Abstract
Although the burden of mental disorders continues to grow worldwide, their neurobiology still remains insufficiently understood. Over the last quarter century, methodological advances in neuroimaging have transformed the field of neuroscience. The advent of magnetic resonance imaging (MRI) and more particularly the development of echo planar imaging (EPI) pulse sequences, enabled novel applications, including functional magnetic resonance imaging (fMRI) and diffusion weighted/tensor imaging (DWI/DTI). Together, both methods allow for a characterization of the neuronal circuitry, which may serve as a specific biomarker for mental disorders. However, the functional architecture of the human brain remains elusive, while methodological limitations are still hampering our scientific progress. The six articles selected for this habilitation thesis address different aspects of EPI based MR neuroimaging with an emphasis on two main aspects: First, the application of fMRI in clinical populations with mental illness to explore associations between the functional connectome and behaviour, disease course and/or neuropathology. Second, the development and optimization of novel DWI/DTI approaches and their subsequent validation in peripheral neuronal structures. Using fMRI, we found a relationship between altered subcortical-cortical functional connectivity and psychotic symptoms in patients with schizophrenia, described an association between aberrant graph-theoretical network- topology and the course of disease in patients with depression and demonstrated an intricate interaction between brain activity during rest, task, cognitive performance and amyloid-β (Aβ) as measured with Aβ-specific positron-emission tomography in patients with prodromal Alzheimer’s disease. In addition, we validated the reproducibility of a novel DWI/DTI approach with optimized slice-wise shimming, tested the feasibility and performance of DTI in fine neuronal structures applying a novel readout segmented EPI and evaluated to which extent the acquisition can be accelerated without impeding the data quality. With its two main focuses within the framework of MR EPI neuroimaging, this work presents potential applications of already established methods to investigate the neurobiology underlying mental disorders as well as novel methodological developments in MR neuroimaging. The integration of methodological developments and applications in clinical research settings according to hypotheses derived from clinical observations may allow for the detection of biomarkers, which might have an influence on diagnostics and clinical decision making in the future.
Manoliu, Andrei