Researchers
Hollie Byrne, Sarah Knight, Elisha Josev, Adam Scheinberg, Richard Beare, Joseph Yang, Stuart Oldham, Katherine Rowe, Marc Seal
Institutions
Murdoch Children’s Research Institute, University of Melbourne, and others, Melbourne, Australia
Publication
Journal of Neuroscience Research, 2024 October; 102(10):e25392
Funding
This study was funded by ME Research UK and the Judith Jane Mason and Harold Stannett Williams Memorial Foundation.
Key findings
- Changes in brain structure and functional connectivity have previously been identified in people with ME/CFS.
- In this study, magnetic resonance imaging was used to investigate hypothalamus connectivity in adolescents with the disease.
- The researchers found evidence of an increased number of connections from the hypothalamus to other areas of the brain in the ME/CFS group, compared with a control group.
- Connectivity was lower among those who had the disease for longer.
- The researchers believe the hypothalamus may therefore be a key target for understanding ME/CFS better, particularly its neurological symptoms.
About the study
Abnormalities in the brain and nervous system could underlie many of the symptoms experienced by people with ME/CFS, including problems with concentration, memory, vision, sleep and heart-rate control.
This is backed up by growing evidence showing changes in brain structure in ME/CFS patients, as well as impairments in connectivity between different regions of the brain, and disruption to the autonomic nervous system (which regulates many body functions).
Dr Sarah Knight and her team at Murdoch Children’s Research Institute have worked extensively in this area, focusing particularly on adolescents with ME/CFS, and have reported on the relationship between functional connectivity and cognition as well as changes in brain white matter.
For their next study, the group turned their attention to the hypothalamus. This is an important control centre of the brain which regulates several functions, including temperature, appetite, the sleep–wake cycle, mood, blood pressure and the production of hormones. Many of these functions are affected in ME/CFS, and the hypothalamus may therefore be involved.
A significant characteristic of the hypothalamus is that it has multiple connections to other areas of the brain, as well as to several glands responsible for hormone production.
The aim of this study was to use magnetic resonance imaging (MRI) to investigate hypothalamus connectivity in adolescents with ME/CFS, and how it correlates with fatigue severity and duration of disease.
What did they do?
The team recruited a group of 25 adolescents with ME/CFS (diagnosed using an adapted version of the Canadian Consensus Criteria) and 23 healthy adolescents with no history of the disease.
All underwent MRI scanning of the brain, and complex image processing methods were used to assess the number and strength of connections from different parts of the hypothalamus to other regions of the brain.
In addition, the researchers assessed the severity of fatigue experienced by the participants, using a questionnaire called the Paediatric Quality of Life Multidimensional Fatigue Scale. They also recorded other characteristics of the illness in those with ME/CFS, including the duration of disease.
Hypothalamus connectivity was compared between the ME/CFS patients and controls, and other analyses determined the associations between hypothalamus connectivity and fatigue severity and illness duration.
What did they find?
The researchers found evidence of a greater number of connections from the hypothalamus (left and right areas) to other areas of the brain (particularly the thalamus and brainstem) in adolescents with ME/CFS than in the healthy control subjects. The strength of those connections was not increased, however.
In general, the number and strength of connections were not associated with the severity of fatigue experienced by those with ME/CFS, although there was a weak relationship between the right intermediate hypothalamus connectivity strength and fatigue severity in the ME/CFS group, which was not present in the controls.
In addition, there was an association between the number of connections from the posterior hypothalamus and the duration of illness in the ME/CFS group, with fewer connections in individuals who had the disease for longer.
Conclusions
In summary, the researchers found that hypothalamus connectivity was increased in adolescents with ME/CFS, but was lower among those who had the disease for longer. There was also a weak association between fatigue severity and the strength of connections from the right intermediate hypothalamus.
So these results do indicate changes in hypothalamus connectivity in adolescents with ME/CFS, although these need to be confirmed in a larger sample of patients.
Research in healthy populations suggests that changes in hypothalamus connectivity are associated with sleep disturbances, as well as with chronic physical and/or psychological stress. Unrefreshing sleep is a common symptom of ME/CFS, while stress has been proposed to help reactivate latent viruses, a potential cause of the disease. All of these factors require more study, however.
The group say that this is one of the first studies to look at the involvement of hypothalamus connectivity in ME/CFS, and they believe the hypothalamus may be a key target for understanding the disease better.
