Brain activity map showing areas of normal and reduced metabolism

Unlocking the Mystery: Brain Metabolism in Chronic Fatigue Syndrome

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Theo Raines in Health & Wellness October 2026 • 5 min read.

"A new study reveals how brain function differs in patients with chronic fatigue syndrome, offering potential insights into diagnosis and treatment."


Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), is a debilitating condition characterized by persistent, profound fatigue that isn't relieved by rest and can't be explained by any underlying medical condition. Beyond the overwhelming fatigue, individuals with CFS/ME often experience a cluster of other symptoms, including muscle and joint pain (arthromyalgias), cognitive difficulties (often described as 'brain fog'), sleep disturbances, and persistent headaches. These symptoms can significantly impact daily life and make it challenging to perform even simple tasks.

Previous research using FDG-PET scans (a type of imaging that measures brain activity) has shown inconsistent results in CFS/ME patients. Some studies have reported non-specific patterns of reduced brain activity (hypometabolism) in the frontal and cingulate cortex – areas involved in higher-level cognitive functions and emotional regulation – in a portion of CFS/ME patients compared to healthy individuals. However, these findings have not been universal, highlighting the complexity of the condition and the need for more targeted research.

Now, a new study utilizing combined PET/MRI technology offers fresh insights into brain function in CFS/ME. This research focuses on a 21-year-old woman meeting established criteria for CFS/ME, presenting a unique case of severe hypometabolism in specific brain regions despite normal blood flow. This finding challenges previous assumptions about the link between brain activity and blood supply in CFS/ME and opens new avenues for understanding the underlying mechanisms of this complex illness.

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ME/CFS Prevalence and Economic Impact

National Health Interview Survey data show that 1.3% of U.S. adults had myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in 2021–2022. The percentage increased with age through ages 60–69, then declined among adults age 70 and older. ME/CFS is described as a multisystem illness involving activity-limiting fatigue and worsening symptoms after activity, and it is estimated to cost the U.S. economy about $18–$51 billion annually.

Unsettled Diagnosis and Treatment

A 2025 systematic review reports that chronic fatigue syndrome (CFS) has not been clearly defined and that no universally accepted treatment protocol exists. It also says diagnostic markers, etiology, and the specific pathophysiology needed to develop effective non-pharmacological treatments remain unknown. A review of therapeutic interventions likewise describes CFS/ME as a complex, multisystem chronic condition whose pathophysiology remains unknown.

A Contested Medical History

A 2018 historical chapter traces medical discussion of fatigue from neurasthenia in the 1800s to chronic fatigue syndrome and discusses three pivotal reports. A historical review notes that the condition is not new: over centuries, its varied features were attributed to environmental, metabolic, infectious, immunologic, and psychiatric disturbances. Another account describes an evolving and contested history in which physicians debated organic disease, psychological disturbance, and social explanations.

Decoding the Brain: Hypometabolism vs. Normal Perfusion

Brain activity map showing areas of normal and reduced metabolism

The PET scans of the young woman in the study revealed a striking pattern of severe and widespread hypometabolism (reduced activity) in several key areas of the brain. These areas included the posterior cortical regions (specifically the precuneus, parietal, temporal, and occipital lobes, responsible for processing sensory information, spatial awareness, and visual processing), the amygdalo-hippocampal complexes (involved in memory and emotional regulation), and the cerebellum (crucial for motor coordination and balance).

Interestingly, despite the significant reduction in metabolic activity in these brain regions, MRI scans using Gadolinium contrast showed that cerebral blood flow was normal. This is a crucial finding, as it suggests that the reduced brain activity is not simply due to a lack of blood supply. This 'uncoupling' of metabolism and perfusion is unusual and points towards a more complex underlying mechanism.

