it tries and fails to interpret parts of the image that were "AI smeared".
shaganer
I'm interested to hear your reasons why you think it's closer to reality. I don't see why the discovery of the brain wastage system would help a brain crash from being possible. Edit: Just looked back at the post and that it involves an image causing the glymphatic system to react.
theGnuMe
Sure, we know imagery can cause fatal seizures so... yes.
null
haccount
It is well established that visual patterns affect brain activity, this is used in clinical practice by neurophysiologists, put on an EEG cap and then do checkerboards, check if the activity is normal.
Now the question is if this provocation and resulting CSF flow is actually beneficial. Do you spike activity and get a rebound attempt at waste clearing due to waste accumulation of the neural spike, or is this like a massage for the brain that gives you a invigorating CSF dump?
I suspect it might not be a health improving activity. (I also suspect that you can get even more CSF flowing if you spin yourself at 6G in a full body centrifuge and that this too would not be conductive to health)
hackernudes
The paper says they used http://psychtoolbox.org/ to generate the images.
> Psychophysics Toolbox Version 3 (PTB-3) is a free set of Matlab and GNU Octave functions for vision and neuroscience research
Scientists almost never want to share their code and it makes me sad. Why wouldn't they want to make their paper more easily reproducible?
MrDresden
Because academic code is horrendous.
I once worked in an IT department of a genetics laboratory, which consistently publishes high impact papers in journals like Science and Nature.
While I was there I got to see some of the R/Python/Java code that had been created for all kinds of studies that had taken place there. It was some of the worst code I have ever seen.
But I do agree, the complete methodology including the code should be shared.
feoren
Staring at the v0.3 produces an effect similar to something I'm able to do trigger manually on command. I've always had the feeling that I'm somehow triggering a "flow" in my brain, but I have no way to confirm what's actually going on. It's actually stronger when I trigger it manually, and it feels like it flows down my spine and eventually some weak signal reaches my extremities. (Maybe that means it's not CSF after all?) Oddly, I do feel like I can think more clearly afterward, but the brain is very bad at judging itself, so it's more likely to be an illusion than anything real. Anyone else able to manually trigger a feeling like this in their brains?
cassianoleal
Yep, I can do that.
It's similar to the effect of being hit with big news (good or bad), and the "sinking" feeling that comes with it, becoming suddenly introspective and oddly calm under pressure.
At least to me, of course. I have no idea if others have that same reaction.
shaganer
I'm interested in how you accomplish this. I can do something along the lines of that by getting myself heated. I actually get a hothead and a tingling comes up to my brain like it's passing in a channel. It could simply be a sensation rising within the brain though, without an actual transport of something.
I can focus better after but it doesn't clear my head, just use that frustration or anger to become determined.
feoren
I'm not quite sure exactly what I'm doing; it feels a bit like tensing a muscle, but that muscle feels like it's in the middle of my head, a bit toward the back. Obviously there are no actual muscles there, so I'm not sure what's actually happening.
If you try raising one eyebrow or wiggling one ear (assuming you can't already do that), you might find that you're briefly activating lots of little muscles around the target as your body tries to figure out where that's mapped in your brain. Once you get the right muscle, you can relax the other false positives, and eventually just have the single muscle isolated. It's similar in my "brain flow" thing: usually a couple random muscles in my head want to join in, but I can intentionally relax them and keep the "flow" going. A common one is the tensor tympani -- the two "muscles" seem to be closely mapped together. If you can rumble your ears (manually activating the tensor tympani), try initiating a rumble, and then "move" the activation in between your ears, right to your mid-back brain. (Again: I know there's no actual muscle there, so /shrug).
sithadmin
That just sounds like ASMR, which some folks can induce without external stimuli.
hobs
I think you are thinking of Frission https://en.wikipedia.org/wiki/Frisson
assadk
How have you trained yourself to do that?
