Connectivity Between Salience and Default Mode Networks and Subcortical Nodes Distinguishes Between Two Classes of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. — CFSMEATLAS
Connectivity Between Salience and Default Mode Networks and Subcortical Nodes Distinguishes Between Two Classes of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Su, Jiasheng, Thapaliya, Kiran, Eaton-Fitch, Natalie et al. · Brain connectivity · 2023 · DOI
Quick Summary
This study used brain imaging (fMRI) to examine how different brain networks communicate in people with ME/CFS compared to healthy controls. Researchers found that people with ME/CFS have different patterns of brain connectivity, particularly in networks involved in attention and the brain's rest-state activity. Importantly, the study discovered that two different diagnostic criteria for ME/CFS (ICC and Fukuda) appear to identify distinct brain differences, suggesting they may represent different disease types.
Why It Matters
This is the first neuroimaging evidence that two clinically distinct ME/CFS diagnostic criteria (ICC vs. Fukuda) reflect different objective brain connectivity patterns, validating the newer ICC diagnostic approach. This finding may help researchers better understand ME/CFS heterogeneity and could guide development of subtype-specific treatments. For patients, it suggests that different ME/CFS subtypes may have different underlying brain mechanisms affecting cognition and sleep-wake regulation.
Observed Findings
During task fMRI, 10 connections differed between ME/CFS and healthy controls (5 unique to ICC class, 5 unique to Fukuda class, with no overlap).
Salience network connections to the hippocampus and brainstem reticular activation system (RAS) were stronger in ME/CFS patients compared to controls.
During resting-state fMRI, only 2 connectivity differences were found from healthy controls, both in Fukuda-defined patients involving salience network hubs.
Eight of ten different connections involved the salience network hub; six were weaker in ME/CFS and four were stronger.
Inferred Conclusions
Different brain regulatory mechanisms (reflected in distinct connectivity patterns) characterize ICC versus Fukuda ME/CFS diagnostic classes, supporting the hypothesis that these represent different disease entities.
Imbalance in salience network regulation of the default mode and executive networks may explain impaired cognitive performance and sleep-wake cycle disturbances in ME/CFS.
Altered connectivity between salience network and subcortical regions (hippocampus, RAS) involved in arousal and memory modulation is central to ME/CFS neurophysiology.
Remaining Questions
Do these distinct connectivity patterns remain stable over time, or do they change with disease progression or treatment?
What structural or molecular brain abnormalities underlie these functional connectivity differences in ICC versus Fukuda ME/CFS?
What This Study Does Not Prove
This study cannot establish causation—it shows correlation between connectivity patterns and diagnostic criteria, not whether altered connectivity causes ME/CFS symptoms or results from the disease. The findings are limited to the specific networks examined and may not generalize to all ME/CFS populations or capture the full complexity of brain dysfunction. Cross-sectional design means we cannot determine if these brain changes are stable over time or how they evolve with disease progression.