Exercise alters brain activation in Gulf War Illness and ME/CFS. Washington et al. 2020

[John Mac]

Full title:
Exercise alters brain activation in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract

Gulf War Illness affects 25–30% of American veterans deployed to the 1990–91 Persian Gulf War and is characterized by cognitive post-exertional malaise following physical effort.

Gulf War Illness remains controversial since cognitive post-exertional malaise is also present in the more common Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

An objective dissociation between neural substrates for cognitive post-exertional malaise in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome would represent a biological basis for diagnostically distinguishing these two illnesses.

Here, we used functional magnetic resonance imaging to measure neural activity in healthy controls and patients with Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome during an N-back working memory task both before and after exercise.

Whole brain activation during working memory (2-Back > 0-Back) was equal between groups prior to exercise.

Exercise had no effect on neural activity in healthy controls yet caused deactivation within dorsal midbrain and cerebellar vermis in Gulf War Illness relative to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients.

Further, exercise caused increased activation among Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients within the dorsal midbrain, left operculo-insular cortex (Rolandic operculum) and right middle insula.

These regions-of-interest underlie threat assessment, pain, interoception, negative emotion and vigilant attention.

As they only emerge post-exercise, these regional differences likely represent neural substrates of cognitive post-exertional malaise useful for developing distinct diagnostic criteria for Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

https://academic.oup.com/braincomms/article/2/2/fcaa070/5885074

The Science Times covers the story here:
https://www.sciencetimes.com/articl...-war-illness-distinguished-brain-activity.htm

Also:
https://medicalxpress.com/news/2020...udy of,brain activity after moderate exercise.

A similar study by the same authors discussed here:
https://www.s4me.info/threads/exerc...gulf-war-illness-2020-washington-et-al.13542/

 

[Marky]

"If confirmed, then deep brain stimulation of the midbrain, or transcranial direct current stimulation or magnetic stimulation of cerebral cortical regions may be considered as therapeutic options for ME/CFS and GWI in the future" - I just have to chuckle at this. It reminds me of something you would be tempted to write in the conclusions-part at uni, when u have no idea what else to say. I remember getting top grades at an experiment review, where I knew all the things i was citing was pure speculation and none of the authors cited really knew what the evidence behind the terminology they had made was.

Not to take anything away from these guys though, I just dont see how deep brain stimulation is gonna magically fix ME/CFS

 

[Amw66]

mmm - there is a therapy based on this i think - is this product placement?

 

[Andy]

These regions-of-interest underlie threat assessment, pain, interoception, negative emotion and vigilant attention.

Hmm, looks like something that the BPSers will love to see.

If confirmed, then deep brain stimulation of the midbrain, or transcranial direct current stimulation or magnetic stimulation of cerebral cortical regions may be considered as therapeutic options for ME/CFS and GWI in the future

Of course, the little detail about whether these changes are cause or effect of ME will be important.

 

[Simon M]

I do like the idea of using sub-maximal exercise and measuring pre/post differences in brain function during a cognitive challenge.

The sample size was big by the standards of fMRI studies (38 ME/CFS; 80 GWI, 31 Healthy) but still small.

I'm not sure that the sub-maximal test, based on 25 minutes at 75% age-predicted max heart-rate, is equivalent for GWI & ME/CFS (SF36 physical function c45) vs healthy controls (SF36=85). It was likely to be much harder for the sick groups. That said the differences for GWI & ME/CFS are often in opposite directions, but at the results for one of the groups could be down to higher exercise intensity.

"If confirmed, then deep brain stimulation of the midbrain, or transcranial direct current stimulation or magnetic stimulation of cerebral cortical regions may be considered as therapeutic options for ME/CFS and GWI in the future" - I just have to chuckle at this. It reminds me of something you would be tempted to write in the conclusions-part at uni, when u have no idea what else to say.

Authors have no place suggesting treatment without replication.

Of course, the little detail about whether these changes are cause or effect of ME will be important.

And that.

I think we need to see a replication before there is any grounds for talking about therapeutic approaches .

