> To better understand fatigue, Pessiglione, Chib and other researchers are trying to bridge an understanding of its biochemical workings with how it affects motivation4. The current hypothesis: cognitive fatigue arises from metabolic changes in parts of the brain that are responsible for cognitive control
This will be interesting to see because for a long time there's been a lot of work saying that "ego depletion" isn't a thing[0] and I swear I have tried to believe this but my own personal experience is completely different. Later in the night, and when I'm mentally tired I do experience this: poor impulse control, lowered emotion regulation, the whole shebang. It'll be interesting to see what the basis is for this, because despite taking all that research at face-value I have to say that now after all these years, I can't help but think it must be wrong.
0: though some have claimed that it is a thing if you believe that it's a thing, i.e. it happens to those who believe in it.
I think Daniel Kahneman's System 1 (habits, unconscious) and System 2 (learning, "error correction", conscious) are physical systems, and System 2 takes a LOT more energy to run.
So, when you get tired, System 2 leans more and more on the much more energy efficient System 1. So you get behaviors that look like unrestrained habits: poor impulse control, lowered emotional regulation, etc
I love the simplicity of the System 1/2 breakdown - but is there any actual evidence behind it? It seems like such a classic pop-psychology observational deduction of how something might work with no science to prove it.
In cognitive psychology there's all sorts of evidence that we have two distinct processes, but I don't think anyone has really mapped it to a physical system yet.
Modeling two physical systems is pretty interesting though because dementia ends up looking like a clear failure of System 2. Really neat idea generator even if imperfect.
Physical fatigue is lack of ATP and happens through the day as oxidation builds up. Cognitive fatigue is a build-up of used neurotransmitters that also build up over the day. These two processes interact with each other though where neurotransmitter reuptake uses a lot of ATP. I see that connection between them as ego depletion. If true, the best solution to it is a nap because that will help clear the junk out.
I feel there is more than one type of mental fatigue. Some of them can be forced through (e.g. the emotional kind that happens when you have to do something you don't want to do) and some can't (e.g. not having enough sleep for prolonged time).
I don’t think its completely bogus. There are lots of things you can do that you don’t realize you can. But 40-50 hours of work a week, even if you don’t even leave your house, still takes a lot out of you.
Truth is we are no closer to having a biomarker for fatigue. There is no particular reason why the normal fatigue that people get from working hard has anything to do with the chronic fatigue that ME/CFS and other chronic diseases face. ME/CFS is unique in its payback where a sufferers pushes through the fatigue and ends up with symptoms worsening and new symptoms 12-72 hours later that can last a day to the rest of their lives. That isn't just fatigue and the UK doctors have been trying to make ME/CFS all about fatigue since the 1980s and it caused immense harm. It actually has about 280 symptoms, of which fatigue is just one and not even the most debilitating or important one.
Something important to keep in mind is that cognitive fatigue is a protective system meant to protect our cells from harm. Pushing through anyways would be unlikely to cause harm in a healthy system. Post-covid is an extremely stressed one though. Would be like going to the gym after tearing a muscle and being surprised it got worse.
One aspect of it might be glucose depletion. I know when I was taking lots of tests at uni I could give myself a boost by eating a honey stick which was recommended by a bio prof.
In any case, this looks fairly complex and it will be interesting to see how this goes.
Not in the UK. We get to email a problem. Wait all day for a reply.
It works! Before a reply comes back - people self triage. It gets better - no problem! It gets worse - A & E.
Long Covid is really not new. It is virtually indistinguishable from the condition long known in the medical lexicon as post-infectious syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Although some have recognized and studied their similarities, it seems no one has made the simplifying observation that they are essentially the same condition.[1]
Symptom wise and quite a lot of the biology they definitely appear similar. The problem is the genetics studies show some overlap, about 80 combined SNPs for ME/CFS out of 270 and out of around 150 for Long Covid.
