There’s nothing like an exercise test to bring out the best, or rather the worst in chronic fatigue syndrome (ME/CFS), and if one exercise test is good, two are surely better. In “Submaximal Exercise Provokes Increased Activation of the Anterior Default Mode Network During the Resting State as a Biomarker of Postexertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome“, Rayhan and Baraniuk at Georgetown University used two (submaximal) exercise tests to explore the effects of exercise on brain functioning in ME/CFS.
The study used blood oxygenation level-dependent (BOLD) MRI scans in the brain before and after exercise to assess brain activity. Brain regions that became either activated (more oxygenated) or inactivated (less oxygenated) were identified as nodes, and then the nodes were stitched together as networks. Networks are important to identify, as most tasks require the activation of multiple brain regions or networks.
The authors wanted to determine if any nodes in a network popped out after exercise. One did.
Damage to one part of a network can impair the functioning of the entire network. In fact, the nerve denegation hypothesis asserts that damage to one network node can spread to other parts of the network. The authors noted that while broad networks may function suboptimally across several diseases, specific diseases might be characterized by damage to specific nodes in a network. Hence the search for specific nodes that might be damaged in ME/CFS.
One note on the so-called submaximal exercise tests used in the study. The tests required that the participants in the study bicycle for 25 minutes at a “submaximal” rate of exercise.
A “submaximal” state of effort was purportedly reached when a participant first hits a heart rate calculated to be 70% of their maximum heart rate (220-age=submaximal heart rate) and later hits 85% of the expected maximum heart rate needed to reach a person’s anaerobic threshold.
Studies suggest, though, that the anaerobic threshold – the point at which a greater reliance on anaerobic energy production occurs – is reached much more quickly in ME/CFS then in healthy people. Something called chronotropic incompetence could also result in people with ME/CFS having significantly lower maximum heart rates than expected. The “submaximal” heart rates and submaximal exercise prescriptions used in this study, then, might be closer to maximal heart rates and maximal exercise efforts in people with ME/CFS. Suffice it to say, participants got a good workout!
Results
There are several ways things can go wrong in the body. You can have too much or too little of something. You can have something that just sits there – doesn’t respond at all. You know you really have a problem, though, when you have what this study found: a complete reversal of normality. In this study, a part of the brain that became deactivated in healthy controls after exercise got turned on in the ME/CFS group.
In what the authors called “a remarkable discordant finding”, blood oxygenation levels (an analog of activity) declined in the medial prefrontal cortex after exercise in the healthy controls but shot up in the people with ME/CFS.
The authors called the upregulation of the default mode network a “remarkable discordance”.
This finding was so strange that the authors suggested it might constitute a biomarker for ME/CFS. It was all the more interesting because except for this region of the brain, the blood oxygenation levels (e.g., the activity levels) in the rest of the ME/CFS patients’ brains were lower than normal after exercise. The activation of the medial prefrontal cortex, in other words, stood out like a sore thumb.
The Gist
- Using a two-day exercise challenge, Georgetown researchers found a part of the brain that gets turned off in the post-exercise period actually gets turned on in people with ME/CFS.
- The authors proposed that something called the default mode network which is associated with rumination and internal assessments had become activated in the post-exercise period in ME/CFS. (It was not activated in the pre-exercise period.
- Because the DMN has to be turned off in order for action to take place, its activation in ME/CFS made tasks more difficult to complete. The authors called the process task-related deactivation.
- The study didn’t measure rumination so we don’t know if was occurring but if you’re experiencing rushing thoughts or are having trouble getting your mind to settle down you may be ruminating.
- Other findings from the study such as reduced blood flows overall, and particularly to regions of the brain involved with autonomic nervous system regulation, interception, pain perception, sleep, and movement could play a role.
- While the authors didn’t say so, the exhaustion of energy reserves and post-exertional malaise seem likely to lend themselves to a protective state in which task avoidance, internalization and isolation make sense.
- As similar findings have shown up in Gulf War Illness, it’s possible that DMN activation post-exercise is a feature of all fatiguing and exertionally intolerant diseases.
Rumination is the antithesis of action. In order to get a task done, you have to turn off your default mode network and focus on the task at hand. In what appears to be something of a recipe about how NOT to get things done, the exercise challenge turned the DMN on in the people with ME/CFS. The authors called it “task-related deactivation”.
Nor is rumination thinking about something – it’s something more on the order of – in Landmark Education parlance – getting thought by something. Meditation, on the other hand, is the opposite of rumination: it actually turns off the DMN. The psychedelic clinical trial underway in fibromyalgia is attempting to turn off the DMN.
Rumination wasn’t assessed in this study, so we don’t know if exercise caused people with ME/CFS to ruminate more. Rumination is associated with patterns of thought that don’t have, as one psychologist puts it, an “off button”. Experiencing “racing thoughts”, feeling like you can’t shut your mind off, dwelling on specific topics – are all signs of rumination. If the richness of life consists of getting outside yourself and experiencing the outside world, getting stuck in a kind of ruminating, internally oriented state isn’t a great thing.
Empirically and energetically, though, the kind of internalization the finding seems to make sense. Sustained exercise is an energy-depleting event that leaves many people with ME/CFS turning to less stimulating environments to rejuvenate themselves. In my experience, too much exertion narrows my world down substantially. Uncomfortable and painful body sensations make it hard to claw my way back to a connection with the outside world and focus on tasks.
