Pupillary unrest is an established indicator of drowsiness or sleepiness. How sympathetic and parasympathetic activity contribute to pupillary unrest is not entirely unclear. In this study, we investigated 83 young healthy volunteers to assess the relationship of pupillary unrest to other markers of the autonomic nervous system. Sample entropy (SE) and the established pupillary unrest index (PUI) were calculated to characterize pupil size variability. Autonomic indices were derived from heart rate, blood pressure, respiration, and skin conductance. Additionally, we assessed individual levels of calmness, vigilance, and mood. In an independent sample of 26 healthy participants, we stimulated the cardiovagal system by a deep breathing test. PUI was related to parasympathetic cardiac indices and sleepiness. A linear combination of vagal heart rate variability [root mean square of heart beat interval differences (RMSSD)] and skin conductance fluctuations (SCFs) was suited best to explain interindividual variance of PUI. Complexity of pupil diameter (PD) variations correlated to indices of sympathetic skin conductance. Furthermore, we found that spontaneous fluctuations of skin conductance are accompanied by increases of pupil size. In an independent sample, we were able to corroborate the relation of PUI with RMSSD and skin conductance. A slow breathing test enhanced RMSSD and PUI proportionally to each other, while complexity of PD dynamics decreased. Our data suggest that the slow PD oscillations (f < 0.15 Hz) quantified by PUI are related to the parasympathetic modulation. Sympathetic arousal as detected by SCFs is associated to transient pupil size increases that increase non-linear pupillary dynamics.

Abstract:The ability to predict when a person is about to fall asleep is an important challenge in recent biomedical research and has various possible applications. Sleepiness and fatigue are known to increase pupillary fluctuations and the occurrence of eye blinks. In this study, we evaluated the use of the pupil diameter to forecast sleep episodes of short duration (>1s). We conducted multi-channel physiological and pupillometric recordings (diameter, gaze position) in 91 healthy volunteers at rest in supine position. Although they were instructed to keep their eyes open, short sleep episodes were detected in 20 participants (16 males, age: 26.2±5.6 years), 53 events in total. Before each sleep event, pupil size was extracted in a window of 30s (without additional sleep event). Mean pupil diameter and its standard deviation, Shannon entropy and wavelet entropy in the first half (15s) were compared to the second half of the window (15s). Linear and nonlinear measures demonstrated an elevation of pupil size variability before sleep onset. Most obviously, WE and SD increased significantly from 0.054±0.056 and 0.38±0.16 mm to 0.113±0.103 (T(102)=2.44, p<0.001) and 0.46±0.18 mm (T(104)=3.67, p<0.05) in the second half of each analysis window. We were able to identify 83% of the pre-sleep segments by linear discriminant analysis. Although our data was acquired in an experimental condition, it suggests that pupillary unrest might be a suitable predictor of events related to transient sleep or inattentiveness. In the future, we are going to involve the other recorded physiological signals into the analysis.

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