Abstract

Pupil size fluctuations during stationary scotopic conditions may convey information about the cortical state activity at rest. An important link between neuronal network state modulation and pupil fluctuations is the cholinergic and noradrenergic neuromodulatory tone, which is active at cortical level and in the peripheral terminals of the autonomic nervous system (ANS). This work aimed at studying the low- and high-frequency coupled oscillators in the autonomic spectrum (0–0.45 Hz) which, reportedly, drive the spontaneous pupillary fluctuations. To assess the interaction between the oscillators, we focused on the patterns of their trajectories in the phase-space. Firstly, the frequency spectrum of the pupil signal was determined by empirical mode decomposition. Secondly, cross-recurrence quantification analysis was used to unfold the non-linear dynamics. The global and local patterns of recurrence of the trajectories were estimated by two parameters: determinism and entropy. An elliptic region in the entropy-determinism plane (95% prediction area) yielded health-related values of entropy and determinism. We hypothesize that the data points inside the ellipse would likely represent balanced activity in the ANS. Interestingly, the Epworth Sleepiness Scale scores scaled up along with the entropy and determinism parameters. Although other non-linear methods like Short Time Fourier Transform and wavelets are usually applied for analyzing the pupillary oscillations, they rely on strong assumptions like the stationarity of the signal or the a priori knowledge of the shape of the single basis wave. Instead, the cross-recurrence analysis of the non-linear dynamics of the pupil size oscillations is an adaptable diagnostic tool for identifying the different weight of the autonomic nervous system components in the modulation of pupil size changes at rest in non-luminance conditions.

Highlights

  • The pupil controls the amount of light radiations reaching the retina, by modulating its diameter through the interaction of two muscles under sympathetic-parasympathetic control

  • The autonomic control of the spontaneous pupil fluctuations is expected to have non-linear/chaotic dynamics which can be well explored by recurrence analysis methods, whose domain is in the phase-space trajectories (Mesin et al, 2013)

  • The empirical mode decomposition (EMD) method was applied to the time series of pupil size variations to extract the low and high frequency components of the signal, which were found in the range of the autonomic nervous system (ANS) band

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Summary

Introduction

The pupil controls the amount of light radiations reaching the retina, by modulating its diameter through the interaction of two muscles under sympathetic-parasympathetic control. Optical imaging and neural networks modeling, indicated that the link between brain state activity and pupil size is related to the neuro-modulatory effect of the noradrenergic and cholinergic systems (Murphy et al, 2014; Costa and Rudebeck, 2016; Joshi et al, 2016; Eckstein et al, 2017) In this respect, a direct relationship between pupil size and moment-to-moment fluctuations in the activity of noradrenergic neurons of the brainstem locus coeruleus (LC) has been verified (Aston-Jones and Cohen, 2005; Nassar et al, 2012). These studies outline a new role for the pupil size monitoring as a reliable and non-invasive peripheral marker of rapid brain state changes (Hartmann and Fischer, 2014; Schwalm and Jubal, 2017)

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