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Phase-amplitude cross-frequency coupling is a mechanism thought to facilitate communication between neuronal ensembles. The mechanism could underlie the implementation of complex cognitive processes, like executive functions, in the brain. This thesis contributes to answering the question, whether phase-amplitude cross-frequency coupling - assessed via electroencephalography (EEG) - is a mechanism by which executive functioning is implemented in the brain and whether an assumed performance effect of stress on executive functioning is reflected in phase-amplitude coupling strength. A huge body of studies shows that stress can influence executive functioning, in essence having detrimental effects. In two independent studies, each being comprised of two core executive function tasks (flexibility and behavioural inhibition as well as cognitive inhibition and working memory), beta-gamma phase-amplitude coupling was robustly detected in the left and right prefrontal hemispheres. No systematic pattern of coupling strength modulation by either task demands or acute stress was detected. Beta-gamma coupling might also be present in more basic attention processes. This is the first investigation of the relationship between stress, executive functions and phase-amplitude coupling. Therefore, many aspects have not been explored yet. For example, studying phase precision instead of coupling strength as an indicator for phase-amplitude coupling modulations. Furthermore, data was analysed in source space (independent component analysis); comparability to sensor space has still to be determined. These as well as other aspects should be investigated, due to the promising finding of very robust and strong beta-gamma coupling for all executive functions. Additionally, this thesis tested the performance of two widely used phase-amplitude coupling measures (mean vector length and modulation index). Both measures are specific and sensitive to coupling strength and coupling width. The simulation study also drew attention to several confounding factors, which influence phase-amplitude coupling measures (e. g. data length, multimodality).
Ausgehend von einem multifaktoriellen biopsychosozialen Modell zur Entstehung und Aufrechterhaltung primärer Kopfschmerzen bei Kindern und Jugendlichen wurden n= 170 Mädchen im Alter von 12-17 Jahren hinsichtlich verschiedener stressbezogener Determinanten untersucht. Es wurde davon ausgegangen, dass sich Mädchen mit wiederkehrenden Kopfschmerzen sowohl in einem kontrollierten, messwiederholten Laborexperiment hinsichtlich ihrer physiologischen Reaktionen (Muskelspannung, Cortisolausschüttung) auf akuten Stress hin wie auch in der Cortisolaufwachreaktion im häuslichen Setting von einer gesunden Kontrollgruppe unterscheiden. Diese Annahmen konnten nach statistischer Auswertung der Studienergebnisse unter Kontrolle der familiären Schmerzbelastung und psychischen Stressbelastung jedoch nicht bestätigt werden. Somit kann nicht von einer dysregulierten Aktivität der Hypothalamus-Hypophysen-Nebennierenrinden-Achse ausgegangen werden, die eine zentrale Rolle in der biologischen Stressantwort spielt und auch die Schmerzverarbeitung mit beeinflusst. Ebenso wenig liegt bei Mädchen mit Kopfschmerzen eine erhöhte basale oder stressbedingte Muskelspannung im Kopf- und Schulterbereich vor. Lediglich auf subjektiver Ebene deutete sich ein tendenziell höheres Empfinden von Anspannung in Ruhephasen an. Auf psychologischer Ebene hingegen zeigte sich erwartungskonform eine höhere Stress-vulnerabilität bei den Mädchen mit Kopfschmerzen. Außerdem wurde bei ihnen der vermehrte Einsatz emotionsregulierender Stressbewältigungsstrategien, wie Ruhe und Entspannung, aber auch destruktiv-ärgerbezogenes Verhalten und Denken, bezogen auf soziale und leistungsbezogene Stresssituationen beobachtet. Auch unterschieden sie sich hinsichtlich der familiären Schmerzbelastung, körperlichen und psychischen Stress-symptomatik und Depressivität sowie Ängstlichkeit von der Kontrollgruppe. Sie zeigten durchweg höhere Ausprägungen auf diesen Variablen, die sich als signifikante Prädiktoren für Kopfschmerzen herausstellten. Die Verknüpfung von physiologischen Reaktionsmaßen mit der Stressverarbeitung zeigte, dass die Nutzung von konstruktiv-palliativer Emotionsregulation umso stärker ist, je höher der stressbedingte Anstieg der Cortisolausschüttung und der Muskelaktivität in der Frontalisregion ausfällt. Je stärker also die körperliche Reaktion auf Stress, umso mehr versuchen jugendliche Mädchen sich zu entspannen und auszuruhen.