There is more to it than just different genetic mappings because while both conditions share mitochondria differences which compartments are different. Depending on how deep you dig into the biology they appear the same or quite different and a number of multiple point blood, urine and saliva tests can distinguish the diseases from each other.
I think at this point its more accurate to say they are overlapping conditions, they have similarities but they are different conditions. Sister diseases much in the same way there is overlap in Fibromylgia and Gulf War syndrome with ME/CFS and each other. Long Covid is another post infection Neurological and immune disease with unknown biomarker/core pathology. There are clearly a lot of measurable changes that are dysfunctional so its every bit as real biological disease as the others. What they definitely share is a high amount of debilitation, severe disability and patient reduction in quality of life on the same set of 280 symptoms in a very similar patter of prevalence.
Its also now a disease with very little research funding world wide as well so the situation is unlikely to improve for the 400m+ sufferers world wide.
There has been a couple of GWAS and also a few SNP combination studies that I have seen, could have been a few more I missed. Nothing full genome yet so that might increase or decrease the overlap.
I really don't understand this comment? Its quite commonly known that this is the same/related?
Your 'source' is btw. from 2023 and as far as i understand it, the main issue is, that due to covid, a lot more people got it but because it was already ignored or played down before, it still is and the people in need just don't get help.
Covid apparently triggered it in more people than before.
I also have the feeling that someone else posted this missconception a few weeks ago on hn. Or was that you too?
Not sure about the ME/CFS thing, but "post-infectious syndrome" is literally what its name says it is which makes it a larger category that "long covid" would taxonomize under.
In the limit, there's no difference between a scientific fact and an unfalsified hypothesis. I'm not aware of anyone falsifying this one, and it's over five years old, so I'm going to say "scientific fact".
At this point, even if it is falsified, that falsification will probably take the form "here is an exception to the general rule", like how we still use Newton's law of gravitation even though it was falsified by Urbain Le Verrier's 1859 observations of Mercury.
I'll put it another way: long COVID has been studied quite a lot over the past 5 years, and I'm not aware of anyone being able to distinguish it from ME/CFS (except by definition). People appear to have stopped trying to draw a distinction, by and large, in favour of trying to identify better category boundaries to use instead. See https://doi.org/10.3390/biomedicines13112797 for a Nov 2025 literature review, which basically says "except for long COVID being caused by SARS-CoV-2, it's very difficult to tell ME/CFS-like long COVID and ME/CFS apart" in excruciating detail. Some things have been found to occur in long COVID but not found to occur in ME/CFS, and vice versa, but afaik there's nothing found to occur in ME/CFS-like long COVID that's been found to not occur in ME/CFS.
(Technically, long COVID is a broader diagnosis, encompassing some long-term conditions caused by a COVID-19 infection that are distinct from ME/CFS, but I consider that a "by definition" distinction rather than anything real. This is what you'd expect if ME/CFS had multiple causes, and COVID-19 infection could cause multiple chronic conditions, and most long COVID is actually ME/CFS.)
> The ME Association (MEA) takes the view that Long Covid and ME/CFS are both examples of a serious and debilitating condition that can follow any type of viral infection.
I'm sharing this more for folks who might have looked in a lot of places and are still seeking answers.
There has been a lot more science in this area it seems in the last 5 years, maybe it's just me, and the attention to do with long covid, or other things that cross the blood/brain barrier.
It's encouraging to see articles like this, since there is no single measure or signal of this, its really about considering brain health in general, and doing everything that is possible to eliminate neuroinflammation that can be.
The challenge for folks suffering with symptoms that includes a neurological thing like brain fog is the challenge of usually having to be the Quarterback integrating between specialists, because specialists don't necessarily integrate. For someone with cognitive fatigue, since it's differnet for everyone on different tasks, it can be a lot.
It's been eye opening to learn how many specialists first overlook proper neck posture and position since it can have a direct effect on what's getting into/out of the brain and downstream symptoms. Advocating for the basic inputs first before trying things is critical.
