Despite the widespread clinical use of anesthetics and the volume of research focused on brain function, few studies have used neuroimaging techniques to better understand the mechanisms of anesthetic agents. Functional MRI relying on the Blood Oxygenation Level Dependent (BOLD) contrast mechanism has rapidly become a valuable tool for neuroscientists and could provide insight into the neurophysiological impact of anesthetic agents. Yet the relationship between BOLD signal changes and neuronal activity is not well understood particularly in the presence of an agent that might alter the normal coupling between BOLD signal changes and the underlying neuronal activity. Changes in baseline brain activity, metabolism or flow may influence the amplitude of the BOLD signal measured in an activation experiment and while many studies have examined such effects in animal studies there are almost no calibrated human studies of these effects. Calibration of the fMRI experiment allows pure physiological changes such as changes in baseline cerebral blood flow (CBF), to be dissociated from changes in neuronal activity normally reflected in the BOLD signal measured. It is particularly challenging when such studies are performed in humans because it is difficult to design informative but passive tasks that are ammenable to the MR setting. This work will focus on a series of hierarchichal but passive tasks involving either sensory/motor stimuli or auditory stimuli, applied to humans in the awake and anesthetized state. Anesthetic agents Sevoflurane and Propofol will be investigated at different dose levels (Sevoflurane 0.25MAC, 0.5MAC, Propofol 1micro-g/kg and 2micro-g/kg) while stimuli are presented and BOLD and CBF measured. Calibration experiments linking flow and metabolism as measured by the cerebral metabolic rate of oxygen consumption (CMRO2) will be performed prior to the activation experiments. Combined measures of BOLD and CBF will allow investigation of the coupling between flow, oxygenation, and CMRO2 across a range of stimuli under different anesthetic conditions. These experiments will provide insight into the brain's response to stimuli under anesthetic conditions and reveal the impact of anesthetics on specific cortical regions as well as larger networks. These experiments will also lay the ground work for future studies investigating higher order cognitive function such as those associated with attention and memory. ? ? ?
