Adamaszek et al. (2026)
- Authors: Michael Adamaszek, Bianca Erdmann-Reusch, Stefan Kolodzie, Jan Mehrholz
- Institutes: Department of Neurology and Neurorehabilitation, Klinik Bavaria Kreischa, Kreischa, Germany, Department of Public Health, Medical Faculty, Dresden University of Technology, Dresden, Germany
- Publisher: Clinical Neurophysiology
- Link: DOI
Summary
This research provides a neurophysiological framework for the ‘brain fog’ experienced by patients with Post-COVID ME/CFS, identifying a state of brain hypoarousal as the underlying cause. By linking objective measures like pupillary movement and processing speed to subjective fatigue, the study validates patient experiences with clinical data. These findings suggest that neurocognitive symptoms are not merely psychological but are rooted in a measurable reduction of central nervous system activation. This work paves the way for targeted therapies that could potentially stimulate brain arousal to alleviate cognitive dysfunction.
What was researched?
The study investigated whether a state of ‘hypoarousal’—a reduction in the brain’s baseline level of alertness—is the primary driver of neurocognitive impairment in patients who developed ME/CFS following a SARS-CoV-2 infection.
Why was it researched?
While cognitive dysfunction (brain fog) and fatigue are hallmark symptoms of Post-COVID ME/CFS, the specific neurological mechanisms linking these symptoms have remained poorly understood. Researchers hypothesized that a lack of central nervous system activation might bridge the gap between subjective mental exhaustion and objective cognitive slowing.
How was it researched?
The researchers compared a cohort of SARS-CoV-2 associated ME/CFS patients with healthy controls using computational modeling based on the Theory of Visual Attention. They measured tonic alertness through visual processing speed (VPS) and assessed central nervous activation using pupillary unrest—a measure of spontaneous pupil fluctuations. Mental fatigue was also self-reported using standardized scales to correlate subjective experience with neurophysiological data.
What has been found?
Patients with ME/CFS showed a significant reduction in visual processing speed and pupillary unrest compared to healthy individuals, indicating a state of hypoarousal. Lower levels of central nervous activation and higher mental fatigue were strong predictors of slower processing speed. The data suggests that the brain’s ‘idle’ state is set too low, making it difficult to maintain the alertness required for normal cognitive tasks.
Discussion
The study’s strength lies in its use of objective neurophysiological markers to quantify cognitive symptoms often dismissed as purely subjective. However, the cross-sectional nature of the study means it cannot determine if hypoarousal is a permanent change or a temporary state that might fluctuate with symptom severity. Further research is needed to determine if this model applies to ME/CFS triggered by other pathogens.
Conclusion & Future Work
The researchers concluded that hypoarousal of the brain is a critical condition underlying neurocognitive impairment in SARS-CoV-2 associated ME/CFS. Future clinical trials should explore whether pharmacological or non-pharmacological interventions designed to increase central arousal can improve cognitive function in this population.