Researchers
Kiran Thapaliya, Sonya Marshall-Gradisnik, Natalie Eaton-Fitch, Markus Barth, Maira Inderyas, Leighton Barnden
Institutions
Griffith University and University of Queensland, Australia
Publication
PLos ONE, 2025 January 13; 20(1):e0316625
Key findings
- Brain scans from people with ME/CFS and those with long COVID were analysed to determine the volumes of different regions of the hippocampus.
- The hippocampus is a brain structure involved in memory and learning.
- Compared with healthy control subjects, individuals in both patient groups had significantly larger volumes of several areas (subfields) of the hippocampus.
- Hippocampus subfield volumes were similar in ME/CFS and long COVID patients.
- These volumes also correlated with symptom severity for measures of pain, illness duration, fatigue, concentration, unrefreshing sleep and physical function.
- Structural alterations in the hippocampus may therefore contribute to the symptoms of both ME/CFS and long COVID.
About the study
Along with a long list of other symptoms, ME/CFS is characterised by problems with concentration, decision-making and information processing – that is, cognitive problems or so-called brain fog.
These symptoms indicate abnormalities in brain function, and Kiran Thapaliya, Leighton Barnden and colleagues have been investigating the root of these abnormalities in a series of experiments, funded by ME Research UK, involving imaging of the brain.
Their findings in ME/CFS to date include brainstem volume changes (which correlated with measures of pain and breathing difficulty), impaired functional connectivity between specific brain regions, and raised brain neurochemical levels.
Another, earlier study also found differences in the hippocampus in people with ME/CFS. The hippocampus is a brain structure involved in memory and learning, and is comprised of different areas, or subfields, which each have specific jobs.
The cognitive problems associated with ME/CFS are largely shared by individuals with long COVID, so it makes sense to look for these changes in long COVID also, and to compare the two illnesses.
What did they do?
The researchers recruited 29 people with ME/CFS, 17 with long COVID and 15 healthy control subjects (with no history of COVID-19 infection).
Each participant underwent brain scanning using 7-Tesla magnetic resonance imaging, which builds up images of the brain using a combination of radio waves and strong magnetic fields.
The images were then analysed in order to estimate the volumes of specific subfields of the hippocampus, and these volumes were compared between the three different subject groups.
Other assessments looked at whether these volumes correlated with measures of symptom severity (which were assessed using the Research Registry questionnaire).
What did they find?
Compared with the healthy control subjects, people with ME/CFS as well as those with long COVID had significantly larger volumes of several areas of the hippocampus, specifically in the left hippocampal subfields including the left subiculum head, presubiculum head, molecular layer hippocampus head, and whole hippocampal head.
It is worth noting that these volumes were similar in ME/CFS and long COVID patients.
The researchers suggest that the enlarged volumes may be due to increased neurogenesis (i.e. the creation of new nerve cells) in response to environmental factors and/or stress.
Another factor may be an increase in volume to compensate for abnormalities in the brainstem, which have previously been reported in both ME/CFS and long COVID.
Another interesting and significant finding is that hippocampus subfield volumes were correlated with symptom severity, and this was true for measures of pain, duration of illness, severity of fatigue, impaired concentration, unrefreshing sleep, and physical function.
Conclusions
This latest study from the researchers at Griffith University have found alterations in the hippocampus of both ME/CFS and long COVID patients, and these subfield volumes were correlated with several measures of symptom severity.
The investigators says that “these findings suggest that structural alterations in the hippocampus may contribute to overlapping symptoms, such as cognitive problems” in both conditions.
The results build on the group’s previous research, revealing a range of brain abnormalities in ME/CFS which are likely to contribute to the cognitive symptoms experienced by individuals with the disease.
Prof. Barnden and colleagues are continuing this work in a follow-up study, funded by ME Research UK, tracking changes in brain structure in ME/CFS over time.