Fatigue in Cancer and Neuroinflammatory and Autoimmune Disease: CNS Arousal Matters

Abstract

The term fatigue is not only used to describe a sleepy state with a lack of drive, as observed in patients with chronic physical illnesses, but also a state with an inhibition of drive and central nervous system (CNS) hyperarousal, as frequently observed in patients with major depression. An electroencephalogram (EEG)-based algorithm has been developed to objectively assess CNS arousal and to disentangle these pathophysiologically heterogeneous forms of fatigue. The aim of this study was to test the hypothesis that fatigued patients with CNS hyperarousal score higher on depressive symptoms than those without this neurophysiological pattern. Methods: Subjects with fatigue (Multidimensional Fatigue Inventory sum-score > 40) in the context of cancer, neuroinflammatory, or autoimmune diseases were drawn from the 60+ cohort of the Leipzig Research Center for Civilization Diseases. CNS arousal was assessed by automatic EEG-vigilance stage classification using the Vigilance Algorithm Leipzig (VIGALL 2.1) based on 20 min EEG recordings at rest with eyes closed. Depression was assessed by the Inventory of Depressive Symptomatology (IDS-SR). Results: Sixty participants (33 female; median age: 67.5 years) were included in the analysis. As hypothesized, fatigued patients with CNS hyperarousal had higher IDS-SR scores than those without hyperarousal (F1,58 = 18.34; p < 0.0001, η2 = 0.240). Conclusion: hyperaroused fatigue in patients with chronic physical illness may be a sign of comorbid depression.

The Big Five Personality Traits and Brain Arousal in the Resting State

“…In comparison to neuroticism facet 'impulsiveness', our analyses did not reveal indications for a link between neuroticism facet 'depression' and brain arousal. By applying the Vigilance Algorithm Leipzig, several previous studies provided supportive evidence for an association between clinical depression and enhanced brain arousal in the resting state [41][42][43][44][45][46][47][48]51]. Although the present study included participants without a current depression diagnosis, it can be assumed that alterations in brain arousal occur in both the normal and pathological range of human behavior.…”

“…One of the most prominent traits approaches to describe and measure the structure of human personality is the Five-Factor Model (FFM) [9,10]. The FFM is a taxonomy that strives for an economic description of the whole range of individual differences in in the resting state [41][42][43][44][45][46][47][48]. Despite these converging lines of research, available EEG studies have not yet provided supportive evidence for an association between brain arousal and neuroticism [25,26,29,31].…”

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

“…In the present study, we assumed that a critical link between cognitive dysfunction, often described as “brain fog”, and fatigue in post-COVID syndrome is a reduction in the brain’s general level of arousal. Arousal exists on a behavioral continuum between sleep and alert hypervigilance and fear [ 65 , 75 ]. Normal waking alertness as a state between the extremes is most optimal for attentional cognitive performance [ 32 , 80 ].…”

Brain Arousal as Measured by EEG-Assessment Differs Between Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) and Depression

“…In terms of dysfunctional brain arousal state, the brain can be upor downregulated. Adult patients with depression often show upregulated brain states, resulting in inner tension and inhibition of drive (2) and prolonged sleep latency (3). The opposite, downregulated brain states with short sleep latency and a high prevalence of excessive daytime sleepiness and sleep and circadian disorders are related to ADHD (4) and mania (1).…”