Fronto-striatal brain circuits involved in the pathophysiology of schizophrenia and affective disorders: FMRI studies of the effects of urbanicity and fearful faces on neural mechanisms of reward processing and self-control
von Bernd Krämer
Datum der mündl. Prüfung:2016-04-21
Betreuer:Prof. Dr. Oliver Gruber
Gutachter:Prof. Dr. Birgit Kröner-Herwig
Gutachter:Prof. Dr. Michael Waldmann
EnglischThis thesis is concerned with two studies which have the common pursuit to improve the investigation of pathomechanisms underlying schizophrenic and affective disorders. They were motivated by the fact, that the diagnosis of mental disorders is a complex process and despite advances still error prone. It is proposed that during the pathogenesis of mental disorders interaction of genes and environment lead to functional changes in brain regions and related brain networks. Indeed, abnormalities in reward, stress and emotion processing are described for mental disorders. It is expected that neuroimaging studies might identify brain activation or connectivity patterns that could aid their differential diagnosis disorders or guide treatment selection. The first study investigated if living in big cities could affect the mesolimbic reward system and densely connected cortical and subcortical structures. 147 healthy subjects provided information about current and residency during their first years of life and performed the Desire-Reason-Dilemma paradigm during functional magnetic resonance imaging. Compared with subjects from less urban areas, city dwellers showed an altered activation and modulation capability of the midbrain dopamine system. City dwellers also revealed exaggerated responses in other brain regions involved in reward processing, and in the regulation of stress and emotions such as amygdala, orbitofrontal and pregenual anterior cingulate cortex. This study provided evidence for an influence of an environmental risk factor on cortico-subcortical networks involved in reward and emotion processing. Dysfunctions of these brain networks are involved in the development of schizophrenic and affective disorders. The aim of the second study was to investigate dynamic functional interactions between amygdala, nucleus accumbens and prefrontal cortex that underlie the influences of emotions, desires and rationality on human decisions because quite little is known about dynamic functional interactions between these brain circuits that underlie reward processing, self-controlled pursuit of long-term goals and emotions. For this purpose, the Desire-Reason-Dilemma paradigm was extended by an affective component. One half of the stimuli showed a gray ellipse representing non-emotional stimuli and the other half showed an emotional face in its center. Seventeen healthy volunteers were included in the study and nine additional subjects were excluded due to excessive head movements. The behavioral data revealed that fearful faces generally increased avoidance tendency to non-reward stimuli leading to significantly slower acceptance and faster rejection of these stimuli. But reward counteracted the avoidance tendency of fearful faces. The functional MRI analysis showed that increased functional connectivity between amygdala and nucleus accumbens facilitated the approach of immediate reward in the presence of emotional information. This was not observed in the absence of reward. Further, increased functional interactions of the anteroventral prefrontal cortex with amygdala and nucleus accumbens were associated with rational decisions in dilemma situations. The second work provided an experimental paradigm that for the first time enabled the in vivo investigation of the interaction between amygdala, nucleus accumbens und antero-ventral prefrontal cortex when emotional-, reward related information and self-controlled pursuit of long-term goals guided human decisions and reward-directed actions. It was shown that the activity in the amygdala, which is hypothesized as an integration region of cognition and emotion, is influenced by a risk factor contributing to development of mental disorders and that the amygdala interacts with cortical regions and the mesolimbic dopamine system to coordinate goal directed behavior. Future application of the affective DRD paradigm and the inclusion of additional information, e.g. genetic variation might provide additional insight in the underlying neuro-mechanisms of schizophrenic and affective disorders.
Keywords: Pathomechanisms; Mental disorders; fMRI; Urbanicity; Emotion; Cognitive control; Midbrain dopamine system; Desire Reason Dilemma