All in your head? Brain research in ME/CFS

From the ME Research UK website –

https://www.meresearch.org.uk/brain-research-in-me-cfs/

Following last week’s introduction to the brain, here is an overview of some of the brain research conducted in ME/CFS in recent years, and how it has helped us understand more about the illness.

The World Health Organisation has classified ME/CFS as a neurological disease, and brain inflammation has long been hypothesised as a potential cause of the condition. What’s more, findings from the field of neurological research have started to show just how significant the brain is in ME/CFS, with evidence of neuroinflammation and changes in brain activity during post-exertional malaise.

As the brain is responsible for regulating and controlling all of the functions of the body – from physical movement to unconscious regulation of the heart and temperature – dysfunction in this organ could easily explain why ME/CFS has the wide range of symptoms illustrated below.

An excellent review summarising studies looking for neurological issues in ME/CFS was published in 2020 by Maksoud and colleagues in the journal PLOS ONE. The paper presented findings, consistencies and discrepancies in fifty-five studies on brain research in ME/CFS.

The authors noted that the vast majority of studies used the less stringent Fukuda diagnostic criteria for patient selection, which may have contributed to inconsistencies between the studies. This meant identification of a single consistent neurological impairment was difficult.

Nevertheless, some consistencies were still found and demonstrated the importance of the brain in this disease. The key findings of the review included:

• Consistent abnormalities in the brain structure of ME/CFS patients, with a decrease in the white matter of the brain, which is responsible for transferring information through nerve connections via the spinal cord.

Disruption of the autonomic nervous system network, which is responsible for regulating unconscious bodily processes such as heart rate, digestion and pupil dilation.

Impaired cognitive processing, including problems with functional connectivity (synchronisation of different regions of the brain) and disruptions to working memory.

Another interesting paper published in 2020 was by Washington and colleagues in the journal Brain Communications. This study examined the effect of exercise on brain activity in ME/CFS patients and in people with Gulf War illness (which is also associated with post-exertional malaise).

Using functional MRI to measure brain activity while participants carried out a working-memory task, the authors found notable differences in several areas of the brain.

People with ME/CFS had an increase in activity in the midbrain, right middle insula and left rolandic operculum after exercise, while people with Gulf War illness had a decrease in activity in the cerebellum and right angular gyrus.

According to the investigators, the regions affected are involved in pain, threat assessment, interoception (the sense of feeling what is wrong with your body), negative emotion and vigilant attention (ability to focus). They even suggest that further investigation may eventually lead to treatment by deep-brain stimulation of specific regions.

Evidence of neuroinflammation in ME/CFS was demonstrated by Nakatomi and colleagues in 2014 in a paper published in the Journal of Nuclear Medicine. In this small study, they authors detected expression of a specific protein linked to activation of microglia or astrocytes (which are types of cell found in the brain with a wide range of regulatory functions).

Activated microglia/astrocytes provides evidence of neuroinflammation in ME/CFS, and the authors were also able to correlate activation in specific areas of the brain to symptom severity. For example, activation in the amygdala, thalamus and midbrain correlated with cognitive impairment symptom severity and activation, while activation in the cingulate cortex and the thalamus correlated with pain.

Finally, a series of papers published by a team in Australia over the past decade has shown repeated anomalies in the brain, which were also linked to symptom severity. In particular, Barnden and colleagues showed impairments in nerve signalling in the brainstem in people with ME/CFS, which the authors claim may explain some of autonomic symptoms seen in the disease.

Next week, we will summarise some of the research on the brain and nervous system that ME Research UK has funded over the last few years, showing what advances in the field have been made possible by your donations.

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