A Gulf War Illness exercise study found similar results – suggesting that this process may play out in other exertion intolerant, fatiguing diseases. Several studies suggest that fatigue and mental exhaustion are associated with increased DMN activity.
That connection results in a vicious circle many of us are well acquainted with: the more fatigued you are, the more the DMN gets activated, making it harder to complete tasks, which we try to overcome with more effort, which produces more fatigue and so on.
Reduced blood flows to parts of the brain involved in many of the major issues in ME/CFS (pain perception, autonomic nervous system regulation, sleep, movement) might present a picture where DMN activation, perhaps as a protective measure, might be expected. By turning off task-oriented behavior, one wonders if DFM activation is just another form of the “sickness behavior” that causes people to isolate themselves during infections.
Conclusions
Once again, an ME/CFS (as well as a Gulf War Illness) exercise study upends norms. In what the authors called a “remarkable discordance”, a part of the brain that became deactivated after exercise in healthy controls actually got turned on when people with ME/CFS were experiencing post-exertional malaise (PEM).
Since turning on that part of the brain increases rumination and makes completing tasks more challenging, the exercise challenge appears to have enhanced task completion in the healthy controls while inhibiting it in the people with ME/CFS. Given how difficult completing tasks is when stuck in a PEM state, the finding made sense.
Reduced blood flows overall, and in particular, to parts of the brain involved in autonomic nervous system regulation, sleep, pain perception, and movement may have set the stage for DMN activation.
As a similar pattern has been found in Gulf War Illness, DMN activation after exercise may be a feature of exertion challenging and fatiguing states in general.
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All of these studies validate if your local doctor and specialists cared to learn about them. But they also say something else. The medical profession and medical science even at highest levels did not believe the collective stories of thousands and they would or will continue to do so except for high technology and money to use them.
This would jibe with my experience. In my early subclinical years of ME/CFS, I could exercise *almost* normally, but it wouldn’t give me the same boost in (task) energy afterwards like it used to. I kept trying though.
I definitely ruminate when in bad PEM, but it makes me more exhausted. Not being able to shut my brain off means no relaxing at all, no sleep, etc. It is all part of the tired-but-wired thing in my experience, & it is very connected to my body being pumped full of adrenaline (SNS triggering fight or flight mode). Even though I’m physically doing nothing, I feel as bad or worse than when I am, because my mind is going so fast. It’s also not possible to focus on things that otherwise help me to relax (like light reading or watching TV). And, it can literally last for days for me.
Also, while any exertion can trigger it to start (even a short conversation), oddly when I was still able to do so, taking a short walk would actually help calm it down some. It seemed that once the adrenaline started pumping into my body as a result of PEM, then it would keep pumping until I used up my entire supply. And at that pt, in the midst of adrenaline pumping onto me, walking would help to use up that supply; not that depleting the body’s supply of adrenaline is a good thing – it’s not, but it was the only way for me to be able to relax.
(And, as backwards as that sounds, it makes sense, because it takes more energy to trigger the parasympathetic nervous system to calm thigns down than it does to trigger the sympathetic – fight or flight…..so no energy due to PEM also means no ability to turn fight or flight into rest & digest; hence ongoing adrenaline & ruminating, etc).
So, if it’s part of this, & I could be wrong, because I only had the energy to skim this & because I did see that they did not study ruminating, it seems that it is backfiring (at least in my case).
Tammie, you describe my experience exactly. Not being able to shut down your brain and not then being able to sleep or rest at all. I try to meditate but my brain races so much that I actually find it more stressful. Everything seems to be back to front with this illness. Interesting that you found walking helped. I used to love walking but bedbound now. I pray for all of us that someone will find answers to PEM.
I have the same experience with meditation, though I find it worth continuing to try, because sometimes there are a few seconds of “turning it off.” You can meditate lying down in bed; not necessary to sit up in a chair, which is usually too painful. Lying down paying relaxed attention to the breath can give a little relief too. Very slowly turning your head about 30 degrees side to side — very slowly, and not going for range — , while lying in bed, can often activate a very deeply relaxing breath.
I think the problem with trying to meditate can often be the “trying”, and “concentrate” conjurs up all sorts of effort which makes the effort backfire.
This for me as well. It makes no sense and usually hits me at night… whether to do with histamine dump as many say attributed to MCAS.
I just get more and more exhausted until I crash.
Very interesting hypothesis.
You just accurately described myself for me, something I usually can’t do with any coherence. Thanks for that. I know it’s not nice to have this disease with this effect of wired/tired but it is nice to know others understand fully.
The DMN (I call it the Default Mode Not-work) is coming up more and more in all kinds of psycho-neuro issues — depression, anxiety, etc. – all characterized by rumination. Psilocybin and ketamine “turn off” the DMN by disconnecting the medial PFC from what they call the “subgenual anterior cingulate cortex.” By contrast, strengthening the connection of the cingulate to the *dorsolateral* PFC can help regulate control over DMN, and this is what psychedelics can accomplish by increasing overall connectivity.
That being said, if that were the only problem, all we’d have to do is take some ketamine or mushrooms and be cured, but unfortunately that doesn’t seem to be the case. Most likely these disruptions in brain functioning are again more symptomatic than causative, except in the sense that, once dysregulated, they then go on to contribute to or perpetuate the overall syndrome. There’s still a long way to go, I’m afraid, but possibly fixing the DMN’s over- and under-connectivity with the various brain regions (medial and dorsolateral PFC, respectively) with psychedelics could help nudge things in the right direction and help other aspects of the syndrome normalize.
