Sympathetic and parasympathetic modulation of pupillary unrest

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

A Cross-Recurrence Analysis of the Pupil Size Fluctuations in Steady Scotopic Conditions

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

Standards in Pupillography

The number of research groups studying the pupil is increasing, as is the number of publications. Consequently, new standards in pupillography are needed to formalize the methodology including recording conditions, stimulus characteristics, as well as suitable parameters of evaluation. Since the description of intrinsically photosensitive retinal ganglion cells (ipRGCs) there has been an increased interest and broader application of pupillography in ophthalmology as well as other fields including psychology and chronobiology. Color pupillography plays an important role not only in research but also in clinical observational and therapy studies like gene therapy of hereditary retinal degenerations and psychopathology. Stimuli can vary in size, brightness, duration, and wavelength. Stimulus paradigms determine whether rhodopsin-driven rod responses, opsin-driven cone responses, or melanopsin-driven ipRGC responses are primarily elicited. Background illumination, adaptation state, and instruction for the participants will furthermore influence the results. This standard recommends a minimum set of variables to be used for pupillography and specified in the publication methodologies. Initiated at the 32nd International Pupil Colloquium 2017 in Morges, Switzerland, the aim of this manuscript is to outline standards in pupillography based on current knowledge and experience of pupil experts in order to achieve greater comparability of pupillographic studies. Such standards will particularly facilitate the proper application of pupillography by researchers new to the field. First we describe general standards, followed by specific suggestions concerning the demands of different targets of pupil research: the afferent and efferent reflex arc, pharmacology, psychology, sleepiness-related research and animal studies

Automatic Stress Classification With Pupil Diameter Analysis

This article proposes a method based on wavelet transform and neural networks for relating pupillary behavior to psychological stress. The proposed method was tested by recording pupil diameter and electrodermal activity during a simulated driving task. Self-report measures were also collected. Participants performed a baseline run with the driving task only, followed by three stress runs where they were required to perform the driving task along with sound alerts, the presence of two human evaluators, and both. Self-reports and pupil diameter successfully indexed stress manipulation, and significant correlations were found between these measures. However, electrodermal activity did not vary accordingly. After training, the four-way parallel neural network classifier could guess whether a given unknown pupil diameter signal came from one of the four experimental trials with 79.2% precision. The present study shows that pupil diameter signal has good discriminating power for stress detection

Simultaneous pupillometry and functional Magnetic Resonance Imaging (fMRI) for the detection of stress-related endophenotypes

Mental diseases constitute a core health challenge of the 21st century. To date, diagnostics in psychiatry have been primarily based on subjective self-reports, largely bypassing the biological underpinnings and phenotypic heterogeneity of psychiatric disorders. As an effort to implement a more biologically valid classification of mental disorders, recent initiatives like the Research Domain Criteria (RDoC) project aim to identify endophenotypes that reflect transdiagnostic core mechanisms of psychiatric disorders. Stress is known to play a fundamental role in the development of mood and anxiety disorders. One key system involved in the physiological response to stress is the brainstem?s noradrenergic (NA) arousal center located in the locus coeruleus (LC), and previous studies indicate that pupil size provides an indirect index for activity of the LC-NA system. In order to investigate the relationship between spontaneous drifts in autonomic arousal and global brain activity in healthy human subjects, we first determined the fMRI correlates of spontaneous pupil fluctuations during the resting state. We found that pupil dilations are strongly coupled to activation of the dorsal anterior cingulate cortex (dACC) and bilateral insula (salience network [SN]). To assess whether this link between the pupil and the SN would also extend to emotional arousal, we next investigated the neural correlates of reward anticipation-induced pupil dilations in healthy subjects. Here, we could show that a cue signaling the possibility to receive a monetary reward evoked strong pupil dilations, the magnitude of which predicted response time to a target cue. Again, pupil dilations were strongly linked to SN activation. Furthermore, our results suggest that pupillometry is helpful to dissect different phases of reward anticipation and associated brain activity, disentangling reward prediction, arousal modulation and attentionrelated processes. These observations led us to the conclusion that the SN modulates arousal levels to optimize task performance, that is, to counteract drowsiness/ transitions to sleep during the resting state and to facilitate reward-directed behaviors in the reward anticipation task. Taken together, pupillometry appears to provide a reliable index for activity of the SN, a core network related to psychiatric disorders, making it a promising tool for the detection of stress-related endophenotypes

Exploring cognition in visual search and vigilance tasks with eye tracking and pupillometry

Recent findings in experimental psychology suggest that pupillometry, the measurement of pupil size, can provide insight into cognitive processes associated with effort and target detection in visual search tasks and monitoring performance in vigilance tasks. With the increasing availability, affordability and flexibility of video-based eye tracking hardware, these experimental findings point to lucrative practical applications such as real-time biobehavioural monitoring systems to assist with socially important tasks in operational settings. The aim of the current thesis was to explore this potential with further experimental work paying close attention to methodological issues which complicate cognitive interpretations of pupillary responses, such as physical stimulus confounds and eye movement-related measurement error in video-based systems. Six original experiments were designed to specifically explore the relationship between pupil size, cognition and behavioural performance in classic visual search and vigilance paradigms. Experiments 1-2 examined the pupillometric effects of effort and target detection in visual search with briefly presented stimuli. Pupil responses showed small variability with respect to manipulations of set size and target presence but were influenced substantially by the requirement for a motor response. Experiments 3-4 explored the cognitive pupil dynamics of free-viewing visual search with data-driven correction for eye movement artefacts. Group-level averages revealed small transient pupil dilations following fixations on targets but not distractors, an effect which was not contingent on a motor response or correction for gaze position artefacts. Experiments 5-6 looked at the relationship between pupil size and detection performance measures in two types of vigilance task. Changes in baseline and stimulus-evoked pupil responses loosely mirrored changes in performance, but the relationships were neither linear nor consistent. Overall, the thesis affirms the practical potential for using cognitive pupillometry in research and applied settings, but emphasises the constraints arising from methodological and theoretical limitations