Exercise alters cerebellar and cortical activity related to working memory in phenotypes of Gulf War Illness (2020) Washington et al.

M

Milo

Senior Member (Voting Rights)
Dr Baraniuk’s team. Full text here


Abstract
Gulf War Illness affects 25–32% of veterans from the 1990–91 Persian Gulf War.

Post-exertional malaise with cognitive dysfunction, pain and fatigue following physical and/or mental effort is a defining feature of Gulf War Illness.

We modelled post-exertional malaise by assessing changes in functional magnetic resonance imaging at 3T during an N-Back working memory task performed prior to a submaximal bicycle stress test and after an identical stress test 24 h later.

Serial trends in postural changes in heart rate between supine and standing defined three subgroups of veterans with Gulf War Illness: Postural Orthostatic Tachycardia Syndrome (GWI-POTS, 15%, n = 11), Stress Test Associated Reversible Tachycardia (GWI-START, 31%, n = 23) and Stress Test Originated Phantom Perception (GWI-STOPP, no postural tachycardia, 54%, n = 46).

Before exercise, there were no differences in blood oxygenation level-dependent activity during the N-Back task between control (n = 31), GWI-START, GWI-STOPP and GWI-POTS subgroups.

Exercise had no effects on blood oxygenation level-dependent activation in controls. GWI-START had post-exertional deactivation of cerebellar dentate nucleus and vermis regions associated with working memory.

GWI-STOPP had significant activation of the anterior supplementary motor area that may be a component of the anterior salience network.

There was a trend for deactivation of the vermis in GWI-POTS after exercise.

These patterns of cognitive dysfunction were apparent in Gulf War Illness only after the exercise stressor.

Mechanisms linking the autonomic dysfunction of Stress Test Associated Reversible Tachycardia and Postural Orthostatic Tachycardia Syndrome to cerebellar activation, and Stress Test Originated Phantom Perception to cortical sensorimotor alterations, remain unclear but may open new opportunities for understanding, diagnosing and treating Gulf War Illness.
 
InfiniteRubix said:
Are there any other illnesses that share this symptom?
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Possibly. Post-exertional fatigue (more so than would normally be expected) and exercise intolerance are reported for some other illnesses. Are they the same thing as we experience, as part of PEM? Who knows, the work hasn't been done to investigate it. Worth keeping in mind, I think, that it can be hard for ME patients to identify and express clearly what is occurring with them - I know it's only in the last 10 years or so that I've been able to talk with reasonable accuracy about what happens when I over-exert.
 
Andy said:
Worth keeping in mind, I think, that it can be hard for ME patients to identify and express clearly what is occurring with them
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It can be twice as hard from a doctor perspective to correctly interpret what the patient is describing. Often time, tired after exercise is viewed as ‘depressed’. The interpretation of that particular doctor will live in the patient’s chart forever. Same with OI. I remember going to my GP the first time i recognized i was feeling worse when vertical and a bit better horizontal. I had used her exam bed while waiting for her. After 10 minutes she came to the exam room and the first comment she had for me was a rude ’what are you doing there? You are not sick! Get up!’

‘Post-exertional malaise’ is not in the database of symptoms that doctors have used. And then PEM experience varies from one patient to another. We can see it here when patients describe in their own words what happens to them after exerting themselves.
 
InfiniteRubix said:
I totally agree - a vulnerable / exploitable reality.
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And the words don’t describe what we’re experiencing, yet we use them because we’re too exhausted and have no other phrase ready. “Malaise”? No, I don’t feel like the audience for a Jimmy Carter speech. It’s more like exhaustion, followed by episodic exhaustion, including brain fog, but if pushed further I can’t sleep yet am too tired to function, a bit further and I can’t digest food .... I believe that’s typical for us, not unusual. What word describes that? “Malaise”? “Crazy complaining psych case?” “Malingerer?” Uhh, no. Make that no.
 
Haven't read the paper in detail, just speculating about the PEM question.
An important clinical finding in GWI is post-exertional malaise with severe symptom exacerbations following physical, cognitive, emotional or other effort (Steele, 2000).
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I looked up the reference Steele, 2000 and it mentions "Feeling unwell after exercise or exertion". Could be PEM, or might not be. I wish people would be more explicit about what they mean!

So in the present study, is what they're actually looking at the unpleasant symptoms of OI, still set off by exertion but more limited in scope than full-blown ME PEM? Who knows, not enough detail.