The last decades of stress research have yielded substantial advancements highlighting the importance of the phenomenon for basic psychological functions as well as physical health and well-being. Progress in stress research heavily relies on the availability of suitable and well validated laboratory stressors. Appropriate laboratory stressors need to be able to reliably provoke a response in the relevant parameters and be applicable in different research settings or experimental designs. This thesis focuses on the Cold Pressor Test (CPT) as a stress induction technique. Three published experiments are presented that show how the advantages of the CPT can be used to test stress effects on memory processes and how some of its disadvantages can be met by a simple modification that retains its feasibility and validity. The first experiment applies the CPT in a substantial sample to investigate the consolidation effects of post-learning sympathetic arousal. Stressed participants with high increases in heart rate during the CPT showed enhanced memory performance one day after learning compared to both the warm water control group and low heart rate responders. This finding suggests that beta-adrenergic activation elicited shortly after learning enhances memory consolidation and that the CPT induced heart rate response is a predictor for this effect. Moreover, the CPT proved to be an appropriate stressor to test hypothesis about endogenous adrenergic effects on memory processes. The second experiment addresses known practical limitations of the standard dominant hand CPT protocol. A bilateral feet CPT modification is presented, the elicited neuroendocrine stress response assessed and validated against the standard CPT in a within-subjects design. The bilateral feet CPT elicited a substantial neuroendocrine stress response. Moreover, with the exception of blood pressure responses, all stress parameters were enhanced compared to the standard CPT. This shows that the bilateral feet CPT is a valid alternative to the standard CPT. The third experiment further validates the bilateral feet CPT and its corresponding control procedure by employing it in a typical application scenario. Specifically, the bilateral feet CPT was used to modulate retrieval of event files in a distractor-response binding paradigm that required lateralized bimanual responses. Again, the bilateral feet CPT induced significant increases in heart rate, blood pressure and cortisol, no such increases could be observed in the warm water control condition. Moreover, stressed participants showed diminished retrieval compared to controls. These results provide further evidence for the feasibility and validity of the bilateral feet CPT and its warm water control procedure. Together the experiments presented here highlight the usefulness of the CPT as a tool in psychophysiological stress research. It is especially well suited to test hypothesis concerning stress effects on memory processes and its applicability can be further increased by the bilateral feet modification.
Stressinduzierte Veränderungen gastrointestinaler Peptidhormone könnten eine biologische Grundlage für Überessen und einen Faktor bei der Entstehung von Adipositas darstellen. Darum wurden die Veränderungen der Plasmakonzentrationen von Ghrelin und Peptid YY (PYY) durch akuten Stress bei 85 adipösen und normalgewichtigen Frauen untersucht. Im Vergleich zu normalgewichtigen Frauen hatten adipöse Frauen eine geringere pre- als auch postprandiale Ghrelin-Sekretion. Darüber hinaus fiel auch der postprandiale Ghrelin-Abfall bei den adipösen Frauen geringer aus als bei der normalgewichtigen Vergleichsgruppe. Akuter Stress inhibierte die PYY-Sekretion in beiden Gruppen. Außerdem wurde der Effekt von akutem Stress auf das Essverhalten erfasst. Stress inhibierte die Nahrungsaufnahme in beiden Gruppen.
