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Title: Investigations into the effects of neuromodulations on the BOLD-fMRI signal
Author: Maczka, Melissa May
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2013
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The blood oxygen level dependent functional MRI (BOLD-fMRI) signal is an indirect measure of the neuronal activity that most BOLD studies are interested in. This thesis uses generative embedding algorithms to investigate some of the challenges and opportunities that this presents for BOLD imaging. It is standard practice to analyse BOLD signals using general linear models (GLMs) that assume fixed neurovascular coupling. However, this assumption may cause false positive or negative neural activations to be detected if the biological manifestations of brain diseases, disorders and pharmaceutical drugs (termed "neuromodulations") alter this coupling. Generative embedding can help overcome this problem by identifying when a neuromodulation confounds the standard GLM. When applied to anaesthetic neuromodulations found in preclinical imaging data, Fentanyl has the smallest confounding effect and Pentobarbital has the largest, causing extremely significant neural activations to go undetected. Half of the anaesthetics tested caused overestimation of the neuronal activity but the other half caused underestimation. The variability in biological action between anaesthetic modulations in identical brain regions of genetically similar animals highlights the complexity required to comprehensively account for factors confounding neurovascular coupling in GLMs generally. Generative embedding has the potential to augment established algorithms used to compensate for these variations in GLMs without complicating the standard (ANOVA) way of reporting BOLD results. Neuromodulation of neurovascular coupling can also present opportunities, such as improved diagnosis, monitoring and understanding of brain diseases accompanied by neurovascular uncoupling. Information theory is used to show that the discriminabilities of neurodegenerative-diseased and healthy generative posterior parameter spaces make generative embedding a viable tool for these commercial applications, boasting sensitivity to neurovascular coupling nonlinearities and biological interpretability. The value of hybrid neuroimaging systems over separate neuroimaging technologies is found to be greatest for early-stage neurodegenerative disease.
Supervisor: Marchini, Jonathan; Woolrich, Mark; Martin, Chris Sponsor: Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Neuroimaging ; Statistics ; Functional Magnetic Resonance Imaging ; fMRI ; Blood Oxygen Level Dependent ; Electroencephalography ; Neurovascular coupling ; Dynamic Causal Modelling ; General Linear Modelling ; Anaesthetics ; Generative Embedding ; Information Theory ; Pre-clinical imaging