Dataset Information

Baseline Pupil Diameter Is Not a Reliable Biomarker of Subjective Sleepiness.

ABSTRACT: Sleepiness is commonly seen as reflecting the basic physiological need to sleep and is associated with physiological and neurobiological changes. Subjective evaluations of sleepiness, however, are neither representative of cognitive and physical performances, nor of physiological sleepiness. Finding a simple, rapid, and objective marker of sleepiness is essential in order to prevent errors and accidents, but this has remained largely unsuccessful. The aim of this study was to determine whether the baseline pupil diameter is a physiological biomarker of sleepiness at all times of day and to isolate the regulatory components involved. Twelve healthy men (20-29 years old) participated in a 56-h experimental protocol, including a 34-h constant routine paradigm with enforced wakefulness. This protocol was used in order to eliminate the potential influence of all environmental rhythms and reveal the endogenous circadian rhythmicity of two physiological measures: sleepiness and pupil diameter. Sleepiness was assessed subjectively every hour on a computerized 10 cm visual analog scale and pupil size was recorded every 2 h with a hand-held video-pupilometer. Our results revealed that subjective sleepiness increased linearly with time awake and displayed a circadian rhythm. Baseline pupil diameter showed a linear decrease with time spent awake as well as a circadian 24-h rhythm. This is the first evidence of a circadian variation of the baseline pupil size in a highly-controlled constant routine paradigm conducted in very dim light conditions. An overall negative correlation between the size of the pupil and the subjective level of sleepiness was observed. Analyzing the contribution of the two sleep regulation components in this correlation, we further showed: (1) a negative correlation between the homeostatic sleep pressure components, (2) a negative correlation between the circadian drives only during half of the 24 hours, corresponding to 62% of the biological day and 25% of the biological night. These results highlight that, due to the dual regulation of sleepiness by the homeostatic and circadian processes, baseline pupil diameter is an index of sleepiness only at certain times and therefore cannot be used as a systematic and reliable biomarker of sleepiness.

SUBMITTER: Daguet I

PROVIDER: S-EPMC6398346 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Baseline Pupil Diameter Is Not a Reliable Biomarker of Subjective Sleepiness.

Daguet Inès I Bouhassira Didier D Gronfier Claude C

Frontiers in neurology 20190225

Sleepiness is commonly seen as reflecting the basic physiological need to sleep and is associated with physiological and neurobiological changes. Subjective evaluations of sleepiness, however, are neither representative of cognitive and physical performances, nor of physiological sleepiness. Finding a simple, rapid, and objective marker of sleepiness is essential in order to prevent errors and accidents, but this has remained largely unsuccessful. The aim of this study was to determine whether t ...[more]

PMID: 30858817

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Project description:Arousal state affects neural activity and vascular dynamics in the cortex, with sleep associated with large changes in the local field potential and increases in cortical blood flow. We investigated the relationship between pupil diameter and blink rate with neural activity and blood volume in the somatosensory cortex in male and female unanesthetized, head-fixed mice. We monitored these variables while the mice were awake, during periods of rapid eye movement (REM), and non-rapid eye movement (NREM) sleep. Pupil diameter was smaller during sleep than in the awake state. Changes in pupil diameter were coherent with both gamma-band power and blood volume in the somatosensory cortex, but the strength and sign of this relationship varied with arousal state. We observed a strong negative correlation between pupil diameter and both gamma-band power and blood volume during periods of awake rest and NREM sleep, although the correlations between pupil diameter and these signals became positive during periods of alertness, active whisking, and REM. Blinking was associated with increases in arousal and decreases in blood volume when the mouse was asleep. Bilateral coherence in gamma-band power and in blood volume dropped following awake blinking, indicating a reset of neural and vascular activity. Using only eye metrics (pupil diameter and eye motion), we could determine the arousal state of the mouse ('Awake,' 'NREM,' 'REM') with >90% accuracy with a 5 s resolution. There is a strong relationship between pupil diameter and hemodynamics signals in mice, reflecting the pronounced effects of arousal on cerebrovascular dynamics.SIGNIFICANCE STATEMENT Determining arousal state is a critical component of any neuroscience experiment. Pupil diameter and blinking are influenced by arousal state, as are hemodynamics signals in the cortex. We investigated the relationship between cortical hemodynamics and pupil diameter and found that pupil diameter was strongly related to the blood volume in the cortex. Mice were more likely to be awake after blinking than before, and blinking resets neural activity. Pupil diameter and eye motion can be used as a reliable, noninvasive indicator of arousal state. As mice transition from wake to sleep and back again over a timescale of seconds, monitoring pupil diameter and eye motion permits the noninvasive detection of sleep events during behavioral or resting-state experiments.

Dataset Information

Baseline Pupil Diameter Is Not a Reliable Biomarker of Subjective Sleepiness.

Publications

Baseline Pupil Diameter Is Not a Reliable Biomarker of Subjective Sleepiness.

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