Stress has been considered one of the most relevant factors promoting aggressive behavior. Animal and human pharmacological studies revealed the stress hormones corticosterone in rodents and cortisol in humans to constitute a particularly important neuroendocrine determinate in facilitating aggression and beyond that, assumedly in its continuation and escalation. Moreover, cortisol-induced alterations of social information processing, as well as of cognitive control processes, have been hypothesized as possible influencing factors in the stress-aggression link. So far, the immediate impact of a preceding stressor and thereby stress-induced rise of cortisol on aggressive behavior as well as higher-order cognitive control processes and social information processing in this context have gone mostly unheeded. The present thesis aimed to extend the hitherto findings of stress and aggression in this regard. For this purpose two psychophysiological studies with healthy adults were carried out, both using the socially evaluated-cold pressor test as an acute stress induction. Additionally to behavioral data and subjective reports, event related potentials were measured and acute levels of salivary cortisol were collected on the basis of which stressed participants were divided into cortisol-responders and "nonresponders. Study 1 examined the impact of acute stress-induced cortisol increase on inhibitory control and its neural correlates. 41 male participants were randomly assigned to the stress procedure or to a non-stressful control condition. Beforehand and afterwards, participants performed a Go Nogo task with visual letters to measure response inhibition. The effect of acute stress-induced cortisol increase on covert and overt aggressive behavior and on the processing of provoking stimuli within the aggressive encounter was investigated in study 2. Moreover, this experiment examined the combined impact of stress and aggression on ensuing affective information processing. 71 male and female participants were either exposed to the stress or to the control condition. Following this, half of each group received high or low levels of provocation during the Taylor Aggression Paradigm. At the end of the experiment, a passive viewing paradigm with affective pictures depicting positive, negative, or aggressive scenes with either humans or objects was realized. The results revealed that men were not affected by a stress-induced rise in cortisol on a behavioral level, showing neither impaired response inhibition nor enhanced aggressive behavior. In contrast, women showed enhanced overt and covert aggressive behavior under a surge of endogenous cortisol, confirming previous results, albeit only in case of high provocation and only up to the level of the control group. Unlike this rather moderate impact on behavior, cortisol showed a distinct impact on neural correlates of information processing throughout inhibitory control, aggression-eliciting stimuli, and emotional pictures for both men and women. At this, stress-induced increase of cortisol resulted in enhanced N2 amplitudes to Go stimuli, whereas P2 amplitudes to both and N2 to Nogo amplitudes retained unchanged, indicating an overcorrection and caution of the response activation in favor of successful inhibitory control. The processing of aggression-eliciting stimuli during the aggressive encounter was complexly altered by stress differently for women and men. Under increased cortisol levels, the frontal or parietal P3 amplitude patterns were either diminished or reversed in the case of high provocation compared to the control group and to cortisol-nonresponders, indicating a desensitization towards aggression-eliciting stimuli in males, but a more elaborate processing of those in women. Moreover, stress-induced cortisol and provocation jointly altered subsequent affective information processing at early as well as later stages of the information processing stream. Again, increased levels of cortisol led opposite directed amplitudes in the case of high provocation relative to the control group and cortisol-nonresponders, with enhanced N2 amplitudes in men and reduced P3 and LPP amplitudes in men and women for all affective pictures, suggesting initially enhanced emotional reactivity in men, but ensuing reduced motivational attention and enhanced emotion regulation in both, men and women. As a result, these present findings confirm the relevance of HPA activity in the elicitation and persistence of human aggressive behavior. Moreover, they reveal the significance of compensatory and emotion regulatory strategies and mechanisms in response to stress and provocation, indorsing the relevance of social information and cognitive control processes. Still, more research is needed to clarify the conditions which lead to the facilitation of aggression and by which compensatory mechanisms this is prevented.
The present thesis addresses the validity of Binge Eating Disorder (BED) as well as underlying mechanisms of BED from three different angles. Three studies provide data discriminating obesity with BED from obesity without BED. Study 1 demonstrates differences between obese individuals with and without BED regarding eating in the natural environment, psychiatric comorbidity, negative affect as well as self reported tendencies in eating behavior. Evidence for possible psychological mechanisms explaining increased intake of BED individuals in the natural environment was given by analyzing associations of negative affect, emotional eating, restrained eating and caloric intake in obese BED compared to NBED controls. Study 2 demonstrated stress-induced changes in the eating behavior of obese individuals with BED. The impact of a psychosocial stressor, the Trier Social Stress Test (TSST, Kirschbaum, Pirke, & Hellhammer, 1993), on behavioral patterns of eating behavior in laboratory was investigated. Special attention was given to stress-induced changes in variables that reflect mechanisms of appetite regulation in obese BED individuals compared to controls. To further explore by which mechanisms stress might trigger binge eating, study 3 investigated differences in stress-induced cortisol secretion after a socially evaluated cold pressure test (SECPT, Schwabe, Haddad, & Schachinger, 2008) in obese BED as compared to obese NBED individuals.
