Intra brainstem connectivity is impaired in chronic fatigue syndrome, Barnden et al., 2019

[Deleted member 3253]

https://www.sciencedirect.com/science/article/pii/S2213158219303924

Abstract:

In myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), abnormal MRI correlations with symptom severity and autonomic measures have suggested impaired nerve signal conduction within the brainstem. Here we analyse fMRI correlations to directly test connectivity within and from the brainstem. Resting and task functional MRI (fMRI) were acquired for 45 ME/CFS (Fukuda criteria) and 27 healthy controls (HC).

We selected limited brainstem reticular activation system (RAS) regions-of-interest (ROIs) based on previous structural MRI findings in a different ME/CFS cohort (bilateral rostral medulla and midbrain cuneiform nucleus), the dorsal Raphe nucleus, and two subcortical ROIs (hippocampus subiculum and thalamus intralaminar nucleus) reported to have rich brainstem connections.

When HC and ME/CFS were analysed separately, significant correlations were detected for both groups during both rest and task, with stronger correlations during task than rest.

Strong hippocampal connections with midbrain and medulla nuclei were detected for ME/CFS. When corresponding correlations from HC and ME/CFS were compared, ME/CFS connectivity deficits were detected within the brainstem between the medulla and cuneiform nucleus and between the brainstem and hippocampus and intralaminar thalamus, but only during task.

In CFS/ME, weaker connectivity between some RAS nuclei was associated with increased symptom severity. RAS neuron oscillatory signals facilitate coherence in thalamo-cortical oscillations. Brainstem RAS connectivity deficits can explain autonomic changes and diminish cortical oscillatory coherence which can impair attention, memory, cognitive function, sleep quality and muscle tone, all symptoms of ME/CFS.

 

[Jaybee00]

Hmmm. They don’t suggest any treatments in the paper.

 

[lansbergen]

When corresponding correlations from HC and ME/CFS were compared, ME/CFS connectivity deficits were detected within the brainstem between the medulla and cuneiform nucleus and between the brainstem and hippocampus and intralaminar thalamus, but only during task.

Could fit.

 

[MyalgicE]

Surprised that they selected cohort using Fukuda criteria rather than CCC or ICC.

 

[Trish]

Surprised that they selected cohort using Fukuda criteria rather than CCC or ICC.

Would you be able to contact them to explain the problem with Fukuda?

 

[Ravn]

Surprised that they selected cohort using Fukuda criteria rather than CCC or ICC.

Yes, it's disappointing that Fukuda remains so popular.

Is anyone up to providing a plain English translation? The conclusion is about all I could understand, and even that only in part.

5. Conclusions

In ME/CFS, connectivity is impaired within the brainstem RAS [ed.: reticular activation system] and from the brainstem to key subcortical structures. This may explain many of the symptoms of ME/CFS. In ME/CFS, multiple hippocampal connections to the midbrain cuneiform nucleus and the medulla are enhanced, suggesting the hippocampus has a compensatory role for the impaired connections.

 

[Philipp]

Seems interesting. I do not know how much fMRIs actually tell us, is anyone able to elaborate a bit on that? How do I have to interpret 'during task' in this context, is it something like 'we challenge this part to do xyz and measure what happens' or is it more like 'we wait till it has to do sth and take measurements' since the brainstem is used in a lot of regulatory operations. Sorry if it is explained in the full text, I am going with the whole too-tired-to-actually-read-but-someone-else-will-have-the-same-questions-as-me-right-now justification on this one.

As far as I know it is also common in brain conditions for unusual connections to be compensatory or otherwise counterintuitive, so... anyone here with a degree? Is it cool if I tag @Woolie because I'd like to hear his interpretation?

 

[Jonathan Edwards]

It looks to me the right sort of study to do. I find interpretation of MRI very hard and need to look at the details. But I think it is worth us going over this very carefully. It may be very important.

 

[Hutan]

https://www.s4me.info/threads/hyper...m-abnormality-in-cfs-2018-barnden-et-al.5032/

Probably worth re-reading this thread on the 2018 study. Jonathan got about as excited as I've seen him about that one.

(I believe Barnden did these studies in conjunction with the Griffith people, and, while Fukuda was reported, there may have been a requirement for PEM? Just a vague recollection, I'm probably wrong.)

I'll link to the Emerge conference material on this study when I find it.
Edit - not much on the Emerge conference thread.
But here's the link to Emerge's You Tube channel - the Barnden presentation is on Day 1 (click on the arrow on the right).

 

[MyalgicE]

Would you be able to contact them to explain the problem with Fukuda?

Will definitely ask why as I’m interested to know.
Might be patronising of me to explain that to the authors of the ICC and CCC and their colleagues!

 

[MyalgicE]

Yes, it's disappointing that Fukuda remains so popular.

Is anyone up to providing a plain English translation? The conclusion is about all I could understand, and even that only in part.

I might not be up to it but I certainly intent to try!

 

[Cheesus]

https://www.s4me.info/threads/hyper...m-abnormality-in-cfs-2018-barnden-et-al.5032/

Probably worth re-reading this thread on the 2018 study. Jonathan got about as excited as I've seen him about that one.

In the above thread, @Jonathan Edwards said (my bold):

For me the message is that this change is not due to inflammatory damage but due to a change in the way the brain is being used. The authors suggest it is secondary to something going on in the brain stem and that would make sense. The problem in the brainstem is also unlikely to be inflammatory in the usual sense because the brain stem is a small structure and even a minimal dose of inflammation there tends to wipe out function to the extent of coma.

Could this be the "something going on in the brainstem"? If so, I find it very exciting that we're beginning to connect tangible abnormalities together.

 

[alex3619]

I might not be up to it but I certainly intent to try!

My guess is it might be funding related. They might have been told that funding was more likely to be approved if they used Fukuda. It would be nice to find out for sure though.

 

[Mithriel]

Problems with the brainstem have been suspected since the 80s so this is very promising.

 

[Sid]

In CFS/ME, weaker connectivity between some RAS nuclei was associated with increased symptom severity.

Sounds plausible. As discussed years ago on the other forum, the RAS is involved in wakefulness/arousal, sleep, attention. If I recall correctly, a previous study found a correlation between brainstem neuroimaging alterations and pulse pressure, which would link in with problems with autonomic control we experience.

 

[Jaybee00]

I agree that this may be an important paper. I am just not optimistic that there will be any way of fixing this. The track record on treatments for other neurological diseases is not so good.

 

[Jaybee00]

No need to open and replace anymore.

https://www.medicalnewstoday.com/articles/241215.php

 

[Marky]

I love this study too!

One thing I wondered is what exactly is meant by "connectivity impairment"?

 

[AliceLily]

The mention of impaired muscle tone really stood out to me because I have never related to this part of my ME as neurological.

I had a significant change in that I have never been able to tone up my muscles properly since my ME onset. Every time I try I get very sick with PEM.

 

[Cinders66]

I like the description they use, given there’s debate on this.

1. Introduction
ME/CFS is a common, debilitating, multisystem disorder of uncertain pathogenesis, for which there exists evidence of dysregulation of the central nervous system, immune system and cellular energy metabolism (Carruthers et al., 2011).