A hypoarousal model of neurological post-COVID syndrome: the relation between mental fatigue,... and cognitive processing speed, 2023, Martin et al

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A hypoarousal model of neurological post-COVID syndrome: the relation between mental fatigue, the level of central nervous activation and cognitive processing speed

Background
Knowledge on the nature of post-COVID neurological sequelae often manifesting as cognitive dysfunction and fatigue is still unsatisfactory.

Objectives

We assumed that cognitive dysfunction and fatigue in post-COVID syndrome are critically linked via hypoarousal of the brain. Thus, we assessed whether tonic alertness as a neurocognitive index of arousal is reduced in these patients and how this relates to the level of central nervous activation and subjective mental fatigue as further indices of arousal.

Methods

40 post-COVID patients with subjective cognitive dysfunction and 40 matched healthy controls underwent a whole-report paradigm of briefly presented letter arrays. Based on report performance and computational modelling according to the theory of visual attention, the parameter visual processing speed (VPS) was quantified as a proxy of tonic alertness. Pupillary unrest was assessed as a measure of central nervous activation. The Fatigue Assessment Scale was applied to assess subjective mental fatigue using the corresponding subscale.

Results

VPS was reduced in post-COVID patients compared to controls (p = 0.005). In these patients, pupillary unrest (p = 0.029) and mental fatigue (p = 0.001) predicted VPS, explaining 34% of the variance and yielding a large effect with f2 = 0.51.

Conclusion

In post-COVID patients with subjective cognitive dysfunction, hypoarousal of the brain is reflected in decreased processing speed which is explained by a reduced level of central nervous activation and a higher level of mental fatigue. In turn, reduced processing speed objectifies mental fatigue as a core subjective clinical complaint in post-COVID patients.

https://link.springer.com/article/10.1007/s00415-023-11819-7
 
According to the neural interpretation of TVA [12, 14], VPS reduction reflects a downscaled activation level in neurons involved in object coding, therefore, expressing hypoarousal of the brain.

VPS is a basic cognitive function determining performance in diverse cognitive tasks, influencing global cognition [23, 52] and functional independence in aging individuals [51]. Therefore, based on our finding of perceptual (attentional) slowing indicative of hypoarousal, it is not astonishing that patients with neurological post-COVID syndrome show considerable long-term problems with respect to reintegration into work and societal life [24, 55]

We cannot directly infer the underlying pathomechanisms of arousal dysfunction in post-COVID patients in our study. However, our results point towards possible neurostructures and -modulators. As tonic alertness regulation depends on input from wakefulness-promoting monoaminergic systems including the noradrenergic locus coeruleus system [2, 45, 58, 64], post-infectious brainstem alterations might lead to decreased cortical activation resulting in slowed information processing speed and feeling of fatigue [10].

Departing from our results demonstrating hypoarousal, future studies implementing appropriate neuroimaging procedures in post-COVID patients can more directly assess the underlying specific neurostructural and –modulatory mechanisms.
 
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