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Institut
- Psychologie (94) (entfernen)
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).
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.
The Role of Dopamine and Acetylcholine as Modulators of Selective Attention and Response Speed
(2015)
The principles of top-down and bottom-up processing are essential to cognitive psychology. At their broadest, most general definition, they denote that processing can be driven either by the salience of the stimulus input or by individual goals and strategies. Selective top-down attention, specifically, consists in the deliberate prioritizing of stimuli that are deemed goal-relevant, while selective bottom-up attention relies on the automatic allocation of attention to salient stimuli (Connor, Egeth, & Yantis, 2004; Schneider, Schote, Meyer, & Frings, 2014). Variations within neurotransmitter systems can modulate cognitive performance in a domain-specific fashion (Greenwood, Fossella, & Parasuraman, 2005). Noudoost and Moore (2011a) proposed that the influence of the dopaminergic neurotransmitter system on selective top-down attention might be greater than the influence of this system on selective bottom-up attention; likewise, they assumed that the cholinergic neurotransmitter system might be more important for selective bottom-up than top-down attention. To test this hypothesis, naturally occurring variations within the two neurotransmitter systems were assessed. Five polymorphisms were selected; two of the dopaminergic system (the COMT Val158Met polymorphism and the DAT1 polymorphism) and three of the cholinergic system (the CHRNA4 rs1044396 polymorphism, the CHRNA5 rs3841324 polymorphism, and the CHRNA5 rs16969968 polymorphism). It was tested whether these polymorphisms modulated the performance in tasks of selective top-down attention (a Stroop task and a Negative priming task) and in a task of selective bottom-up attention (a Posner-Cuing task). Indeed, the dopaminergic polymorphisms influenced selective top-down attention, but exerted no effects on bottom-up attention. This aligned with the hypothesis proposed by Noudoost and Moore (2011a). In contrast, the cholinergic polymorphisms were not found to modulate selective bottom-up attention. The three cholinergic polymorphisms, however, affected the general response speed in the Stroop task, Negative priming task, and Posner-Cuing task (irrespective of attentional processing). In sum, the findings of this study provide strong indications that the dopaminergic system modulates selective top-down attention, while the cholinergic system is highly relevant for the general speed of information processing.
Death is perceived as a severe threat to the self. Although it is certain that everyone has to die, people usually don't think about the finiteness of their life. Everything reminding of death is ignored, rationalized and death-related thoughts and fears are pushed out of mind (TMT; Pyszczynski et al., 1999). However, people differ in their ability to regulate negative affect and to access their self-system (Kuhl, 2001). As death is assumed to arouse existential fears, the ability to regulate such fears is particularly important, higher self-access could be relevant in defending central personal values. This thesis aimed at showing existential fears under mortality salience and effects of self-regulation of affect under mortality salience. In two studies (Chapter 2) implicit negative affect under mortality salience was demonstrated. An additional study (Chapter 3) shows the effects of self-regulation on implicit negative affect, whereas four studies in Chapter 4 displayed differences in self-access under mortality salience depending on people- ability of self-regulating negative affect.
Evaluative conditioning (EC) refers to changes in liking that are due to the pairing of stimuli, and is one of the effects studied in order to understand the processes of attitude formation. Initially, EC had been conceived of as driven by processes that are unique to the formation of attitudes, and that occur independent of whether or not individuals engage in conscious and effortful propositional processes. However, propositional processes have gained considerable popularity as an explanatory concept for the boundary conditions observed in EC studies, with some authors going as far as to suggest that the evidence implies that EC is driven primarily by propositional processes. In this monograph I present research which questions the validity of this claim, and I discuss theoretical challenges and avenues for future EC research.
Stress related disorders increase continuously. It is not yet clear if stress also promotes breast cancer. This dissertation provides an analyses of the current state of research and focuses on the significance of pre-/postnatal stress factors and chronic stress. The derived hypotheses are empirically examined on breast cancer patients. The clinical study investigates the links between those factors and prognosis and outcome.
