These Australian researchers, overseen by Dr. Vollmer-Conna, begin their quest for  the source of  the cognitive difficulties in chronic fatigue syndrome  by turning things on their ‘head’ (pun intended)  a bit.

PLoS One. 2012;7(11):e49518. doi: 10.1371/journal.pone.0049518. Epub 2012 Nov 14.Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome. Beaumont A, Burton AR, Lemon J, Bennett BK, Lloyd A, Vollmer-Conna U.

They noted that each of the  cognitive abnormalities  in ME/CFS appears to be fairly mild but taken together  there are enough of them to perhaps turn them into something significant.

memory loss in brain

Cognitive tests reveal relatively mild cognitive problems which taken together can produce something significant

An Aside – The finding that the cognitive abnormalities test out as relatively mild in this disorder will  undoubtedly cause  people with really severe cognitive issues to shriek in dismay but it surely reflects the heterogeneity in our population.  There are people like me – who test out with some cognitive dysfunction but who are fine otherwise and people who literally can’t read anymore and  who probably don’t show up in many studies.

Also, few studies incorporate the issue of  cognitive post-exertional malaise into their designs.  Exertion is exertion. People with ME/CFS can ‘fake it’ for a while; they can make it through that first day of work or that first hour of testing OK; it’s the second or third or fifth day, or that second or third  hour, when things start to go south.  Most cognitive tests, though,  don’t capture ‘the fade’….

In any case, throw all the ‘mild’ issues together and you do have something significant.

The Cause

Figuring out the ’cause’ of those issues   (the slowed response speeds, the low working memory) hasn’t been easy. Since both of these are found in depression, depression seemed to be an easy answer given that, well,   ME/CFS is a depressing  illness,  but attempts to link the cognitive problems in ME/CFS to depression have failed. (Collective groan from the psychologists….)

In an earlier study this group found that  heart rate variability (HRV) tests explained sleep issues better than classical sleep tests (REM sleep, sleep architecture problems, etc.) so they tried that approach again, this time with cognitive issues.

The Study

Seventy people either with ME/CFS or as healthy controls did a series of self-report symptom and psychological  tests and cognitive tests designed to challenge various cognitive areas (working memory, sustained attention, response flexibility and speed) while they were hooked up to an electrocardiograph (ECG)  that measured heart rate.


The Missing Plateau

More broadly, our findings add to the growing body of evidence linking autonomic dysfunction to the symptomatology in this poorly understood disorder.

ME/CFS patient performance on accuracy and spatial working memory results were similar to the healthy controls, but they had slower reaction times.  In contrast to the healthy controls  heart rate which increased early in the test and then leveled off, the ME/CFS patients heart rate was increased  at baseline relative to the healthy controls, then increased, and then continued to increase throughout the test in the ME/CFS patients.

‘Post-Exertional’ Without the ‘Post’ – System Overshoot in ME/CFS

“a  loss of sensitivity to task difficulty”

In this case the study revealed chronic fatigue syndrome patients were over 10 x’s less  likely to return to their resting heart rates (which was in any case increased :)) in the first minute of the recovery period than the healthy controls.

dropping HRV

While the HRV readings ot the healthy controls levels off, those in people with chronic fatigue syndrome to drop, indicating a loss of system stability.

The authors called this inability to quickly return to a ‘baseline’ “a  loss of sensitivity to task difficulty”. The CFS patients’ systems continued on as if they were still engaged in a difficult task, when in fact they were not. We’ve see this kind of overshoot in which ME/CFS patients have trouble turning off a system once it gets turned on several times.

The heart rate variability (HRV) readings – which measure the robustness of  the autonomic nervous system  – were almost ‘significantly’ (p<.06) reduced in the ME/CFS patients.  (More variable is better with regards to heart rate variability.)  During the test that same ‘missing plateau’ pattern  returned, with the HRV readings dipping as the healthy controls were put under the stress of the cognitive tests but then plateauing, while those of the ME/CFS group dropped and dropped and dropped.

(Does it ever seem like you’re expending too much energy to produce a task? Muscles ever feel tightened as if you were about to try to pick up a truck when all you’re trying to do is pick up a book? I find that I often exert myself in easy tasks as if they’re difficult ones. )

Accuracy – Yes, Speed – No 

A correlational analysis found that the slower reaction times in the chronic fatigue syndrome patients were not associated with somatic symptoms, levels of psychological distress, degree of functional impairment, or even fatigue or energy, but appeared to be  ‘highly significantly’ related  to the reduced HRV readings.

