Study Finds Fatigued ME/CFS Brains Unable to Adapt to Cognitive Stress

[southwestforests]

Hey Y'all;

Just got newsletter with this in it from Health Rising.
Have only skimmed through article at this point.

Study Finds Fatigued ME/CFS Brains Unable to Adapt to Cognitive Stress​

by Cort Johnson | Aug 15, 2024 | Brain, Cardiovascular, Homepage, Ion Channels, Motor Cortex | 6

While I am fully aware of the value of specific, documentable, testable, studies, the emotional part of my being wants to say something along the lines of, "Seriously, Sherlock, it took a Study??????"

https://www.healthrising.org/blog/2024/08/15/chronic-fatigue-syndrome-brain-cognitive-stressor/

It turns out that when healthy people do the same task twice their brains use less energy the second time around – they’ve adapted to the task.

The study found partial evidence that people with ME/CFS used more of their brains than healthy controls to complete the task. The major finding, though, was that their brains did not adapt – in what seemed to signal that postexertional malaise was present – their brains used more energy not less to complete the second task. Somehow doing the task the first time around had made things worse.

The authors proposed an inadequate activation of a calcium signaling pathway that increases blood flows to distinct parts of the brain was present and noted that several Australian studies have found problems with calcium mobilization in TRPM3 ion channels in natural killer cells in ME/CFS.

They didn’t mention it but the finding also appears to fit well with Wirth and Scheibenbogen’s hypothesis regarding calcium mobilization problems in the mitochondria and blood vessels. They believe that the inability of the Na+/K+-ATPase enzyme to remove sodium from ME/CFS cells causes the sodium-calcium exchanger (NCX) to import, rather than remove, calcium from the cells. The calcium buildup that results then impacts mitochondrial functioning and the blood vessels.

Wirth and Lohn recently proposed that dysfunctional TRPM3 ion channels are wreaking havoc not just in immune cells but in cells across the body. They believe further investigations of this ion channel are “crucial” to understanding ME/CFS. (A blog is coming up.)

The authors of the present study did not mention energy production. One wonders, though, if the exertion of the first cognitive test might have dampened energy production in the same way that physical exertion does.

If the authors are correct then cognitive stress at least temporarily impairs the ability of the brain to speed resources (in the form of oxygen in the blood) to parts of the brain that need it – producing fatigue. (That sounds like postexertional malaise of the brain to me.) This group has been engaged in a large study (n=288 (!)) https://pubmed.ncbi.nlm.nih.gov/36188362/ examining neurovascular coupling in ME/CFS from different angles.We should learn much more about that soon.

 

[southwestforests]

And so it won't be a twelve kilometer long post, the other bit I want to include,

Results​

The idea that ME/CFS patients need to recruit broader regions of the brain during cognitive tasks was only partially confirmed. The within-group analysis found broader recruitment in the right dorsolateral prefrontal cortex and the left somatosensory cortex. The between-group analysis (the ME/CFS patients and the healthy controls) did not find significant differences in the number of brain regions recruited. The authors noted the high variability in the results – which is not unusual in ME/CFS (we can be a heterogeneous group) – which would require larger studies to make sense of. They also questioned whether the cognitive test was difficult enough.

Adaptation was another and potentially more important story. Increased activation of the motor, sensory, and cognitive cortices in ME/CFS made sense given the movement, sensory, and cognitive problems found in the disease. The increased activity during the second test indicated that the ME/CFS brains did not adapt to the first cognitive test. Instead of becoming more efficient and using less energy during the second test, their brains used more energy during the second test. This is the same pattern found in multiple sclerosis and traumatic brain injury.

The authors highlighted problems with energy – not a lack of energy – but the strained energy resources and fatigue caused by the inefficient allocation of blood to the active brain regions.

 

[Dysfunkion]

This is what a lot of the research about what is going on in a nutshell seems to say, there's too much over activity but too many byproducts and resources being depleted. But at the same time if I let activity drop everything just shuts down for example if I stop taking my methyl-b12 which I can't live without anymore. This is probably why a lot of us including myself react badly to consuming large amounts of calcium, I also need to take K2 every day. That tired and wired feeling is the worst thing in the world. You feel in some way really speedy BUT your cognition is barely holding together, it's that "I'm gonna lose my mind at any moment!" feeling that really gets to me at times and if I'm actually stressed out it's even worse. It's not an energy problem specifically it's stability problem with a highly complex set of variables in each individual with the problem. I had a feeling from my weird D3 reactions that there was something going horribly wrong in the ion channels specifically the calcium one's causing all sorts of fallout on the body that presents as the general CFS blanket and all the immune chaos that comes with it.

"The study found partial evidence that people with ME/CFS used more of their brains than healthy controls to complete the task. The major finding, though, was that their brains did not adapt – in what seemed to signal that postexertional malaise was present – their brains used more energy not less to complete the second task. Somehow doing the task the first time around had made things worse."

