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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.
There is a lot of evidence for the impact of acute glucocorticoid treatment on hippocampus-dependent explicit learning and memory (memory for facts and events). But there have been few studies, investigating the effect of glucocorticoids on implicit learning and memory. We conducted three studies with different methodology to investigate the effect of glucocorticoids on different forms of implicit learning. In Study 1, we investigated the effect of cortisol depletion on short-term habituation in 49 healthy subjects. 25 participants received oral metyrapone (1500 mg) to suppress endogenous cortisol production, while 24 controls received oral placebo. Eye blink electromyogram (EMG) responses to 105 dB acoustic startle stimuli were assessed. Effective endogenous cortisol suppression had no effect on short-term habituation of the startle reflex, but startle eye blink responses were significantly increased in the metyrapone group. The latter findings are in line with previous human studies, which have shown that excess cortisol, sufficient to fully occupy central nervous system (CNS) corticosteroid receptors, may reduce startle eye blink. This effect may be mediated by CNS mechanisms controlling cortisol feedback. In Study 2, we investigated delay or trace eyeblink conditioning in a patient group with a relative hypocortisolism (30 patients with fibromyaligia syndrome/FMS) compared to 20 healthy control subjects. Conditioned eyeblink response probability was assessed by EMG. Morning cortisol levels, ratings of depression, anxiety and psychosomatic complaints as well as general symptomatology and psychological distress were assessed. As compared to healthy controls FMS patients showed lower morning cortisol levels, and trace eyeblink conditioning was facilitated whereas delay eyeblink conditioning was reduced. Cortisol measures correlate significantly only with trace eyeblink conditioning. Our results are in line with studies of pharmacologically induced hyper- and hypocortisolism, which affected trace eyeblink conditioning. We suggest that endocrine mechanisms affecting hippocampus-mediated forms of associative learning may play a role in the generation of symptoms in these patients.rnIn Study 3, we investigated the effect of excess cortisol on implicit sequence learning in healthy subjects. Oral cortisol (30 mg) was given to 29 participants, whereas 31 control subjects received placebo. All volunteers performed a 5-choice serial reaction time task (SRTT). The reaction speed of every button-press was determined and difference-scores were calculated as a proof of learning. Compared to the control group, we found a delayed learning in the cortisol group at the very beginning of the task. This study is the first human investigation, indicating impaired implicit memory function after exogenous administration of the stress hormone cortisol. Our findings support a previous neuroimaging study, which suggested that the medial temporal lobe (including the hippocampus) is also active in implicit sequence learning, but our results may also depend on the engagement of other brain structures.
In this thesis, three studies investigating the impact of stress on the protective startle eye blink reflex are reported. In the first study a decrease in prepulse inhibition of the startle reflex was observed after intravenous low dose cortisol application. In the second study a decrease in reflex magnitude of the startle reflex was observed after pharmacological suppression of endogenous cortisol production. In the third study, a higher reflex magnitude of the startle reflex was observed at reduced arterial and central venous blood pressure. These results can be interpreted in terms of an adaption to hostile environments.
The catechol-O-methyltransferase gene (COMT) plays a crucial role in the metabolism of catecholamines in the frontal cortex. A single nucleotide polymorphism (Val158Met SNP, rs4680) leads to either methionine (Met) or valine (Val) at codon 158, resulting in a three- to fourfold reduction in COMT activity. The aim of the present study was to assess the COMT Val158Met SNP as a risk factor for attention-deficit/hyperactivity disorder (ADHD), ADHD symptom severity and co-morbid conduct disorder (CD) in 166 children with ADHD. The main finding of the present study is that the Met allele of the COMT Val158Met SNP was associated with ADHD and increased ADHD symptom severity. No association with co-morbid CD was observed. In addition, ADHD symptom severity and early adverse familial environment were positive predictors of lifetime CD. These findings support previous results implicating COMT in ADHD symptom severity and early adverse familial environment as risk factors for co-morbid CD, emphasizing the need for early intervention to prevent aggressive and maladaptive behavior progressing into CD, reducing the overall severity of the disease burden in children with ADHD.
