Pupil size reveals arousal level dynamics in human sleep

Abstract

Changes in arousal level are a determining characteristic of healthy and pathological sleep in humans, but how they are conventionally measured lack sensitivity and temporal precision. Recent animal research has revealed the intricate dynamics of arousal levels that are potentially crucial for maintaining proper sleep resilience and memory consolidation. To investigate whether similar dynamics exist in humans, we measured pupil size, an established indicator of arousal levels, for the first time during overnight sleep and tested the cortical response to auditory stimulation at different levels of arousal. Here we show that pupil size dynamics correspond to sleep macrostructure and microstructural events, while exhibiting an inverse relationship with fluctuations of sleep spindles, a marker of sleep resilience and memory consolidation. Additionally, pupil size prior to auditory stimulation influences its effectiveness to enhance delta power, a marker of several restorative and regenerative functions of sleep. These pupil size dynamics provide novel insights into the interplay between arousal levels and sleep, opening avenues for future research and clinical applications in diagnosing and treating pathological sleep associated with abnormal arousal levels.

Cardiovascular responses to natural and auditory evoked slow waves predict post-sleep cardiac function

“…Our observed stronger cortico-cardiovascular coupling in type I slow waves supports the idea of an enhanced subcortical involvement because the processes underlying type I slow waves likely activate the sympathoexcitatory locus coeruleus 30 , a small nucleus in the brain stem serving as noradrenergic center of the brain. Supporting this idea, we recently showed a pupil dilation alongside K-complexes 31 , indirectly pointing towards a potential increase in locus coeruleus activity concurrent with highlysynchronized slow waves 32 . Additionally, K-complexes coincide with spikes in muscle sympathetic nerve activity 18,20 , also supporting the stronger cardiovascular activation response compared to type II slow waves.…”

Noradrenergiclocus coeruleusactivity functionally partitions NREM sleep to gatekeep the NREM-REM sleep cycle

“…One example is a singular, large low-frequency EEG wave that is prominent in human NREMS stage 2, referred to as ‘K-complex’ 58 . K-complexes are associated with small but consistent increases in heart rate 59,60 , yet they have been variably described as sleep-protecting or arousal-related EEG hallmarks 58 . The data we present now indicate that increases in low-frequency activity in the EEG can be a forebrain manifestation of activated brainstem arousal circuits, which is in line with suggestions on the origins of K-complexes based on EEG source analyses 61 .…”

“…We suggest that some K-complexes in human sleep should be examined with respect to a possible implication of LC activity in human NREMS. A recent study using pupillometry as a proxy for LC activity in human sleep demonstrates that such progress is in reach 60 .…”

Fractal cycles of sleep: a new aperiodic activity-based definition of sleep cycles

“…Circumstantial evidence suggests that fractal activity is a measure of sleep homeostasis or sleep intensity, reflecting sleep-wake history, sleep stage differences, sleep cycles, age-effects, local sleep and sleep disorders (Bódizs et al, 2023). Recently, it has been reported that during human sleep, spectral slopes positively correlate with pupil size, a marker of arousal levels linked to the activity of the locus coeruleus-noradrenergic system (Carro-Domínguez et al, 2023).…”