Neuroimaging markers of cognitive fatigue in individuals with post-acute sequelae of SARS-CoV-2 infection, 2025, Niemczak et al.

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Neuroimaging markers of cognitive fatigue in individuals with post-acute sequelae of SARS-CoV-2 infection
Niemczak; Ford; Roth; Leigh; Parsonnet; Martin; Soule; Haron; Buckey Jr.; Wylie

Persistent cognitive fatigue (CF) is the most reported symptom in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), but little is known about its underlying neural basis. This pilot study examined fMRI brain activation patterns during a fatiguing task in those with and without PASC. We hypothesized that individuals with PASC would show changes in CF-related brain activation within fatigue network.

Participants were 10 adults with PASC and persistent CF and 10 age-and gender-matched healthy controls. The 2-back working memory task was used during fMRI to induce CF. Patients with PASC reported greater CF, as measured using a Visual Analogue Scale of Fatigue (VAS-F), throughout the task.

The relationship of brain activation in the fatigue network to increased CF during the fatiguing task did not differ between groups. There were, however, more areas inside and outside the fatigue network that were activated in the PASC group as reported CF increased. The relationship between brain activation and scores on the 2-back did differ between groups, with the PASC group showing more frontal activation.

Findings suggest that individuals with PASC and CF may need to exert greater mental effort during demanding cognitive tasks, reflected in recruitment of a broader network of brain regions.

Link | PDF (Brain and Cognition)

 

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Conclusion —

The present findings shed new light on the well-replicated finding that individuals with PASC report high levels of [cognitive fatigue]. The PASC group demonstrated lower accuracy, increased 2-back-related brain activation, and higher initial CF ratings compared to controls, indicating they had to exert more effort. However, their ability to detect and manage CF remained relatively intact, showing a similar CF slope and heightened activation in the fatigue network. Future research should replicate and extend the findings reported here related to CF and should investigate why individuals with PASC require more cognitive resources to perform cognitive tasks.