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dc.contributor.advisor Gruber, Oliver Prof. Dr.
dc.contributor.author Brodmann, Katja
dc.date.accessioned 2016-11-15T10:48:27Z
dc.date.available 2016-11-15T10:48:27Z
dc.date.issued 2016-11-15
dc.identifier.uri http://hdl.handle.net/11858/00-1735-0000-002B-7CA8-9
dc.language.iso eng de
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc 570 de
dc.title Oxytocin - not only a "social" neuropeptide de
dc.title.alternative Implications from social and non-social task-based and task-free neuroimaging studies de
dc.type doctoralThesis de
dc.contributor.referee Gruber, Oliver Prof. Dr.
dc.date.examination 2016-10-24
dc.description.abstracteng Research on the effects of oxytocin on social cognition and behavior is constantly growing. Moreover, oxytocin is already discussed to be used as a drug supporting common therapies for a range of disorders displaying deficits in social cognition. Although, the knowledge about its neurophysiological mechanisms lacks in particular regarding its functioning in the non-social domain of behavior, cognition and related brain responses. Therefore, the present thesis had the aim to explore whether the neuropeptide oxytocin has an effect on non-social cognitive processes and their underlying neural correlates, how the neural mechanisms of oxytocin are modulated by additional social input and which basal changes are driven by the effects of oxytocin. I addressed these questions by the use of functional magnetic resonance imaging (fMRI) with task-based and resting-state designs and with a neuroimaging genetics approach. Oxytocin is synthesized in subnuclei of the hypothalamus and was originally known for its involvement in inducing labor. The oxytocin receptor is distributed largely across the brain, covering areas of the mesolimbic system such as the ventral striatum (vStr), the ventral tegmental area (VTA) and the amygdala, but also frontal areas and regions which are not prominently involved in social cognition. Generally, oxytocin is thought to affect social behavior and cognition, including parenting, affiliative behavior, but also emotion-regulation. It is also assumed to be sensitive for context, gender and personality characteristics. Whereas many studies explored the impact of oxytocin on socio-emotional actions such as on emotion-processing in the amygdala, only very few studies focused on the non-socioemotional domain, as for example memory processing or reward-related decision-making. With regard to the aims of this thesis, two of the three experiments employed a non-social decision making paradigm to reveal effects of oxytocin on non-social behavior and related brain activity. Indeed, oxytocin also modulated neural circuits during non-social tasks and even during the resting-state paradigm in the third experiment. This indicates that a social context might not be required to observe changes in neural activity and connectivity by oxytocin. Several theories have been proposed to explain the mechanisms by which oxytocin might function. The social cognition theory suggests that oxytocin might modulate prosocial affiliative behaviors and self-referential processing, the fear/stress approach emphasized its anxiolytic and stress reducing effects, the general approach-avoidance hypothesis of oxytocin assumes that oxytocin acts on approach and avoidance motivation and the social salience hypothesis implies that oxytocin regulates the salience of social stimuli. In conclusion, currently there is no general theory accounting for all the social and non-social effects of oxytocin as described in the literature. In the same perspective, the overall results from the current thesis contradict aspects of each theory, while specific patterns of effects may be best reconciliated with the framework of the approach-avoidance theory and the social salience hypothesis. In the first study a neuroimaging genetics approach was applied to investigate whether common variants of the oxytocin receptor gene influenced behavior and neural responses in a non-social reward-based decision-making paradigm. Specifically, due to dopaminergic-oxytocinergic interactions oxytocin-induced changes were expected in bottom-up reward-related and in top-down cognitive control-related activity. Two of the three candidate single-nucleotide-polymorphism (SNP) of the oxytocin receptor gene (OXTR) were associated with a modulation of reward-related activity during desire and reason situations in the paradigm used. The desire context was formed by allowing to obtain a presented reward, whereas in the reason context the same reward had to be rejected. Participants who were homozygous for the major allele of the OXTR SNP rs1042778 expressed more bottom-up related activity in the vStr in the desire context. In contrast to this, minor allele carriers showed a greater suppression of the reward-related activity in the reason context. This might have led to better cognitive control and therefore to significantly better performance in the rejection of reward stimuli in reason situations. According to this, major allele carriers had a stronger coupling between the vStr and the VTA in desire