Alzheimer’s disease (AD) is a neurodegenerative disease characterized by memory loss and declined cognitive functioning. Brain changes in AD involve grey matter atrophy and changes in brain... Show moreAlzheimer’s disease (AD) is a neurodegenerative disease characterized by memory loss and declined cognitive functioning. Brain changes in AD involve grey matter atrophy and changes in brain function. These different brain characteristics can respectively be visualized with structural and functional MRI scans. These MRI modalities have been used for AD classification, but studies typically only include a limited number of features. In this thesis we derived multiple types of features from each MRI modality, and combined those to discriminate AD patients and elderly controls. First, we showed that AD classification accuracy increases when combining multiple types of measures from a single MRI modality. This was shown for structural MRI scans in chapter 2, and for resting state fMRI scans in chapter 3. In chapter 4 we evaluated whether MRI based AD classification models can discriminate AD in a diverse clinical population as well. This worked to some extent, and it worked best using structural MRI scans. In chapter 5 we used baseline multimodal MRI scans from the same diverse clinical population to predict two-year follow-up cognitive decline. Decline was predicted above chance level for the MMSE, but not for six other neuropsychological tests. Show less
Bauduin, S.E.E.C.; Rooijen, I.L.B. den; Meijer, M.; Werff, S.J.A. van der; Keo, A.; Dzyubachyk, O.; ... ; Mahfouz, A. 2021
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
Objective: A sensorimotor network structural phenotype predicted motor task performance in a previous study in Huntington's disease (HD) gene carriers. We investigated in the visual network whether... Show moreObjective: A sensorimotor network structural phenotype predicted motor task performance in a previous study in Huntington's disease (HD) gene carriers. We investigated in the visual network whether structure - function - behaviour relationship patterns, and the effects of the HD mutation, extended beyond the sensorimotor network.Methods: We used multimodal visual network MRI structural measures (cortical thickness and white matter connectivity), plus visual evoked potentials and task performance (Map Search; Symbol Digit Modalities Test) in healthy controls and HD gene carriers.Results: Using principal component (PC) analysis, we identified a structure - function relationship common to both groups. PC scores differed between groups indicating white matter disorganization (higher RD, lower FA) and slower, and more disperse, VEP signal transmission (higher VEP P100 latency and lower VEP P100 amplitude) in HD than controls while task performance was similar.Conclusions: HD may be associated with reduced white matter organization and efficient visual network function but normal task performance.Significance: These findings indicate that structure - function relationships in the visual network, and the effects of the HD mutation, share some commonalities with those in the sensorimotor network. However, implications for task performance differ between the two networks suggesting the influence of network specific factors. (C) 2019 Published by Elsevier B.V. on behalf of International Federation of Clinical Neurophysiology. Show less
Although the outcomes of our daily-life risky decisions are often unknown (e.g., receiving or not receiving a fine after running a red light), the probabilities of these outcomes may also vary in... Show moreAlthough the outcomes of our daily-life risky decisions are often unknown (e.g., receiving or not receiving a fine after running a red light), the probabilities of these outcomes may also vary in uncertainty. That is, the probabilities may be known (risk) or unknown (ambiguity), which influences risk taking behavior to a great extent. A developmental phase associated with heightened risk taking is adolescence, yet how adolescents process risk and ambiguity, and the relation with real-life risk taking, remain elusive. Moreover, individual differences in observed risk taking behavior remain largely overlooked. In this PhD thesis risk and ambiguity processing in adolescents were decomposed using behavioral economics and fMRI, and related to real-life risk taking. The results indicated that risk and ambiguity differentially impact risk-taking behavior, and are processed by different neural mechanisms. In addition, individual variation in task-related and real-life risk taking highlighted that adolescence is not a phase of heightened risk taking for everyone. Moreover, it was found that real-life risk-taking and prosocial tendencies were both predicted by fun seeking, suggesting this trait may make individuals differentially susceptible to positive or negative outcomes. Together, this thesis points towards a more nuanced perspective on adolescent risk taking and its underlying components. Show less
Bas-Hoogendam, J.M.; Steenbergen, H. van; Tissier, R.L.M.; Houwing-Duistermaat, J.J.; Westenberg, P.M.; Wee, N.J.A. van der 2018