Additionally, tools like QEEG and FMRI are promising, not super mainstream yet but appear to have decent information it can provide of what is happening in the brain. In addition to this, the area of neurofeedback (devices like mendi, bellabee, etc seem to have some promise to help in some cases).
Another thing that too often gets missed is first ensuring things are OK physiologically. A simple xray of the neck and where nerves, blood and more go up into the brain is too often a step that's missed, and quite often there might be some compression, tightness or pinches there limiting the brain to recieve what it normally may have - and instead effort is spent trying to figure out how to get the brain operating better with a garden hose that's been slightly pinched.
Fatigue to the extent I understand it neurologically seems to at least two sided dice: energy and nutrition being available when and where it's needed on one side, and the things needed in place to use that energy effectively.
Chronic depletion or deficiencies in certain vitamins, amino acids, etc can also build up over time. Doing what we can for nutrition is critical, including any research backed neuroinflammation reducing supplements (magnesium threonate, saffron, omega 3, tumeric, etc).
> To better understand fatigue, Pessiglione, Chib and other researchers are trying to bridge an understanding of its biochemical workings with how it affects motivation4. The current hypothesis: cognitive fatigue arises from metabolic changes in parts of the brain that are responsible for cognitive control
This will be interesting to see because for a long time there's been a lot of work saying that "ego depletion" isn't a thing[0] and I swear I have tried to believe this but my own personal experience is completely different. Later in the night, and when I'm mentally tired I do experience this: poor impulse control, lowered emotion regulation, the whole shebang. It'll be interesting to see what the basis is for this, because despite taking all that research at face-value I have to say that now after all these years, I can't help but think it must be wrong.
0: though some have claimed that it is a thing if you believe that it's a thing, i.e. it happens to those who believe in it.
I think Daniel Kahneman's System 1 (habits, unconscious) and System 2 (learning, "error correction", conscious) are physical systems, and System 2 takes a LOT more energy to run.
So, when you get tired, System 2 leans more and more on the much more energy efficient System 1. So you get behaviors that look like unrestrained habits: poor impulse control, lowered emotional regulation, etc
Edit: I wrote more about this idea if anyone is curious: https://1393.xyz/writing/alzheimers-is-the-symptom-not-the-p...
I love the simplicity of the System 1/2 breakdown - but is there any actual evidence behind it? It seems like such a classic pop-psychology observational deduction of how something might work with no science to prove it.
In cognitive psychology there's all sorts of evidence that we have two distinct processes, but I don't think anyone has really mapped it to a physical system yet.
Modeling two physical systems is pretty interesting though because dementia ends up looking like a clear failure of System 2. Really neat idea generator even if imperfect.
I do appreciate when people write up their ideas like this. It would be great if you had an RSS feed.
Physical fatigue is lack of ATP and happens through the day as oxidation builds up. Cognitive fatigue is a build-up of used neurotransmitters that also build up over the day. These two processes interact with each other though where neurotransmitter reuptake uses a lot of ATP. I see that connection between them as ego depletion. If true, the best solution to it is a nap because that will help clear the junk out.
I feel there is more than one type of mental fatigue. Some of them can be forced through (e.g. the emotional kind that happens when you have to do something you don't want to do) and some can't (e.g. not having enough sleep for prolonged time).
Ego depletion isn't a thing if you don't believe in it? Who said that? Dr. Goggins?
Haha! Listen, the "you can do it if you believe in yourself" stuff always sounds bogus. But there was some stuff around ten years ago about this. Here's an example: https://www.pnas.org/doi/full/10.1073/pnas.1313475110#F1
I don’t think its completely bogus. There are lots of things you can do that you don’t realize you can. But 40-50 hours of work a week, even if you don’t even leave your house, still takes a lot out of you.
