A Thought Experiment on Muscles

[jnmaciuch]

I would slightly amend that to say that even mild ME can have that 'poisoned feeling'. To me it's pretty much the first warning sign that I have overdone it. In fact I've experienced it long before I had a disabling level of fatigue

I think it's pretty common, definitely not restricted to the severe end, and it could be some early step in that cascade.

Yes sorry, what I meant was that the discussion thread I’m referencing was primarily among more severe people. I’ve experienced it myself when I was more moderate (though it was under some weird circumstances for me)

https://www.s4me.info/threads/poisoned-feeling.43442/

 

[wigglethemouse]

But my impression is that people think there is a change in muscle with use. Perhaps use induces changes in mitochondria in muscle cells?

I took a look at Table 2 and Table 3 from the CureME thread/paper "Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study" and there is a significant difference in Ck.
Thread : https://s4me.info/threads/evidence-...analytic-cross-section-2019-nacul-et-al.9024/

From abstract:

After corrections for multiple comparisons, most results were within the normal range, but people with severe ME/CFS presented with lower median values (p < 0.001) of serum creatine kinase (CK; median = 54 U/L), compared to healthy controls (HCs; median = 101.5 U/L) and non-severe ME/CFS (median = 84 U/L). The differences in CK concentrations persisted after adjusting for sex, age, body mass index, muscle mass, disease duration, and activity levels (odds ratio (OR) for being a severe case = 0.05 (95% confidence interval (CI) = 0.02–0.15) compared to controls, and OR = 0.16 (95% CI = 0.07–0.40), compared to mild cases). This is the first report that serum CK concentrations are markedly reduced in severe ME/CFS, and these results suggest that serum CK merits further investigation as a biomarker for severe ME/CFS.

Is it worth revisiting that data with respect to the subject of this thread?

 

[Murph]

To be honest the phrase 'we are learning' tends to ring the bell on my bullshitometer rather loudly.

can we just call each others posts bullshit now? brb going to drop this format in a few threads.

 

[Jonathan Edwards]

I took a look at Table 2 and Table 3 from the CureME thread/paper "Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study" and there is a significant difference in Ck.

I have taken that to just be a reflection inactivity. We know that even in healthy life CK goes up significantly with vigorous activity. So normal values will reflect the range of normal people's activity.

 

[Ravn]

I haven’t been able to read the whole thread but in case it hasn’t been mentioned yet, here’s another possible confounder to the muscle involvement puzzle: some of us don’t loose muscle nearly as quickly as one would expect given our level of extreme sedentariness. I don’t know how common this is but a few people have reported it

It may just be that some individuals have a genetic predisposition to an enhanced ability to maintain muscle mass and that this has nothing to do with ME at all and is actually a bit of good luck protecting against frailty

On the other hand, could whatever pathways direct resources to maintaining muscle mass somehow be entangled with whatever pathways end up creating PEM?

 

[hotblack]

I've literally had nightmares about that, for years - recurring ones. There would come a point in real life where I coudn't go on, but I've never allowed myself to get into a situation where I've been forced to do that. It's just been in the nightmares.

It was weird when ME/CFS started appearing in my dreams. And sometimes it’s there and sometimes not. I can dream and be aware of my ME/CFS or not at first so be running or cycling and suddenly go ‘wait I shouldn’t be able to do this’ or it can not pop up at all, which is obviously a lovely experience.

 

[hotblack]

I can’t say I’ve been able to keep up with the biology of this all, but have certainly found it interesting and thought provoking. Thanks everyone. There’s certain ways I’ve thought about aspects of this that have been challenged and other new thoughts introduced. I’m no clearer on what is happening, but happily unsure about it all.

 

[Sasha]

@Jonathan Edwards mentioned that mental exertion uses little extra energy, so it probably doesn't fit with thinking triggering PEM through simple energy demand.

In a nutshell: normal walking burns over 200 calories an hour. Thinking uses maybe 10 calries an hour.

Some figures from this BBC article illustrate the point:

Total brain energy demand = about 20% of total body energy use, say 500 calories a day (20 calories an hour)
If we were asleep all day, we'd use about half that. And most of the rest "is concerned with the largely automatic process of controlling your muscles and processing sensory input".
So maybe 80 calories a day for thinking tops. That would be 5 calories an hour overy 16 hours
For comparison, walking at normal speed uses over 200 calories an hour.

