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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.
Salivary alpha-amylase (sAA) influences the perception of taste and texture, features both relevant in acquiring food liking and, with time, food preference. However, no studies have yet investigated the relationship between basal activity levels of sAA and food preference. We collected saliva from 57 volunteers (63% women) who we assessed in terms of their preference for different food items. These items were grouped into four categories according to their nutritional properties: high in starch, high in sugar, high glycaemic index, and high glycaemic load. Anthropometric markers of cardiovascular risk were also calculated. Our findings suggest that sAA influences food
preference and body composition in women. Regression analysis showed that basal sAA activity is inversely associated with subjective but not self-reported behavioural preference for foods high in sugar. Additionally, sAA and subjective preference are associated with anthropometric markers of cardiovascular risk. We believe that this pilot study points to this enzyme as an interesting candidate to consider among the physiological factors that modulate eating behaviour.
Dysfunctional eating behavior is a major risk factor for developing all sorts of eating disorders. Food craving is a concept that may help to understand better why and how these and other eating disorders become chronic conditions through non homeastatically-driven mechanisms. As obesity affects people worldwide, cultural differences must be acknowledged to apply proper therapeutic strategies. In this work, we adapted the Food Craving Inventory (FCI) to the German population. We performed a factor analysis of an adaptation of the original FCI in a sample of 326 men and women. We could replicate the factor structure of the FCI on a German population.rnThe factor extraction procedure produced a factor solution that reproduces the fourfactors described in the original inventory, the FCI. Our instrument presents high internal consistency, as well as a significant correlation with measures of convergent and discriminant validity. The FCI-Deutsch (FCI-DE) is a valid instrument to assess craving for particular foods in Germany, and it could, therefore, prove useful in the clinical and research practice in the field of obesity and eating behaviors.
Cortisol is a stress hormone that acts on the central nervous system in order to support adaptation and time-adjusted coping processes. Whereas previous research has focused on slow emerging, genomic effects of cortisol likely mediated by protein synthesis, there is only limited knowledge about rapid, non-genomic cortisol effects on in vivo neuronal cell activity in humans. Three independent placebo-controlled studies in healthy men were conducted to test effects of 4 mg cortisol on central nervous system activity, occurring within 15 minutes after intravenous administration. Two of the studies (N = 26; N = 9) used continuous arterial spin labeling as a magnetic resonance imaging sequence, and found rapid bilateral thalamic perfusion decrements. The third study (N = 14) revealed rapid cortisol-induced changes in global signal strength and map complexity of the electroencephalogram. The observed changes in neuronal functioning suggest that cortisol may act on the thalamic relay of non-relevant background as well as on task specific sensory information in order to facilitate the adaptation to stress challenges. In conclusion, these results are the first to coherently suggest that a physiologically plausible amount of cortisol profoundly affects functioning and perfusion of the human CNS in vivo by a rapid, non-genomic mechanism.
During the last decade, anatomic and physiological neuroscience research has yielded extensive information on the physiological regulators of short-term satiety, visceral and interoceptive sensation. Distinct neural circuits regulate the elements of food ingestion physiologically. The general aim of the current studies is to elucidate the peripheral neural pathways to the brain in healthy subjects to establish the groundwork for the study of the pathophysiology of bulimia nervosa (BN). We aimed to define the central activation pattern during non-nutritive gastric distension in humans, and aimed to define the cognitive responses to this mechanical gastric distension. We estimated regional cerebral blood flow with 15O-water positron emission tomography during intragastric balloon inflation and deflation in 18 healthy young women of normal weight. The contrast between inflated minus deflated in the exploratory analysis revealed activation in more than 20 brain regions. The analysis confirmed several well known areas in the central nervous system that contribute to visceral processing: the inferior frontal cortex, representing a zone of convergence for food related stimuli; the insula and operculum referred to as "visceral cortex"; the anterior cingulate gyrus (and insula), processing affective information; and the brainstem, a site of vagal relay for visceral afferent stimuli. Brain activation in the left ventrolateral prefrontal cortex was reproducible. This area is well known for higher cognitive processing, especially reward-related stimuli. The ventrolateral prefrontal cortex with the insular regions may provide a link between the affective and rewarding components of eating and disordered eating as observed in BN and binge-eating obesity. Gastric distension caused a significant rapid, reversible, and reproducible increase in the feelings of fullness, sleepiness, and gastric discomfort as well as a significant rapid, reversible, and reproducible decrease in the feeling of hunger. We showed that mechanical activation of the neurocircuitry involved in meal termination led to the described phenomena. The current brain activation studies of non-painful, proximal gastric distension could provide groundwork in the field of abnormal eating behavior by suggesting a link between visceral sensation and abnormal eating patterns. A potential treatment for disordered eating and obesity could alter the conscious and unconscious perception and interoceptive awareness of gastric distension contributing to meal termination.