Dang, now I know why it is SO hard to get anything done most days. Endless lists, psyching myself up, ‘finding the Fun’, schedules, timers…..and still it’s somehow late afternoon and all I’ve managed is the washing up. If that.
I’ve tried meditation, though that’s like trying to drive around a supermarket in a Ferrari, with the constant wired+tired. Though it does sound like if I managed to switch off the DMN I would simply be a puddle of nothing.
Maybe DMN activation is yet another symptom of PEM? It’s hard to imagine”rumination” causing so much difficulty as CFS patients in PEM face. It still could be a visible, diagnostic hallmark though.
It would be just one piece of a complex puzzle.
Hi Cort, and hi everyone.
Since I became friends with a 65 year old woman 18 months ago who was properly diagnosed with Fibro, cfs, Raynaud’s syndrome , venous insufficiency and FOUR MORE… I felt there was NO WAY that these could each have a unique cause, and I set about reading physiology, nutrition and research papers, as Cort does so well. I bother him once in a while with my unlicensed logic. I read Naviaux and Younger thanks to this site and I try to work in ideas that veer from my own.
I wasnt convinced that there was brain inflammation in cfs but now I am.
I tried to find one weak link in a systemic intolerance and that info contradicted itself from one symptom or nutrient to the next.
So the logical route was to zoom out and understand how systemic dysregulation of the various components of homestasis. The one thing that never stopped nagging me was kidney dysfunction since it controls the blood electrolytes and those fuel exertion then recovery. System-wide.
My position now is that , yes, some sort of Dauer state or hibernation seems to keep you at or near anaerobic metabolism which generates only 1/13th the ATP, and tonnes of lactic acid and I believe alerts * low* level inflammation and cortisol into to a high state– a dangerous state.
But why?
Like covid19, which is a novel flu, after all, the previous flus that perhaps many if you have suffered from in the past indeed
blocked vascular receptor sites,
even though they were not the ACE2 preferred in BOTH covid 19 AND SARS. Previously they preferred sialic receptors a2-3 or a2-6 or both, research reports. But they mutate. Its all a big accident. Truly.
Vascular.
The research community is now uniting around the signs that covid is about all 3 sizes of blood vessel and — in my opinion especially — the microvessels in the kidneys. I believe that adrenal fatigue RESULTS, from autoimmune perpetual self- attack –on something– and I even read today that on occasion a brand new/unique protein can form on DNA during the cytokine storm and in cancer. It may even be intentional by the cell.
It is called a neoantigen, because its a new and foreign protein, and the suggestion was that the immune system knows about it, makes a self-antibody, but likely its in most vascular endithelial cells … so thats a never-ending story.
If you woukd lije to know what I have a hunch us the biggest kidney dysfunction in this whole mess, it is calcium management. Endothelial “”repair” is just a bandaid in this case, starting with calcium deposition to strengthen the veins where damaged. One paper examines using vitamin K2 to treat covid infection along with Vitamin D and (maybe zinc). I mean yes zinc shuts down Replicase, I just dont recall clearly if they included it.
The problem would be that calcitonin is suoposed to assist the parathyroid gland when that gland tells the bones to release or store calcium. If there is enough, then excess should be urinated out. If the kidney is functioning correctly. So the key idea here is that the virus attacks all smooth muscle having the preferred receptor and that that blockage plus the cytokine storm, if there (was) one impairs most kidney function by altering microvessels.
I am writing based on Cort’s review above. Why would a peculiar cause affect the WHOLE system? Because the endothelium RUNS THROUGH the whole system. I learned that the cells that comprise the tight-junction blood-brain-barrier are ENDOTHELIAL cells, contrasting with leaky gut which is epithelial TJs.
So to my mind (and pleasev do read up and dont take my educated guess as truth) , the flu storm that triggers endothelials to launch cytokines and control clotting while you feel bagged and feverish, could CAUSE the leaks in the BBB. And even sustain it if this neoantigen exists. Any stress (even positive– exercise) could trigger instant escalation of chronic inflammation.
But why would that trigger all the brain problems including the anomaly above? The SET POINT.
In a flu fever , the Hypothalamus responds to PYROkines from the endothelium. So the Hypothalamus registers this as a need for fever. A new *thermostat* set point is set temporarily which forces anaerobic metabolism because the mitichondria circle the wagons at that fever point to starve the virus and thus slow replication. The immune cells are anaerobic. Neat.
But such a temperature is not sustainable. You would die. The brain does not allow the metabolism to overheat it. It MUST function. Or you will die.
This is because you would now have endothelial dysfunction (constant cytokines and clotting tendency etc) against a phantom enemy,
THE BRAIN CAN NO LONGER COOL WELL USING VASODILATION when there is system-wide endithelial dysfunction. The endotheial cells are supposed to CONTROL vasodilation
Enter frequent ischemia and frequent hypoxia. And the skeletal muscles? The hypothalamus MUST keep them from generating heat. Aerobic metabolism exertion is likely to violate the set point quickly.