I'd previoiusly liked the idea that simple energy demand - mental or physical - triggers PEM. But I hadn't done the maths.

The Internet (vague, but I'm feeling lazy) says we burn about 50-75 cals/hour just lying down and resting. Google's AI summary thing says, 'The process of vision involves light entering the eye, being processed by the retina, and then relayed to the brain, but this is a low-energy process.' I'd be amazed if it's even a single calorie.

 

[Yann04]

The Internet (vague, but I'm feeling lazy) says we burn about 50-75 cals/hour just lying down and resting. Google's AI summary thing says, 'The process of vision involves light entering the eye, being processed by the retina, and then relayed to the brain, but this is a low-energy process.' I'd be amazed if it's even a single calorie.

It wouldn't be the process of vision but the process of interpreting that vision. Your brain does a lot of work processing the input into your retina and turning it on "what you see" and making sense of it.

This is a really interesting video diving into the complexities of this:
(the first part, the latter half seems to be more a philosophical opinion)

 

[Sasha]

It wouldn't be the process of vision but the process of interpreting that vision. Your brain does a lot of work processing the input into your retina and turning it on "what you see" and making sense of it.

This is a really interesting video diving into the complexities of this:
(the first part, the latter half seems to be more a philosophical opinion)

Thanks, @Yann04 - I don't doubt that the brain is doing some processing but is it doing 'a lot of work' in the sense of 'expending a lot of energy'? I'm afraid I don't have time to watch the video.

 

[Utsikt]

Thanks, @Yann04 - I don't doubt that the brain is doing some processing but is it doing 'a lot of work' in the sense of 'expending a lot of energy'? I'm afraid I don't have time to watch the video.

The brain does a lot of filtering because the input from the eyes is extremely noisy.

People with Visual Snow Syndrome presumably have a faulty filtering mechanism. Which is why my entire field of vision is filled with visible floaters, blinking lights, strobe light effects, afterimages, etc.

 

[Jonathan Edwards]

This is a really interesting video diving into the complexities of this:
https://www.youtube.com/watch?v=wo_e0EvEZn8

It's a neat video. The only thing wrong is where at the end it talks about the conscious 'you'. I don't think there is any single conscious you. Certainly neuroscience gives no hint of such a thing.

 

[InitialConditions]

People with Visual Snow Syndrome presumably have a faulty filtering mechanism. Which is why my entire field of vision is filled with visible floaters, blinking lights, strobe light effects, afterimages, etc.

I also have visual snow syndrome (7 years of), along with tinnitus (13 years of). Quite clear that my brain has malfunctioned with regards to how it's processing information, and I don't doubt for one second that these issues are in some way related to my ME.

 

[jnmaciuch]

Thanks, @Yann04 - I don't doubt that the brain is doing some processing but is it doing 'a lot of work' in the sense of 'expending a lot of energy'? I'm afraid I don't have time to watch the video.

I’ve been looking into this question recently as I’m decently acquainted with both neuroscience and cell metabolism but not an expert in either. I have this review that I have only briefly skimmed (so can’t comment on its quality at the moment).

Energy metabolism of the visual system

It states:

Neuronal activity and energy metabolism are thus tightly coupled24,30(Figure 1). As long as the two are kept in proper balance, the nervous system will function adequately. An imbalance that tilts the scale in either direction, can be tolerated up to a point. However, beyond a certain threshold level, which undoubtedly varies among neurons and among brain regions, dire consequences can result. The visual system with its high energy demand is particularly vulnerable to functional deficits induced by deficiencies in energy metabolism.

So it seems to be a consensus that visual processing is one of the most energy demanding activities of the brain, and that the brain consumes a pretty steady 20% of the entire body’s energy which will be dynamically distributed across different regions and activities according to need.

What I can’t answer at the moment is how that energy expenditure compares to something like muscle use for walking. I suspect it might be a difficult question to answer experimentally given that the metabolic infrastructure of the brain and muscle is very very different by necessity so the same methods of in-vivo measurement may not be applicable to both.

