Two neurocognitive domains identified for patients with myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of COVID-19. — ME/CFS Atlas
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Two neurocognitive domains identified for patients with myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of COVID-19.
Sandoval, Ariadna, Li, Mingqi, Jason, Leonard A · Frontiers in neurology · 2025 · DOI
Quick Summary
This study looked at brain-related symptoms in over 2,600 people with ME/CFS and COVID long-haul (PASC), finding that their cognitive problems fall into two main categories. The first group includes classic memory and concentration difficulties, while the second group involves being overwhelmed by sensory input like loud noises or bright lights. The research suggests that doctors and researchers should pay more attention to sensory overload as an important part of cognitive problems in these conditions.
Why It Matters
Many ME/CFS patients report both cognitive problems and overwhelming sensitivity to sensory stimuli, yet previous research often treated these as separate issues rather than related aspects of brain dysfunction. By identifying sensory overload as a distinct neurocognitive domain, this study validates patient experiences and suggests that doctors should assess both memory/concentration AND sensory sensitivity together as interconnected features of post-viral illness. This broader understanding could improve diagnosis, treatment planning, and patient recognition of their symptoms.
Observed Findings
Two distinct neurocognitive factors were identified in both the ME/CFS group (n=2,313) and PASC group (n=299).
Factor 1 consistently included classic memory and concentration complaints across both patient populations.
Factor 2 distinctly captured sensory hypersensitivity symptoms including sensitivity to noise and light.
Sensory overload phenomena have been underrecognized in previous neurocognitive assessments of post-viral illness.
The two-factor structure was replicated across different post-viral patient groups.
Inferred Conclusions
Neurocognitive dysfunction in ME/CFS and PASC comprises at least two dissociable domains rather than a single cognitive impairment syndrome.
Sensory hypersensitivity should be recognized and assessed as a formal neurocognitive domain in post-viral illnesses, not merely as a comorbid symptom.
Researchers and clinicians should expand their neurocognitive assessment tools to include sensory overload dimensions alongside traditional memory and concentration measures.
The similar factor structure across ME/CFS and PASC suggests shared neurocognitive signature patterns in post-viral conditions.
Remaining Questions
What biological mechanisms underlie the distinction between memory/concentration and sensory overload domains—are they related to different brain regions or neurochemical systems?
What This Study Does Not Prove
This study does not prove that sensory overload and cognitive dysfunction have the same biological cause—only that they cluster together as reported symptoms. The cross-sectional design means we cannot determine whether these neurocognitive patterns change over time or what causes them. The findings are based on patient self-reports rather than objective cognitive testing, so they reflect how patients perceive and describe their symptoms rather than measured brain function.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
Do these two neurocognitive factors change over disease course, and can their trajectory predict recovery or disease severity?
How do these patient-reported neurocognitive factors correlate with objective neuropsychological testing and neuroimaging findings?
Which interventions or treatments specifically target sensory overload versus traditional cognitive symptoms, and are different approaches needed for each domain?