Distinct functional connectivity patterns in myalgic encephalomyelitis and long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study. — CFSMEATLAS
Distinct functional connectivity patterns in myalgic encephalomyelitis and long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study.
Inderyas, Maira, Thapaliya, Kiran, Marshall-Gradisnik, Sonya et al. · Journal of translational medicine · 2026 · DOI
Quick Summary
This study used advanced brain imaging to compare how the brains of ME/CFS patients, long COVID patients, and healthy people work during a challenging thinking task. Researchers found that patients' brains show different patterns of communication between regions compared to healthy controls, particularly in areas related to motivation, memory, and emotional processing. These brain differences appeared to worsen as fatigue built up during the task.
Why It Matters
This research provides potential brain-based markers (biomarkers) that could help objectively identify ME/CFS and long COVID at the neurobiological level. Understanding how brain regions fail to coordinate properly during cognitive effort could explain why patients experience worsening fatigue and cognitive dysfunction with activity, ultimately supporting better diagnosis and targeted treatments.
Observed Findings
Long COVID patients showed reduced connectivity between the nucleus accumbens and cerebellum (vermis) before fatigue onset, and reduced connectivity between medulla and hippocampus after fatigue worsened.
ME/CFS patients demonstrated increased connectivity between the left cuneiform nucleus and right medulla compared to healthy controls.
Healthy controls showed increased subcortical connectivity during task progression, while both patient groups showed reduced or dysregulated connectivity patterns.
Core network connectivity to the cerebellum, amygdala, caudate, and red nucleus correlated with cognitive symptom severity in both ME/CFS and long COVID patients.
Hippocampus and cerebellar connectivity correlated with illness duration in ME/CFS patients.
Inferred Conclusions
Aberrant functional connectivity in dopaminergic pathways (nucleus accumbens-hippocampus) suggests blunted motivation and cognition in both patient groups.
Reduced and dysregulated regional brain coordination in ME/CFS and long COVID indicates failed task engagement mechanisms, potentially serving as candidate biomarkers of symptomatology.
Brain connectivity patterns—particularly in subcortical and core networks—may objectively differentiate patient populations from healthy controls and correlate with symptom severity.
Remaining Questions
Do these functional connectivity abnormalities normalize with treatment or recovery, or are they stable features of these illnesses?
What This Study Does Not Prove
This cross-sectional study cannot establish cause-and-effect relationships—abnormal brain connectivity patterns may be consequences of illness rather than causes. The findings cannot determine whether these brain differences would improve with treatment or whether they could predict disease progression. Small sample sizes and single time-point assessment limit generalizability and cannot establish whether these patterns are stable diagnostic markers.