'One of the great unsolved mysteries of science': What general anaesthetic reveals about our brains

How general anaesthetics work is still not fully understood, but they are revealing clues about the nature of consciousness.

In 1797, the British naval commander Admiral Horatio Nelson had his right arm amputated. The operation saved his life. But according to legend the only anaesthetic he was offered was a swig of rum. 

For the majority of human history, even the removal of limbs was done on patients who were fully awake. The introduction of general anaesthetics in 1846 was game-changing. Now consciousness could be temporarily switched off anytime, anywhere, in anyone. Nelson could have skipped the amputation but still turned up for breakfast the next day. 

Today there are over 350 million surgeries performed under general anaesthesia every year. But how these mysterious medicines put us to sleep is still not entirely clear. Now emerging clues are teaching scientists about the fundamental workings of our brains. They're even hinting at the origins of consciousness itself.

There are several categories of anaesthetics. Some work by blocking pain directly, while others make you sleepy and relaxed. General anaesthetics go one step further. These drugs make you unconscious, so you have no awareness whatsoever of what is going on.  

There are a whole plethora of anaesthetics which can induce a state of unconsciousness. These range from seemingly inert gases such as xenon, which are rarely used in practice, to propofol, which is the most widely and commonly used general anaesthetic.

General anaesthetics can have widely different chemical structures. In each case, the overall effect is to interfere with the communication of nerve cells in the brain, preventing them from talking to each other. What is clear from magnetic resonance imaging (MRI) scans is that there is a global reduction in brain activity.

However, exactly how this results in a patient being put to sleep is less well understood.

For one thing, it's not yet clear whether the state of unconsciousness induced by anaesthetics requires the total shutdown of the whole brain. Or perhaps certain regions are more important than others.

"Even if the whole brain shuts down, because it [the brain] is so interconnected it's very hard to dissect out what triggered the global shutdown," says Nick Franks, professor of biophysics and anaesthetics at Imperial College London, UK. "If you look at brain scans, it's clear there are certain regions that are more sensitive that shut down first, and that begs the question whether these then trigger a global shutdown." 

Franks points to the thalamus, an egg-shaped structure deep in the brain that acts as a central hub between brain regions. This area appears to power down first when someone is given a general anaesthetic. The thalamus plays a crucial role in initiating and maintaining sleep, among other things. So do anaesthetics work by "hijacking" the brain's natural sleep circuitry?

"If you anaesthetise an animal and then stimulate a very selective part of the thalamus, you can wake the animal up," says Franks. "Studies also show that [some] people in a coma can be woken up by thalamic........

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