That is my current understanding of physiology and research papers. So a new *hypothermic* set point is established by the hypothalamus to gaurantee that 1. the brain will not overheat and 2. the iower level inflammatiion will ensure basic survival. . So then your cooler body STILL inhibits energy production for viruses by not being 99 degrees F, but can still continueLOW(er) LEVEL inflammation.
The hypothalamus automatically shuts down aerobic exercise. It must. Textbooks state that the brain can not sustain a change in temperature of even one whole degree, plus or minus. Damage will occur. If you didnt believe that the autonomic part of the brain was self-serving for making first dibs on oxygen and glucose, maybe this brings it all home.
Lets give this new hypothalamus martial law a name: “The cold treatment”
My muscles want to run.
(“I dont”)
Please can I have some thyroid hormone to trigger normal metabolism and warmth?
(“No way”)
But exercise would get me healthier!
(” I cant hear you”.)
So my whole point here, which is to interpret the study with wonderful direction from Cort, is that of course that relaxing part of the brain he mentioned gets active paradoxically. Because either we dont yet understand it… OR… it is well aware that if it drains the resources on purpose by its activity… or lets say… hoardes them
away from the cognitive brain and voluntary exertion, then you wont even WANT to continue… then this will maintain the safe hypothermic set point and at least it minimizes brain heating or damage with almost neutralized vessels that dont help the heart push blood or help perfuse the muscles anyway. Not for long.
The vessels would definitely be ischemic instead of actually doing their job of cooling the brain.
So I do feel that its SURVIVAL, or as Cort said, cells barely clinging to life. Its not their choice, though. It is all coordinated by the Hypothalamus-Pituitary-Adrenal axis. If the hypothalamus is not able to achieve homeostasis system-wide, it still has the option if allostasis. That is, unhealthy, but at least consistent level control.
What you need to recall from all the exertion tests that Cort has described, if you wish to yest these ideas is that you shut down BEFORE It’s necessary. If your brain waited until necessary that might mean brain damage or even near-death.
Is that any consolation? Not really.
But it shows us two possible key targets of therapy:
autoimmunity against those neoantigens ,
or if that does not prove to be true,
Lowering and managing inflammation through herbs and mushrooms. Its the first and most important step. End the emergency and the Dauer state of self-defense might start to ease up.
Fibro literature has said that the greatest help came from anti-inflammatory drugs (or Lyrica) only that kind anti-inflammatory medication long term will destroy you. But herbs are wise.
Smooth muscle like organs and vessels can remain closed (clenched) with very very little ATP. Whereas skeletal muscle can have up to 4 mitichondria and requires far more endrgy to flex from a resting state. I nean this comment with high respect for each you:
So your cognitive brain, emotions, skeletal muscles and pain relief systems feel like dying. Not enough energy for them. The autonomic no longer cares at that point. Looking out for Number 1.
Dumb question of the year.
What ARE flu symptoms anyway?
Answer:
-low energy
-often fever.. or chills
-sore muscles (lactic acid maybe?)
-weakness
-some kind of nauseating toxins in your digestive system. Your own, perhaps.
So do you really “have” the flu, or did a flu merely trigger a worst case metabolism scenario to save you and FORCE you to rest and wait?
Chris
My husband and I call that state “tharn”. It was a term used in the book Watership Down to describe a rabbit facing the oncoming headlights of a car. The rabbit would just stare as if nothing was happening and didn’t get out of the street.
I often get stuck just staring out to space but really my mind is running. Rumination is probably a much better word for a human being.
Never thought I’d see a watership down reference here! I remember that term too.
More silflay, less tharn
Love these Watership Down references. My people!!
For me it’s that “sickness behavior” aspect that hits home — feeling like a small child with the measles just wanting to pull the covers over my head and be left alone. Impossible to deal with anything “out there.” Accompanied by all the signs of a bad flu except for me no fever — ever. My face and neck feel very hot to me but no temperature is registered.
And this starting up not with the exertion/exercise itself — but hitting me like a locomotive hours later. 6-8 hours I’d say. This makes one so wary of EVER over-exerting, to begin with, that all sorts of deconditioning has got to be going on in our bodies over time.
Anyway — and don’t yell at me for this — it makes me wonder about trauma. Our symptoms are not in our heads, and the origin (definitely for me) is infectious and viral — but it sounds a lot like traumatic injury, also. I can tell the difference between my CFS/ME and, in contrast, an occurrence of depression — which used to be terrible until my depressions responded to certain meds and now it is not a problem. But it almost sounds like the exertion is — in our case — triggering a kind of ptsd-like reaction of trauma-avoidance. And PEM is definitely a traumatic experience.
Just some reactions — but HURRAY for another clinical finding that signals our condition. And yes, doctors in general are definitely NOT interested in learning this stuff.. But the conditions in which they are forced to work don’t encourage curiosity and keeping up with new research that isn’t mainstream yet. They are trying stay afloat themselves in the constant financial pressure and squeeze that governs medical practice in general these days.
25 minites sub maximal “was it cycling”? allready forgot and i am laying down.
they have once again taking an ME/cfs group that can still do “a lot”! Going for testing takes energy to! and the 2 times the test, 4 times up and back, get dressed and washed, eating, drinking, and all the stuff. I do not believe that excercise testing brings for all of us the best up. what about the 25% group, what about the 100% or 98% bedridden group, what about the group that never makes it to a specialist, a clinic? Can simply do not such testing. The most studys are on the 75% group and even then… where are we in the 25% group? what brings for us the best out? And those that are declining and declining? Those that stay on the same level? those that get over years (somewhat) better?
