White matter matters: a multimodal approach to investigate white matter microstructure and metabolism

Giezendanner, Stéphanie (2014). White matter matters: a multimodal approach to investigate white matter microstructure and metabolism (Unpublished). (Dissertation, Universitätsklinik für Psychiatrie und Psychotherapie, Psychiatrische Neurophysiologie, Medizinische Fakultät)

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White matter connects different brain areas and applies electrical insulation to the neuron’s axons with myelin sheaths in order to enable quick signal transmission. Due to its modulatory properties in signal conduction, white matter plays an essential role in learning, cognition and psychiatric disorders (Fields, 2008a). In respect thereof, the non-invasive investigation of white matter anatomy and function in vivo provides the unique opportunity to explore the most complex organ of our body. Thus, the present thesis aimed to apply a multimodal neuroimaging approach to investigate different white matter properties in psychiatric and healthy populations. On the one hand, white matter microstructural properties were investigated in a psychiatric population; on the other hand, white matter metabolic properties were assessed in healthy adults providing basic information about the brain’s wiring entity. As a result, three research papers are presented here.
The first paper assessed the microstructural properties of white matter in relation to a frequent epidemiologic finding in schizophrenia. As a result, reduced white matter integrity was observed in patients born in summer and autumn compared to patients born in winter and spring. Despite the large genetic basis of schizophrenia, accumulating evidence indicates that environmental exposures may be implicated in the development of schizophrenia (A. S. Brown, 2011). Notably, epidemiologic studies have shown a 5–8% excess of births during winter and spring for patients with schizophrenia on the Northern Hemisphere at higher latitudes (Torrey, Miller, Rawlings, & Yolken, 1997). Although the underlying mechanisms are unclear, the seasonal birth effect may indicate fluctuating environmental risk factors for schizophrenia. Thus, exposure to harmful factors during foetal development may result in the activation of pathologic neural circuits during adolescence or young adulthood, increasing the risk of schizophrenia (Fatemi & Folsom, 2009). While white matter development starts during the foetal period and continues until adulthood, its major development is accomplished by the age of two years (Brody, Kinney, Kloman, & Gilles, 1987; Huang et al., 2009). This indicates a vulnerability period of white matter that may coincide with the fluctuating environmental risk factors for schizophrenia. Since microstructural alterations of white matter in schizophrenia are frequently observed, the current study provided evidence for the neurodevelopmental hypothesis of schizophrenia.
In the second research paper, the perfusion of white matter showed a positive correlation between white matter microstructure and its perfusion with blood across healthy adults. This finding was in line with clinical studies indicating a tight coupling between cerebral perfusion and WM health across subjects (Amann et al., 2012; Chen, Rosas, & Salat, 2013; Kitagawa et al., 2009). Although relatively little is known about the metabolic properties of white matter, different microstructural properties, such as axon diameter and myelination, might be coupled with the metabolic demand of white matter. Furthermore, the ability to detect perfusion signal in white matter was in accordance with a recent study showing that technical improvements, such as pseudo-continuous arterial spin labeling, enabled the reliable detection of white matter perfusion signal (van Osch et al., 2009).
The third paper involved a collaboration within the same department to assess the interrelation between functional connectivity networks and their underlying structural connectivity.

Item Type:	Thesis (Dissertation)
Division/Institute:	04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Translational Research Center 04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Psychiatric Neurophysiology [discontinued]
UniBE Contributor:	Giezendanner, Stéphanie, Federspiel, Andrea
Subjects:	600 Technology > 610 Medicine & health
Language:	English
Submitter:	Stéphanie Giezendanner
Date Deposited:	10 Dec 2014 09:25
Last Modified:	05 Dec 2022 14:38
URI:	https://boris.unibe.ch/id/eprint/60639