BTW, this group has used fMRI (single day, no exercise challenge) to find differences between ME/CFS and controls (and GWI, I think). I don't ever recall seeing that one replicated.

 

[Andy]

I think we need to see a replication before there is any grounds for replication.

I'm not following this bit.

 

[Simon M]

I'm not following this bit.

Sorry, no grounds for talking therapeutic approaches without a replication. Corrected now

 

[Forbin]

In the study, functional magnetic resonance imaging (fMRI) revealed that the brains of veterans with GWI and those of patients with CFS behaved differently when performing the same memory task after moderate exercise. Veterans with GWI showed a decrease in brain activity in the periaqueductal gray, a pain processing region within the brainstem, and in the cerebellum, a part of the brain responsible for fine motor control, cognition, pain, and emotion.

On the other hand, patients with CFS showed increased activity in the periaqueductal gray and in parts of the cerebral cortex related to maintaining vigilance and attention. In healthy subjects, these areas of the brain had no changes at all.

https://www.sciencetimes.com/articl...-war-illness-distinguished-brain-activity.htm

So, wouldn't this actually then be a biomarker for both ME/CFS and GWI?

...or might be if the CFS recruitment criteria wasn't just Fukuda.

Subjects had history and physical examinations to ensure their inclusion by meeting Chronic Multisymptom Illness (Fukuda et al., 1998) and Kansas (Steele, 2000) criteria for GWI, Fukuda criteria for ME/CFS (Fukuda et al., 1994) confirmation of sedentary lifestyle for control subjects (less than 40 min of aerobic activity per week) and exclusion because of serious medical or psychiatric conditions such as psychosis.

https://academic.oup.com/braincomms/article/2/2/fcaa070/5885074

 

[Hutan]

Lots of potential for bias with fMRI studies
Variability in the analysis of a single neuroimaging dataset by many teams, 2019, Botvinik-Nezer et al
The paper says nothing about any effort to control for 'time of day' variance.

Fukuda criteria, Chalder Fatigue questionnaire used - surely Baraniuk knows better than that?

There's a big difference in the gender percentages of the ME/CFS group compared to the other two groups. There's also a difference in BMI. Together those two differences might result in some systematic error in spatial assumptions about regions of interest (ROI) in the brain. Corrections were made for age and gender, but such corrections can be a source of error when the sample populations are different.

There are enormous differences in the incidence of 'major depression' (0% health controls; 18% ME/CFS; 50% GWI), with PTSD having a similar range of incidence. Different co-morbidities are likely to confuse any comparisons.
Edit - having got to the end of the paper, I see the authors acknowledge this:

The high prevalences of PTSD and depressive symptoms in GWI may also have contributed to the opposite trends for midbrain activation after exercise in ME/CFS and GWI.

Potential problems aside, the findings in the discussion look worth picking through, and I agree with Simon that pre and post-exercise studies with a cognitive challenge are a good approach to fMRI studies.

Exercise either increased activation or deterred deactivation of BOLD signal in the right middle insula and left Rolandic operculum during the cognitive task in the ME/CFS group. This activity may be interpreted as a component of post-exertional malaise with increased perception of bodily discomfort while attempting to maintain attention during the 2-Back cognitive challenge.

It would be good to see future studies record levels of perceived pain/bodily discomfort during the scans and look for associations between that and the results.
And for some analysis of the impact of major depression on results (i.e. did having major depression explain results better than the GWI/MECFS split?)

 

[Hutan]

General patterns of BOLD activation for the 2-Back > 0-Back condition after corrections for age and gender were similar between HC, ME/CFS and GWI groups before and after exercise, and showed activation of frontal parietal executive control regions as anticipated for this working memory task

The study is maybe as interesting as much for the differences it didn't find as what it did find.

Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) depicts changes in deoxyhemoglobin concentration consequent to task-induced or spontaneous modulation of neural metabolism.

So is BOLD just a contrast signal - it doesn't tell us about the absolute level of blood oxygenation?

I don't know how long the cognitive task was for; it would be interesting to see what would happen if the task was for a relatively long time. Also, of course the scanning was done lying down - so it misses the impact of being upright on cognitive tasks.