Opinion Post-exertional malaise – A functional brain aberration?, 2024, Wyller

SNT Gatchaman

SNT Gatchaman

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Post-exertional malaise – A functional brain aberration?
Bruun Bratholm Wyller

Comment on Exercise does not cause post-exertional malaise in Veterans with Gulf War Illness: A randomized, controlled, dose–response, crossover study (2024, Brain, Behavior, and Immunity)

Last paragraph —

If confirmed that PEM are best understood as a functional brain aberration, the clinical implications are large. As long as PEM is regarded a consequence of “peripheral” pathophysiological processes, it seems logical to avoid symptom-provoking activities for the fear of harm; indeed, the evolutionary “meaning” of salience signals is to promote avoidance of the situations that provoke them. However, if PEM is a consequence of too dominant a priori-expectations, the goal should be to “re-set” the expectations rather than avoid symptoms, for instance through behavioural approaches that include individually adjusted exertions in a way that facilitate associative learning. This should be further investigated in clinical trials which can be performed without undue safety concerns: The study by Boruch et al. adds to an increasing body of evidence confirming that physical activity is not harmful in conditions characterised by PEM (Tryfonos et al., 2024).

Link | Paywall (Brain, Behavior, and Immunity)
 
So far, mechanistic PEM research has sought to establish a causal link to distinct and “peripheral” pathophysiological processes […] The evidence is quite inconsistent, however, which may not be surprising: Across several chronic conditions, the association between symptoms (which are subjective experiences that cannot be externally measured) and pathophysiological variables (which can be objectively verified) is rather poor (Fink et al, 2015).
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Preliminary evidence links PEM to some of the same anatomical structures (e.g., the insular cortex) (Washington et al., 2020; Manca et al., 2021). This is sensible from a functional point of view: Both pain and PEM may be conceptualized as salience signals, prompting avoidance of the situations causing them as well as eliciting the autonomic, endocrine and immunological adjustments that characterizes a stress response (McEwen & Akil, 2020).
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It has long been acknowledged that pain can be elicited without nociceptive afferent input, leading to a discrepancy between the subjective experience (the symptom) and the objective state of the body. The predictive processing model of brain function provides an explanation for such phenomena (Parr et al, 2022). Briefly, this model posits that perception is a product of incoming sensory information (bottom-up) and the brain’s a priori-expectations (top-down). The latter – labelled priors within the established terminology – may in certain situations “overrule” the sensory signals. This explains visual illusions
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predictive processing provides a credible explanation of symptom persistence, which may be attributed to too strong priors that are not “updated” by new sensory information, and symptom fluctuation, which may stem from variable and context-dependent weight given to priors vs. current sensory signals
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this theory does not preclude aberrations of other organ systems, e.g., immunological disturbances; such aberrations, however, are primarily seen as consequences of autonomic and endocrinological adjustments during a stress response rather than causes of the symptom.
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So far, PEM has not been investigated within the framework of predictive processing. However, the findings reported by Boruch and co-workers seem to fit with functional brain aberration as the underlying mechanism
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Future studies in the field should specifically address the relevance of predictive processing for PEM experience in different patient populations by exploiting validated experimental paradigm, e.g., the “virtual hill bicycle” paradigm where sensory input (pedal resistance) and a priori-expectations (virtual hill slope delivered by virtual reality-googles) can be manipulated independently
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SNT Gatchaman said:
Post-exertional malaise – A functional brain aberration?
Bruun Bratholm Wyller

Comment on Exercise does not cause post-exertional malaise in Veterans with Gulf War Illness: A randomized, controlled, dose–response, crossover study (2024, Brain, Behavior, and Immunity)

Last paragraph —

If confirmed that PEM are best understood as a functional brain aberration, the clinical implications are large. As long as PEM is regarded a consequence of “peripheral” pathophysiological processes, it seems logical to avoid symptom-provoking activities for the fear of harm; indeed, the evolutionary “meaning” of salience signals is to promote avoidance of the situations that provoke them. However, if PEM is a consequence of too dominant a priori-expectations, the goal should be to “re-set” the expectations rather than avoid symptoms, for instance through behavioural approaches that include individually adjusted exertions in a way that facilitate associative learning. This should be further investigated in clinical trials which can be performed without undue safety concerns: The study by Boruch et al. adds to an increasing body of evidence confirming that physical activity is not harmful in conditions characterised by PEM (Tryfonos et al., 2024).

Link | Paywall (Brain, Behavior, and Immunity)
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o wow they are determined to get their money's worth out of that same old material

This is basically just trying to say PEM is a false belief

maybe with adding in that real nonsense theory about 'the expectation effect'.