It's interesting though that GWI seems to play out quite differently in different patients, and on objective measures.
These results suggest that the exercise stressor paradigm affected different neural mechanisms in the GWI phenotypes and that distinct neural networks may mediate the cognitive dysfunction, post-exertional malaise and exertional exhaustion in these veterans.
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Does anyone have sufficient working neural networks to compare this study with ME brain scan studies - do any of the dysfunctional regions overlap?
 
Ravn said:
Could be PEM, or might not be. I wish people would be more explicit about what they mean!
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I think this is such a new concept and so I'm not sure they know precisely what they mean.

Andy said:
Worth keeping in mind, I think, that it can be hard for ME patients to identify and express clearly what is occurring with them - I know it's only in the last 10 years or so that I've been able to talk with reasonable accuracy about what happens when I over-exert.
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Definitely. Many of us suffer cognitive dysfunction when in PEM and that makes it harder for us to observe and assess what is actually happening or find the words to describe it. By the time our language skills come back, we may not remember precisely because memory can be affected too.

It's only by discussing it with each other that the picture is becoming clearer as each of us remember & fill in tiny pieces of the same big puzzle. Sometimes I read something someone else said and it's like a light bulb coming on. They've accurately described something I couldn't even begin to articulate.
 
I think the way the Bansal Score Chart operationalises PEM (see point 2) is perhaps the best way we have yet: https://www.me-pedia.org/wiki/Bansal_Score_Chart_for_ME/CFS
  1. Need 8 or more from 13 points to confirm CFS/ME with an absolute requirement for some form of PEM.
  2. Delayed (>12 hours) prolonged (24hrs+) PEM gives 3 points while an immediate PEM (<3 hours) of >24 hours gives 2 points. Immediate PEM (<3Hours) lasting <24 hours gives 1 point.
  3. Non-restorative sleep with difficulty initiating and maintaining this at night time and present >5+ nights per week gives 2 points. The non-restorative nature of the sleep disturbance must persist with hypnotics. Non-restorative sleep without difficulty initiating and or staying asleep gives 1 point.
  4. Impaired concentration that is reduced further by external stimuli gives 1 point.
  5. Reduced short term memory with word finding difficulty gives 1 point.
  6. New headaches (>2/mth & different in character from previous headaches) give 1 point.
  7. Myalgia affecting multiple groups and exacerbated by mild exertion gives 1 point.
  8. Arthralgia affecting several joints (with stiffness >1 hr but no swelling) gives 1 point.
  9. Postural instability (NMH/POTS) - feeling unstable on standing/sitting gives 1 point.
  10. Hypersensitivity to sounds and lights (smells as well with nausea) gives 1 point.
  11. Sore throat with cervical tenderness/recurrent flu-like episodes gives 1 point.
  12. The fatigue, neurocognitive problems, myalgia, arthalgia, hypersensitivity issues must be significant and cause disability for >50% of the time.
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Thus patients with less clear PEM require more symptoms elsewhere to make up for it, and some of the features of PEM are captured in other domains (e.g., where brain fog worsens with exertion, hypersensitivities, myalgia after exertion, etc).

Something like that for PEM, combined with some of the DePaul Symptom Questionnaire elements might help diagnose the illness more accurately.

For me, the prolonged and delayed nature are really strong indicators of something beyond usual exercise intolerance, and I'd also say that it's usually disproportionate to whatever exertion triggered the flare/crash/relapse (in the sense that small amounts of exertion cause relapse but also in that cognitive exertion causes physical worsening, and vice versa).
 
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Although unproved as yet I still think that something similar to a diabetes blood sugar spike is a way to 'explain' PEM in pwME. (I think Montoya mentioned this)
ie that there is a build up of x and/or deficiency of y which eventually 'tips' you into PEM.

the issue of fatigue is a red herring (IMO).

in diabetes:
Symptoms of a blood sugar spike include:
  • frequent urination
  • fatigue
  • increased thirst
  • blurred vision
  • headache
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Sly Saint said:
Although unproved as yet I still think that something similar to a diabetes blood sugar spike is a way to 'explain' PEM in pwME. (I think Montoya mentioned this)
ie that there is a build up of x and/or deficiency of y which eventually 'tips' you into PEM.

the issue of fatigue is a red herring (IMO).

in diabetes:
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Red blood cell deformability issues are also found in diabetes too BTW, albeit OMF findings probably need more replication I guess.
 
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