Every day we are exposed to a large set of appetitive food cues, mostly of high caloric, high carbohydrate content. Environmental factors like food cue exposition can impact eating behavior, by triggering anticipatory endocrinal responses and reinforcing the reward value of food. Additionally, it has been shown that eating behavior is largely influence by neuroendocrine factors. Energy homeostasis is of great importance for survival in all animal species. It is challenged under the state of food deprivation which is considered to be a metabolic stressor. Interestingly, the systems regulating stress and food intake share neural circuits. Adrenal glucocorticoids, as cortisol, and the pancreatic hormone insulin have been shown to be crucial to maintain catabolic and anabolic balance. Cortisol and insulin can cross the blood-brain barrier and interact with receptors distributed throughout the brain, influencing appetite and eating behavior. At the same time, these hormones have an important impact on the stress response. The aim of the current work is to broaden the knowledge on reward related food cue processing. With that purpose, we studied how food cue processing is influenced by food deprivation in women (in different phases of the menstrual cycle) and men. Furthermore, we investigated the impact of the stress/metabolic hormones, insulin and cortisol, at neural sites important for energy metabolism and in the processing of visual food cues. The Chapter I of this thesis details the underlying mechanisms of the startle response and its application in the investigation of food cue processing. Moreover, it describes the effects of food deprivation and of the stress-metabolic hormones insulin and cortisol in reward related processing of food cues. It explains the rationale for the studies presented in Chapter II-IV and describes their main findings. A general discussion of the results and recommendations for future research is given. In the study described in Chapter II, startle methodology was used to study the impact of food deprivation in the processing of reward related food cues. Women in different phases of the menstrual cycle and men were studied, in order to address potential effects of sex and menstrual cycle. All participants were studied either satiated or food deprived. Food deprivation provoked enhanced acoustic startle (ASR) response during foreground presentation of visual food cues. Sex and menstrual cycle did not influence this effect. The startle pattern towards food cues during fasting can be explained by a frustrative nonreward effect (FNR), driven by the impossibility to consume the exposed food. In Chapter III, a study is described, which was carried out to explore the central effects of insulin and cortisol, using continuous arterial spin labeling to map cerebral blood flow patterns. Following standardized periods of fasting, male participants received either intranasal insulin, oral cortisol, both, or placebo. Intranasal insulin increased resting regional cerebral blood flow in the putamen and insular cortex, structures that are involved in the regulation of eating behavior. Neither cortisol nor interaction effects were found. These results demonstrate that insulin exerts an action in metabolic centers during resting state, which is not affected by glucocorticoids. The study described in Chapter IV uses a similar pharmacological manipulation as the one presented in Chapter III, while assessing processing of reward related food cues through the startle paradigm validated in Chapter II. A sample of men was studied during short-term food deprivation. Considering the importance of both cortisol and insulin in glucose metabolism, food pictures were divided by glycemic index. Cortisol administration enhanced ASR during foreground presentation of "high glycemic" food pictures. This result suggests that cortisol provokes an increase in reward value of high glycemic food cues, which is congruent with previous research on stress and food consumption. This thesis gives support to the FNR hypothesis towards food cues during states of deprivation. Furthermore, it highlights the potential effects of stress related hormones in metabolism-connected neuronal structures, and in the reward related mechanisms of food cue processing. In a society marked by increased food exposure and availability, alongside with increased stress, it is important to better understand the impact of food exposition and its interaction with relevant hormones. This thesis contributes to the knowledge in this field. More research in this direction is needed.
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.
