How would a deficit in processing of physiological signals lead to ME/CFS?

[jnmaciuch]

Isn’t one factor here that we see these mechanisms for activity in healthy people but don’t see them or know why people are more fatigued when ill? Not necessarily with ME/CFS but generally. Additionally almost everyone describes their ME/CFS fatigue as very different from this normal fatigue. That would seem to be people’s motivation for looking for an additional, and indeed different, mechanism?

But we don’t know that the known mechanisms are working properly in ME/CFS. The things that we’ve checked amount to checking if the gas tank has a leak without checking anything else in the engine or engine sensors, to go back to my earlier analogy.

And indeed there are plenty of unknowns about those mechanisms, there are probably many regulatory aspects we have yet to discover. But the key is that whatever’s going wrong is much more likely to be related to the known mechanisms than a made up mechanism for activity logging. The problem would be novel in ME/CFS, not the machinery it occurs in per se.

 

[hotblack]

But we don’t know that the known mechanisms are working properly in ME/CFS.

Sure, I get your approach and argument for the line that you’re pursuing. You make it very convincingly and I’m not taking issue with that. What I’m less convinced about is that it’s therefore pointless to look at other ideas, at there being no benefit in also looking at other potential mechanisms, which I took from the “essentially superfluous” comment. I like that we have people interested in both.

 

[jnmaciuch]

Sure, I get your approach and argument for the line that you’re pursuing. You make it very convincingly and I’m not taking issue with that. What I’m less convinced about is that it’s therefore pointless to look at other ideas, at there being no benefit in also looking at other potential mechanisms, which I took from the “essentially superfluous” comment. I like that we have people interested in both.

I understand your concern here—but my argument isn’t “we already know one promising direction to look so let’s not waste time looking elsewhere”, it’s that the redundancy of this proposed mechanism makes it extremely unlikely to even exist in the first place.

Complete redundancy [edit: for complex processes like what is being discussed here] is pretty rare in biological systems, so proposing a completely separate and entirely redundant system carries a high burden of proof for why we even ought to believe it exists in addition to what we already know exists [edit: and the related unknowns therein]

It would be like claiming that there must be an additional mechanism that tracks how many cups of water we drink via purely cognitive processes and triggers thirst but has nothing to do with any of the known biological mechanisms that are tied to actually detecting water content in the body. The proposed alternative mechanism itself is the thing that’s superfluous.

 

[Utsikt]

I understand your concern here—but my argument isn’t “we already know one promising direction to look so let’s not waste time looking elsewhere”, it’s that the redundancy of this proposed mechanism makes it extremely unlikely to even exist in the first place.

Complete redundancy [edit: for complex processes like what is being discussed here] is pretty rare in biological systems, so proposing a completely separate and entirely redundant system carries a high burden of proof for why we even ought to believe it exists in addition to what we already know exists [edit: and the related unknowns therein]

It would be like claiming that there must be an additional mechanism that tracks how many cups of water we drink via purely cognitive processes and triggers thirst but has nothing to do with any of the known biological mechanisms that are tied to actually detecting water content in the body. The proposed alternative mechanism itself is the thing that’s superfluous.

Isn’t it possible was developed for another purpose, but it has other redundant applications as well?

 

[jnmaciuch]

Isn’t it possible was developed for another purpose, but it has other redundant applications as well?

Sure, but that's true of any vaguely plausible-sounding mechanism. You're still just explaining unknowns with more unknowns and the vague possibility of something maybe being true.

From my perspective it's just a bizarre leap to make without any additional justification, like invoking the unknowns of quantum mechanics to explain why a piece of code is throwing an error. Like sure, quantum mechanics explains all kinds of weird phenomena and who can say whether or not its relevant here, but it seems like you jumped to quantum mechanics because you wanted to talk about the great magical unknowns of quantum mechanics, rather than quantum mechanics actually making the most sense as an explanation here. [Edit: if you want to seriously invoke the great unknowns of quantum mechanics, you have to either present a strong reason why quantum mechanics is the only thing that fits, or thoroughly rule out every other possible explanation]

The problem here is I don't see any benefits of a neural "accountant" for activity that aren't thoroughly covered by actual sensing of metabolic correlates of cellular activity and circadian rhythm, which is itself quite intertwined with metabolism. The only other thing that has been brought up is the capability to roughly gauge the passage of time, but I have not seen any convincing argument for why the capability to track time is coupled with "activity tracking" in any way.

