The most primitive part of the brain, the brainstem – a part of “the reptilian brain” – doesn’t get much respect in medical research. VanElzakker pointed out that most brain scan studies focus on the upper, more highly developed parts of the brain. Because brain imaging techniques can’t effectively capture the upper and lower parts of the brain, these studies often miss the brainstem.
The brainstem may be “primitive” in the sense that it was one of the earliest parts of the brain to develop, but that doesn’t mean simple, and it certainly doesn’t mean unimportant. Just the opposite, in fact. In this case, primitive means fundamentally important.
Located at the bottom of the brain where it meets the spinal cord, the brainstem is the first recipient of all the sensory and “motor” signals from the spinal cord. It regulates very basic functions – like breathing, heart rate, blood pressure, digestion, alertness, sleep – the fundamental stuff you really don’t want to go wrong.
If you want to walk or move your arm, or type on a keyboard, you need your brainstem to do that. Coordination, balance, equilibrium and muscle tone – these fine-tuned processes essential to movement – are all regulated by the brainstem. Severely damage your brainstem and you’re pretty much toast – destined to live out what’s left of your life in a care facility.
Lastly, the brainstem is densely packed with mast cells – an emerging problem in ME/CFS.
Most ME/CFS brain imaging studies have focused on the upper part of the brain, but one Australian researcher, Leigh Barnden, has been bucking the trend.
One study found neuronal damage in the brainstem which could be causing autonomic nervous system problems.
Another study which found impaired communication from ME/CFS patients’ brainstems to other parts of their brain suggested the same. Interestingly, the study also found what appeared to be a compensatory response – increased signs of myelination in the sensorimotor cortex of the brain. Barnden believed the sensorimotor region was bulking up in an attempt to understand what the wonky brainstem was telling it. Barnden suggested those hard-to-understand signals from the brainstem could explain some of the problems with movement in ME/CFS.
Barnden’s next study found inadequate communication between the brainstem and other parts of the brain (vasomotor region, hypothalamus and prefrontal cortex) that regulated autonomic nervous system functioning in ME/CFS.
Neuroimage Clin. 2019; Intra brainstem connectivity is impaired in chronic fatigue syndrome. Leighton R Barnden,a,⁎ Zack Y Shan,a,b Donald R Staines,a Sonya Marshall-Gradisnik,a Kevin Finegan,c Timothy Ireland,c and Sandeep BhutaC. 10.1016/j.nicl.2019.102045
This year, Barnden, our brainstem pioneer, is at it again. His Oct. 2019 study, “Intra brainstem connectivity is impaired in chronic fatigue syndrome“, used a functional MRI to see how areas within the brainstem and some areas outside the brainstem were communicating with each other – at rest, and during a cognitive task.
Barnden mostly examined the reticular activation system (RAS), a network of neurons that regulate wakefulness and sleep, the fight and flight response, posture, and the ability of the brain to stop paying attention to innocuous stimuli, etc. (Your brain is powerful but it can only process so much stimuli at one time and if your RAS is not doing its job you may have trouble focusing, etc.)
The bilateral medulla and cuneiform nucleus regions in the medulla and midbrain, the thalamus, the midbrain dorsal Raphe, hippocampus and left culmen, as well as the connections within the brainstem, were all tested.
The fMRI assessed brain activity levels using blood oxygen levels. The higher the blood oxygen level in a part of the brain, the better connection between parts of the brain.
Very quickly, a key theme in ME/CFS research reared its head once again. At rest, everything was normal but when put under a cognitive stressor, the ME/CFS patients’ brains appeared Abby-normal indeed. Some studies which use patients at rest do show abnormalities but apparently there’s nothing like putting people ME/CFS under some sort of mental or physical stressor to produce results. This is, after all, the exertion disease.
It turned out that the people with ME/CFS demonstrated something of a “communication breakdown”. Different parts of their brainstem weren’t talking well with each other. Nor was their brainstem communicating well with other parts of the brain.
The most problematic connection for people with ME/CFS was between both parts of the medulla oblongata and the left cuneiform nucleus. While it was difficult to pin down the exact impact, Barnden reported that weakened connections between these two areas of the brain could produce such issues as maintaining movement, sleep quality, autonomic function and cortical arousal levels, which affect memory, learning and problem solving,
ME/CFS patients’ brainstems’ connection with two nuclei in the thalamus, and between the rostral medulla and hippocampus, were also impaired – suggesting that whatever damage has occurred in the brainstem is also affecting connectivity or traffic to the midbrain as well. Because the thalamus relays motor signals to the motor cortex and regulates sleep, alertness and wakefulness, a bad connection could impact all of those.
Barnden’s results were given an extra boost when he found that weaker connections within the brainstem and outside of it were associated with more severe symptoms.
Barnden, and Jeff’s and Jen Brea’s experiences with craniocervical instability gave us a vivid display of what a tweaked brainstem can produce. In their case – and in the cases of a surprising number of other patients – lax ligaments were allowing their skull to settle onto their brainstems. The results were severe ME/CFS-like symptoms – symptom which disappeared when surgery corrected that issue. Problems with the brainstem could conceivably, then, produce many of the symptoms – if not all the symptoms – associated with ME/CFS.
Barnden has not, to my knowledge, mentioned craniocervical instability in any of his studies. It’s not clear if it would show up in them but it seems inconceivable, on the other hand, that CCI/AAI could be responsible for all the brainstem issues he’s found in ME/CFS. If that’s true, then the brainstem in some patients is being impacted another way – perhaps by a hit-and-run virus or an inflammatory or autoimmune response.
We clearly need studies that will tease out different factors that could be impacting the brainstem. The first ME/CFS CCI/AAI paper is about to be published – and will helpfully alert more researchers and physicians to this problem. Avindra Nath’s assessment of CCI/AAI in its ME/CFS intramural study will help bring some clarity as well.
We should be hearing more about the role the brainstem – or the “reptilian brain” – and its control of basic processes plays in ME/CFS. VanElzakker is pursuing his own brainstem studies and the NIH is incorporating brain imaging into their intramural study as well.
With four studies under his belt, Barnden’s brainstem studies have become a model of consistency. Barnden has found evidence of damage to the brainstem (demyelination) which may have sparked a compensatory response outside the brainstem (remyelination), reduced functioning within and outside of the brainstem, and evidence that brainstem issues are associated with more symptoms.
All this suggests that this so-called primitive, but oh-so-fundamental part of the brain is not working well in ME/CFS.
Jeff and Jen Brea have shown just how devastating brainstem issues can be. Problems with the brainstem could help explain the problems with alertness, sleep, the autonomic nervous system, difficulties with focus and attention, mental fatigue and even coordination and movement. In fact, if you’re looking for one issue that could explain some of the really fundamental problems in ME/CFS, the brainstem could very well be it.
Just why brainstem problems appear to be occurring in ME/CFS is unclear but several studies underway should help to clarify the role it plays.
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