Attitudes are "the most distinctive and indispensable concept in contemporary social psychology" (Allport, 1935, p. 798). This outstanding position of the attitude concept in social cognitive research is not only reflected in the innumerous studies focusing on this concept but also in the huge number of theoretical approaches that have been put forth since then. Yet, it is still an open question, what attitudes actually are. That is, the question of how attitude objects are represented in memory cannot be unequivocally answered until now (e.g., Barsalou, 1999; Gawronski, 2007; Pratkanis, 1989, Chapter 4). In particular, researchers strongly differ with respect to their assumptions on the content, format and structural nature of attitude representations (Ferguson & Fukukura, 2012). This prevailing uncertainty on what actually constitutes our likes and dislikes is strongly dovetailed with the question of which processes result in the formation of these representations. In recent years, this issue has mainly been addressed in evaluative conditioning research (EC). In a standard EC-paradigm a neutral stimulus (conditioned stimulus, CS) is repeatedly paired with an affective stimulus (unconditioned stimulus, US). The pairing of stimuli then typically results in changes in the evaluation of the CS corresponding to the evaluative response of the US (De Houwer, Baeyens, & Field, 2005). This experimental approach on the formation of attitudes has primarily been concerned with the question of how the representations underlying our attitudes are formed. However, which processes operate on the formation of such an attitude representation is not yet understood (Jones, Olson, & Fazio, 2010; Walther, Nagengast, & Trasselli, 2005). Indeed, there are several ideas on how CS-US pairs might be encoded in memory. Notwithstanding the importance of these theoretical ideas, looking at the existing empirical work within the research area of EC (for reviews see Hofmann, De Houwer, Perugini, Baeyens, & Crombez, 2010; De Houwer, Thomas, & Baeyens, 2001) leaves one with the impression that scientists have skipped the basic processes. Basic processes hereby especially refer to the attentional processes being involved in the encoding of CSs and USs as well as the relation between them. Against the background of this huge gap in current research on attitude formation, the focus of this thesis will be to highlight the contribution of selective attention processes to a better understanding of the representation underlying our likes and dislikes. In particular, the present thesis considers the role of selective attention processes for the solution of the representation issue from three different perspectives. Before illustrating these different perspectives, Chapter 1 is meant to envision the omnipresence of the representation problem in current theoretical as well as empirical work on evaluative conditioning. Likewise, it emphasizes the critical role of selective attention processes for the representation question in classical conditioning and how this knowledge might be used to put forth the uniqueness of evaluative conditioning as compared to classical conditioning. Chapter 2 then considers the differential influence of attentional resources and goal-directed attention on attitude learning. The primary objective of the presented experiment was thereby to investigate whether attentional resources and goal-directed attention exert their influence on EC via changes in the encoding of CS-US relations in memory (i.e., contingency memory). Taking the findings from this experiment into account, Chapter 3 focuses on the selective processing of the US relative to the CS. In particular, the two experiments presented in this chapter were meant to explore the moderating influence of the selective processing of the US in its relation to the CS on EC. In Chapter 4 the important role of the encoding of the US in relation to the CS, as outlined in Chapter 3, is illuminated in the context of different retrieval processes. Against the background of the findings from the two presented experiments, the interplay between the encoding of CS-US contingencies and the moderation of EC via different retrieval processes will be discussed. Finally, a general discussion of the findings, their theoretical implications and future research lines will be outlined in Chapter 5.
The distractor-response binding effect (Frings & Rothermund, 2011; Frings, Rothermund, & Wentura, 2007; Rothermund, Wentura, & De Houwer, 2005) is based on the idea that irrelevant information will be integrated with the response to the relevant stimuli in an episodic memory trace. The immediate re-encounter of any aspect of this saved episode " be it relevant or irrelevant " can lead to retrieval of the whole episode. As a consequence, the previously executed and now retrieved response may influencing the response to the current relevant stimulus. That is, the current response may either be facilitated or be impaired by the retrieved response, depending on whether it is compatible or incompatible to the currently demanded response. Previous research on this kind of episodic retrieval focused on the influence on action control. I examined if distractor response binding also plays a role in decision making in addition to action control. To this end I adapted the distractor-to-distractor priming paradigm (Frings et al., 2007) and conducted nine experiments in which participants had to decide as fast as possible which disease a fictional patient suffered from. To infer the correct diagnosis, two cues were presented; one did not give any hint for a disease (the irrelevant cue), whereas the other did (the relevant cue). Experiments 1a to 1c showed that the distractor-response binding effect is present in deterministic decision situations. Further, experiments 2a and 2b indicate that distractor-response binding also influences decisions under uncertainty. Finally, experiments 3a to 3d were conducted to test some constraints and underlying mechanisms of the distractor-response binding effect in decision making under uncertainty. In sum, these nine experiments provide strong evidence that distractor-response binding influences decision making.
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.