 

[Utsikt]

The only other thing that has been brought up is the capability to roughly gauge the passage of time, but I have not seen any convincing argument for why the capability to track time is coupled with "activity tracking" in any way.

I was thinking of the general ability to track things. If that exists, why can’t it be applied elsewhere?

If the metabolics can change based on loads of factors that are unrelated to the amount of physical work that’s being done, having another ability to track effort or work might be useful for the organism.

 

[jnmaciuch]

If the metabolics can change based on loads of factors that are unrelated to the amount of physical work that’s being done, having another ability to track effort or work might be useful for the organism.

Now that you mention it, we do--you can consciously recall all the things you did in a day and compare that to the average amount done by a human and then make the conscious choice to rest. So really, the proposed idea of a neural accountant that generates the subjective feeling of fatigue by cognitively tracking activity is triple redundant.

I was thinking of the general ability to track things. If that exists, why can’t it be applied elsewhere?

Again, if you're invoking the great final frontier of medicine as an explanatory mechanism, it's not enough to say that it might theoretically be useful for a system like that to exist in addition to the things we definitively know exist. You can say the same thing for literally anything. Lots of things might influence the body's normal system for sensing water content, so it would theoretically be useful to have an additional neural circuit that counts how many glasses of water you drink and generates the subjective feeling of thirst without any input from the normal systems. But that doesn't provide any convincing evidence of that additional neurological system existing--and it's the same exact fallacy the brain retraining folks have a field day with.

 

[Utsikt]

Now that you mention it, we do--you can consciously recall all the things you did in a day and compare that to the average amount done by a human and then make the conscious choice to rest. So really, the proposed idea of a neural accountant that generates the subjective feeling of fatigue by cognitively tracking activity is triple redundant.

I don’t think there is a need to know anything about what an average human does. I assume a neuron or multiole would be genetically coded to send a signal when X has occurred, and something else is genetically coded to start the fatigue process when they receive said signal.

Like how burrowing owls chicks know from birth when to mimic the rattlesnake sound.

Or how you can place a newborn at the stomach of the mother, and it will make its way to the breast.

I’m not invoking beliefs or thoughts.

Again, if you're invoking the great final frontier of medicine as an explanatory mechanism, it's not enough to say that it might theoretically be useful for a system like that to exist in addition to the things we definitively know exist.

It’s more that I’m saying that this accounting mechanism probably exists because somehow our brains are able to add thing and keep track of things, and if it does it is probably used for something.

 

[jnmaciuch]

I don’t think there is a need to know anything about what an average human does. I assume a neuron or multiole would be genetically coded to send a signal when X has occurred, and something else is genetically coded to start the fatigue process when they receive said signal.

Like how burrowing owls chicks know from birth when to mimic the rattlesnake sound.

Or how you can place a newborn at the stomach of the mother, and it will make its way to the breast.

I’m not invoking beliefs or thoughts.

My point was a somewhat facetious one--if you're saying that it would be beneficial to have an additional mechanism that can track activity beyond the ones we already know about, I'm saying we already have one (that is not related to feelings of fatigue). So what you're positing is an additional third mechanism that both tracks activity independent of known sensing metabo-sensing mechanisms and is also not based in deductive reasoning.

My point is that we're basically going endlessly in circles positing new things which could potentially exist even thought their function is already explained by other mechanisms. And that we have no concrete reason to believe there is yet another system that accomplishes the same thing and exists because of some unknown benefit.

It’s more that I’m saying that this accounting mechanism probably exists because somehow our brains are able to add thing and keep track of things, and if it does it is probably used for something.

We don't have reason to believe that anything about activity is being independently accounted for outside of integration of this actual sensory information. Just like we don't have reason to believe that feelings of hunger or thirst arise from systems that have absolutely no input from biological mechanisms that actually sense water or nutrient content in the body. It doesn't make sense to argue that just because our memory might log when we ate our last meal, that feelings of hunger are therefore instigated by this memory mechanism [edit: rather than anything we already know generates those feelings].

What we know about central fatigue is that it is quite definitively mediated by ongoing sensory input. So the most logical conclusion is if there is additional neurological processing happening, it's using that sensory input in some way. Positing a whole new system independent of that sensory input is entirely superfluous, and there's no positive evidence to support why that superfluous system actually must exist.

 

[Utsikt]

My point was a somewhat facetious one--if you're saying that it would be beneficial to have an additional mechanism that can track activity beyond the ones we already know about, I'm saying we already have one (that is not related to feelings of fatigue).

Your second system can’t exist in the way you described it. It’s am impossibility.

