Summary: | The structural and functional integrity of the brain relies on a close balance between the metabolic demands of neurons and supporting glia, and substrate delivery in the form of blood flow. Disruption of the communication of neural cells and vascular smooth muscle, controlling the dilation and delivery of blood to specific brain regions may exacerbate the negative consequences of neurodegenerative and neuroinflammatory conditions. However, there has been little research done to measure the relationship between neural activity and changes in blood flow, or neurovascular coupling. Disruption of neurovascular coupling could lead to hypoxic conditions in the brain, or more precisely ‘virtual hypoxic’ conditions. Conditions such as these, if severe enough can go on to cause apoptosis or necrosis; particularly during periods of increased metabolic stress such as inflammation. In this thesis, I begin by exploring how cerebrovascular reactivity, the process behind normal neurovascular coupling, is affected in the neuro-inflammatory condition – multiple sclerosis (chapter 5). I use this as the basis for beginning my attempt to empirically define neurovascular coupling in the healthy brain, using non-invasive neuroimaging techniques. I begin to define neurovascular coupling in the 6 chapter, using a multiple methods of measuring neural activity and blood flow changes using a graded visual task in MEG and fMRI environments. In the 7 chapter I focus on refining this protocol, and assess the repeatability of my empirical neurovascular coupling measure. Finally, using this protocol, I examine if and how this crucial process is altered during an inflammatory disease like multiple sclerosis.
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