 

[Sasha]

We've just been talking on the PEM factsheet thread (most recently starting here) about the need for a thread specifically on this issue of whether people experiencing PEM from light/noise etc. can possibly be related to exertion or is being driven by some other aspect of biology. It might be a bit of a job to pull all that stuff out, though.

I can't remember whether I asked if this tricky issue would be covered in your Grand Theory of Everything, @Jonathan Edwards? It's such a weird thing.

@JemPD

 

[Utsikt]

I also have visual snow syndrome (7 years of), along with tinnitus (13 years of). Quite clear that my brain has malfunctioned with regards to how it's processing information, and I don't doubt for one second that these issues are in some way related to my ME.

I’ve seen reports from others that VSS is overrepresented amongst ME/CFS patients, but I don’t know if that’s true. Mine started during my worst crash when I barely slept for a month.

 

[Jonathan Edwards]

So it seems to be a consensus that visual processing is one of the most energy demanding activities of the brain, and that the brain consumes a pretty steady 20% of the entire body’s energy which will be dynamically distributed across different regions and activities according to need.

What this may obscure is that the brain needs a lot of fuel in order just to remain viable, and yet more to support a conscious state. My understanding is that the additional metabolic activity over and above this associated with an increase in activity of specific neurons in specific areas is small. Moreover, I doubt we have any evidence that reading words involves greater metabolic activity in the visual cortex than peering peacefully into the distance while drinking a sundowner.

The real question is whether visual cortical activity that involves concentration and so-called exertion costs much.

 

[EndME]

We've just been talking on the PEM factsheet thread (most recently starting here) about the need for a thread specifically on this issue of whether people experiencing PEM from light/noise etc. can possibly be related to exertion or is being driven by some other aspect of biology. It might be a bit of a job to pull all that stuff out, though.

I can't remember whether I asked if this tricky issue would be covered in your Grand Theory of Everything, @Jonathan Edwards? It's such a weird thing.

@JemPD

I'm not sure if this has been discussed (I think it has) and this is not the place to do so (feel free to move this elsewhere), but I'd be extremely sceptical of a grand theory of everything. This seems to hardly exists for many illnesses that have been far better understood for several decades. I think what one should be hoping for is a far more specific theory that builds on understanding very specific pathways in all its details that can explain some main aspects of the illness, doesn't try to explain all of them yet is consistent with everything that is known. A hypothesis that can be easily verified in trials and studies, avoiding any vague reference.

I can only see it being a starting point rather than an end. I think the ideal scenario would be that the interested people come up with their conjecture, discuss their conjecture, test it, realise that things aren't as they initially thought but can still make sense of things in a different way than initially anticipated and take things from there. The first idea is never going to get it just right. Hopefully it can be a starting point for people to later do exactly that.

 

[jnmaciuch]

The real question is whether visual cortical activity that involves concentration and so-called exertion costs much.

Specifically, in my theory, it would not matter even if it is a relatively small cost. It would be a combined factor of the degree of increase in demand on a certain part of the brain, the duration of that increased demand, and rates of malate and FAD shuttling.

What would have to be measured is if the activity of sensory processing exceeds the baseline diffuse neural activity in the associated part of the brain, and then whether than threshold being crossed in one part of the brain results in propagation of a signaling cascade that can then spread to other cortical regions (which is why I’m looking at microglia, for example).

my experiences during my worst periods would indicate that both reading and looking at a peaceful sunset with a drink could both be enough to trigger PEM, since simply leaving my room exposed me to much higher sensory stimulation in all respects. I had a lot of trouble explaining to my professors that simply sitting in a classroom with other people would “cost” me much more than working on my laptop in a dark and quiet room.

Perhaps the trick would be to determine that, if energy “cost” could be ranked between various tasks, if the same person in the same conditions wrt to prior activity would always be triggered by tasks that rank the same or above the lowest ranked task.

Basically, if reading does happen to cost more than watching a sunset in terms of energy demand, you’d expect that a person triggered by watching a sunset would also be triggered by reading, but they would never be triggered by a sunset and not by reading.

 

[Jonathan Edwards]

Unless they were exerting themselves desperately:
pour voir le rayon vert.