There is considerable evidence for an association between chronic dysregulation of the hypothalamus-pituitary adrenal (HPA) axis, atrophy of the hippocampus (HC) and cognitive and mood changes in clinical populations and in aging. The present thesis investigated this relationship in young healthy male subjects. Special emphasis was put on measures of HC volume and function derived from structural and functional magnetic resonance imaging (MRI). Higher cortisol levels after awakening were observed in subjects with higher levels of depressive symptomatology. Larger HC volume was associated with higher cortisol levels after awakening and in response to acute stress, whereas cognitive performance was impaired in subjects with larger HC volumes. Hippocampal activation during picture encoding was reduced after stress induction, and positive associations between activation and cognitive performance before stress were not present anymore afterwards. The present findings underscore the importance of structural and functional brain imaging for psychoneuroendocrinological research. The investigation of the association between cortisol levels and hippocampal integrity in young healthy subjects elicited unexpected results and adds to the understanding of HPA dysfunction and HC atrophy in clinical and aged populations.
Cognitive performance is contingent upon multiple factors. Beyond the impact of en-vironmental circumstances, the bodily state may hinder or promote cognitive processing. Af-ferent transmission from the viscera, for instance, is crucial not only for the genesis of affect and emotion, but further exerts significant influences on memory and attention. In particular, afferent cardiovascular feedback from baroreceptors demonstrated subcortical and cortical inhibition. Consequences for human cognition and behavior are the impairment of simple perception and sensorimotor functioning. Four studies are presented that investigate the mod-ulatory impact of baro-afferent feedback on selective attention. The first study demonstrates that the modulation of sensory processing by baroreceptor activity applies to the processing of complex stimulus configurations. By the use of a visual masking task in which a target had to be selected against a visual mask, perceptual interference was reduced when target and mask were presented during the ventricular systole compared to the diastole. In study two, selection efficiency was systematically manipulated in a visual selection task in which a target letter was flanked by distracting stimuli. By comparing participants" performance under homogene-ous and heterogeneous stimulus conditions, selection efficiency was assessed as a function of the cardiac cycle phase in which the targets and distractors were presented. The susceptibility of selection performance to the stimulus condition at hand was less pronounced during the ventricular systole compared to the diastole. Study one and two therefore indicate that inter-ference from irrelevant sensory input, resulting from temporally overlapping processing traces or from the simultaneous presentation of distractor stimuli, is reduced during phases of in-creased baro-afferent feedback. Study three experimentally manipulated baroreceptor activity by systematically varying the participant- body position while a sequential distractor priming task was completed. In this study, negative priming and distractor-response binding effects were obtained as indices of controlled and automatic distractor processing, respectively. It was found that only controlled distractor processing was affected by tonic increases in baro-receptor activity. In line with study one and two these results indicate that controlled selection processes are more efficient during enhanced baro-afferent feedback, observable in dimin-ished aftereffects of controlled distractor processing. Due to previous findings that indicated baro-afferent transmission to affect central, rather than response-related processing stages, study four measured lateralized-readiness potentials (LRPs) and reaction times (RTs), while participants, again, had to selectively respond to target stimuli that were surrounded by dis-tractors. The impact of distractor inhibition on stimulus-related, but not on response-related LRPs suggests that in a sequential distractor priming task, the sensory representations of dis-tractors, rather than motor responses are targeted by inhibition. Together with the results from studies one through three and the finding of baroreceptor-mediated behavioral inhibition tar-geting central processing stages, study four corroborates the presumption of baro-afferent signal transmission to modulate controlled processes involved in selective attention. In sum, the work presented shows that visual selective attention benefits from in-creased baro-afferent feedback as its effects are not confined to simple perception, but may facilitate the active suppression of neural activity related to sensory input from distractors. Hence, due to noise reduction, baroreceptor-mediated inhibition may promote effective selec-tion in vision.
