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

Respiratory influences on pupil size dynamics and visual recognition memory

Breathing, a fundamental rhythm of life, has traditionally been associated with the exchange of oxygen and carbon dioxide. However, recent research in both animal models and humans has unveiled additional roles of respiration in modulating cortical neuronal activity, influencing sensory, motor, emotional, and cognitive processes. This dissertation aims to explore the impact of respiration on pupil size dynamics and visual recognition memory in humans. In Study I, we synthesized the research conducted on respiratory influences on pupil size dynamics in humans by conducting a systematic literature review. We discovered that the evidence for respiratory influences on pupil size dynamics in humans is less solid and extensive than previously believed. After more than 50 years of research, only 12 studies have directly investigated this topic. Not only was the underlying evidence for an effect of breathing phase, depth, and rate on pupil size dynamics weak, but the influence of breathing route (oral or nasal breathing) had not been investigated at all. In Study II, we conducted an experimental study to answer the outstanding questions identified in Study I. We collected pupil size data from participants during periods of rest while they breathed through their nose and mouth, on separate occasions. We demonstrated small but significant effects of breathing phase on pupil size and a spurious correlation and phase synchronization between the breathing and the pupil signal that is largely driven by breathing rate. After accounting for this spurious correlation and phase synchronization, we show that a small but significant interaction between the breathing and the pupil signal remains. Importantly, we show that, contrary to common belief, pupil size does not increase during inhalation, but rather during exhalation. Furthermore, we did not find any changes in pupil size in the time around inhalation and exhalation, and our results were not affected by the breathing route. In conclusion, we confirmed the influence of breathing on pupil size dynamics, while uncovering a more complex and intricate relationship than previously conceived. In Study III, we investigated the influence of breathing phase and breathing route on performance in a visual recognition memory task with a within-subject design and with stimuli presentation phase-locked to the inhalation or exhalation onset. We show that neither breathing phase nor breathing route affect memory performance. However, we did find an effect of breathing phase on response bias, with participants using a more conservative response bias during exhalation. Furthermore, we found that breathing route and breathing phase shape the Late Parietal Effect (LPE), but not the Frontal Negative Component (FN400), amplitude during encoding. Additionally, during recognition, both the LPE and FN400 component amplitudes were not, or only to a small extent, affected by breathing route and phase. While we demonstrated that breathing does not shape visual recognition memory performance, we also showed that breathing influences brain activity related to memory functions. Therefore, we highlight the importance of further research to elucidate the extent of respiratory influence on perception, cognition, and behavior. In Study IV, we further investigated the impact of breathing on visual memory performance by investigating the effects of nasal breathing phase on memory of repeated images presented in a rapid serial visual presentation (RSVP) task. In two separate, high-powered experiments, we did not find an effect of breathing phase on task performance. An exploratory analysis in the first experiment discovered a potential performance increase for stimuli presented approximately one second after inhalation. However, this was not replicated in the second, larger, and pre-registered study. Thus, we find no effect of breathing phase on performance in this RSVP task and urge for caution regarding the notion that visual memory is broadly affected by the breathing phase. Finally, in Study V, we investigated whether oral hormonal contraceptives (OC) affect chemosensory sensitivity and perception. Whereas previous research focused nearly exclusively on olfaction, we expanded this to also study the taste and trigeminal sense. Making use of Bayesian statistics, we evaluated the performance differences between a group of women taking OC, and a control group of normal cycling women. Our results indicated that the use of OC does not affect odor, trigeminal, or taste detection thresholds. Furthermore, neither odor nor taste perception were affected, with Bayes factors weighing the evidence in favor of the null hypothesis. We therefore conclude it to be unlikely that OC affect chemosensory perception to a degree that is of behavioral relevance. Collectively, this doctoral thesis challenges prevailing myths while paving the way for a more intricate understanding of the relationship between respiration and pupil size, and perceptual and cognitive processes. Importantly, it underscores the importance of implementing rigorous methodological paradigms in future research

Veränderungen des autonomen Nervensystems bei Patientinnen mit Anorexia nervosa

Die Anorexia nervosa gilt als die psychiatrische Erkrankung mit der höchsten Mortalität. Da dies mitunter an kardialen Komplikationen liegt, soll diese Arbeit die Ursachen hierfür genauer untersuchen und damit Angriffspunkte für neue Therapieansätze liefern. Aus einigen vorausgehenden Studien ist bekannt, dass bei magersüchtigen Patientinnen Veränderungen im autonomen Nervensystem vorliegen, wobei meist eine Überaktivität des Vagotonus bei Reduktion des Sympathotonus konstatiert wurde. In dieser sowie in einigen weiteren Arbeiten wurde bereits festgestellt, dass Patientinnen mit Anorexia nervosa eine erniedrigte Hauttemperatur aufweisen. Eine Zentralisation durch eine Erhöhung des Sympathotonus wäre ein möglicher Erklärungsansatz. Durch Messung weiterer vegetativer Parameter ist das Ziel der Arbeit zu erfassen, ob die verringerte Hauttemperatur tatsächlich durch einen gesteigerten Sympathotonus verursacht wird. Wir konnten in unserer Studie vorherige Untersuchungen bestätigen, welche eine Erhöhung des Vagotonus konstatierten. Hinweise hierfür waren beispielsweise eine signifikante Verminderung der Herzfrequenz sowie eine Steigerung der Herzfrequenzvariabilität. Durch die Erniedrigung des tonischen Hautleitniveaus konnten Rückschlüsse auf eine Reduktion des Sympathotonus gezogen werden. Hierdurch lässt sich schlussfolgern, dass die erniedrigte periphere Temperatur bei den Anorexie-Patientinnen nicht durch einen erhöhten Sympathotonus, sondern durch andere Mechanismen bedingt sein muss. Unsere Auswertungen führten also zu dem Ergebnis, dass bei der Anorexia nervosa eine Veränderung des sympathovagalen Gleichgewichts im Sinne einer Dominanz des Parasympathikus bei Reduktion der peripheren sympathischen Antwort vorliegt. Da diese autonome Imbalance lebensbedrohlich sein kann, sollten bei der Behandlung der Anorexia nervosa die Überwachung vegetativer und dabei besonders kardialer Parameter durchgeführt werden und gegebenenfalls eine therapeutische Intervention erfolgen