Sandoval et al. (2025)
- Authors: Ariadna Sandoval, Mingqi Li, Leonard A. Jason
- Institutes: Center for Community Research, DePaul University, Chicago, IL, United States.
- Publisher: Frontiers in Neurology
- Link: DOI
Summary
This study provides statistical evidence that the “brain fog” experienced by patients with ME/CFS and Long COVID is not a single entity, but is composed of at least two distinct types of problems: traditional cognitive difficulties (memory, focus) and sensory overload (hypersensitivity to light, noise, smells). By formally identifying sensory issues as a separate but core component of neurocognitive impairment, this research validates a key aspect of the patient experience. This framework could improve diagnostic criteria, allow for more precise symptom tracking in clinical trials, and guide researchers to investigate specific brain networks, like the Salience Network, as potential targets for future treatments.
What was researched?
This study investigated the structure of self-reported neurocognitive symptoms in large groups of patients with ME/CFS and Post-Acute Sequelae of COVID-19 (PASC). Researchers aimed to determine if symptoms like sensory hypersensitivity, which are often overlooked, group together with more classic “brain fog” symptoms like memory and concentration problems, or if they form a separate category.
Why was it researched?
While memory and concentration problems are well-recognized neurocognitive symptoms in ME/CFS and PASC, sensory issues like hypersensitivity to light and noise have been less formally studied as part of this symptom cluster. Some diagnostic criteria, like the Canadian Consensus Criteria, include these sensory disturbances. This research was prompted by the need to statistically evaluate whether these sensory symptoms constitute a distinct domain of neurocognitive impairment in these post-viral illnesses.
How was it researched?
This was a patient data analysis study using self-report surveys. The researchers aggregated data from 2,313 patients with ME/CFS and 299 patients with PASC who had completed the DePaul Symptom Questionnaire (DSQ-1). They then used a statistical method called exploratory factor analysis on 13 neurocognitive symptom items from the questionnaire to identify underlying patterns and group related symptoms into distinct “factors” for each illness group.
What has been found?
The analysis revealed a similar two-factor structure for both the ME/CFS and PASC groups. The first factor consisted of classic cognitive symptoms such as problems with memory, slowness of thought, and difficulty paying attention. The second, distinct factor consisted of sensory and perceptual disturbances, including sensitivity to light, noise, and smells. The study also found that patients who reported more severe functional impairment scored significantly worse on both of these neurocognitive factors.
Discussion
The authors note several limitations, including the reliance on self-reported diagnoses and symptoms rather than clinical confirmation, and the unequal sample sizes between the ME/CFS and PASC groups. They suggest the two identified factors may correspond to dysfunction in different brain networks, with the memory/concentration factor relating to the Central Executive Network and the sensory factor relating to overactivation of the Salience Network. The influence of comorbid conditions on these networks was acknowledged as a complex area for future study.
Conclusion & Future Work
The authors conclude that the neurocognitive symptoms in ME/CFS and PASC can be classified into two distinct domains: one related to memory and concentration, and another related to sensory overload. These findings suggest that research and clinical assessment should expand beyond traditional cognitive complaints to include sensory disturbances as a core feature. Future research should aim to connect these self-reported symptom domains with objective biological measures and further explore the underlying brain network abnormalities.