The influence of affect on vocal parameters has been well investigated in speech portrayed by actors, but little is known about affect expression in more natural or authentic speech behavior. This is partly due to the difficulty of generating speech samples that represent authentic expression of speaker affect. The present work investigates the influence of speaker affect on the vocal fundamental frequency (F0) in comparatively authentic speech samples. Three well-documented psychophysiological research methods were applied for the induction of affective states in German native speakers in order to obtain speech samples with authentic affect expression: the Cold Pressor Test (CPT), the Stroop Color-Word Test (SCWT) and the presentation of slides from the International Affective Pictures System (IAPS). The here reported results show that the influence of affect on F0 is differentially modulated by psychophysiological processes as well as socio-cultural influences. They also indicate that this approach may be useful for future research and further to gain a deeper understanding of authentic vocal affect expression. Moreover, F0 may constitute an additional non-invasive, easy to obtain measure for the established psychophysiological research methodology.
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.
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, &amp;amp; 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, &amp;amp; Schachinger, 2008) in obese BED as compared to obese NBED individuals.
In this thesis, in order to shed light on the biological function of the membrane-bound Glucocorticoid Receptor (mGR), proteomic changes induced by 15 min in vivo acute stress and by short in vitro activation of the mGR were analyzed in T-lymphocytes. The numerous overlaps between the two datasets suggest that the mGR mediates physiologically relevant actions and participates in the early stress response, triggering rapid early priming events that pave the way for the slower genomic GC activities. In addition, a new commercially available method with suitable sensitivity to detect the human mGR is reported and the transcriptional origin of this protein investigated. Our results indicates that specific GR-transcripts, containing exon 1C and 1D, are associated with the expression of this membrane isoform.
The stress hormone cortisol as the end-product of the hypothalamic-pituitary-adrenal (HPA) axis has been found to play a crucial role in the release of aggressive behavior (Kruk et al., 2004; Böhnke et al., 2010). In order to further explore potential mechanisms underlying the relationship between stress and aggression, such as changes in (social) information processing, we conducted two experimental studies that are presented in this thesis. In both studies, acute stress was induced by means of the Socially Evaluated Cold Pressor Test (SECP) designed by Schwabe et al. (2008). Stressed participants were classified as either cortisol responders or nonresponders depending on their rise in cortisol following the stressor. Moreover, basal HPA axis activity was measured prior to the experimental sessions and EEG was recorded throughout the experiments. The first study dealt with the influence of acute stress on cognitive control processes. 41 healthy male participants were assigned to either the stress condition or the non-stressful control procedure of the SECP. Before as well as after the stress induction, all participants performed a cued task-switching paradigm in order to measure cognitive control processes. Results revealed a significant influence of acute and basal cortisol levels, respectively, on the motor preparation of the upcoming behavioral response, that was reflected in changes in the magnitude of the terminal Contingent Negative Variation (CNV). In the second study, the effect of acute stress and subsequent social provocation on approach-avoidance motivation was examined. 72 healthy students (36 males, 36 females) took part in the study. They performed an approach-avoidance task, using emotional facial expressions as stimuli, before as well as after the experimental manipulation of acute stress (again via the SECP) and social provocation realized by means of the Taylor Aggression Paradigm (Taylor, 1967). Additionally to salivary cortisol, testosterone samples were collected at several points in time during the experimental session. Results indicated a positive relationship between acute testosterone levels and the motivation to approach social threat stimuli in highly provoked cortisol responders. Similar results were found when the testosterone-to-cortisol ratio at baseline was taken into account instead of acute testosterone levels. Moreover, brain activity during the approach-avoidance task was significantly influenced by acute stress and social provocation, as reflected in reductions of early (P2) as well as of later (P3) ERP components in highly provoked cortisol responders. This may indicate a less accurate, rapid processing of socially relevant stimuli due to an acute increase in cortisol and subsequent social provocation. In conclusion, the two studies presented in this thesis provide evidence for significant changes in information processing due to acute stress, basal cortisol levels and social provocation, suggesting an enhanced preparation for a rapid behavioral response in the sense of a fight-or-flight reaction. These results confirm the model of Kruk et al. (2004) proposing a mediating role of changed information processes in the stress-aggression-link.
