Brain functional connectivity in people with ME/CFS


Maira Inderyas, Kiran Thapaliya, Sonya Marshall-Gradisnik, Markus Barth, Leighton Barnden


Griffith University and University of Queensland, Australia


Frontiers in Neuroscience, 2024 January 29; 17:1318094


ME Research UK with the financial support of the Fred and Joan Davies Bequest

Key findings

  • Detailed MRI scans were used to investigate communication between different areas of the brain – or functional connectivity – in people with ME/CFS.
  • Functional connectivity was impaired between areas of the brain involved in movement, cognitive function, sensory processing, the sleep–wakefulness cycle, self-awareness and autonomic responses.
  • In addition, functional connectivity was associated with respiration, length of illness, fatigue severity, pain intensity and memory scores.
  • These results highlight the involvement of the brainstem and cerebellum in the mechanisms underlying ME/CFS, and suggest that there are ongoing changes in the brain.

Dr Barnden explains more about his research in this short video:

About the study

Many of the symptoms experienced by people with ME/CFS – including problems with concentration, memory, vision and heart-rate control – suggest abnormalities in the brain and nervous system. Indeed, research has demonstrated changes in brain structure in ME/CFS patients, as well as impairments in the connectivity between different regions of the brain, and disruption to the autonomic nervous system (which regulates many body functions).

Dr Barnden and his team aimed to build on their previous research by using a stronger 7-Tesla MRI scanner, which provides increased sensitivity and resolution, with the goal of uncovering more information about brain abnormalities in people with ME/CFS.

Jiasheng Su, Leighton Barnden and Kiran Thapaliya

The groups’s first results identified specific areas of the brainstem that were increased in volume in people with ME/CFS (and in those with long COVID), compared with healthy control subjects. Importantly, these differences in volume correlated with measures of pain and breathing difficulty. The brainstem is responsible for many of the vital functions of life, such as breathing, consciousness, blood pressure, heart rate and sleep.

Their new findings look at communication between different areas of the brain – or functional connectivity – in people with ME/CFS, and how this is linked to other measures including the duration of illness and memory.

What did they do?

A brain network is a collection of areas of the brain that work together to perform a function. Connections within and between these networks are therefore crucial. In this study, the researchers used MRI scanning to look at four areas of the brain:

  1. The default mode network is active when you are daydreaming or letting your mind wander while you are at rest.
  2. The salience network is thought to be involved in switching between different brain networks, as well as in processing pain, emotion and motivation.
  3. The cerebellum is involved in maintaining balance and coordinating voluntary movements.
  4. The pontine nuclei allow us to perform skilled movement by linking the motor cortex and the cerebellum.
Regions of the brain

MRI scans of the brain were obtained in 31 people with ME/CFS and in 15 healthy control subjects while they were undergoing a sequence of tests assessing concentration and attention difficulties (known as the Stroop Colour Word Test). Information on respiratory rate was also collected during the scans, and questionnaires were used to collect information from participants about their duration of disease, quality of life, ability to carry out tasks of daily living, and the characteristics and severity of ME/CFS symptoms.

What did they find?

In general, participants with ME/CFS had impaired functional connectivity compared with that in the healthy controls.

These abnormalities affected areas of the brain involved in a number of important processes.

  • Control of movement.
  • Cognitive function.
  • Self-awareness (perception and understanding of the things that make you who you are).
  • Sensory processing.
  • Sleep–wakefulness cycle and consciousness.
  • Autonomic responses such as blood pressure and temperature regulation.

In addition, functional connectivity in people with ME/CFS was associated with respiration, length of illness, fatigue severity, pain intensity and memory scores.

Strengths and limitations

This is the first study to examine differences in brain functional connectivity between people with ME/CFS and healthy controls using such a detailed type of MRI scan. However, it was a cross-sectional study, and therefore only provides information at a single point in time, rather than looking at changes over time.

Most clinical measures were self-reported, and therefore not only subjective but also potentially dependent on how participants were feeling at the time of the study. While the sample size was relatively small, it was sufficient to detect significant differences between the groups.


Dr Barnden and his team say that their findings highlight the involvement of the brainstem and cerebellum in the mechanisms of ME/CFS. They also suggest that their results indicate that ME/CFS may be associated with ongoing changes in the brain. For this reason, research that follows individuals over time is needed.

We look forward to seeing more results from this research, and how Dr Barnden and his team will build on these findings in their ongoing studies.

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