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.

The neurological wake-up test, NWT, is a clinical monitoring tool that can be used to evaluate the level of consciousness in patients with traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH) during neurocritical care (NCC). Since patients with severe TBI or SAH are often treated with mechanical ventilation and sedation, the NWT requires that the continuous sedation is interrupted. However, interruption of continuous sedation may induce a stress response and the use of the NWT in NCC is controversial. The effects of the NWT on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were evaluated in 21 patients with TBI or SAH. Compared to baseline when the patients were sedated with continuous propofol sedation, the NWT resulted in increased ICP and CPP (p<0.05). Next, the effects of the NWT on the stress hormones adrenocorticotrophic hormone (ACTH), cortisol, epinephrine and norepinephrine were evaluated in 24 patients. Compared to baseline, the NWT caused a mild stress response resulting in increased levels of all evaluated stress hormones (p<0.05). To compare the use of routine NCC monitoring tools, the choice of sedation and analgesia and the frequency of NWT in Scandinavian NCC units, a questionnaire was used. The results showed that all 16 Scandinavian NCC units routinely use ICP and CPP monitoring and propofol and midazolam were primary choices for patient sedation in an equal number of NCC units. In 2009, the NWT was not routinely used in eight NCC units whereas others used the test up to six times daily. Finally, intracerebral microdialysis (MD), brain tissue oxygenation (PbtiO2) and jugular bulb oxygenation (SjvO2) were used in 17 TBI patients to evaluate the effect of the NWT procedure on focal neurochemistry and cerebral oxygenation. The NWT did not negatively alter interstitial markers of energy metabolism or cerebral oxygenation. In conclusion, the NWT induced a mild stress response in patients with TBI or SAH that did not result in a detectable, significant secondary insult to the injured brain. These results suggest that the NWT may safely be used as a clinical monitoring tool in the NCC of severe TBI and SAH in a majority of patients.