Modulatory effects of cognitive exertion on regional functional connectivity of the salience network in women with ME/CFS: A pilot study, 2021, Manca

John Mac

John Mac

Senior Member (Voting Rights)
Highlights
  • •
    Cognitive effort can induce PEM and worsening of ME/CFS symptoms.
  • •
    PEM is associated with changes in functional connectivity of the salience network.
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    Increased right insular FC with frontal areas is associated with symptom worsening.
Abstract
Background
A common symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is post-exertional malaise (PEM). Various brain abnormalities have been observed in patients with ME/CFS, especially in insular and limbic areas, but their link with ME/CFS symptoms is still unclear. This pilot study aimed at investigating the association between PEM in ME/CFS and changes in functional connectivity (FC) of two main networks: the salience network (SN) and the default-mode network (DMN).
Methods
A total of 16 women, 6 with and 10 without ME/CFS, underwent clinical and MRI assessment before and after cognitive exertion. Resting-state FC maps of 7 seeds (3 for the SN and 4 for the DMN) and clinical measures of fatigue, pain and cognition were analysed with repeated-measure models. FC-symptom change associations were also investigated.
Results
Exertion induced increases in fatigue and pain in patients with ME/CFS, compared to the control group, while no changes were found in cognitive performance. At baseline, patients showed altered FC between some DMN seeds and frontal areas and stronger FC between all SN seeds and left temporal areas and the medulla. Significantly higher FC increases in patients than in controls were found only between the right insular seed and frontal and subcortical areas; these increases correlated with worsening of symptoms.
Conclusions
Cognitive exertion can induce worsening of ME/CFS-related symptoms. These changes were here associated with strengthening of FC of the right insula with areas involved in reward processing and cognitive control.
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https://www.jns-journal.com/article/S0022-510X(21)00019-8/fulltext
 
‘A common symptom’: I have not checked which clinical definition they are using, but surely PEM is a core symptom, and if they were looking at people who did not have this symptom, not all their sample had ME/CFS.
 
Andy said:
I've not read the paper but this seems counter-intuitive to me.
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Exertion induced increases in fatigue and pain in patients with ME/CFS, compared to the control group, while no changes were found in cognitive performance.
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I think a Melbourne imaging study of teenagers with ME/CFS found the same result (Sarah Knight was involved). People with ME/CFS are working harder to achieve similar results as those of people without ME/CFS. It's not sustainable - eventually they won't be able to keep up the quality of the performance, but the observation period probably wasn't long enough.
 
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I get visibly weak after long sustained mental activity. This seems very unusual to me. It doesn't make any sense that my limbs would lose strength, my gait become slow and insecure when all I did was mental activity. I also don't feel well in these circumstances but nothing too bad.
 
Exertion induced increases in fatigue and pain in patients with ME/CFS, compared to the control group, while no changes were found in cognitive performance
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This only means their measurement of cognitive performance is inadequate. I can't say for the rest but this is a huge flaw and huge flaws are not very encouraging as to the validity of the rest of the study.

Also why restrict to those two parts? Makes no sense to make such a decision without a valid reason.

Meh.
 
This may illustrate floor/ceiling effects in the cognitive tests used in study conditions.

For example I suspect I would score above average or average on a relatively time limited reading task, even though I have only managed to read one entire book in the last six years and that took me over six months. Pre ME onset I would read between four and six books a week even when working long hours in a demanding clinical and managerial post.
 
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Hutan said:
I think a Melbourne imaging study of teenagers with ME/CFS found the same result
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Here's the study I mentioned:
Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with CFS (2019) Josev

the 2021 study said:
(cognitive) Exertion induced increases in fatigue and pain in patients with ME/CFS, compared to the control group, while no changes were found in cognitive performance.
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the 2019 Josev study said:
Results revealed little evidence for a differential effect of cognitive exertion in CFS/ME compared with controls. Both groups demonstrated a similar rate of reduced intrinsic functional connectivity within the default mode network (DMN), reduced sustained attentional performance, slower processing speed, and increased subjective fatigue as a result of cognitive exertion. However, CFS/ME adolescents consistently displayed higher subjective fatigue, and controls outperformed the CFS/ME group overall on cognitive measures of processing speed, sustained attention and new learning. No brain-behavior relationships were observed between DMN connectivity, cognitive function, and fatigue over time. These findings suggest that effortful cognitive tasks may elicit similar levels of energy expenditure across all individuals in the form of reduced brain functioning and associated fatigue. However, CFS/ME may confer a lower starting threshold from which to access energy reserves and cognitive resources when cognitive effort is required.
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It gets complicated, there are lots of things potentially being compared. I'm not up to sorting it out just now.
 
