Investigating neurovascular and metabolic function in healthy and Multiple Sclerosis populations using multi-modal neuroimaging (MEG and fMRI)

The brain requires a constant supply of glucose and oxygen to meet metabolic needs at rest and during increased activity. If blood flow is disrupted, or if tissue has difficulty extracting or metabolising nutrients, cell damage or death may occur. Vascular and metabolic impairments in Multiple Sclerosis (MS) are hypothesised to contribute to disease progression. This thesis develops empirical measures of neurovascular coupling using the relationship between magnetoencephalography (MEG) and functional Magnetic Resonance Imaging (fMRI). Visual MEG and fMRI responses were reduced in MS. The relationship between them was unchanged suggesting preserved neurovascular coupling. Addressing the same questions with a naturalistic movie stimulus in MS, no coupling differences were found. In a healthy population, results show neurovascular coupling is dependent on brain region and frequency of neural oscillations. Under the hypothesis of reduced cerebral metabolic rate of O2 (CMRO2) contributing to damage in MS, we quantified baseline CMRO2 and cerebral blood flow (CBF), amongst other parameters. This is the first application of dual-calibrated fMRI in MS, involving biophysical modelling of fMRI signals in response to changing inspired CO2 and O2. Reduced baseline CBF and CMRO2 were found in MS, correlating with lesion and grey matter volumes. Relative visual-induced CBF and CMRO2 signals were investigated in MS; a reduction in CBF was found in a small visual region but no visual CMRO2 changes were found, or differences in CBF-CMRO2 coupling. Baseline CBF and CMRO2 signals predicted visual stimulus responses, in both groups. As an alternative to externally supplied gases, we used a breath-hold design to create a CMRO2 movie time-series but report no significant relationships between CMRO2 and MEG. Quantitative functional imaging can detect impairments in resting and stimulus-induced neural oscillations, blood flow and oxygen metabolism in MS, which should be explored further to understand their exact role in disease progression