The role of cortisol and cortisol dynamics in patients after aneurysmal subarachnoid hemorrhage
(2011)
Spontaneous aneurysmal subarachnoid hemorrhage (SAH) is a form of stroke which constitutes a severe trauma to the brain and often leads to serious long-term medical and psychosocial sequels which persist for years after the acute event. Recently, adrenocorticotrophic hormone deficiency has been identified as one possible consequence of the bleeding and is assumed to occur in around 20% of all survivors. Additionally, a number of studies report a high prevalence of post-SAH symptoms such as lack of initiative, fatigue, loss of concentration, impaired quality of life and psychiatric symptoms such as depression. The overlap of these symptoms and those of patients with untreated partial or complete hypopituitarism lead to the suggestion that neuroendocrine dysregulations may contribute to the psychosocial sequels of SAH. Therefore, one of the aims of this work is to gain insights into the role of neuroendocrine dysfunction on quality of life and the prevalence of psychiatric sequels in SAH-patients. Additionally, as data on cortisol dynamics after SAH are scarce, diurnal cortisol profiles are investigated in patients in the acute and chronic phase, as well as the cortisol awakening response and feedback sensitivity in the chronic phase after SAH. As a result, it can be shown that some SAH patients exhibit lower serum cortisol levels but at the same time a higher cortisol awakening response in saliva than healthy controls. Also, patients in the chronic phase after SAH do have a stable diurnal cortisol rhythm while there are disturbances in around 50% of all patients in the acute phase, leading to the conclusion that a single baseline measurement of cortisol is of no substantial use for diagnosing cortisol dysregulations in the acute phase after SAH. It is assumed that in SAH patients endocrine changes occur over time and that a combination of adrenal exhaustion and a subsequent downregulation of corticosteroid binding globulin may be the most probable causes for the dissociation of serum cortisol concentrations and salivary cortisol profiles in the investigated SAH patients. These changes may be an emergency response after SAH and, as elevated free cortisol levels are connected to a better psychosocial outcome in patients in the chronic phase after SAH, this reaction may even be adaptive.
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.
Educational researchers have intensively investigated students" academic self-concept (ASC) and self-efficacy (SE). Both constructs are part of the competence-related self-perceptions of students and are considered to support students" academic success and their career development in a positive manner (e.g., Abele-Brehm & Stief, 2004; Richardson, Abraham, & Bond, 2012; Schneider & Preckel, 2017). However, there is a lack of basic research on ASC and SE in higher education in general, and in undergraduate psychology courses in particular. Therefore, according to the within-network and between-network approaches of construct validation (Byrne, 1984), the present dissertation comprises three empirical studies examining the structure (research question 1), measurement (research question 2), correlates (research question 3), and differentiation (research question 4) of ASC and SE in a total sample of N = 1243 psychology students. Concerning research question 1, results of confirmatory factor analysis (CFAs) implied that students" ASC and SE are domain-specific in the sense of multidimensionality, but they are also hierarchically structured, with a general factor at the apex according to the nested Marsh/Shavelson model (NMS model, Brunner et al., 2010). Additionally, psychology students" SE to master specific psychological tasks in different areas of psychological application could be described by a 2-dimensional model with six factors according to the Multitrait-Multimethod (MTMM)-approach (Campbell & Fiske, 1959). With regard to research question 2, results revealed that the internal structure of ASC and SE could be validly assessed. However, the assessment of psychology students" SE should follow a task-specific measurement strategy. Results of research question 3 further showed that both constructs of psychology students" competence-related self-perceptions were positively correlated to achievement in undergraduate psychology courses if predictor (ASC, SE) corresponded to measurement specificity of the criterion (achievement). Overall, ASC provided substantially stronger relations to achievement compared to SE. Moreover, there was evidence for negative paths (contrast effects) from achievement in one psychological domain on ASC of another psychological domain as postulated by the internal/external frame of reference (I/E) model (Marsh, 1986). Finally, building on research questions 1 to 3 (structure, measurement, and correlates of ASC and SE), psychology students" ASC and SE were be differentiated on an empirical level (research question 4). Implications for future research practices are discussed. Furthermore, practical implications for enhancing ASC and SE in higher education are proposed to support academic achievement and the career development of psychology students.
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.