Understanding anaesthesia

The advent of anaesthesia is one of the great revolutions of modern medicine. Without it commonplace surgical procedures would be nightmares. Yet exactly how the anaesthetic process works still largely remains a mystery.

Now a paper published in PLOS Computational Biology challenges a popular idea about how anaesthesia induces loss of consciousness – that it decouples different parts of the brain by interrupting information transmission via the nerve fibres that connect them.

Instead, anaesthesia might actually work by hindering information processing in the “source” area, suggests research led by Patricia Wollstadt of the Brain Imaging Center at Goethe University in Frankfurt, Germany. It may not be so much that the transfer of information is blocked as that there is simply less information to transfer.

The findings come from experiments that monitored the brain activity of ferrets given isoflurane, a general anaesthetic administered through inhalation. The simultaneous electrical signals of the ferrets’ primary visual cortex and prefrontal cortex were recorded (using electrodes embedded in the animals’ heads). The researchers used a computer model to estimate the amount of information available in the different brain areas.

The research reports that “source” brain areas showed bigger decreases in available information than “target” areas, thus “changes in information transfer under isoflurane seem to be a consequence of changes in local processing more than of decoupling between brain areas”.

These results – of a decrease in “top-down information transfer” under anaesthesia, driven by the suppression of locally available information at the source — can be interpreted, the study notes, according to a popular theoretical framework, called “predictive coding”, about how cognition and consciousness works.

The predictive coding theory suggests the brain constructs and maintains an internal model of the world, using this model to predict future sensory input at lower levels of the cortical hierarchy, and then refining that model according to whether predictions match actual future input.

“Theories of conscious perception within this predictive coding framework propose that conscious perception is ‘determined’ by the internal prediction (or ‘hypothesis’) that matches the actual input best,” the researchers write. “It may be conversely assumed that the absence of predictions leads to an absence of conscious perception.” In other words, to loss of consciousness.

The researchers caution that the signals they have measured “merely reflect a coarse-grained view of the underlying neural information processing,” and that different anaesthetics may lead to loss of consciousness by very different mechanisms.

David Liley, a neuroscientist at the Centre for Human Psychopharmacology at Swinburne University of Technology in Melbourne, agrees the results need to be verified using other anaesthetic agents. “Isoflurane is thought to act predominantly at inhibitory synapses, which are well-known to directly regulate local neural activity,” he says.

“In contrast, other well-known anaesthetic agents such as ketamine, nitrous oxide and the noble gas xenon – often collectively referred to as dissociative anaesthetics – act at molecular sites associated with synaptic excitation, which is involved in the co-ordination of activity of different and widely separated parts of the brain.”

As a neuroscientist, Liley is particularly interested in the mechanism of anaesthetic action because of what it might help us about the deep mysteries of the mind. So far all we have to explain how anaesthesia works are theories, he says, because we still know very little about the relationship “between the physical substance of our brain and the subjective content of our minds”.

Reading too much into these new results, he notes, is complicated by the complexity of the processes under study, and the difficulty of isolating cause and effect when “everything is connected to everything else”.

Though he does not regard the findings as a “particularly radical revisioning of how anaesthetics work”, he acknowledges the novelty of “the definite empirical suggestion that changes in the complexity of brain function are not just driven by disconnecting the coordinated behaviours of different parts of the brain – our current best understanding – but by altering the actual behaviours of these different parts as well”.

“This article is a welcome contribution to the search for the mechanisms of understanding how anaesthetics act to impair consciousness,” he says. “Despite the successful use of anaesthetics for over 150 years there is still no clear understanding of how they produce unconsciousness, amnesia and immobility.”