The neurophysiology of sedation

Thesis

We recognise consciousness in ourselves and in those around us. Consciousness is the essence of our existence, who and what we are, but we are willing and able to let go of it daily during sleep, which we welcome and associate with rest, recovery and well being, knowing that consciousness will return reliably, when we are ready. Yet we cannot define this thing or process which makes us "us". We do not understand how it is constructed from the activity in our brains, how it is deconstructed by sleep, drugs or disease, or how it can be reconstructed by waking or recovery. Our ignorance renders us reliant on inadequate means of measuring consciousness, dependent on movement for its detection.

Propofol is an intravenous anaesthetic drug with the capacity to safely, rapidly and reliably produce sedation and anaesthesia, providing an ideal model of unconsciousness for study. Functional magnetic resonance imaging (fMRI) provides a non-invasive means of measuring activity within the brain. EEG is a convenient broad measure of neuronal activity. This thesis exploits the advantages of each of these techniques, fMRI and EEG, first separately and then together, to link highly informative, spatially specific fMRI observations to convenient, reproducible electrophysiological surface measurements.

A safe and reliable model of unconsciousness suitable for fMRI interrogation is first developed and explored. Changes in the spatial extent and interregional correlation of neuronal activity when subjects become unresponsive show that the functional connectivity of the striatum is specifically impaired as perception fails. Disruption of the brain’s internal temporal frame of reference impairs the synthesis of perceptions from their fragments. The second experimental chapter specifically examines the behaviour of sleep oscillations during ultraslow increases and decreases in the depth of sedation with propofol. Functional activity shows that the brain is intensely active despite loss of consciousness and reveals measurable transitions in neuronal activity. Combined simultaneous EEG/FMRI then shows that these transitions reflect stepwise changes in the processing of experience and a shift from externally modulated thalamocortical signaling to an internal dialogue.

Authors: Ni Mhuircheartaigh, R; Roisin Ni Mhuircheartaigh

• Publication date: 2012
• DOI: 10.5287/ora-8n9mxo4rd
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: consciousness; propofol; anaesthesia; sedation
• Subjects: Physiology; Anaesthetics