The human brain is characterised by two apparently symmetrical cerebral hemispheres. However, the functions attributed to each half of the brain are very distinct with a relative specialisation of the left hemisphere for language processing. Most laterality research has been performed on a behavioural level, using techniques such as visual half-field presentation. The visual half-field technique involves the presentation of stimuli in the left or right visual field for a very short time (about 200 ms). During the presentation of lateralized stimuli, the gaze of the participants is fixated on a centrally presented fixation cross. This technique takes advantage of the anatomy of the visual pathway as the temporal hemiretinae project ipsilateral, while the nasal hemiretinae project contralateral. Thus, stimuli presented in the left or right visual field are initially processed in the contralateral hemisphere. Language organisation can also be directly investigated using functional magnetic resonance imaging (fMRI). Both behavioural and neuroimaging studies showed that about 95% of right-handed men have a left hemispheric specialisation for language. In contrast, data on language organisation in women are ambiguous. It is supposed that this ambivalent picture might be associated with changes in gonadal steroid levels in blood during the menstrual cycle. However, gonadal steroid effects are complex and their role in functional cerebral lateralization is still open to discussion. The aim of this PhD project was to investigate, using fMRI: (1) the processing of linguistic information initially received in the specialised, non-specialised or both hemispheres; (2) linking the associated brain activation pattern with progesterone levels during the menstrual cycle. Firstly, brain activation was measured in 16 right-handed, healthy males during processing of different components of language (orthography, phonology and semantics) after reception in the left, right or both hemispheres. Secondly, to investigate changes in language organisation during the menstrual cycle, we conducted an event-related fMRI study during semantic and phonological processing also using visual half-field and central presentation of linguistic stimuli. Our results revealed higher BOLD signal intensity change in the visual cortex contralateral to the visual field of stimulus presentation compared to the ipsilateral visual cortex reflecting the crossing of visual pathways. We also found support for the hypothesis that the superiority of word recognition in the left VWFA is the result of a reduced activity in the right VWFA under left hemispheric control. Further, linguistic information received in the subdominant RH, is interhemispheric transferred to the left hemisphere for phonological processing. Semantic processing in contrast occurs in the specialised and in the non-specialised hemisphere. For the group of women, data analysis revealed that during semantic processing, salivary progesterone levels correlated positively with brain activity of the left superior frontal gyrus, left middle and inferior occipital gyri and bilateral fusiform gyrus. In contrast, the brain activation pattern for phonological processing did not change significantly across the menstrual cycle. In conclusion, the effect of serum progesterone levels on brain activity is task and region specific.
Background: We evaluated depression and social isolation assessed at time of waitlisting as predictors of survival in heart transplant (HTx) recipients. Methods and Results: Between 2005 and 2006, 318 adult HTx candidates were enrolled in the Waiting for a New Heart Study, and 164 received transplantation. Patients were followed until February 2013. Psychosocial characteristics were assessed by questionnaires. Eurotransplant provided medical data at waitlisting, transplantation dates, and donor characteristics; hospitals reported medical data at HTx and date of death after HTx. During a median followâ€up of 70 months (<1"93 months postâ€HTx), 56 (38%) of 148 transplanted patients with complete data died. Depression scores were unrelated to social isolation, and neither correlated with disease severity. Higher depression scores increased the risk of dying (hazard ratio=1.07, 95% confidence interval, 1.01, 1.15, P=0.032), which was moderated by social isolation scores (significant interaction term; hazard ratio = 0.985, 95% confidence interval, 0.973, 0.998; P=0.022). These findings were maintained in multivariate models controlling for covariates (P values 0.020"0.039). Actuarial 1â€year/5â€year survival was best for patients with low depression who were not socially isolated at waitlisting (86% after 1 year, 79% after 5 years). Survival of those who were either depressed, or socially isolated or both, was lower, especially 5 years posttransplant (56%, 60%, and 62%, respectively). Conclusions: Low depression in conjunction with social integration at time of waitlisting is related to enhanced chances for survival after HTx. Both factors should be considered for inclusion in standardized assessments and interventions for HTx candidates. We evaluated depression and social isolation assessed at time of waitlisting as predictors of survival in heart transplant (HTx) recipients.\r\n\r\nMethods and Results: Between 2005 and 2006, 318 adult HTx candidates were enrolled in the Waiting for a New Heart Study, and 164 received transplantation. Patients were followed until February 2013. Psychosocial characteristics were assessed by questionnaires. Eurotransplant provided medical data at waitlisting, transplantation dates, and donor characteristics; hospitals reported medical data at HTx and date of death after HTx. During a median followâ€up of 70 months (<1"93 months postâ€HTx), 56 (38%) of 148 transplanted patients with complete data died. Depression scores were unrelated to social isolation, and neither correlated with disease severity. Higher depression scores increased the risk of dying (hazard ratio=1.07, 95% confidence interval, 1.01, 1.15, P=0.032), which was moderated by social isolation scores (significant interaction term; hazard ratio = 0.985, 95% confidence interval, 0.973, 0.998; P=0.022). These findings were maintained in multivariate models controlling for covariates (P values 0.020"0.039). Actuarial 1â€year/5â€year survival was best for patients with low depression who were not socially isolated at waitlisting (86% after 1 year, 79% after 5 years). Survival of those who were either depressed, or socially isolated or both, was lower, especially 5 years posttransplant (56%, 60%, and 62%, respectively).