Of course I think that the perfect paper that debunks the suggestions of the expectation effect is actually that same old one that has Knoop as part of it, Heins et al (2013):
The process of cognitive behaviour therapy for chronic fatigue syndrome: Which changes in perpetuating cognitions and behaviour are related to a reduction in fatigue? - ScienceDirect
Thread here: The process of CBT for CFS: Which changes in perpetuating cognitions and behaviour are related to a reduction in fatigue?, 2013, Knoop et al. | Science for ME (s4me.info)

The thread initially focuses on the part of the paper where there are graphs showing the objective activity and perceived activity.

Basically the various pseudophil ramblings in this try and put some spiel around people think that CBT 'made them less fatigue' based on it making them think they'd done more, when they hadn't. So they were surprised they weren't as tired - but only because they'd metaphorically actually only walked 1 mile and not 2, and thought this CBT must have therefore solved some specific type of fatigue 'response' to the 2miles.

But the graphs (and it gets a bit more complicated than this, as they have 'fast responders and slow responders' to the CBT separated out) show that everyone ended up at the same place with objective activity. No amount of thinking your way around it over the 4 time periods. Which are in essence measuring the 'ME/CFS' impact of this ie the fact you can't just 'increase' activity and still feel OK. Putting aside the PEM in between that may or may not have happened.

I'll underline that's them conning the medical profession, funders and patients into pretending they've fixed something when they instead brainwashed people into losing their calibration of what they'd done, to their advantage.

I can't help but emphasise that this same 'school' ie biopsychosocial then moved to decide to remove reporting any of the objective measures anymore. Papers since came up with every weak excuse under the sun as to why they chose poor subjective measures in unblinded trials (when that would be one of the only ways to make it near triangulated to be accurate), but really this shows that it is because there is no objective effect.

I can only assume because they found they could use this 'CBT tool' to programme in discrepancies in what people subjectively report (because they've been misled into thinking they've done more) instead, because they've brainwashed them or used social pressure/bias so that is higher than reality/objective measures.

It's basically fraudulent isn't it? except they get away with it because they are using the patient sample as the 'vessel' through which to insert this lie into their research - and you can't blame the patients for the fraud because they've been brainwashed/coerced/conned.

I also note that the patients targeted and situations created have always begun with those most vulnerable, and indeed the biggest power differential - hence the coercion being solidly involved. It hardly ever escapes me that the two areas of ME, where people have been actively campaigned against to be maligned, and soldiers who once enlisted are under more control than other citizens must be two of the most obviously vulnerable groups, and noone is picking up on it being sus/weird and that those who are attracted to such groups need to be viewed with extra oversight given other historical things we now look back and on and realise 'how did we not see that the wrong types would be attracted to places where vulnerable x, y, z are'. It is a potential huge ethical scandal to me so I'm always shocked outsiders don't pick up on this.


I knew that post-guideline certain individuals would try and attack the concept of PEM. And this new article is just the same blather with an 'insert a different word' really. I can't believe they'll use this and try and pretend it isn't just fancy words for 'hysterical woman/drama queen/hypochondriac' ie their attitude problem disguised, a sociology paper in them expounding what is behind the bigotry/mis-thinking rather than some sort of medical or scientific observation. Pure propaganda by literally hooking tropes together in sequence and one big claim, but it is all non-sequitur?
 
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Isn't GWI like Long Covid, in the sense that people have all sorts of different things? My understanding is that only a subset would have PEM, as with Long Covid. There's no point in testing exercise in people who aren't reporting PEM, which seems to be what they did. Since they found nothing, Wyller's conclusions or comments have no bearing on anything.
 
dave30th said:
There's no point in testing exercise in people who aren't reporting PEM, which seems to be what they did.
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Exactly. Apart from it being in the title, the discussion says:

Boruch et al said:
The degree to which our primary findings conflict with prior literature depends on the outcome that was measured. For instance, exercise-related symptom exacerbation is particularly well documented across CMI [Chronic multisymptom illnesses] populations, as indicated by our own laboratory studies involving Veterans with GWI and meta-analyses of acute pain and fatigue responses in people with ME/CFS and Fibromyalgia. Notably, the meta-analytic studies found smaller effects for studies measuring symptoms at earlier (e.g., <2 hours post) versus later (e.g., 4-72 hours post) timepoints, so perhaps the null findings in our study are explained by focusing on symptoms measured within one hour post-exercise. However, exploratory analyses of symptoms measured 1-7 days following exercise testing also failed to provide evidence of exercise-induced symptom exacerbation.
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PEM is difficult to manage because if I listen to my body, it can feel very capable of doing activities and I tend to be motivated as well. Later, I "discover" that I can't actually do as much as it felt like I would be able to do and that it was too much and is causing a higher symptom burden than I would have been willing to accept. This idea of having excessively negative expectations is contrary to the lived experience. If anything the tendency is strongly to underestimate PEM.