Also when I last checked, "willpower as a finite resource isn't a thing" was simply the scientific consensus
But I agree that doesn't necessarily translate to "willpower is infinite"
Truth is we are no closer to having a biomarker for fatigue. There is no particular reason why the normal fatigue that people get from working hard has anything to do with the chronic fatigue that ME/CFS and other chronic diseases face. ME/CFS is unique in its payback where a sufferers pushes through the fatigue and ends up with symptoms worsening and new symptoms 12-72 hours later that can last a day to the rest of their lives. That isn't just fatigue and the UK doctors have been trying to make ME/CFS all about fatigue since the 1980s and it caused immense harm. It actually has about 280 symptoms, of which fatigue is just one and not even the most debilitating or important one.
Something important to keep in mind is that cognitive fatigue is a protective system meant to protect our cells from harm. Pushing through anyways would be unlikely to cause harm in a healthy system. Post-covid is an extremely stressed one though. Would be like going to the gym after tearing a muscle and being surprised it got worse.
I wonder when they get tired thinking about the problem, do they get more motivated?
Are you thinking of some kind of “hungry intelligence” but for fatigue?
One aspect of it might be glucose depletion. I know when I was taking lots of tests at uni I could give myself a boost by eating a honey stick which was recommended by a bio prof. In any case, this looks fairly complex and it will be interesting to see how this goes.
I start to go blind when programming for too long. Does that count?
You should probably talk to ChatGPT about that. …or see a doctor, if that’s still a thing people do?
Not in the UK. We get to email a problem. Wait all day for a reply. It works! Before a reply comes back - people self triage. It gets better - no problem! It gets worse - A & E.
I had some eye strain, chatGPT recommended a Lutein + Zeaxanthain supplement. It has worked great!
You sound like you're writing from the future.
"or see a doctor, if that’s still a thing people do?"
Yep. People still do that.
Lutein helps me.
https://archive.is/5Ty0K
Long Covid is really not new. It is virtually indistinguishable from the condition long known in the medical lexicon as post-infectious syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Although some have recognized and studied their similarities, it seems no one has made the simplifying observation that they are essentially the same condition.[1]
[1]: https://www.statnews.com/2023/09/14/long-covid-me-cfs-myalgi...
Symptom wise and quite a lot of the biology they definitely appear similar. The problem is the genetics studies show some overlap, about 80 combined SNPs for ME/CFS out of 270 and out of around 150 for Long Covid.
There is more to it than just different genetic mappings because while both conditions share mitochondria differences which compartments are different. Depending on how deep you dig into the biology they appear the same or quite different and a number of multiple point blood, urine and saliva tests can distinguish the diseases from each other.
I think at this point its more accurate to say they are overlapping conditions, they have similarities but they are different conditions. Sister diseases much in the same way there is overlap in Fibromylgia and Gulf War syndrome with ME/CFS and each other. Long Covid is another post infection Neurological and immune disease with unknown biomarker/core pathology. There are clearly a lot of measurable changes that are dysfunctional so its every bit as real biological disease as the others. What they definitely share is a high amount of debilitation, severe disability and patient reduction in quality of life on the same set of 280 symptoms in a very similar patter of prevalence.
Its also now a disease with very little research funding world wide as well so the situation is unlikely to improve for the 400m+ sufferers world wide.
Is that from GWAS/MR Studies?
There has been a couple of GWAS and also a few SNP combination studies that I have seen, could have been a few more I missed. Nothing full genome yet so that might increase or decrease the overlap.
I really don't understand this comment? Its quite commonly known that this is the same/related?
Your 'source' is btw. from 2023 and as far as i understand it, the main issue is, that due to covid, a lot more people got it but because it was already ignored or played down before, it still is and the people in need just don't get help.
Covid apparently triggered it in more people than before.
I also have the feeling that someone else posted this missconception a few weeks ago on hn. Or was that you too?
Because COVID got political if you drop COVID from the name your ability to get funding and attention to study it falls off a cliff.
Oh i get it. So "AI" got political? Because I don't think you can get funding for anything else in IT right now.
Is this a scientific fact or a hypothesis?