feoren
I'm not 100% sure, but it's something like this:
If you try raising one eyebrow or wiggling one ear (assuming you can't already do that), you might find that you're briefly activating lots of little muscles around the target as your body tries to figure out where that's mapped in your brain. Once you get the right muscle, you can relax the other false positives, and eventually just have the single muscle isolated. It's similar in my "brain flow" thing: usually a couple random muscles in my head want to join in, but I can intentionally relax them and keep the "flow" going. A common one is the tensor tympani -- the two "muscles" seem to be closely mapped together. If you can rumble your ears (manually activating the tensor tympani), try initiating a rumble, and then "move" the activation in between your ears, right to your mid-back brain. (Again: I know there's no actual muscle there, so /shrug). Another closely mapped muscle, at least for me, is a small one around/under/behind the ears that has a "face tightening" effect. It's like there are three muscles conceptually mapped to similar brain space: one tightens my ears/eyes/temples, one rumbles my tensor tympani, and one induces a feeling of "flow" down my spine and through my brain.
mettamage
In me, there seemed to be an illusion going on. It felt like a tunnel and it felt as immersive as a "dream world" (albeit a bit of a boring one).
What I also noticed were the after image effects. A strong blue dot every time it flashed and circles divided into 8 sections like a star.
This was trippy.
boringg
Noticed that as well. Very trippy
pedalpete
The 40hz visual + auditory stimulation is showing to be surprisingly effective in mice and humans. [1] When I first heard this, I thought the open-loop nature, and the fixed frequency across subjects sounded improbable, but I'm happy to be proven wrong.
We work in the neurotech/sleeptech space doing slow-wave enhancement which, it is believed, increases glymphatic activity [2]. Recent studies have looked at the promise of alzheimer's prevention [3].
More links to research papers are on our website https://affectablesleep.com/science
[1] - https://www.nature.com/articles/s41586-024-07132-6 [2] - https://www.frontiersin.org/journals/neuroscience/articles/1... [3] - https://pmc.ncbi.nlm.nih.gov/articles/PMC10758173/
flotzam
Very cool! Five minutes of this felt strangely soothing in my head, after a few nights of not enough sleep.
Being able to set a max duration would be neat, in case it's unsafe to lose track of time and let the pattern run for too long?
Classic outdated comment BTW ;)
setInterval(flickerImage, 250); // 8hzbdd8f1df777b
When I open the page, the image rotates for about ten seconds then vanishes. How do you watch it for five minutes? What did I do wrong?
gertlex
As per the first line of the writeup on the page: It toggles between on and off every 16 seconds.
null
froh
give it a bit, it then reappears (as described in the paper, btw)
elric
It's taken 12 years to get from "this stuff exists in mice" to "we now know it actually exists in humans and is not vestigial". That seems like a long time. People get brain MRIs with contrast all the time, is there any reason why this never showed up? Because no one was looking? Or because it's a slow mechanism?
jhrmnn
Looking up “brain MRI with contrast”, the biggest difference seems to be that in a regular MRI the contrast goes to the blood, but here it goes straight to the brain cerebrospinal fluid. You need open brain for that, so indeed doesn’t seem trivial.
elric
Cerebrospinal fluid is produced in the brain, I would imagine that the contrast would end up in newly produced fluid as well, but maybe that assumption is wrong.
sithadmin
Even assuming that the contrast could show up in newly excreted CSF (maybe, maybe not), MRI contrast elimination half lives are very short (mostly all under ~2 hrs, excepting cases like renal dysfunction), and cerebrospinal fluid doesn’t replenish particularly quickly.
physPop
Unfortunately no, that is not how the contrast agent gets around. Most Gd agents are huge and don’t leak out of the vasculature unless there is a disruption (tumour etc).
