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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Lena Palaniyappan, McGill University, Canada
- Second opponent: Professor Asta Kristine Håberg, NTNU - Norwegian University of Science and Technology
- Third member and chair of the evaluation committee: Professor Ping Qin, University of Oslo
Chair of the Defence
Associate Professor Pål Zeiner, University of Oslo
Principal Supervisor
Professor Ingrid Agartz, University of Oslo
Summary
Dysmyelination has been proposed as a neurobiological mechanism underlying schizophrenia spectrum and bipolar disorders, with proposed links to auditory hallucinations (AH). In this project, we employed two MRI-based neuroimaging techniques to assess myelin-related tissue properties: for cortical grey matter we used the ratio of T1- and T2-weighted MRI images, i.e., the T1w/T2w-ratio, and for subcortical white matter we used diffusion tensor imaging (DTI), which is sensitive to tissue properties including myelination.
In the first study, we found overall low test-retest reliability of the T1w/T2w-ratio and poor agreement with known myeloarchitecture for some datasets. Intensity normalisation and nonuniformity correction improved these issues but not consistently across datasets. In the second study, we found no differences in the T1w/T2w-ratio between patients and controls. However, patients with schizophrenia spectrum disorders exhibited more positive age-related T1w/T2w-ratio trajectories, influenced by antipsychotic medication use and dose. In the third study, patients without AH showed higher mean diffusivity (MD) and radial diffusivity (RD) in widespread fibre tracts compared to controls, whereas patients with current AH only displayed limited differences. Dimensionality reduction improved sensitivity to differences in axial diffusivity (AD).
In conclusion, intensity normalisation and nonuniformity correction improved the test-retest reliability of the T1w/T2w-ratio and its agreement with expected myeloarchitecture. The divergent T1w/T2w-ratio age trajectories in patients may be linked to antipsychotic medication use. The limited relationship with current AH questions the connection between DTI metrics and AH, while higher MD and RD suggest myelin-related alterations in patients without AH. The findings support the involvement of myelin in schizophrenia spectrum disorders and emphasise the importance of validating myelin imaging techniques.
Additional information
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