Yes, they are taking a group that can do at least some exercise. They’ll have more papers out on how they did at that but they did say that the ME/cFS group failed to reach the heart rates expected.
At some point. we’re going to get the results from the severe ME/CFS big data study that Ron Davis did. They looked at just about everything they could. Going to be interesting.
Yes, that’s the thing! So many of us are too sick to get to the doctor a lot of the time, much less participate in an exercise study! I have an exercycle which I enjoy riding, but I am rarely able to do it. When I am able, 5-6 minutes on it will usually put me down aching and miserable for the rest of the day, sometimes for 2 or 3 days. I think doctors and researchers don’t even see the sickest patients— they’re at home, too sick to go anywhere.
It is a nasty beast, and impossible to explain to other people— usually we don’t look that sick. The 1st of March will be 34 years of it for me. I’ll tell you what— people who live with this are STRONG. You, all of you, are amazingly strong—we have to be to deal with this! Cort, thank you so much for the time, effort, and intelligence you devote to this website— it is much appreciated.
Hi cort,
can you please put in your blog or summary the amount of people tested. it takes so much effort for me to look up. And again (ofcource i am glad with every research), but again it is in only a verry small group.
and they say; “The dynamic increase in activation of the anterior DMN node after exercise may be a biomarker of postexertional malaise and symptom exacerbation in CFS.” they “like” to say a fat may be, in all the articles because they just do not know.
why can they do not work together for a few really big studys and replicate them? with so little numbers, it is a waste of money and there are so many studys with so little numbers. probebly because of there ego to find IT…??? In the past i heared Anthony Komaroff allways say, ME is real, thousands of studys… in really research terms like oncology or so, they laugh with us/them. And the many numbers of criteria and the tiny studys. In this way, they will never take us serious i am afraid. Not even mentioning if they will really find things and when.
Study says 34 people with ME/CFS and 24 control subjects
Thanks. That’s actually a pretty good size for a brain scan study.
This just seems like another nothing burger. What actionable information does it provide to improve the neuroimmune condition we know as ME/CFS?
🙂 What – you want the answer? I agree it’s not an earthshaking finding; it’s not like finding that immune cells are invading the brain. It does do a couple things that I can see: a) it demonstrates that PEM is real and impacts brain functioning. While that’s obvious to you and me it’s still not to many in the scientific community. By doing that it validates this strange after exertion effect that’s really only been studied in ME/CFS (and therefore is probably not accepted by many). It also points to a part of the brain that appears to have gone awry – which might be amenable, I suppose but don’t know, to rTMS (?) or some other treatment or drug that might be able to tamp down the activation there. It also appeared to find low blood flows to the brain in general – which validates other study findings – and in particular low blood flows to certain parts of the part – which again might potentially be amenable (I don’t know) to some sort of targeted treatment. Finally, the fact that it suggests that exertion tosses people with ME/CFS into a ruminative state – raises the possibility of recognize that happening when it does – and trying to get out of it or reduce it.
This is very promising, but what about creating a test that can be safely done on all patients? I imagine only mild patients can participate in such a study. I can’t even stand up for more than 5 minutes, so an exercise test is out of the question for me and for thousands of others with moderate to severe ME.
For me this was very exciting. Over the last 20 years or so I have tried to make a health scale for self-evaluation. Using symptoms doesn’t work. There are too many. Using just an overall lump is useless. Over time, I developed a scale that, in its bottom half, where I get to play a lot, is all about what I call ‘making.’ At 1, I can’t ‘make.’ At 2, I can do little things but without a plan (I call it Putting One Foot in Front of the Other.) At 3, I can take on a project, then collapse and that’s it for the day… and so on. If the definition of ‘rumination’ were less pejorative, I would say I do a lot of rumination at the bottom part of the scale. (For me, ruminating itself is not bad, it is just that it is hard to lead a practical life–very, very hard, almost by definition hard–while in the ruminating soup.) So–how cool! To find this study and Cort’s excellent summary that seems to validate this scale. I’m glad I trusted myself to make and use it, because it sounds pretty crazy without this information–to think of CFS/ME as fundamentally about my relation with the outside world, my willingness to make an imprint on the outside world. To ‘make,’ in the artistic sense. Just the one thing– the 1 is scary but the lower parts of the scale aren’t all bad. Maybe they are the ‘opposite’ of meditation, but that soup sure seems to have some meditation-like treasures in it. I feel I have found some wisdom down in there. You?
I was in this study – in 2016! I was told that I was one of the last participants and also that I was possibly the sickest. For sure, simply packing and traveling to the hospital put me in the early phase of PEM, before I started on the bicycle. Participants didn’t go home overnight; we stayed in the hospital. When I joked about going dancing that night, the researchers took me seriously because some other participants actually had asked about things to do in the area. In my case, I could barely walk by the time it was done, and it took me several weeks to recover from the “sub-maximal” effort.
Overall, I suffered a lot, but I also learned a lot – and contributed to understanding of ME/CFS. I’d recommend participating in such research to anyone who can. I’d also recommend that researchers 1) recognize that we’re often in early-stage PEM before the exercise starts and 2) find and use less-extreme methods of inducing PEM, so more people will want to contribute.
