Anaesthesia and PET of the Brain

Although drugs have been used to administer general anaesthesia for more than a century and a half, relatively little was known until recently about the molecular and cellular effects of the anaesthetic agents and the neurobiology of anaesthesia. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have played a valuable role in improving this knowledge. PET studies using 11C-flumazenil binding have been used to demonstrate that the molecular action of some, but not all, of the current anaesthetic agents is mediated via the GABAA receptor. Using different tracers labelled with 18F, 11C and 15O, PET studies have shown the patterns of changes in cerebral metabolism and blood flow associated with different intravenous and volatile anaesthetic agents. Within classes of volatile agents, there are minor variations in patterns. More profound differences are found between classes of agents. Interestingly, all agents cause alterations in the blood flow and metabolism of the thalamus, providing strong support for the hypothesis that the anaesthetic agents interfere with consciousness by interfering with thalamocortical communication.</p

Brain network disintegration during sedation is mediated by the complexity of sparsely connected regions.

The precise mechanism of anaesthetic action on a neural level remains unclear. Recent approaches suggest that anaesthetics attenuate the complexity of interactions (connectivity) however evidence remains insufficient. We used tools from network and information theory to show that, during propofol-induced sedation, a collection of brain regions displayed decreased complexity in their connectivity patterns, especially so if they were sparsely connected. Strikingly, we found that, despite their low connectivity strengths, these regions exhibited an inordinate role in network integration. Their location and connectivity complexity delineated a specific pattern of sparse interactions mainly involving default mode regions while their connectivity complexity during the awake state also correlated with reaction times during sedation signifying its importance as a reliable indicator of the effects of sedation on individuals. Contrary to established views suggesting sedation affects only richly connected brain regions, we propose that suppressed complexity of sparsely connected regions should be considered a critical feature of any candidate mechanistic description for loss of consciousness