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

Abstract

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.

Long COVID is associated with severe cognitive slowing: a multicentre cross-sectional study

“…found a persistent deficit in perceptual processing speed in patients with PCC with cognitive complaints. 10 , 31 …”

“…This has been reported in several investigations conducted in both acute and chronic phases of COVID-19, especially in those with self-reported cognitive symptoms. 6 , 7 , 8 , 9 , 10 , 11 , 12 However, due to the lack of consensus on the precise definition of PCC 13 , 14 and vast differences in cognitive task design and administration, it remains unclear whether PCC is associated with generalised cognitive slowing.…”

Long COVID is associated with severe cognitive slowing

“…30 In addition, Martin et al found a deficit in perceptual processings speed in PCC patients with cognitive complaints. 10…”

Persistent cognitive slowing in post-COVID patients: longitudinal study over 6 months

“…Given the high prevalence of PCS, the suitability of conventional, clinically established tests for disclosing processing speed deficits would be of great practical significance. Second, in our preceding study [12], we were not able to assess whether cognitive domains other than processing speed are also affected by the underlying arousal deficit. A demonstration that processing speed is selectively impaired in PCS patients would bear strong support for our hypoarousal model.…”

“…Recently, we proposed that fatigue is caused by hypoactivity within the brain's arousal network, reflected by a fundamental slowing of processing speed in PCS patients [12]. In particular, the variance of (visual) processing speed in a laboratory task was explained by a neurophysiological measure of central nervous arousal, i.e., pupillary unrest, and the level of subjective mental fatigue.…”