Not sure about the ME/CFS thing, but "post-infectious syndrome" is literally what its name says it is which makes it a larger category that "long covid" would taxonomize under.
https://pubmed.ncbi.nlm.nih.gov/40627388/#&gid=article-figur... (figure one)
In the limit, there's no difference between a scientific fact and an unfalsified hypothesis. I'm not aware of anyone falsifying this one, and it's over five years old, so I'm going to say "scientific fact".
At this point, even if it is falsified, that falsification will probably take the form "here is an exception to the general rule", like how we still use Newton's law of gravitation even though it was falsified by Urbain Le Verrier's 1859 observations of Mercury.
If a hypothesis has not been falsified that does not mean there is consensus around it in the scientific community.
Your statement can also be applied to the inverse of the hypothesis, after all.
I'll put it another way: long COVID has been studied quite a lot over the past 5 years, and I'm not aware of anyone being able to distinguish it from ME/CFS (except by definition). People appear to have stopped trying to draw a distinction, by and large, in favour of trying to identify better category boundaries to use instead. See https://doi.org/10.3390/biomedicines13112797 for a Nov 2025 literature review, which basically says "except for long COVID being caused by SARS-CoV-2, it's very difficult to tell ME/CFS-like long COVID and ME/CFS apart" in excruciating detail. Some things have been found to occur in long COVID but not found to occur in ME/CFS, and vice versa, but afaik there's nothing found to occur in ME/CFS-like long COVID that's been found to not occur in ME/CFS.
(Technically, long COVID is a broader diagnosis, encompassing some long-term conditions caused by a COVID-19 infection that are distinct from ME/CFS, but I consider that a "by definition" distinction rather than anything real. This is what you'd expect if ME/CFS had multiple causes, and COVID-19 infection could cause multiple chronic conditions, and most long COVID is actually ME/CFS.)
The ME Association came to this conclusion a couple of years ago: https://meassociation.org.uk/2023/05/updated-booklet-long-co...
> The ME Association (MEA) takes the view that Long Covid and ME/CFS are both examples of a serious and debilitating condition that can follow any type of viral infection.
I'm sharing this more for folks who might have looked in a lot of places and are still seeking answers.
There has been a lot more science in this area it seems in the last 5 years, maybe it's just me, and the attention to do with long covid, or other things that cross the blood/brain barrier.
It's encouraging to see articles like this, since there is no single measure or signal of this, its really about considering brain health in general, and doing everything that is possible to eliminate neuroinflammation that can be.
The challenge for folks suffering with symptoms that includes a neurological thing like brain fog is the challenge of usually having to be the Quarterback integrating between specialists, because specialists don't necessarily integrate. For someone with cognitive fatigue, since it's differnet for everyone on different tasks, it can be a lot.
It's been eye opening to learn how many specialists first overlook proper neck posture and position since it can have a direct effect on what's getting into/out of the brain and downstream symptoms. Advocating for the basic inputs first before trying things is critical.
Additionally, tools like QEEG and FMRI are promising, not super mainstream yet but appear to have decent information it can provide of what is happening in the brain. In addition to this, the area of neurofeedback (devices like mendi, bellabee, etc seem to have some promise to help in some cases).
Another thing that too often gets missed is first ensuring things are OK physiologically. A simple xray of the neck and where nerves, blood and more go up into the brain is too often a step that's missed, and quite often there might be some compression, tightness or pinches there limiting the brain to recieve what it normally may have - and instead effort is spent trying to figure out how to get the brain operating better with a garden hose that's been slightly pinched.
Fatigue to the extent I understand it neurologically seems to at least two sided dice: energy and nutrition being available when and where it's needed on one side, and the things needed in place to use that energy effectively.
Chronic depletion or deficiencies in certain vitamins, amino acids, etc can also build up over time. Doing what we can for nutrition is critical, including any research backed neuroinflammation reducing supplements (magnesium threonate, saffron, omega 3, tumeric, etc).