Magnet Resonance Imaging (MRI) and Electroencephalography (EEG) are tools used to investigate the functioning of the working brain in both humans and animal studies. Both methods are increasingly combined in separate or simultaneous measurements under the assumption to benefit from their individual strength while compensating their particular weaknesses. However, little attention has been paid to how statistical analyses strategies can influence the information that can be retrieved from a combined EEG fMRI study. Two independent studies in healthy student volunteers were conducted in the context of emotion research to demonstrate two approaches of combining MRI and EEG data of the same participants. The first study (N = 20) applied a visual search paradigm and found that in both measurements the assumed effects were absent by not statistically combining their results. The second study (N = 12) applied a novelty P300 paradigm and found that only the statistical combination of MRI and EEG measurements was able to disentangle the functional effects of brain areas involved in emotion processing. In conclusion, the observed results demonstrate that there are added benefits of statistically combining EEG-fMRI data acquisitions by assessing both the inferential statistical structure and the intra-individual correlations of the EEG and fMRI signal.
The complicated human alternative GR promoter region plays a pivotal role in the regulation of GR levels. In this thesis, both genomic and environmental factors linked with GR expression are covered. This research showed that GR promoters were susceptible to silencing by methylation and the activity of the individual promoters was also modulated by SNPs. E2F1 is a major element to drive the expression of GR 1F transcripts and single CpG dinucleotide methylation cannot mediate the inhibition of transcription in vitro. Also, the distribution of GR first exons and 3" splice variants (GRα and GR-P) is expressed throughout the human brain with no region-specific alternative first exon usage. These data mirrored the consistently low levels of methylation in the brain, and the observed homogeneity throughout the studied regions. Taken together, the research presented in this thesis explored several layers of complexity in GR transcriptional regulation.
The contribution of three genes (C15orf53, OXTR and MLC1) to the etiology of chromosome 15-bound schizophrenia (SCZD10), bipolar disorder (BD) and autism spectrum disorder (ASD) were studied. At first, the uncharacterized gene C15orf53 was comprehensively analyzed. Previous genome-wide association studies (GWAS) in bipolar disorder samples have identified an association signal in close vicinity to C15orf53 on chromosome 15q14. This gene is located in exactly the genomic region, which is segregating in our SCZD10 families. An association study with bipolar disorder (BD) and SCZD10 individual samples did not reveal any association of single nucleotide polymorphisms (SNPs) in C15orf53. Mutational analysis of C15orf53 in SCZD10-affected individuals from seven multiplex families did not show any mutations in the 5'-untranslated region, the coding region and the intron-exon boundaries. Gene expression analysis revealed that C15orf53 was expressed in a subpopulation of leukocytes, but not in human post-mortem limbic brain tissue. Summarizing these studies, C15orf53 is unlikely to be a strong candidate gene for the etiology of BD or SCZD10. The second investigated gene was the human oxytocin receptor gene (OXTR). Five well described SNPs located in the OXTR gene were taken for a transmission-disequilibrium test (TDT) in parents-child trios with ASD-affected children. Neither in the complete sample nor in a subgroup with children that had an intelligence quotient (IQ) above 70, association was found, independent from the application of Haploview or UNPHASED for analysis. The third gene, MLC1, was investigated with regards to its implication in the etiology of SCZD10. Mutations in the MLC1 gene lead to megalencephalic leukoencephalopathy with subcortical cysts (MLC) and one variant coding for the amino acid methionine (Met) instead of leucine (Leu) at position 309 was identified to segregate in a family affected with SCZD10. For further investigation of MLC1 and its possible implication in the etiology of SCZD10, a constitutive Mlc1 knockout mouse model should be created. Mouse embryonic stem cells (mES) were electroporated with a knockout vector construct and analyzed with respect to homologous recombination of the knockout construct with the genomic DNA (gDNA) of the mES. Polymerase chain reaction (PCR) on the available stem cell clones did not reveal any homologous recombined ES. Additionally, we conducted experiments to knockdown MLC1 and using microRNAs. The 3'-untranslated region of the MLC1 gene was analyzed with the bioinformatics tool TargetScan to screen for potential microRNA target sites. In the 3'-untranslated region of the MLC1 gene, a potential binding site for miR-137 was identified. The gene expression level of genes that had been linked to psychiatric disorders and carried a predicated miR-137 binding site has been proven to be immediately responsive to miR-137. Thus, there is new evidence that MLC1 is a candidate gene for the etiology of SCZD10.