Introduction: Cushing's disease (CD) is a rare and severe endocrine disease characterized by hypercortisolemia. Previous studies have found structural brain alterations in remitted CD patients... Show moreIntroduction: Cushing's disease (CD) is a rare and severe endocrine disease characterized by hypercortisolemia. Previous studies have found structural brain alterations in remitted CD patients compared to healthy controls, specifically in the anterior cingulate cortex (ACC). However, potential mechanisms through which these persistent alterations may have occurred are currently unknown. Methods: Structural 3T MRI's from 25 remitted CD patients were linked with gene expression data from neurotypical donors, derived from the Allen Human Brain Atlas. Differences in gene expression between the ACC and an unaffected control cortical region were examined, followed by a Gene Ontology (GO) enrichment analysis. A cell type enrichment analysis was conducted on the differentially expressed genes, and a disease association enrichment analysis was conducted to determine possible associations between differentially expressed genes and specific diseases. Subsequently, cortisol sensitivity of these genes in existing datasets was examined. Results: The gene expression analysis identified 300 differentially expressed genes in the ACC compared to the cortical control region. GO analyses found underexpressed genes to represent immune function. The cell type specificity analysis indicated that underexpressed genes were enriched for deactivated microglia and oligodendrocytes. Neither significant associations with diseases, nor evidence of cortisol sensitivity with the differentially expressed genes were found. Discussion: Underexpressed genes in the ACC, the area vulnerable to permanent changes in remitted CD patients, were often associated with immune functioning. The specific lack of deactivated microglia and oligodendrocytes implicates protective effects of these cell types against the long-term effects of cortisol overexposure. Show less
Dissociation, emotion dysregulation, and cognitive disturbances are key features of Borderline Personality Disorder (BPD). The aim of this thesis was to investigate associations between... Show moreDissociation, emotion dysregulation, and cognitive disturbances are key features of Borderline Personality Disorder (BPD). The aim of this thesis was to investigate associations between dissociation and activity in networks relevant to affective-cognitive processing in patients with BPD compared to healthy controls. In the first part of this thesis, associations between self-reported dissociation and functional connectivity of the amygdala and anterior cingulate during resting-state and during an Emotional Working Memory Task (EWMT) were examined. The second part of this neuroimaging research combined script-driven imagery with the EWMT and with an Emotional Stroop Task. Findings suggest a detrimental effect of dissociation on cognitive functioning in BPD. After dissociation induction, patients showed reduced activity in the amygdala, posterior cingulate, superior temporal gyrus, and occipital areas (cuneus, fusiform gyrus, lingual gyrus), along with increased activity in frontal areas (inferior frontal gyrus, dlPFC). Altered interactions between the amygdala and the afore-mentioned regions may underlie disturbed information processing during dissociation in BPD. Further research with larger sample sizes and clinical control groups is needed to gain more insight into the neural mechanisms of stress-related dissociation in BPD. A combination of neuroimaging techniques with subjective, behavioral, and psychophysiological measurements may be a helpful step into this direction. Show less
The studies described in this thesis aimed to investigate how affect and motivation impact cognitive control, in terms of both behavior and brain activation. Six out of the eight empirical studies... Show moreThe studies described in this thesis aimed to investigate how affect and motivation impact cognitive control, in terms of both behavior and brain activation. Six out of the eight empirical studies found support for indirect effects on cognitive control, as measured with sequential trial-to-trial adaptations in cognitive control tasks. Only two studies resulted in evidence for a direct modulation of cognitive control (Chapter 4 and 9). Indirect effects occurred on trial-to-trial adaptation in cognitive control tasks involving a random presentation of compatible and incompatible trials. We found that conflict adaptation, the transient improvement of behavioral control after incompatible in comparison to compatible trials, was subject to affective regulation. In particular, we found that after incompatible trials, positive emotional states reduced and negative emotional states increased adaptation. These effects occurred for both short-term (Chapters 2 and 3) and long-term affect manipulations (Chapters 5, 6, and 7). Motivation and task difficulty also interacted with conflict adaptation (Chapter 8). The neuroimaging studies described in Chapter 3 and 6 demonstrate the role of fronto-striatal interactions in this affective regulation of cognitive control. Taken together, this thesis demonstrates the role that positive and negative emotions play in the adaptation of behavior and mental effort. Show less
