| Summary: | This thesis investigates the application of physiological measures made using magnetic resonance imaging (MRI) to study cerebral haemodynamics and the pharmacological modulation of brain activity. Blood Oxygen Level Dependent (BOLD) functional MRI (fMRI), together with Arterial Spin Labelling (ASL), were used to study of the effect of beta-blockers on the brain’s response to emotional visual stimuli at 3 T. The study aimed to test the James-Lange theory, which states that emotions result from the perception of bodily arousal. Autonomic nervous system responses to emotional stimuli can be predicted by the level of activity in the limbic system (including amygdala, brainstem and salience network). This thesis assesses the action of the peripherally acting beta-blocker, nadolol, on the fMRI response to neutral, pleasant and unpleasant visual stimuli, and during rest. 80 mg nadolol and placebo tablets were administered to twenty healthy human subjects in a double blinded, randomised, placebo controlled crossover design. Drug induced reduction in anterior insula response to emotional stimuli supports results from previously published studies, and the James-Lange theory. The preliminary finding of drug induced increase in amygdala response is contradictory. Territorial ASL (TASL) and multi-phase ASL were used in combination for advanced investigation of the vascular territories, and quantitative perfusion and blood transit times. These measures were used for the assessment of the location and haemodynamic properties of the cerebral watershed regions. Watershed region masks formed from TASL and multi-phase ASL data exhibited reduced perfusion and lengthened transit times compared to other cortical regions. The accuracy of watershed delineation was shown to be enhanced by the use of both techniques in combination. Furthermore, TASL is developed and implemented at 7 T. Alternative labelling schemes were compared and parameters optimised for control condition efficiency, and TASL assessment was performed in three healthy volunteers.
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