  • Hypometabolism: Reduced activity in key brain areas (posterior cortical regions, amygdalo-hippocampal complexes, and cerebellum).
  • Normal Perfusion: Regular blood flow in the same regions, despite reduced activity.
  • Uncoupling: Mismatch between brain activity and blood supply, suggesting complex underlying mechanisms.
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Emerging Metabolic Neuroimaging

A report on metabolic neuroimaging describes Sahbai and colleagues’ evaluation of brain metabolism using FDG-PET and perfusion using MRI in a 21-year-old woman who met the Fukuda criteria for ME/CFS. It reports significant hypometabolism in various posterior cortical regions. A separate comparative study notes that functional imaging has described cellular and metabolic abnormalities in ME/CFS, raising the question of whether episodic-memory disorders may relate to dysfunction in internal temporal structures.

The researchers compared this pattern to that seen in patients with aluminum-induced macrophagic myofasciitis (MMF), a rare condition linked to specific vaccine adjuvants, previously studied at their center. While the brain activity patterns were similar, the patient in this study had no evidence of MMF based on muscle biopsies, suggesting a different underlying cause for her CFS/ME.

What Does This Mean for CFS/ME?

This study's unique finding of hypometabolism with normal perfusion challenges the idea that reduced brain activity in CFS/ME is simply a result of decreased blood flow. It suggests that other factors, potentially at the cellular or molecular level, are contributing to the reduced brain function.

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A Multisystem Condition

ME/CFS is described as a complex, multisystem disease associated with severe fatigue, cognitive dysfunction, sleep disturbances, autonomic dysfunction, and post-exertional malaise that can impair daily activities. A 2024 Harvard Health article reports that an NIH study adds to research identifying objective markers across the brain, immune system, gut, and other areas. The article also notes commonly reported sympathetic hyperactivity, disturbed and non-restorative sleep, nocturnal hypervigilance, and a feeling of overstimulation.

The study authors propose that the uncoupling of perfusion and metabolism may indicate that the posterior hypometabolism is not related to neuronal loss but to an inflammatory or immunological process. This suggests that inflammation or immune system dysfunction could be playing a significant role in the brain dysfunction seen in CFS/ME.

While this is only a single case study, it highlights the need for further research using advanced imaging techniques like simultaneous PET/MRI in larger groups of CFS/ME patients. Future studies are needed to confirm these findings, investigate the potential role of inflammation and immune dysfunction, and ultimately identify targeted therapies to improve brain function and alleviate the debilitating symptoms of CFS/ME.

How this imaging report fits with other brain studies

Earlier PET reports described hypometabolism in the right mediofrontal cortex and brainstem, or in the cingulate and nearby mesial cortical areas; some also reported cuneus or precuneus involvement. These findings overlap only partly with the posterior-region pattern described in the metabolic-imaging review.[1] [2] [3]

A later 7 Tesla MRI comparison examined functional connectivity in 31 people with ME/CFS and 15 healthy controls, and reported reduced connectivity between the pontine nucleus and cerebellar vermis IX. It measured connectivity during a cognitive task, a different imaging outcome from glucose metabolism.[4]

Questions the brain-imaging evidence leaves open

  • Would a link between posterior associative-region hypometabolism and episodic-memory difficulties appear in comparisons that measure both directly? Functional-imaging accounts raise this possibility but do not resolve it.[5]
  • How much do incomplete participant descriptions affect conclusions about the wider evidence base? An evidence map notes gaps in reporting gender, ethnicity, and illness severity, which may limit how precisely study populations can be characterized.[6]

Questions about the wider research

Why is the biology still difficult to interpret?