This is a BIG finding.  People with depression or psychological distress can have reduced performance speeds and it would make sense that fatigue would at least be associated with reduced cognitive speed, but it wasn’t either; instead it was the reduced heart rate variability readings  – those findings that indicated the ANS was imbalanced, that were significantly linked to cognitive issues.

Having reduced performance speed doesn’t mean being a bit slower – it also means more difficulty concentrating and focusing. It takes a certain amount of  cognitive speed after all, to keep up with someone’s conversation…

This finding put the autonomic nervous system right in the bull’s-eye of a major symptom in ME/CFS.

More Work, More Energy Expended = More Fatigue

ME/CFS patients were as accurate as the healthy controls at the tests, but their slowness made the tasks more effortful – hence the much greater degree of mental fatigue reported by our slower processors – the ME/CFS patients.

The Cost of ‘Distraction’


The repeated loss of focus during a task means people with ME/CFS have to expend energy refocusing on the task that others do not

Interestingly, the ME/CFS group’s  response speeds were  all over the map, which appeared to reflect patients’ focusing on their task, getting their focus knocked off, and then refocusing again…(Note that the healthy controls simply focused on the task and responded.)

Imagine how much more energy it takes  to focus on something,  lose your way and then have to refocus on it do this again and again and again, instead of simply staying with the objective.  Nailing a key problem, the  authors aptly referred to the  ‘ongoing struggle to keep attention focused on the task at hand’ which  the chronic fatigue syndrome group had.

The Brain/Body Connection and a ‘Loss of Dynamic Flexibility’

Heart rate variability (HRV) tests in ME/CFS have indicated that the fight or flight side of the ANS (the sympathetic nervous system) is going gangbusters while the rest and digest side (the parasympathetic nervous system) is going to sleep.  That hyper-vigilant state – that constant feeling  of ‘being in danger’ – results in reduced activity of pre-frontal cortex –  which is involved in planning and organization –  and  ‘vagal control’ – which tells the body to ‘rest and digest’.

Under normal circumstances, the  prefrontal cortex tells the fear center of the brain, the amygdala, that everything’s OK – that you can quiet down now  – but if the brain is in hypervigilant mode; ie if it thinks its survival’s at stake,  it will blow off the prefrontal cortex’s signals to calm the body down.

The authors pointed out  that ‘increasing evidence’ suggests that chronic fatigue syndrome patients exhibit a kind  chronic, sympathetic nervous system based state of ‘hyper-arousal’  present even when they are asleep. ( I imagine  army sentries put out at their posts  waiting, waiting for the attack  without relief…..Something certainly is going to give at some point. )

Little wonder, the authors speak of a system that has lost ‘dynamic flexibility’  – an term that resonated with me.  Among other things, having ME/CFS  has been synonymous with a loss of grace and spontaneity  – a loss of a kind of ‘dynamic flexibility’ that was present before.

The Vagus Nerve

Why the inability to ramp down and turn off the ‘arousal’? It probably has something to do with the vagus nerve. It’s the vagus nerve, after all, that’s responsible for turning down the heart rate at the end of a task and telling the body to rest.  Several times the authors called the vagus nerve ‘sluggish’.  Let’s take a look at this interesting nerve.

 This novel finding supports our results obtained from HRV and indicates that CFS is associated with a significant loss of vagal modulation which becomes particularly apparent when dealing with challenging tasks.


The vagus nerves calming and rejuvenating effects are blunted in chronic fatigue syndrome

Derived from the Latin  word for ‘wandering’, the vagus nerve emerges from the brain stem and then ‘wanders’ all the way down to the abdomen, branching off along the way to receive information from and then regulate heart, lung, voice box, stomach and other activity. Every time your heart beats, every time you breathe, every bit of food you digest, and every time you move your muscles, you’re using the vagus nerve.

The vagus nerve generally doesn’t initiate activity, it regulates it. In service of the parasympathetic nervous system (i.e., the rest and digest system), the vagus nerve turns down the heart beat, reduces the breathing rate, lowers our  blood pressure,  stops abdominal motility in order to give food a chance to digest, etc.  The ying to the sympathetic nervous system’s yang, the vagus nerve is responsible for turning the fight/flight response off.

Next Up – we ‘re going to follow this thread a bit deeper over the next week or two. We’re going to look at cardiovascular issues and cognition,  check out the Dr. De Meirleir video on circulation, examine two models of ME/CFS and then wrap up with a look at stunning study that just might throw everything together.

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