Exercise Challenge Reveals a “Remarkable Discordance” in the Brains of People with ME/CFS

SWAlexander

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There are several ways things can go wrong in the body. You can have too much or too little of something. You can have something that just sits there – doesn’t respond at all. You know you really have a problem, though, when you have what this study found: a complete reversal of normality. In this study, a part of the brain that became deactivated in healthy controls after exercise got turned on in the ME/CFS group.

In what the authors called “a remarkable discordant finding”, blood oxygenation levels (an analog of activity) declined in the medial prefrontal cortex after exercise in the healthy controls but shot up in the people with ME/CFS.

This finding was so strange that the authors suggested it might constitute a biomarker for ME/CFS. It was all the more interesting because except for this region of the brain, the blood oxygenation levels (e.g., the activity levels) in the rest of the ME/CFS patients’ brains were lower than normal after exercise. The activation of the medial prefrontal cortex, in other words, stood out like a sore thumb.
The authors proposed that a radical perturbation in something called the default mode network, (DMN) had occurred. The default mode network is most activated when a person is at “wakeful rest” and is not focused on the outside world. Instead, the brain is kind of ruminating; thinking about what’s going on, thinking about others, thinking about themselves.

Rumination is the antithesis of action. In order to get a task done, you have to turn off your default mode network and focus on the task at hand. In what appears to be something of a recipe about how NOT to get things done, the exercise challenge turned the DMN on in the people with ME/CFS. The authors called it “task-related deactivation”.

Nor is rumination thinking about something – it’s something more on the order of – in Landmark Education parlance – getting thought by something. Meditation, on the other hand, is the opposite of rumination: it actually turns off the DMN. The psychedelic clinical trial underway in fibromyalgia is attempting to turn off the DMN.
https://www.healthrising.org/blog/2022/01/05/exercise-brain-discordance-chronic-fatigue-syndrome/
 

hmnr asg

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I have had cfs for 12 years and I have to still hear from anyone who managed to cure or even improve their CFS with mindfulness meditation (known to attenuate DMN).

I have also interacted with a lot of people on the CFS subreddit who have experimented with psilocybin (magic mushrooms) for their CFS with no improvements.

I only heard one anecdotal story from a person who got benefits from DMT, but that is just one person.
Not saying their findings is incorrect, just not sure if psychedelics will be the solution. (but i would be very happy to be proven wrong of course)
 

Pyrrhus

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And here's the article being discussed:

Submaximal Exercise Provokes Increased Activation of the Anterior Default Mode Network During the Resting State as a Biomarker of Postexertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Rayhan and Baraniuk, 2021)
https://dx.doi.org/10.3389/fnins.2021.748426

Excerpt:
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by disabling fatigue and postexertional malaise. We developed a provocation paradigm with two submaximal bicycle exercise stress tests on consecutive days bracketed by magnetic resonance imaging, orthostatic intolerance, and symptom assessments before and after exercise in order to induce objective changes of exercise induced symptom exacerbation and cognitive dysfunction.

Method: Blood oxygenation level dependent (BOLD) scans were performed while at rest on the preexercise and postexercise days in 34 ME/CFS and 24 control subjects. Seed regions from the FSL data library with significant BOLD signals were nodes that clustered into networks using independent component analysis. Differences in signal amplitudes between groups on pre- and post-exercise days were determined by general linear model and ANOVA.

Results: The most striking exercise-induced effect in ME/CFS was the increased spontaneous activity in the medial prefrontal cortex that is the anterior node of the Default Mode Network (DMN). In contrast, this region had decreased activation for controls. Overall, controls had higher BOLD signals suggesting reduced global cerebral blood flow in ME/CFS.

Conclusion: The dynamic increase in activation of the anterior DMN node after exercise may be a biomarker of postexertional malaise and symptom exacerbation in CFS. The specificity of this postexertional finding in ME/CFS can now be assessed by comparison to post-COVID fatigue, Gulf War Illness, fibromyalgia, chronic idiopathic fatigue, and fatigue in systemic medical and psychiatric diseases.
 

Consul

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I have had cfs for 12 years and I have to still hear from anyone who managed to cure or even improve their CFS with mindfulness meditation (known to attenuate DMN).
I have improved on meditation and i have heard a number of anecdotes about others as well, some on yoga. There would have to be rigorous studies to determine if it works in general though.
 

nerd

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Another recent article by the same author, James Baraniuk:

Review of the Midbrain Ascending Arousal Network Nuclei and Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (M... (Baraniuk, 2022)
https://forums.phoenixrising.me/thr...ronic-fatigue-syndrome-m-baraniuk-2022.86742/
Another lesson learned for me, thanks for sharing. It's a good explanation for the finding, if I understand your implication correctly, in that the first receiver of the ascending arousal network is the prefrontal cortex.

I'm not sure if they looked at the stem brain, but it should be visible in typical imaging methods, so I presume they have.

The reason for the lack of oxygenation in the stem brain despite of glutamatergic overactivity (when compared with references and with healthy controls) might just be an impaired mitochondrial activity, as viruses happen to do, or even viral residuals, as Prusty suspects in the form of miRNA. So it doesn't necessarily translate into higher oxygenation as they might presume. However, the stem brain should somehow still differentiate itself over the course, so it might still be visible somehow.