Hi Tracey
Thanks for taking one for the team and doing the study. Let’s hope all this research gets us closer to treatment.
Regards Andy
I totally understand your early pem with pakking and getting there. And point 1 and 2 is really needed. Point 2 also for the bedridden ones. what did you learn from it? your anaerobic treashold? other things? i al glad you recovered from this tests because i can imagine some do not. thanks!!! i hope they learn your point 1 and 2 and go on with that.
Good for you! It sure takes a long time to get these things written up and published doesn’t it?
To be fair, Baraniuk et al. have published other results from this study earlier. It’s also fair to note that it still took years for those earlier publications to come out. I think the try-everything approach championed by Ron Davis and now accidentally put in motion by the spread of ‘Long COVID’ is the only way we’ll see timely results.
Konjin, I’m sorry I can’t neatly summarize what I learned. Some tidbits include: the way medical research gets done, Baraniuk’s ideas about many things, whether I meet various criteria for different conditions (GWI yes, fibromyalgia no), that I’m subtly more sensitive to pain while in PEM, …
One of my several motivations for participating was to get the results of the 2-day CPET for my disability application. I couldn’t imagine cycling to exhaustion, as at Workwell, so this was a better alternative. (Nonetheless, the ‘sub-maximal’ effort was so hard that I cried at the end of each session.) Anyway, the other results from the various tests they gave me also helped my application (which, maddeningly, was denied).
Yes! Totally agree we need less-extreme methods. I hope you made a full recovery after participating in this study and thank you so much for participating to help all patients. I walked just a little more than normal in April 2018 and still haven’t recovered from that. Haven’t been able to go for a walk since. I went from being able to walk 30 minutes a day, drive my kids to and from school as well as a small grocery shop, to being mostly housebound for the last 3.5 years. So participating in a study like this can have devastating consequences for some people with ME. I hope the researchers are aware of this and don’t accept patients who they feel might not recover from such a test.
Very interesting, thanks for the write up Cort.
I wondered if doing that significantly exhausting test would have caused participants to worry whether they’d overdone it… mind you this is not so different from real life for us, constantly worrying about having overdone things.
Interesting to know whether the same effect comes after a very short walk (or whatever is considered sustainable for the individual)
I’m trying to decide whether I ruminate or not (as described in your blog as racing or obsessive thoughts etc.) There have been days where I have been tired yet wired but that happens when I take a double dose of Modafinil or if something is especially troubling–which isn’t so often.
Love this looking into to what is happening in the mind during exertion and post exertion (PEM). As for myself, I wake, usually after the pain meds kick in, with a batch of energy and focus which dwindles as the day progresses. Often I get to my ‘off’ button before bedtime.
Mostly my default state of mind is rather like mindfulness with hardly any rumination going on. I do feel frustrated when I contemplate what I want to do as opposed to what I am able to do.
I know that stress (like doctor’s visits) can quickly deplete energy–and my accelerating heart rate backs this up. Perhaps tamping down ANY kind of stress, whether mental or physical, can help with energy.
I also notice that if I do next to nothing for one day, the next I have extra energy–rather like a battery that needs some time to charge.
This is a very interesting topic to ‘ruminate’ on… 😉
The ruminating mind…the ruminating mind…the ruminating mind…
I’ve always been “busy-minded.” Since I became ill and more isolated, I have suspected that I ruminate even more than before. (Though it is possible rumination was always going on in the default network, and I was just not so conscious of it.)
So, I posted about ketamine last week. Going into ketamine, I did not know that one thing it does is suspend rumination, so no self-fulfilling prophecy here. But my #1 observation afterwards? It stopped rumination.
Rumination may be bad because of the energy (and blood flow) it requires. It also may be a damaging mental state, as it creates anxiety and may get us stuck in negative-bias patterns.
Anyway, I don’t want to sound like a ketamine salesman, but again in this thread it became applicable.
(To take one second to add to “nothing burgers” and “wild hares”? I think ski sickness is the clue to explaining CFS.) (Did I just lose all my credibility?)
Could you explain what you mean by that? Thanks!
Did the participants in Thai study complete a VO2 max test to begin with as this would help to gain a better understanding of how intense the submaximal exercise was for these people. It is not suffice enough to use the formula 220-age for these individuals and we need to move away from this. It does not allow us to understand the impact of submaximal exercise. Also did the authors report Watts for power output. In a recent trial of mine, some of my participants could not even complete five minutes of exercise at a submaximal level and we standardised this by them all competing an initial VO2 max test.
I assume they didn’t. They’re more brain researchers than exercise researchers and it looks like they just used that standard formula. There’s been quite a controversy over the use of submaximal exercise tests in ME/CFS and how submaximal they actually are. They are going to report on the exercise aspects of the study.
Exactly! Instead of “rumination” my idea of this problem is it is like having a number if small planes (thoughts/stuff I need to figure out and do, etc) circling around above the airport, but I cant seem to get them down to land. I cant focus on just one and get it down—ie accomplish the associated task. I end up doing so little, being in a constant state of procrastination, so to speak. I am distracted and distracted, leaving so much undone. I can still “think” and be oriented in reality ok, it is just operationalizing that is being scattered to the winds.
Cecilia, Some doctors might suggest trying an attention deficit drug to help that. A friend of mine developed the need for such drugs as he became older, because he has so much trouble focussing, but he’s just as intelligent as ever. He started taking something at about age 55.