A review describes ME/CFS and Long COVID as complex conditions and says that incomplete understanding of their pathophysiology contributes to limited diagnostics and treatments.[7]

Sources

  1. Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data. (pubmed.ncbi.nlm.nih.gov)
  2. A systematic review of neurological impairments in myalgic encephalomyelitis/ chronic fatigue syndrome using neuroimaging techniques (pmc.ncbi.nlm.nih.gov)
  3. Metabolic neuroimaging of myalgic encephalomyelitis/chronic fatigue syndrome and Long-COVID (2025)
  4. Subcortical and default mode network connectivity is impaired in myalgic encephalomyelitis/chronic fatigue syndrome (Frontiers in Neuroscience, 2024)
  5. Comparative Study Between Cognitive Phenotypes of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Multiple Sclerosis (Diagnostics, 2025)
  6. Recent research in myalgic encephalomyelitis/chronic fatigue syndrome: an evidence map (Health Technology Assessment, 2025)
  7. Metabolic neuroimaging of myalgic encephalomyelitis/chronic fatigue syndrome and Long-COVID (Immunometabolism, 2025)

About this Article -

Written with AI assistance from published research, and reviewed by the Mystum team. See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1007/s00259-018-4229-3, Alternate LINK

Title: Severe Posterior Hypometabolism But Normal Perfusion In A Patient With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Revealed By Pet/Mri

Subject: Radiology, Nuclear Medicine and imaging

Journal: European Journal of Nuclear Medicine and Molecular Imaging

Publisher: Springer Science and Business Media LLC

Authors: S. Sahbai, P. Kauv, M. Abrivard, P. Blanc-Durand, M. Aoun-Sebati, B. Emsen, A. Luciani, J. Hodel, F-J. Authier, E. Itti

Published: 2018-12-14

Everything You Need To Know

1

What is Chronic Fatigue Syndrome?

Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), is a debilitating condition where individuals experience persistent, overwhelming fatigue that isn't relieved by rest. Beyond fatigue, symptoms often include muscle and joint pain, cognitive difficulties, sleep disturbances, and headaches. These symptoms significantly impact daily life and make even simple tasks challenging. This condition is characterized by persistent, profound fatigue and a range of other symptoms.

2

What does hypometabolism mean in the context of this study?

In the context of brain function in CFS/ME, hypometabolism refers to reduced activity in specific brain regions. The study found severe hypometabolism in the posterior cortical regions (precuneus, parietal, temporal, and occipital lobes), the amygdalo-hippocampal complexes, and the cerebellum. These areas are responsible for sensory information processing, spatial awareness, memory, emotional regulation, motor coordination, and balance. The presence of hypometabolism suggests that these brain regions are not functioning at the same level as in healthy individuals, potentially explaining some of the cognitive and physical symptoms associated with CFS/ME.

3

What does normal perfusion mean in this study?

Normal perfusion, in this study, means that cerebral blood flow was found to be normal in the brain regions of a patient, despite significant hypometabolism. This finding is crucial as it contradicts the expectation that reduced brain activity is directly caused by decreased blood supply. The presence of normal perfusion alongside hypometabolism suggests a more complex mechanism underlying the reduced brain function in CFS/ME, possibly related to cellular or molecular factors within the brain.

4

What does 'uncoupling' of metabolism and perfusion mean?

The uncoupling of metabolism and perfusion is a key finding. This refers to the mismatch between brain activity (hypometabolism) and blood supply (normal perfusion). This 'uncoupling' is unusual and challenges previous assumptions. The fact that brain regions showed reduced activity (hypometabolism) while receiving adequate blood supply (normal perfusion) implies that the problem isn't simply a lack of oxygen or nutrients due to reduced blood flow. It suggests that other factors, such as cellular or molecular dysfunction, may be playing a role in the reduced brain function observed in CFS/ME.

5

What is the significance of these findings for our understanding of CFS/ME?

The study's findings of hypometabolism with normal perfusion challenge the understanding of CFS/ME by suggesting that reduced brain activity isn't just a result of decreased blood flow. It implies that other underlying mechanisms, possibly at the cellular or molecular level, are contributing to the reduced brain function. This opens new avenues for research, potentially leading to more targeted treatments. These findings suggest that the underlying causes of the condition may be more complex than previously thought.

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