A hypoarousal model of neurological post‑COVID syndrome

The study “A Hypoarousal Model of Neurological Post-COVID Syndrome:the relation between mental fatigue, the level of central nervousactivation and cognitive processing speed” investigates the relationship between cognitive dysfunction, mental fatigue, and hypoarousal of the brain in post-COVID patients.

Here’s a detailed summary:

Background and Objectives: Post-COVID syndrome often includes neurological and neuropsychiatric sequelae, particularly cognitive dysfunction and fatigue. This study hypothesized that these symptoms in post-COVID syndrome are linked to hypoarousal of the brain. It aimed to assess whether tonic alertness, a neurocognitive index of arousal, is reduced in post-COVID patients and how this relates to central nervous activation and subjective mental fatigue​​.

Methods: The study involved 40 post-COVID patients with subjective cognitive dysfunction and 40 healthy controls. They underwent a whole-report paradigm of briefly presented letter arrays, which assessed their visual processing speed (VPS), a proxy for tonic alertness. Additionally, pupillary unrest, a measure of central nervous activation, and mental fatigue (assessed by the Fatigue Assessment Scale) were evaluated​​.

Neurophysiological Measure: Pupillary unrest was used as a neurophysiological measure of central nervous activation, reflecting the brain’s level of arousal. The Pupillary Unrest Index (PUI) was determined by assessing the absolute values of cumulative dark-adapted pupil size changes​​.


  • VPS was found to be reduced in post-COVID patients compared to healthy controls.
  • Both pupillary unrest and mental fatigue predicted VPS, explaining 34% of the variance, indicating a significant relationship between these factors and tonic alertness.
  • The study’s findings support the hypothesis that hypoarousal is present in post-COVID patients with subjective cognitive dysfunction​​.

Additional Findings:

  • There was a correlation between lower VPS and lower visual short-term memory capacity (vSTM capacity K), indicating that hypoarousal affects multiple cognitive functions​​.

Conclusion: The study concludes that in post-COVID patients with subjective cognitive dysfunction, hypoarousal of the brain is reflected in decreased processing speed, which is explained by reduced central nervous activation and higher mental fatigue. This research highlights the potential for addressing hypoarousal in treating cognitive dysfunction and fatigue in post-COVID syndrome​​.

In summary, this study provides valuable insights into the neurocognitive underpinnings of post-COVID syndrome, particularly the role of hypoarousal in cognitive dysfunction and fatigue. It opens avenues for targeted therapeutic strategies to address these debilitating symptoms.

Read More: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511382/

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