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.

Decoding the 2-day Cardiopulmonary Exercise Test (CPET) in Chronic Fatigue Syndrome (ME/CFS)

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!


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.

discordant ME/CFS brain

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.


The authors proposed that a radical perturbation in something called the default mode network, (DMN) had occurred. The default mode network is most activated when a person is at “wakeful rest” and is not focused on the outside world. Instead, the brain is kind of ruminating; thinking about what’s going on, thinking about others, thinking about themselves.

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.

Letting the Sun Shine In? Psychedelics Are Being Trialed in Fibromyalgia


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.


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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With just days left in HR’s year-end (and year-beginning) donation drive, a big thanks to the over 500 people who are keeping HR on the web this year.

Health Rising is drawn to discordant findings like bees to honey, and the exercise studies seem to bring them out. From muscles that don’t turn off, to energy production that plunges, to brains that stubbornly stay activated, Health Rising has explored many unusual findings in these diseases.

If being informed about the discordant findings that make diseases like ME/CFS/FM, and long COVID so unusual spikes your interest, please support Health Rising.






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