NeuroCoder
Two things:
1. Blood brain barrier and CSF should be separate for all but tiny molecules. It's why CT angiograms are able to visualize distinct vessels. So it is pretty hard to directly interact with this sort of thing in vivo
2. A good chunk of the neuro community have been operating under the assumption that some of those mouse model findings are mechanisms in humans too. Since we couldn't easily prove it, people used a bunch of next best tools with fancy imaging that demonstrated it was very likely. On top of furter proof, this sort of study allows us to begin pinpointing exactly how close our next best tools are at estimating in vivo processes without opening up the head.
rozab
They injected a dye into the cerebrospinal fluid to confirm the pattern of diffusion into the brain.
I imagine this procedure would have to be confirmed safe in humans first. Also they needed subjects who already happened to be undergoing a specific type of brain surgery.
physPop
Its because we don’t normally inject Gad in CSF. Its kind of wild west to even do so, and these researchers were able to identify this unique dataset and ask some interesting questions.
jb1991
The main reason is because 12 years ago we didn't have ChatGPT to tell the researchers the answer.
sharpshadow
“Other studies have suggested that the glymphatic system may be most active during sleep.”
Not only that but also the right sleeping position is relevant here. I don’t recall the scientist but he studied primates and their natural sleeping position, exactly this position also opens up the channels for the cerebrospinal fluid to flush the accumulated brain waste.
lazypenguin
Do you recall which position?
mfro
> Glymphatic transport is most efficient in the right lateral sleeping position
https://pmc.ncbi.nlm.nih.gov/articles/PMC7698404/ Section 3.4.3
sharpshadow
Yes that’s the position. Good to see it verified in the study. Having a partner and sleeping in the same bed can lead to alterations from the optimal sleeping position, especially sleeping on the back is not good. Sleeping on the back is also one of the main causes of snoring, which often occurs in people which have a big belly and can’t really sleep lateralish anymore.
Sleep quality is important too and one big factor is not to go to sleep with a full stomach. Sleep quality will suffer because of the active digestion which probably will not let the glymphatic transport do it’s job properly.
Also good to know that “…low doses of alcohol (0.5 g/kg) increased glymphatic clearance…”.
pragma_x
That's great that there's a way to passively optimize that process every day. But it's also bad news considering it's contrary to what you need if you have GERD.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10643078/
> A limited number of studies have demonstrated that sleeping in the left lateral decubitus (LLD) decreases nocturnal reflux in patients with gastroesophageal reflux disease (GERD) compared to right lateral decubitus (RLD) and supine.
abdullahkhalids
> Glymphatic transport is most efficient in the right lateral sleeping position, with more CSF clearance occurring compared to supine and prone [6]
Reference [6] is a study on rats! The authors suggest further investigation in humans.
Even though I would bet on this still holding for humans.
boringg
Interesting - whats the frequency - response hypothesis? I don't think you would want to do lymphatic drainage everyday unless you had a problem with your system (?)
canadiantim
Really shows the slow slow slow glacial pace of science and how fragmented the information distribution mechanisms are…
knodi
Or the brain is high complex organ and full of MANY known and unknown functions which meet a specific or general need. Don't forget, it took us 100k years as human to get here, our current understanding of brain. you're being a little harsh here.
s5300
[dead]
There have been a couple of papers [1] that can induce this process while awake using particular image patterns as confirmed in an MRI. I think the NIH confirmation is running behind in the science, independent research is quite a bit ahead of them. I came across the paper on this last year and implemented a very simple page with the parameters they used [2].
There is a number of disease models that show reduced or no glymphatic clearance and as such these people need treatments to clear out their brains and these image routines seem to help. A lot of people find this pattern extremely taxing to watch especially for the recommended number of cycles, you can feel the effect on the brain its hard to describe the sensation its a bit numbing and the image has the sensation of changing as the cycle runs like its a visual trick. You might get left feeling like you have been clubbed over the head the first time.
I find it interesting this is one aspect of disease research I am looking into and is related to Long Covid and ME/CFS.
[1] https://journals.plos.org/plosbiology/article?id=10.1371/jou...
[2] https://www.paulkeeble.co.uk/posts/cff/