Has anyone been able to access the full paper?

PEM induced by cognitive exertion is underexplored, or should I say it's even more underexplored than PEM induced by physical exertion so research into this is welcome.

Unfortunately, based on the abstract alone, it's hard to tell if they're looking at PEM-proper or at cognitive fatiguability (which is common in many other conditions, just ask anyone after a stroke or traumatic brain injury). Of course it's still worthwhile looking at cognitive fatiguability but it would be helpful if people made it clearer which of the two phenomena they're investigating.

It would also be useful to look at some disease controls at some point, anything where patients also complain of vague cognitive symptoms and brain fog would probably be suitable. Just to see if we're looking at ME-specific findings or something more general.
 
Ravn said:
Has anyone been able to access the full paper?

PEM induced by cognitive exertion is underexplored, or should I say it's even more underexplored than PEM induced by physical exertion so research into this is welcome.

Unfortunately, based on the abstract alone, it's hard to tell if they're looking at PEM-proper or at cognitive fatiguability (which is common in many other conditions, just ask anyone after a stroke or traumatic brain injury). Of course it's still worthwhile looking at cognitive fatiguability but it would be helpful if people made it clearer which of the two phenomena they're investigating.

It would also be useful to look at some disease controls at some point, anything where patients also complain of vague cognitive symptoms and brain fog would probably be suitable. Just to see if we're looking at ME-specific findings or something more general.
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The abstract does mention there was an increase in pain as well as fatigue.
 
I think it is important not to confuse cause and effect.

If there is increased afferent signalling, why wouldn't we expect increased salience network activity?
This may be necessary to maintain increased concentration during a cognitive task and it is that increased effort that is often perceived as fatigue.
 
Dolphin said:
The abstract does mention there was an increase in pain as well as fatigue.
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Yeah, but they didn't specify what sort of pain. The fatigue and headache combo after cognitive exertion is not unknown outside of ME. Plus they didn't say how long the symptoms took to resolve. My guess is they measured soon after the exertion but impossible to tell from the abstract. Guess no point speculating until we can read the full paper.
 
A problem I have is that when I am talking to medical professionals I sound much, much better than I really am. It is completely involuntary.

I call it being full of adrenalin though I don't know if that is what it is. It is the same effect as when I visit my grandchildren or go shopping (rare occasions!), I can't manage anything without it.

Byron Hyde says that he finds his patients are bright when he first sees them but after a few hours they start to fade. I doubt that these tests are long enough to counteract the adrenalin needed to do the test in the first place for many people with ME.
 
Mithriel said:
A problem I have is that when I am talking to medical professionals I sound much, much better than I really am. It is completely involuntary.

I call it being full of adrenalin though I don't know if that is what it is. It is the same effect as when I visit my grandchildren or go shopping (rare occasions!), I can't manage anything without it.

Byron Hyde says that he finds his patients are bright when he first sees them but after a few hours they start to fade. I doubt that these tests are long enough to counteract the adrenalin needed to do the test in the first place for many people with ME.
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‘Start to fade’ is a good description. If I attend a social event, either of 2 things can happen. Either I start to fade when everyone else is still raring to go or I don’t fade at all, but when I get home and go to bed the adrenaline is still coursing through my veins and I can’t switch off and go to sleep, so I’m exhausted the next day. The worst thing is if I try to carry on once I’ve ‘faded’. I know that I’m really hammering myself if I do that.
I can’t rest or sleep during the day, as if I do, I can’t get going again and feel sluggish for the rest of the day. I have to take my time in the morning and then keep going for the limited number of hours left until it’s time for bed.
 
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