Surely this study only shows what is obvious – when people are exhausted they will feel awful and seek rest ? If it were ethical to study healthy people who were pushed past their limits you might find the same result.
Actually you probably wouldn’t. The reason that the authors called the DMN finding a “remarkable discordance” is because the results were not expected or obvious at all. Submaximal and maximal exercise studies have been done in many illnesses and this type of result has not shown up before. it and the postexertional malaise it was assessing appears, at this point, to be mostly found in diseases like ME/CFS and GWI.
Maximal exercise tests, by the way, push both healthy people and people with illnesses to the edge of exhaustion. Those challenges – which last at most about 10 minutes and slowly ramp up the exercise needed – may be less challenging that than this study which required 20 minutes of exercise at a pretty high rate. This was a submaximal test but since they used sedentary healthy controls they were surely pushed hard.
Really interesting to read all the comments.
My doctor won’t allow me to participate in an exercise study because she fears it would permanently reduce my functioning. I’ve had ME since 1995.
But recently I took a nuclear stress test for the heart with an adrenaline like substance injected to simulate activity. Because of my ME (but the cardiologist said he does it a lot with other patients too), they injected an “anti” drug to “stop” the effects of the adrenaline at the same time. Idea being, I suppose, to prevent PEM.
Whatever it was, I survived fine and didn’t get any PEM. My only side effect was worry about anything nuclear being injected into anyone’s body including mine.
But I wonder what that second agent was, to “stop” the effect of the adrenaline, and whether that could help ME patients at all.
Probably not; someone probably would have recommended it by now. But just mentioning it here anyway.
It stopped the PEM – that is really interesting. I wonder what the drug was.
I’ll try to find out. Plus I’ll ask my CFS doc if my perception about it was possibly off.
This all helps make more of my experiences understandable to a better degree. Still, after decades of no longer being able to work, and yet no Social Security ever forthcoming, as I haven’t made it to age 62 yet, it can be anxiety provoking, knowing how sick I have been, and not knowing how things will unfold as I wait for SSI when I turn 62, having given up the multiple trying battles to win benefits, and having run out of my own money years ago, except for what others have shared with me now and then. It is hard to be stigmatized and treated the way we are as sick as we are.
I’m in the same boat as you! Catch-22 limbo. Nigh-impossible to explain.
Cort, I don’t know how you do it, but your articles are amazing, and get better and better.
Thank you.
I have a difficult time when I read “sickness behavior”
Behaviour being as if it is something within a person’s control.
Probably not a good example, but is like calling vomiting “sickness behaviour.” Not a helpful descriptor.
“not dying behaviour” but also “not living behaviour”
So tired of this all, thank you for not giving up on helping us.
No, as I understand it, “sickness behavior” is something that is genetically programmed into all mammals. It’s why cats go away and hide when they are dying. In an extreme state of bodily injury or illness, the organism shuts down to conserve strength. It’s what we do when we have a severe infectious disease like measles or flu. The disease is serious, but the sickness behavior is a programmed response to that situation. Of course you can’t get upland run around or play scrabble or write a paper, and no one would expect you to. But for us with ME, this shut-down seems to occur when there’s no obvious extreme insult or traumatic injury or infectious disease process going on. But our brains say that it is going on and that the situation is extremely urgent. I am not AT ALL saying that this is “all in our heads.” I’m saying the opposite — that when the brain reacts that way, no one can help entering a state of being prostrated and feeling extremely ill. And this study might be showing that the brain is reacting that way — with programmed sickness behavior — but in response to what would normally be only a comparatively mild degree of exertion. Something is triggering that extreme shutdown that normally is programmed to happen only with very severe and life-threatening conditions. Maybe. But the point is, sickness behavior in science isn’t something voluntary or controllable.
Hi Cort, what an interesting article – the discussion of ruminating is really interesting since it was such a massive feature of both bouts of CFS Ive had. I’m going to do a mini-test on myself to look at SpO2 levels before and after exercise. Landmark Education also caught my eye.
What had most impact however was the discussion of the DMN – it explained why I’ve had such a problem with meditation – clearing my mind is always a huge challenge and after 7-8 years of daily sitting it’s just as problematic as it was in the beginning.
In the last para before your conclusion you mention DFM – I can’t find a reference to this anywhere else – did you mean DMN?
Thanks, as ever.
@Sue Townsin: my meditation teacher told me to meditate lying down. It is easier. She also told me not to “try”, which runs counter to what meditation is about, but to “allow”. I use a mantra. I don’t know how people can meditate without one. I do think it helps, though. Especially when I can’t sleep in the middle of the night. Slowly moving my head very slightly from side to side before starting meditation (lying down) also helps to calm thoughts down. Maybe these things will help you too.
I know an increasing feeling of tension (“wired”) that gets stronger the longer I am active and often the point where I reach an energy limit coincides with also feeling wired-up. A friend with fibromyalgia described sth similar (getting wired up during activity).
Interesting article. IIRC, the prefrontal cortex also involves planning & decision making – both of which are near impossible when you have PEM. I wonder if the oxygenation increases as a compensatory mechanism?
P.S. I think you’ve referred to the Landmark organisation before. Very disappointing to see a cult quoted on HR.
The healty controls in this group relaxes after exercise, because they now from experience that exercise is good for their health. No rumination.
