Researchers
Tanoj Bahadur Singh, Sonya Marshall-Gradisnik, Leighton Barnden, Natalie Eaton-Fitch, Tuong Hieu Huynh, Maira Inderyas, Kiran Thapaliya
Institution
National Center for Neuroimmunology and Emerging Diseases (NCNED), Griffith University, Gold Coast, Queensland, Australia
Publication
Frontiers in Medicine – Translational Medicine, 2026 July 17; 13:1824498
Funding
This research was funded by ME Research UK (SCIO Charity Number SC036942) with the financial support of The Fred and Joan Davies Bequest.
Key findings
- Advanced MRI techniques were used to look at very-small-scale brain tissue changes in 37 people with ME/CFS and 19 with long COVID, compared with 27 healthy controls.
- Both patient groups showed signs of altered brain microstructure, suggesting that these illnesses may involve measurable biological changes in the brain.
- The findings may help explain symptoms such as brain fog, fatigue, pain, sleep problems and post-exertional malaise, and supports the idea that ME/CFS and long COVID may share some underlying neurological or biological features.
- The study was relatively small, so the results need to be confirmed in larger groups of participants.
About the study
Researchers at Griffith University in Australia have carried out a series of ME Research UK-funded imaging studies investigating brain structure and function in people with ME/CFS and long COVID.
The cognitive difficulties often described as ‘brain fog’ by people with these conditions point to possible abnormalities in brain function, and this has been supported by the group’s findings so far, including brainstem volume changes linked to pain and breathing difficulty, impaired functional connectivity between specific brain regions, raised brain neurochemical levels and alterations in the hippocampus, a region involved in memory and learning.
The group’s latest results were reported by doctoral student Tanoj Bahadur Singh and colleagues in the journal, Frontiers in Medicine – Translational Medicine, and explore whether people with ME/CFS and those with long COVID have subtle differences in brain tissue.
What did they do?
The researchers recruited 37 people with ME/CFS, 19 people with long COVID and 27 healthy controls. Participants with ME/CFS met either the Canadian Consensus Criteria or the International Consensus Criteria and had received a formal diagnosis from a physician. Participants with long COVID met the WHO working case definition.
The research team used two advanced MRI techniques — diffusion tensor imaging and diffusion kurtosis imaging — to identify very small changes in brain structure that may not be visible on standard MRI scans.
The researchers also looked at whether clinical measures such as duration of illness and fatigue severity correlated with the brain imaging results.
What did they find?
The findings from this study were complex but, in simple terms, suggest that ME/CFS and long COVID may involve subtle changes in the brain’s microstructure — very small-scale differences in the organisation of brain tissue.
People with ME/CFS had microstructural alterations in:
- The cingulum – a nerve pathway deep inside the brain that connects different regions of the limbic system to regulate emotion, memory and pain.
- Supplementary motor areas – a part of the brain that contributes to movement control.
- Parts of the corpus callosum – a bundle of nerve fibres which plays a role in how we think, remember and communicate by allowing the left and right sides of the brain to communicate.
People with long COVID had microstructural alterations in regions including:
- The fusiform gyrus – part of the brain that is critical for visual processing such as recognising faces and identifying objects.
- The precentral gyrus – a very important structure involved in executing voluntary movements.
- Major white matter tracts – bundles of myelinated axons (nerve fibres wrapped in a fatty, insulating layer called a myelin sheath) that act as communication highways connecting different parts of the brain and spinal cord.
A direct comparison between the ME/CFS and long COVID groups found a difference in the left corona radiata. This can be thought of as a superhighway in the brain that transmits motor, sensory and cognitive information between the outer cerebral cortex (the wrinkly layer of grey matter responsible for things like conscious thought, reasoning, memory, sensory processing and muscle control) and deeper brain structures such as the thalamus (an egg-shaped structure deep in the brain that acts as the body’s primary information relay station) and spinal cord.
This difference suggests that ME/CFS and long COVID may have partly distinct patterns of brain involvement.
Overall, these changes could help explain neurological symptoms such as cognitive difficulties and fatigue, although the study does not prove cause and effect.
It is worth noting that the participants with ME/CFS had a significantly longer illness duration than those with long COVID, a factor that may limit the comparability of the two groups. Additionally, as noted by the research team, those with long COVID were not screened for ME/CFS (or vice versa) – again, something which may complicate interpretation of the findings.
Conclusions
The research adds to growing evidence that ME/CFS and long COVID are associated with measurable biological changes – in this case, specifically in brain tissue. However, because the study involved a relatively small number of participants, larger studies that follow participants up over time are needed, to validate these findings and to establish whether the abnormalities progress over time.
And this is precisely why the Griffith group are conducting their ongoing ME Research UK-funded study tracking changes in the structure and function of the brain over time in ME/CFS.
