The Psychoneurobiology of Insomnia: Hyperarousal and REM Sleep Instability

Abstract

Chronic insomnia (insomnia disorder—ID) afflicts up to 10% of the adult population, increases with age and affects more women than men. ID is associated with significant daytime impairments and an increased risk for developing major somatic and mental disorders, especially depression and anxiety disorders. Almost all insomnia models assume persistent hyperarousal on cognitive, emotional, cortical and physiological levels as a central pathophysiological component. The marked discrepancy between only minor objective alterations in polysomnographic parameters of sleep continuity and the profound subjective impairment in patients with insomnia is still puzzling. We and others have proposed that alterations in the microstructure of sleep, especially in REM sleep (REM sleep instability), may explain this discrepancy and be at the core of the experience of fragmented and poor sleep in ID. The REM sleep instability concept is based on evidence showing REM time to be related to subjective wake time in insomnia as well as increased micro- and macro-arousals during REM sleep in insomnia patients compared to good-sleeper controls. Our own work showed that ID patients awoken from REM sleep more frequently reported the perception of having been awake than good sleepers as well as having had more negative ideations. The continuous measurement of event-related potentials throughout the whole night demonstrated reduced P2 amplitudes specifically during phasic REM sleep in insomnia, which points to a mismatch negativity in ID reflecting automatic change detection in the auditory system and a concomitant orienting response. REM sleep represents the most highly aroused brain state during sleep and thus might be particularly prone to fragmentation in individuals with persistent hyperarousal, resulting in a more conscious-like wake experience reflecting pre-sleep concerns of patients with ID, i.e., worries about poor sleep and its consequences, thus leading to the subjective over-estimation of nocturnal waking time and the experience of disrupted and non-restorative sleep. Chronic REM sleep instability might also lead to a dysfunction in a ventral emotional neural network, including limbic and paralimbic areas activated during REM sleep. Along with a postulated weakened functioning in a dorsal executive neural network, including frontal and prefrontal areas, this might contribute to emotional and cognitive alterations and an elevated risk of developing depression and anxiety.