Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome, 2024, Walitt et al

The NIH have selected this study as part of their 2024 highlights. Which is seriously puzzling since it provided zero useful insights and was generally speaking a total bust.

https://www.nih.gov/news-events/nih...esearch-highlights-promising-medical-findings

I have no idea how those two adjacent sentences can be reconciled, but I don't think anyone involved in this thought about this for more than a microsecond:

 

They really chose the worst part to put in the highlights... I thought they were trying to avoid provoking us any further given all the drama and backlash. I guess whoever compiled this page might be oblivious.

That sentence also really shows they had no clue what living with condition was like. You say that to anyone with ME and they will reply "yeah I can do more than I let myself, but it will lead to worsening of my condition"

 

The funny thing is, out of context, "fatigue may arise from a mismatch between what someone thinks they can achieve and what their bodies perform” sounds like it means "people with ME think they can do more than their bodies are actually capable of performing and that's why they're always so tired."

 

Exactly! It's perversely somewhat not entirely wrong, but misinterpreted out of ambiguity that is obviously on purpose. Not that "fatigue arises" from that makes any sense though. That's just word salad, and completely absurd to make this the main takeaway. But that's just psychobehavioral ideologues doing their thing.

 

Can someone refresh my blurry memory on something in this study? The much-hyped "effort preference" finding is based on differences in activation of the temporo-parietal junction in the (small numbers of) pwME and healthy controls in the button-pressing reward test. Did they also look at TPJ activation during the handgrip test, the cycling or anything else?

 

The "Effort preference" findings are based on the fact that in a repetitive task (EEfRT) pwME choose the hard-task slightly less often on average than healthy controls (PHTC). In everyday terms "they are lazy because they try less hard". It gets a little muddled because they bring in the subconscious and the possibility of an antigen in the brain causing these phenomena but the message is that "Effort preference is how much effort a person subjectively wants to exert." and that this is altered in pwME.

Connecting the EEfRT results to anything else seems to be rather speculative. As far as I'm aware there were no statistically significant connections to TMS or fMRI data.

 

Notably: this is only barely significant because they dropped a single participant for arbitrary reasons that may or not may not have everything to do with the fact that if they didn't do this, it would be a null result and they wouldn't be able to make the paper about this odd, weak and unremarkable fake thing. As is tradition.

And that's besides the fact that this 'effort preference' thing is an entirely made-up concept they invented themselves, out of nothing, for the purpose of this paper. They basically just slapped a psychosomatic-sounding label on what is essentially the practiced art and science of putting their finger on the scale just the right way at just the right place and time to get their fake results.

 

This isn't the main finding, but this MRI on a subset of effort preference participants while doing handgrip (I think) is very interesting and received v little attention. Though based on only 8 peeps, IIRC, so not much to hang our hat on.

 

If I remember (and understood) correctly, the ‘effort preference’ was measured using a test that’s designed to measure ‘effort preference’ in patients with e.g. depression.

You play a game with a time limit where you have to repeatedly choose between an easy and a hard task of quickly pressing a button X times within Y seconds. For easy tasks, both X and Y are low. For hard tasks, X and Y are higher - you have press the buttom more times and for a longer duration. The values for X and Y are not constant, so you have to figure out if the given task is relatively trivial or difficult for its category.

Each task gives a reward. The easy tasks give a lower reward than the hard tasks. However, the rewards are also randomized. So you might end up with a trivial ‘easy’ task that gives a higher reward than the previous difficult ‘easy’ task.

Your job is to maximize your reward. So they measure ‘effort preference’ in terms of how ‘motivated’ you are to play strategically and try to pick the tasks that gives the most bang for your buck, so to speak.

Additionally, one very important premisse is that the participants have to be able to complete all tasks. But as we know, people with ME/CFS might tire out more quickly, and might not be able to complete the hard tasks because they are physically too demanding. Not surprisingly, the data showed that some of the ME/CFS patients were unable to complete the hard tasks, so they scored way lower because of that. This data was NOT excluded, but the data shows that people with ME/CFS that are able to complete the test actually has a marginally higher ‘effort preference’ than the healthy controls.

Furthemore, the test has a fatal flaw. The participants get real life money from playing, but not based on the total score. They get the money from just two randomly chosen tasks that they managed to complete.

This means that the optimal strategy is to only complete high value hard tasks. If you don’t get a high value hard task that you believe you can complete, you always pick the easy (and shorter task) and fail it on purpose.
(Edit: I forgot to say that this strategy gives you a lower score in the test. So playing optimally is worse - which makes no sense at all.)

There’s also something about how they intepreted the results in a different way than the creators of the test, but I can’t remember the details.

To sum it up: They used a fatally flawed test that isn’t suitable for physically ill people. They also deviated from the data intepretation protocol without explaining why.

 

The effort preference is the same thing as the psychosocial ideology has always been.

They see our high levels of disability and quick fatiguability and automatically assume that it’s because we don’t want to do the thing. Instead of the more obvious well we are ill and so we can’t do the thing or get tired quicker. I mean try the effort preference with Healthy Controls vs people with the flu and you’ll likely get the same result as ME vs HC.

The interpretation of the results, especially in a biomedical study like this one — is just laughably ludicrous.

 

I don’t believe there’s a reason to believe that pwFlu would score lower than HC, because they would presumably able to complete the tasks at the same rate.

Just as how the pwME that were able to complete the test scored the same as the HC.

It’s a flawed test designed for a different patient group, and not used according to the instructions of the creators. The results are meaningless, even without the null result.

 

Chronic Fatigue Syndrome: Pulling Back the Curtains

Link (The Neuroscientist) [Paywall]

---

I'm not sure what this paper is as I can't access it. There's only one reference (the deep phenotyping study) so I assume it's just a short comment.

 

It's a very brief comment on the NIH paper. It starts with:

followed by a description of the paper's findings. It concludes:

 

Someone is being tactful.

 

"It provides multiple clues that may help to unravel the mystery of chronic fatigue syndrome/myalgic encephalomyelitis."

While true, it doesn't mean that they are useful clues. Our world provided plenty of clues that the world was round, but it still took centuries for someone to put the clues together properly. I think every PWME provides multiple clues about ME's mechanism, but we're still waiting for that "Eureka!".

 

https://openurl.ebsco.com/EPDB:gcd:...82949997&crl=c&link_origin=scholar.google.com

Title
Chronic Fatigue Syndrome: Pulling Back the Curtains.
Abstract
The article "Chronic Fatigue Syndrome: Pulling Back the Curtains" discusses the complexities of chronic fatigue syndrome, also known as myalgic encephalomyelitis, highlighting the various symptoms and potential underlying mechanisms of the disorder. A team of scientists and clinicians conducted a comprehensive study on 17 patients with postinfectious chronic fatigue syndrome/myalgic encephalomyelitis, analyzing physiological, cognitive, biochemical, and immunological aspects over a five-year period. The study revealed abnormalities in cognitive complaints, grip force maintenance, brain activity, neurotransmitter levels, immune cell composition, and fecal microbiota, providing valuable insights for future research on this enigmatic disorder.
Subjects
CHRONIC fatigue syndrome; PERIPHERAL nervous system; REWARD (Psychology); IMMUNOASSAY; MEDICAL scientists; NEUROPSYCHOLOGY; B cells
Publication
Neuroscientist, 2025, Vol 31, Issue 1, p5
ISSN
1073-8584
Publication type
Academic Journal
DOI
10.1177/10738584241308723

 

Do you or anyone have access (free), out of curiosity?

 

Yes it actually scared me it was a Pacing Up type paper at first.