Fast and Slow Effects of Cortisol on Several Functions of the Central Nervous System in Humans
(2014)
Cortisol is one of the key substances released during stress to restore homeostasis. Our knowledge of the impact of this glucocorticoid on cognition and behavior in humans is, however, still limited. Two modes of action of cortisol are known, a rapid, nongenomic and a slow, genomic mode. Both mechanisms appear to be involved in mediating the various effects of stress on cognition. Here, three experiments are presented that investigated fast and slow effects of cortisol on several functions of the human brain. The first experiment investigated the interaction between insulin and slow, genomic cortisol effects on resting regional cerebral blood flow (rCBF) in 48 young men. A bilateral, locally distinct increase in rCBF in the insular cortex was observed 37 to 58 minutes after intranasal insulin admission. Cortisol did not influence rCBF, neither alone nor in interaction with insulin. This finding suggests that cortisol does not influence resting cerebral blood flow within a genomic timeframe. The second experiment examined fast cortisol effects on memory retrieval. 40 participants (20 of them female) learned associations between neutral male faces and social descriptions and were tested for recall one week later. Cortisol administered intravenously 8 minutes before retrieval influenced recall performance in an inverted U-shaped dose-response relationship. This study demonstrates a rapid, presumably nongenomic cortisol effect on memory retrieval in humans. The third experiment studied rapid cortisol effects on early multisensory integration. 24 male participants were tested twice in a focused cross-modal choice reaction time paradigm, once after cortisol and once after placebo infusion. Cortisol acutely enhanced the integration of visual targets and startling auditory distractors, when both stimuli appeared in the same sensory hemi-field. The rapidity of effect onset strongly suggests that cortisol changes multisensory integration by a nongenomic mechanism. The work presented in this thesis highlights the essential role of cortisol as a fast acting agent during the stress response. Both the second and the third experiment provide new evidence of nongenomic cortisol effects on human cognition and behavior. Future studies should continue to investigate the impact of rapid cortisol effects on the functioning of the human brain.
Cortisol exhibits typical ultradian and circadian rhythm and disturbances in its secretory pattern have been described in stress-related pathology. The aim of this thesis was to dissect the underlying structure of cortisol pulsatility and to develop tools to investigate the effects of this pulsatility on immune cell trafficking and the responsiveness of the neuroendocrine system and GR target genes to stress. Deconvolution modeling was set up as a tool for investigation of the pulsatile secretion underlying the ultradian cortisol rhythm. This further allowed us to investigate the role of the single cortisol pulses on the immune cell trafficking and the role of induced cortisol pulses on the kinetics of expression of GR target genes. The development of these three tools, would allow to induce and investigate in future the significance of single cortisol pulses for health and disease.
The startle response in psychophysiological research: modulating effects of contextual parameters
(2013)
Startle reactions are fast, reflexive, and defensive responses which protect the body from injury in the face of imminent danger. The underlying reflex is basic and can be found in many species. Even though it consists of only a few synapses located in the brain stem, the startle reflex offers a valuable research method for human affective, cognitive, and psychological research. This is because of moderating effects of higher mental processes such as attention and emotion on the response magnitude: affective foreground stimulation and directed attention are validated paradigms in startle-related research. This work presents findings from three independent research studies that deal with (1) the application of the established "affective modulation of startle"-paradigm to the novel setting of attractiveness and human mating preferences, (2) the question of how different components of the startle response are affected by a physiological stressor and (3) how startle stimuli affect visual attention towards emotional stimuli. While the first two studies treat the startle response as a dependent variable by measuring its response magnitude, the third study uses startle stimuli as an experimental manipulation and investigates its potential effects on a behavioural measure. The first chapter of this thesis describes the basic mechanisms of the startle response as well as the body of research that sets the foundation of startle research in psychophysiology. It provides the rationale for the presented studies, and offers a short summary of the obtained results. Chapter two to four represent primary research articles that are published or in press. At the beginning of each chapter the contribution of all authors is explained. The references for all chapters are listed at the end of this thesis. The overall scope of this thesis is to show how the human startle response is modulated by a variety of factors, such as the attractiveness of a potential mating partner or the exposure to a stressor. In conclusion, the magnitude of the startle response can serve as a measure for such psychological states and processes. Beyond the involuntary, physiological startle reflex, startle stimuli also affect intentional behavioural responses, which we could demonstrate for eye movements in a visual attention paradigm.
Im querschnittlichen Vergleich zwischen 10- bis 18-jährigen Mädchen mit Major Depression und gleichaltrigen gesunden Probandinnen wiesen die depressiven Mädchen mehr Probleme, mehr körperliche und psychische Stresssymptome, erhöhte Cortisolsekretion sowie eine ungünstigere Stressverarbeitung auf. Im Längsschnitt zeigte sich die Bedeutsamkeit von psychischer Stressbelastung und der Einfluss von Bewältigungsstrategien auf den Verlauf der Depression.