That is very interesting because that's specifically what I noticed happens with me. Let's say I start listening to music and I'm pretty mild that day by some miracle. When I firs t start on a day I can really feel it and it feels good that music will have a certain smoothness to my sensory enjoyment it, it'll be like sensory silk through my brain. I remember why I love it so much and how powerful it can be so I decide to do something terrible forgetting about my condition and listen too 4+ albums on end. Something starts to happen, my brain over focuses on every aspect of it automatically, starts AUTOMATICALLY trying to map everything it's hearing through all brain regions very strongly, suddenly it starts to get less enjoyable, and then the brain starts straining as it processes the thing even harder against my will. If I keep going the signalling gets so erratic that all processing of information gets mixed up. It's the same exact thing with socializing from the same start point and occurs even quicker with that. Too much signalling --> brain adjusts by amplifying everything --> signalling gets messed up --> body systems caught in the crossfire collapse most notably the CNS and it's partner the immune system --> this starts to loop in on itself as more problems require more attention and the brain only ramps things up more.

 

[hapl808]

"The study found partial evidence that people with ME/CFS used more of their brains than healthy controls to complete the task. The major finding, though, was that their brains did not adapt – in what seemed to signal that postexertional malaise was present – their brains used more energy not less to complete the second task. Somehow doing the task the first time around had made things worse."

Would be great to figure out something that addressed this issue.

 

[Wishful]

An interesting finding. Hopefully they can now follow up with a different technique to verify the hypothesis. If there aren't techniques for measuring calcium channel function or calcium concentrations in and around cells, they can probably develop some. Are there chemicals that affect calcium channels?

This discovery reminds me of a recent article I read about discovering that the brain stores memories in three different locations, with different characteristics. The brain keeps getting more complex the more they study it.

 

[junkcrap50]

An interesting finding. Hopefully they can now follow up with a different technique to verify the hypothesis. If there aren't techniques for measuring calcium channel function or calcium concentrations in and around cells, they can probably develop some. Are there chemicals that affect calcium channels?

There is MR Spectroscopy so they can measure metabolites in tissues using an M. Like they can measure GABA and Glutamate levels in the brain, and there was a study of using it to measure/look at the brains of Long Covid patients. Maybe something like that could be used.

 

[alcasa]

I’m still writing the book about the glutamate-calcium theory of CFS, and this aligns very closely with my perspective. The ATPase function is crucial, and it’s highly probable that calcium channels are more active than normal in CFS, which could drive elevated glutamate levels, reduced NMDA receptor activity, increased spillover, then reduced dopamine and nor signaling and ruminative thoughts.


EXTREMELY IMPORTANT: the reverse transporter mechanism; I believe that the reversal of the Na+/K+ ATPase due to excess glutamate/calcium+sodium is, in fact, the cause of the “tired but wired” sensation because it leads to self-reinforcing excitation. I wouldn’t attribute this as much to the NCX since it’s not primarily intended to halt excitation like the Na/K pump.

 

[SlamDancin]

@alcasa Look forward to your write up. In the meantime, does this mean we want to look for inhibitors of the Na/K atpase? Any other quick suggestions for treatments?

 

[SlamDancin]

@alcasa Any thoughts on whether or not Potassium supplements could be helpful?

 

[Vladimir]

@alcasa Any thoughts on whether or not Potassium supplements could be helpful?

In my personal case, Potassium Citrate gives huge benefits on cognitive, mental and physical levels.

I found that the powder dissolved in a cup of water is the best way to take it - it tastes great (milk-like - you just need to find the ideal proportion - around 3g of PC per cup, otherwise it will be other bitter if too much or salty if too little), it does not irritate stomach, and you can easily get a higher dose.

I take it three-four times per day, so 3-4x3g - 9-12g of PC, or about 3g of elemental Potassium.

 

[SlamDancin]

Thanks for the reply @Vladimir ! There’s papers on how the Na+/K+ ATPase activity changes depending on K+ levels/supplementation but I couldn’t tell whether it would be beneficial. I’m going to try to supplementing it

 

[Dysfunkion]

In my personal case, Potassium Citrate gives huge benefits on cognitive, mental and physical levels.

I found that the powder dissolved in a cup of water is the best way to take it - it tastes great (milk-like - you just need to find the ideal proportion - around 3g of PC per cup, otherwise it will be other bitter if too much or salty if too little), it does not irritate stomach, and you can easily get a higher dose.

I take it three-four times per day, so 3-4x3g - 9-12g of PC, or about 3g of elemental Potassium.

Same here but it destroys my digestive system if I take even the smallest amount and I haven't found a way to bypass that. I've even put it in something fatty to make it easier hitting my guts but that's didn't make a difference.