contexts. Moreover, minor allele carriers displayed an enhanced connectivity between the vStr and the anteroventral prefrontal cortex (avPFC) in reason situations. For the OXTR SNP rs237897 an interaction of gender with the activity in the VTA could be detected. Female participants, homozygous for the major genotype, presented more activation in the left VTA compared to males. Altogether, this study could show that OXTR polymorphisms are able to modulate reward-related as well as control-related activity even in a non-social decision-making paradigm. In study 2 a neuroimaging experiment was performed with the application of intranasal oxytocin and a modified reward-based decision-making paradigm including non-social as well as social stimuli. The main question was whether exogenous oxytocin alters behavioral and neural processes during the non-social condition in this task. Additionally, I was interested in possible changes of oxytocin effects by the presentation of emotional stimuli. Furthermore, by the additional use of both positive and fearful stimuli, I wanted to shed light on the ongoing discussion whether oxytocin acts valence-dependent or irrespective of valence on the activity of the amygdala. An opposite modulation of activity and functional connectivity regarding non-social compared with social context was shown after oxytocin treatment. In the non-social desire situation oxytocin reduced bottom-up activity within the vStr, probably by enhancing top-down control due to strengthening the negative coupling to a frontal region. In contrast, in non-social reason contexts the vStr was less deactivated, maybe due to decreased top-down control. By presenting fearful faces in the social condition, the pattern of neural responses and functional connectivity reversed. In this condition, oxytocin increased the activation in the vStr in desire situations, while it reduced the activation in reason situations. This change in activity was paralleled by stronger positive coupling in the desire context and less coupling as well as negative coupling in the reason context. Furthermore, depending on valence oxytocin decreased amygdala activation for fearful faces and increased amygdala activation for positive faces. The altered activity within the reward system by oxytocin might be the reason for an impaired performance during both desire and reason trials. After oxytocin treatment participants were less accurate in selecting target stimuli than in rejecting the reward stimulus and vice versa for the placebo. This suggests rather an impaired working memory than disturbed stimulus-association learning. To sum up, the comparison between the effects of oxytocin in the non-social and social condition yielded that oxytocin influences corticomesolimbic regions in a context-sensitive manner. The last study used a resting-state fMRI technique with additional administration of intranasal oxytocin. Of particular interest was the possible alteration of functional connectivity within and between large-scale networks by oxytocin. The analysis focused on functional networks indicated to play a major role in salience processing (the salience network - CO), social cognition and self-referential processing (the default mode network - DM) and attention processing (the ventral attentional network - VA). Thereby, basal changes by which oxytocin might influence neuronal responses were shown providing results for the ongoing debate on the underlying function of oxytocin. Although, I expected significant changes of functional connectivity within the DM network. The modulation of the CO and the VA networks were seen. Indeed, oxytocin changed the functional connectivity within and between large-scale networks even without engagement in a task. Oxytocin mainly influenced the VA by decreasing the cross-talk to regions typically part of the DM nodes; and oxytocin strengthened the functional connectivity to the edges of the CO, involving regions linked to salience processing. Additionally, oxytocin directly impacted the functional connectivity within the CO. Therefore, one basic effect of oxytocin might be to redirect attention (VA) from self-referential processing (DM) to the external environment, preparing for reception of salient information (CO). Taken together, the purpose of the present thesis was to extend the knowledge about the effects of oxytocin as well as basic mechanisms of oxytocin’s influence on cognition, behavior and neural activation and connectivity in non-social, social and task-free conditions. The results clearly demonstrated effects on neural activation, functional connectivity and on behavior in all three studies; supporting the claim that oxytocin does not only play an important role in socio-emotional processing. de
dc.contributor.coReferee Kagan, Igor Dr.
dc.subject.eng oxytocin, fMRI, non-social, decision-making, reward, salience, large-scale networks de
dc.identifier.urn urn:nbn:de:gbv:7-11858/00-1735-0000-002B-7CA8-9-2
dc.affiliation.institute Biologische Fakultät für Biologie und Psychologie de
dc.subject.gokfull Psychologie (PPN619868627) de
dc.identifier.ppn 872564649

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