Scientists find a link between brain imbalance and chronic fatigue syndrome
Scientists have found compelling evidence of abnormalities in the brain and immune system of patients with chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME).
The findings, from one of the most rigorous studies to date, begin to clarify the biological basis for the disease that can cause debilitating fatigue. The study is the first to show a link between imbalances in brain activity and feelings of fatigue, and suggests that these changes may be caused by abnormalities in the immune system.
“People with ME/CFS have very real and disabling symptoms, but uncovering their biological basis has been extremely difficult,” says Walter Koroshetz, director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS) in the US. “This in-depth study of a small group of people has identified a number of factors likely contributing to their ME/CFS.”
The study involved just 17 patients and the findings need to be confirmed by a larger group before they can be claimed as a roadmap to new treatments. It is also not clear to what extent the findings apply to long Covid, as the patients were recruited and assessed before the pandemic. But scientists have described the work as a long-awaited deep dive into the biology of the condition.
“This is such an important paper and I’m so happy to see it come out,” says Prof. Karl Morten, who researches ME/CFS at the John Radcliffe Hospital, University of Oxford, and was not involved in the latest work. “We’ve had a lot of small studies showing that there may be a problem with this cell or that cell, but no one has really looked at everything in one patient before.”
The patients in the study, carefully selected from an initial group of 300, had all had an infection before becoming ill. During the study, they stayed at an NIH clinic for a week and received a wide range of physiological assessments.
Results from functional magnetic resonance imaging (fMRI) brain scans showed that people with ME/CFS had lower activity in a brain region called the temporal-parietal junction (TPJ), which can cause fatigue by disrupting the way the brain makes decisions how to make their effort. . The motor cortex, a brain region that controls body movements, also remained abnormally active during tiring tasks. However, there were no signs of muscle fatigue.
This suggests that fatigue in ME/CFS could be caused by a dysfunction in the brain areas that control the motor cortex and that changes in the brain may alter patients’ tolerance for exercise and their perception of fatigue.
“We may have identified a physiological focal point for fatigue in this population,” said Brian Walitt, associate professor at NINDS and first author of the study, published in Nature communication. “Rather than physical exhaustion or a lack of motivation, fatigue may stem from a discrepancy between what a person thinks they can achieve and what their body is performing.”
Morten said the discovery of abnormalities in brain function does not suggest that patients are psychologically driving their own disease or have any control over it. “The brain can respond to stimuli and influence the body,” he said. “The brain does not function properly physically and biochemically and it is the disease that does that, not the patient.”
The patients also had an increased heart rate and it took longer for their blood pressure to normalize after exercise. There were also changes in patients’ T cells sampled from cerebrospinal fluid, indicating that these immune cells were trying to fight something. This could indicate that the immune system has failed to fight back after an infection has cleared or that a chronic infection is present in the body unnoticed.
The authors outline a possible cascade of events, starting with a sustained immune response, that could cause changes in the central nervous system, leading to changes in brain chemistry and ultimately affecting the function of specific brain structures that control motor function and the perception of fatigue.
“We think that immune activation affects the brain in different ways, causing biochemical changes and downstream effects such as motor, autonomic and cardiorespiratory dysfunction,” said Avindra Nath, clinical director at NINDS and senior author of the study.
The findings have been welcomed by scientists as an important step toward uncovering the underlying biological causes of the disease. Until now, the lack of a clear biological basis for the disease has led to patients being dismissed, stigmatized and forced to opt for ineffective treatment options.