I mean - what other explanations exist that make sense of this discrepancy? Can it be the other way round, in that there's some pathology in the frontal cortex that deflects to other regions? What's the trigger then? How can exercise in particular trigger trauma to re-emerge and bring the frontal cortex to enable the DMN? The DMN is associated with PTSD, but that's it, and this doesn't tell us anything about the mechanism and the directionality. Because exercise enables the fight mode and fight mode is coupled with trauma?

What might still be a possibility is an unbalanced oxygen supply from the vascular system by microvascular changes that affect the anterior cerebral artery most dominantly. This also seems to be a bit far-fetched though. Why is only this artery heterogeneous while other arteries show homogenous oxygenation? I'm speculating too much...
 

Wishful

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When I'm feeling too brainfogged to do any mentally challenging task, I might shovel a few tons of snow or soil. I can get that sort of task done ... and that exercise doesn't make me more brainfogged (may reduce it).
 

wabi-sabi

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This is a great theory, but as i mentioned, none of the things that modulate the activity of the DMN have any impact on CFS: antidepressants, meditation, psychedelics...
I think the idea here is to show one more way that exercise hurts us when it doesn't hurt healthy people. How many times have we been told that exercise benefits mental health as well as physical health? My mental health has definitely gotten worse now that I can no longer go and play in the woods.

The findings don't imply that fixing the DMN would help alleviate ME/CFS (at least based on reading the abstract) so much as show us one more thing that's harmful about exercise. Seems like a downstream consequence of exercise, not an upstream cause of the illness.

At least that's my best guess.
 

hmnr asg

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I have improved on meditation and i have heard a number of anecdotes about others as well, some on yoga. There would have to be rigorous studies to determine if it works in general though.
That is very interesting. I have no doubt that meditation improves one's quality of life, but did it in fact improve your CFS? did it reduce the frequency/severity/duration of your PEM? did it reduce brain fog? also, what style of meditation do you practice and how often? I used to be an avid meditator and yogi before CFS but now I find that the basic act of paying attention to my breath to be just as exhausting as trying to read a book.

The findings don't imply that fixing the DMN would help alleviate ME/CFS (at least based on reading the abstract) so much as show us one more thing that's harmful about exercise. Seems like a downstream consequence of exercise, not an upstream cause of the illness.
So the article doesnt imply that but OP mentioned that there is a trial for using psychedelics for fibromyalgia, thats why i mentioned that i have doubts it can work because of the stories I have read.

@Pyrrhus
is it possible that this malfunction of the DMN could be downstream from another process? like in Alzheimer's disease there is also disfunction of the DMN but its due to the plaques. So, DMN issue could be just a symptom of CFS rather than the cause.
 

wabi-sabi

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there is a trial for using psychedelics for fibromyalgia
Yes, this sounds very weird to me. I am wondering why they think that would work, other than the usual BPS nonsense. Pyschedelics are used for mental health issues like depression and PTSD quite well. Someone still thinks fibro is a mental illness instead of a physical one.
 
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Pyrrhus

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is it possible that this malfunction of the DMN could be downstream from another process? like in Alzheimer's disease there is also disfunction of the DMN but its due to the plaques. So, DMN issue could be just a symptom of CFS rather than the cause.
I'm afraid I'm not familiar enough with the default mode network, so I couldn't comment on this study...
 

Consul

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That is very interesting. I have no doubt that meditation improves one's quality of life, but did it in fact improve your CFS? did it reduce the frequency/severity/duration of your PEM? did it reduce brain fog? also, what style of meditation do you practice and how often? I used to be an avid meditator and yogi before CFS but now I find that the basic act of paying attention to my breath to be just as exhausting as trying to read a book.
Improve CFS? Yes and at first i experienced clear improvement over night. I went from not beng able to sit on my computer (screen) at all to being able to use my computer for multiple hours every day (screen sensitivity). The duration has increased to many hours and getting less and less fatigued by it. Also i went from only being able to walk on straight gravel road for about 60-90 minutes per day to being able to walk in the wood/terrain in about 1-2 weeks for just as long. I cant say that it touched PEM in any way, i just got increased capacity. I have outlined my meditation technique in the "alternative treatment" section of the forum, regular meditation didnt help me. And i agree that paying attention to the breath is exhausting. Would be interrested in knowing if you get any benefits from my technique though.
 

bread.

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The DMN is likely a mechanism that the brain is in to conserve energy. Meditation can soften "that grip" somewhat, but why would it make you better longterm?
 
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Would be interesting if they did the same teat on people with the flu. Could just be that when you are sick your body/brain tells you “exercise is bad you fool, you gotta rest”. When you are well it says “ok I get it, you are telling me you need to be doing something. Activate action mode”??
 

wabi-sabi

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Could just be that when you are sick your body/brain tells you “exercise is bad you fool, you gotta rest”. When you are well it says “ok I get it, you are telling me you need to be doing something. Activate action mode”??
Yes, this is partly how sickness works.

The issue is if you turn that message off when you are still sick, bad things will happen because the Rest you fool! message is there for a reason.