What we know about central fatigue is that it is quite definitively mediated by ongoing sensory input. So the most logical conclusion is if there is additional neurological processing happening, it's using that sensory input in some way. Positing a whole new system independent of that sensory input is entirely superfluous, and there's no positive evidence to support why that superfluous system actually must exist.

Do we know that sensory input is the only thing that causes (central) fatigue?

I have no issue with the assertion that sensory input can cause (central) fatigue. What I’m not convinced by is that one of the most generic symptoms can’t be caused by anything else.

Just as an example: when I was healthy, what caused me to experience a rush of fatigue when I got home from work and sat down? I don’t see how that can be explained by metabolic sensory input.

Unless you’d argue that the fatigue was there all along and it was masked by something?

Or maybe we’re talking about different kinds of fatigue?

 

[jnmaciuch]

Your second system can’t exist in the way you described it. It’s am impossibility.

I think my point there is being misinterpreted. I'm not arguing that the second system is how the brain generates fatigue.

You said:

If the metabolics can change based on loads of factors that are unrelated to the amount of physical work that’s being done, having another ability to track effort or work might be useful for the organism.

I said that we do have one example of a system independent from known fatigue-sensing mechanisms that can serve to track effort or use. It's the one that enables rational deduction. Which is a clear example of a system with benefits outside of its redundancy with activity tracking.

If you're proposing that we ought to have yet another system that tracks activity and generates fatigue when both functions are already accomplished elsewhere, you need extra justification for why it must exist despite the redundancy. Not just the possibility of extra justification we don't know about, because that possibility is true for literally any system one could dream up no matter how implausible.

Not to mention that "the inputs could be scrambled" doesn't mean another "backup" system ought to exist. Basically all of our biological systems go funny and get influenced by a million unhelpful things.

Do we know that sensory input is the only thing that causes (central) fatigue?

I have no issue with the assertion that sensory input can cause (central) fatigue. What I’m not convinced by is that one of the most generic symptoms can’t be caused by anything else.

Just as an example: when I was healthy, what caused me to experience a rush of fatigue when I got home from work and sat down? I don’t see how that can be explained by metabolic sensory input.

Unless you’d argue that the fatigue was there all along and it was masked by something?

Or maybe we’re talking about different kinds of fatigue?

I haven't been arguing what you're attributing to me here. I'm specifically arguing against the idea that there must exist a neural accounting mechanism which tracks activity and that this mechanism is responsible for feelings of fatigue.

Saying that we know about systems fundamental to central fatigue does not mean that every part of that system always works as it should. Nor does it mean that we have complete knowledge of all the relevant parts of those systems or all the things that could modulate them in unexpected ways.

But there's a huge difference between theorizing about something in that set of unknowns and positing an unsubstantiated, separate, and still redundant mechanism that specifically tracks activity and generates fatigue after a certain threshold with absolutely no specifics for how it could work or why it must exist.

The only thing in support of such a completely unsubstantiated mechanism is "why not?" Which means that it has the same explanatory power as
"but why not consider that your coding error could be caused by a quantum mechanical quangle?" We can keep the door open for that vague possibility without making it seem like the explanation is more concrete and useful than it actually is.

 

[Utsikt]

I said that we do have one example of a system independent from known fatigue-sensing mechanisms that can serve to track effort or use. It's the one that enables rational deduction. Which is a clear example of a system with benefits outside of its redundancy with activity tracking.

Why is «keeping track of things» part of whatever enables rational deduction? But this part is getting very off track, so we might be better off by dropping it.

Saying that we know about systems fundamental to central fatigue does not mean that every part of that system always works as it should. Nor does it mean that we have complete knowledge of all the relevant parts of those systems or all the things that could modulate them in unexpected ways.

What I intended to say was that the system you described that depends on metabolic sensory inputs, is unable in its current form to explain many instances of someone experiencing fatigue. And some of those instances are so far removed from immediate shifts in metabolics, that I don’t think it’s unreasonable to think that those episodes of fatigue might be caused by something else entirely.

When it comes to testing a hypothesis that includes something in the brain experiencing fatigue due to some other accountant of activity that has reached a given threshold, it can’t really ever be definitively proven. But you can try to disprove it by testing if predictions based on the hypothesis holds up.

And to be clear: I’m not saying that this is a promising avenue of research or that it should ever be a priority for ME/CFS research. All I’m saying is essentially that just because system X can cause fatigue, doesn’t mean that all fatigue is caused by system X. So only looking at system X might not get us to the answer.