This thesis presents a study of the visual change detection mechanism. This mechanism is thought to be responsible for the detection of sudden and unexpected changes in our visual environment. As the brain is a capacity limited system and has to deal with a continuous stream of information from its surroundings only a part of the vast amount of information can be completely processed and be brought to conscious awareness. This information, which passes through attentional filters, is used for goal-directed behaviour. Therefore, the change detection mechanism is a very useful aid to cope with important information which is outside the focus of our attention. rnIt is thought that a neural memory trace of repetitive visual information is stored. Each new information input is compared to this existing memory trace by a so-called change or mismatch detection system. Following a sudden change, the comparison process leads to a mismatch and the detection system elicits a warning signal, to which an orienting response can follow. This involves a change in the focus of attention towards this sudden environmental change which can then be evaluated for potential danger and allows for a behavioural adaptation to the new situation. rnTo this purpose a paradigm was developed combining a 2-choice response time task with in the background a mismatch detection task of which the subjects were not aware. This paradigm was implemented in an ERP and an fMRI study and was used to study the the change detection mechanism and its relationship with impulsivity.rnIn previous studies a change detection system for auditory information had already been established. As the brain is a very efficient system it was thought to be unlikely that this change detection system is only available for the processing of auditory information. rnIndeed, a modality specific mismatch response at the sensory specific occipital cortex and a more general response at the frontocentral midline, both resembling the components shown in auditory research, were found in the ERP study.rnAdditionally, magnetic resonance imaging revealed a possible functional network of regions, which responded specifically to the processing of a deviant. These regions included the occipital gyrus, premotor cortex, inferior frontal cortex, thalamas, insula, and parts of the cingular cortex. rnThe relationship between impulsivity measures and visual change detection was established in an additional study. More impulsive subjects showed less detection of deviant stimuli, which was most likely due to too fast and imprecise information processing.rnIn summary it can be said, that the work presented in this thesis demonstrates that visual mismatch negativity was established, a number of regions could be associated with change detection and additionally the relevance of change detection in information processing was shown.rn
At any given moment, our senses are assaulted with a flood of information from the environment around us. We need to pick our way through all this information in order to be able to effectively respond to that what is relevant to us. In most cases we are usually able to select information relevant to our intentions from what is not relevant. However, what happens to the information that is not relevant to us? Is this irrelevant information completely ignored so that it does not affect our actions? The literature suggests that even though we mayrnignore an irrelevant stimulus, it may still interfere with our actions. One of the ways in which irrelevant stimuli can affect actions is by retrieving a response with which it was associated. An irrelevant stimulus that is presented in close temporal contiguity with a relevant stimulus can be associated with the response made to the relevant stimulus " an observation termed distractor-response binding (Rothermund, Wentura, & De Houwer, 2005). The studies presented in this work take a closer look at such distractor-response bindings, and therncircumstances in which they occur. Specifically, the study reported in chapter 6 examined whether only an exact repetition of the distractor can retrieve the response with which it was associated, or whether even similar distractors may cause retrieval. The results suggested that even repeating a similar distractor caused retrieval, albeit less than an exact repetition. In chapter 7, the existence of bindings between a distractor and a response were tested beyond arnperceptual level, to see whether they exist at an (abstract) conceptual level. Similar to perceptual repetition, distractor-based retrieval of the response was observed for the repetition of concepts. The study reported in chapter 8 of this work examined the influence of attention on the feature-response binding of irrelevant features. The results pointed towards a stronger binding effects when attention was directed towards the irrelevant feature compared to whenrnit was not. The study in chapter 9 presented here looked at the processes underlying distractor-based retrieval and distractor inhibition. The data suggest that motor processes underlie distractor-based retrieval and cognitive process underlie distractor inhibition. Finally, the findings of all four studies are also discussed in the context of learning.
The search for relevant determinants of knowledge acquisition has a long tradition in educational research, with systematic analyses having started over a century ago. To date, a variety of relevant environmental and learner-related characteristics have been identified, providing a wide body of empirical evidence. However, there are still some gaps in the literature, which are highlighted in the current dissertation. The dissertation includes two meta-analyses summarizing the evidence on the effectiveness of electrical brain stimulation and the effects of prior knowledge on later learning outcomes and one empirical study employing latent profile transition analysis to investigate the changes in conceptual knowledge over time. The results from the three studies demonstrate how learning outcomes can be advanced by input from the environment and that they are highly related to the students" level of prior knowledge. It is concluded that the effects of environmental and learner-related variables impact both the biological and cognitive processes underlying knowledge acquisition. Based on the findings from the three studies, methodological and practical implications are provided, followed by an outline of four recommendations for future research on knowledge acquisition.