The CFS people start ruminating after exercise, simpy because they have learned from very negative experiences in the past to expect a “crash” after exercise. They have been traumatised by previous experiences, and THAT is the cause of the rumintation, not the exercise per se.
This study is groundbreaking. Before, most chronic health disorder research (like CFS, FM, Gulf War, etc) fell into two distinct camps: physical pathology or psychiatric. You don’t know how many years I’ve wasted trusting well-intentioned doctors and psychotherapists slowly convincing me my widespread pain, fatigue, and motivation issues were simply major depression, or, depression manifesting as physical symptoms. I have lived in several states across the US and that has been my typical experience at over 50 doctor’s offices since 2004 when my nightmare begun – “we believe your pain is ‘real’- here, have some Cymbalta.” Zero capacity to think outside of the box or dig deeper.
Now, there is finally an established link between these two worlds- physical pathology in the brain and psychology/neuropsychology via the Default Mode Network. For me, the research that has emerged in recent years on the DMN and depression and chronic pain provides the most hope.
After I push myself, I feel exhausted and frozen on the couch, it’s almost like I’m an animal trying to hibernate. Endless rumination about what I’d like to be doing if I had energy, anger and negative emotions that I’ve ended up like this, and of course, fear, and the repeated mantra in my mind that overrules everything, “rest, you need to rest.” Now, there is science that seems to identify the me the rough mechanism that causes this catastrophic feedback loop. At the very least, this is a critical piece of the puzzle.
I do not understand comments calling this finding a “nothing burger.” First of all, it’s quite offensive to the researchers and trial participants that have dedicated time and precious energy. Second, this is how science works, in slow steps. We are not ever going to wake up one morning and read “X found to cause CFS; cure being developed soon.” The chronic diseases Cort writes about are multisystem, complex disorders- the chicken or the egg problem to the nth degree. I know we are all suffering, but we need to celebrate these important steps, not criticize them for not being enough.
Such a simple thing but I’ve noticed that when I’m in PEM, I just cannot get off my phone. My head starts hurting more, I don’t eat or drink and forget my supplements. Its literally happening now. I know everything I need to do to recover from a crash and in what feels like self sabotage I do the opposite.
My career (when I was well enough to work!) is in wellbeing and mental health. I’ve sometimes felt shamed for my insomnia from professionals since sleep hygiene is something I teach. And getting off your phone, taking rest breaks, meditation etc are all in my life’s work. And yet I fail so often in PEM. I’m grateful to this study for at least providing validation for why. As for the phone, I sometimes feel my brain keeps me scrolling to stop me doing any real activity.
My little timer has made all the difference in the world.
For me the list is endless as to what can be done. Businesses need to wake up and smell the coffee to the changes that are needed. But if you want to take care about yourself, mindfulness is the best way. I can recommend the best guide for beginners – net-bossorg/mindfulness-by-julia-hanner – worked for me very well.
Thank you for pointing out that the exercise level, where they were clearly trying for some nuance between ME/CFS people and not-ME/CFS, still may have resulted in a misleading comparison. Am I understanding aright that it is possible that the ME/CFS people were nearer ‘too much’ and the controls were more likely to be at ‘just right?’ In which case is it possible that a subsequent study could find “people turn off their Default Network Mode when they have the Goldilocks level of exertion and turn it on when they have too much AND for ME/CFS people the ‘too much’ level comes on much sooner.” ? So everyone turns off their DNM at ‘just right’ and everyone turns it back on at ‘too much,’ but where ‘just right’ and ‘too much’ lie depends on a host of other factors we just don’t know yet. I’m not saying this to negate the interest in the research–I am very excited by this. Mostly I’d just like to know whether I am reading this clearly. And, yes, ok, if I have a bias I’d like to de-pathologize the DNM a bit. I have found some amazing treasures there.
Oh, yes, Cort, you wrote this above. (Copied below) So.. if I understand you, healthy people, pushed to the wall, don’t turn on the DMN?. There is no tipping point for them?
You: The reason that the authors called the DMN finding a “remarkable discordance” is because the results were not expected or obvious at all. Submaximal and maximal exercise studies have been done in many illnesses and this type of result has not shown up before. it and the postexertional malaise it was assessing appears, at this point, to be mostly found in diseases like ME/CFS and GWI.
Maximal exercise tests, by the way, push both healthy people and people with illnesses to the edge of exhaustion. Those challenges – which last at most about 10 minutes and slowly ramp up the exercise needed – may be less challenging that than this study which required 20 minutes of exercise at a pretty high rate. This was a submaximal test but since they used sedentary healthy controls they were surely pushed hard.
I wish that authors off all of the studies that use exercise as a precursor would note that they do so because ANY form of activity can lead to PEM. Otherwise they can seem to point out only exercise intolerance and not the impact of activities of daily living.
Like the term Post Exertional Malaise, we would do well to find another term to describe this discordance of the Default Mode Network other than “rumination.” “Ruminating” would so easily be interpreted by many to be “anxiety” and lead to unhelpful psychological diagnoses and judgements rather than furthering understanding of the impact of any kind of “pushing through” for people with ME/CFS.
I write that because of my growing understanding of my mother (bless her soul, gone 12 years now) as I age with ME/CFS and EDS. She had so many of the disabling same symptoms I have but hers were diagnosed as psychological. It’s no wonder the “treatments” didn’t help: they weren’t recognizing or treating the root causes.