My impression is that, since patients can't trust how their body feels and what it's telling them, they tend to develop a strategy to minimize PEM that relies heavily on conscious effort, rules and memories rather than emotional state and current perception of the body's capabilities. This strategy is pacing. Outside observers might observe the thoughts and beliefs associated with pacing and misinterpret them as a maladaptive because it differs from the norm.

I'm also wondering if associative learning is inadequate when it comes to PEM because PEM is delayed with respect to the trigger so it becomes difficult to associate the trigger with the response.

Associative learning might work better with symptoms that occur during the activity, like fatigue.
 
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Future studies in the field should specifically address the relevance of predictive processing for PEM experience in different patient populations by exploiting validated experimental paradigm, e.g., the “virtual hill bicycle” paradigm where sensory input (pedal resistance) and a priori-expectations (virtual hill slope delivered by virtual reality-googles) can be manipulated independently
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There's a reason patients are so interested in explanations for PEM that involve basic physiological processes. Having PEM willl alter one's mental state (thoughts, beliefs, expectations, emotions, motivation, etc.) while these things don't seem to have any role in causing PEM. We live with PEM and know how it behaves.

Why bother trying to manipulate the patient's perception of the activity when there is no apparent correlation between that and PEM?

If the perception was important, it would be obvious.
 
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Hoopoe said:
If the perception was so important, it should be very obvious.
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And it has been tested - in the PACE trial.
Treatments aimed at changing perceptions did change (reported) perceptions, but made no difference to objective measures of disability.

The weird thing is that if the predictive coding model is right then the CBT therapist should be telling patients to expect exercise to feel really terrible and for muscles to be really painful. The brain would then be pleasantly surprised and want to do more exercise. Since when did CBT tell people to think things are much worse than they already do?
 
Jonathan Edwards said:
And it has been tested - in the PACE trial.
Treatments aimed at changing perceptions did change (reported) perceptions, but made no difference to objective measures of disability.
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Exactly! Always a lot of words about what could be if the stars align, but failing to ask the most central question: What experiments would confirm this, and how do they differ from the work that has already been done?
 
Hoopoe said:
PEM is difficult to manage because if I listen to my body, it can feel very capable of doing activities and I tend to be motivated as well. Later, I "discover" that I can't actually do as much as it felt like I would be able to do and that it was too much and is causing a higher symptom burden than I would have been willing to accept. This idea of having excessively negative expectations is contrary to the lived experience. If anything the tendency is strongly to underestimate PEM.

My impression is that, since patients can't trust how their body feels and what it's telling them, they tend to develop a strategy to minimize PEM that relies heavily on conscious effort, rules and memories rather than emotional state and current perception of the body's capabilities. This strategy is pacing. Outside observers might observe the thoughts and beliefs associated with pacing and misinterpret them as a maladaptive because it differs from the norm.

I'm also wondering if associative learning is inadequate when it comes to PEM because PEM is delayed with respect to the trigger so it becomes difficult to associate the trigger with the response.

Associative learning might work better with symptoms that occur during the activity, like fatigue.
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Precisely. All of this sticking of ideas on people is what is so terrible. It always feels like the opposite of what is actually going on and can’t have come from interviewing real people and actually hearing them

would it happen for other conditions that it is acceptable that they would say eg I push through and at the time feel really happy with myself for doing it then two days later am unable to wake up so I didn’t make the connection and some horrible person instead has this attitude of not listening to their words but treating them like a deluded person to be talked about as if this isn’t real insight into their condition- because it’s the disgusting part of how we’ve been approached and why we’ve got nowhere with understanding of the condition moving firward
 
Hoopoe said:
PEM is difficult to manage because if I listen to my body, it can feel very capable of doing activities and I tend to be motivated as well. Later, I "discover" that I can't actually do as much as it felt like I would be able to do and that it was too much and is causing a higher symptom burden than I would have been willing to accept. This idea of having excessively negative expectations is contrary to the lived experience. If anything the tendency is strongly to underestimate PEM.
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Exactly. Also if symptoms are a result of the stress response, how come i feel massively better when stressed?

bobbler said:
Precisely. All of this sticking of ideas on people is what is so terrible. It always feels like the opposite of what is actually going on and can’t have come from interviewing real people and actually hearing them
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But instead from listening to people who are tired. And who feel more tired after exercise, because they dont understand what PEM actually is. Everyone feels fatigued the day or two after they exercise more than usual. They think thats what PEM is.
 
Well, in my unscientific and totally subjective opinion of this “paper” (which is amazingly similar to the apparent level of understanding of ME by the author), what a complete, aromatically steaming heap of crap.

Edited for punctuation.
 
Bps beliefs - a functional brain aberration

I can’t believe the disgusting phrases these people think they can get away with pretending they aren’t designed to be bigoted and to incite insults
 
This author publishes a lot. He should consider publishing less, preferably nothing, since he is convinced of the wrong things and seems incapable of learning from feedback from people with lived experiences of the concepts that are only an abstraction to him.
 
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