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.
A universal sleep
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 stimulation. So it’s a critical area for arousal.” However, more studies are needed to find out if this is what’s going on.
Other scientists believe that the cerebral cortex – the brain’s outer wrinkly layer – is the main “home of consciousness” and therefore must be where anaesthetics exert their main effects. But there are other brain regions implicated too. For example, the frontal and parietal lobes. The former sits just behind your forehead, and is responsible for many higher-level activities such as critical thinking. The latter sits further back and is involved in processing sensory information, such as touch.
A third state
But there are emerging clues that our brains might be capable of an in-between state of consciousness – one which is neither asleep nor awake.
For most people, being “put under” means losing total consciousness and therefore all memory of events. However, that isn’t the case for everyone. An estimated one in 15,000 patients undergoing surgery can remember aspects of their surgery after waking, a phenomenon known as accidental awareness.
Jaideep Pandit, a consultant anaesthetist at the Oxford University Hospitals, believes that such individuals are experiencing a “third state” of consciousness somewhere between sleeping and waking, or consciousness and unconsciousness.
In tests, Pandit gave patients an anaesthetic along with a muscle relaxant, but used a tourniquet to prevent the muscle relaxant from paralysing the forearm. This allowed unconscious patients to move their hand if they so wished. He found that one third of patients were able to squeeze the experimenter’s fingers on command, despite not showing any signs of being awake or in pain during surgery. According to Pandit, this suggests there is a third level of consciousness.
The uniqueness of consciousness thought
The so-called “hard problem” of consciousness remains one of the great unsolved mysteries of science. But looking at what’s different when you lose this ability is helping to unlock its secrets. While regular sleep also involves a loss of consciousness, general anaesthetics allow it to be switched off at any moment, so they make it easier to study.
Take the uniqueness of our conscious experiences. It’s generally accepted that each person or animal’s conscious experience is entirely subjective and special to them.
Andrea Luppi, a neuroscientist at the University of Cambridge investigated if general anaesthetics can shed light on how this works. He looked at the brains of people under general anaesthesia using functional MRI scans. This technology can record blood flow in the brain, to see what impact the drugs have.
Luppi was particularly interested in functional connectivity – a measure of how well different regions of the brain communicate and coordinate their activity. Normally, this type of neural activity follows a pattern that is so unique that it can act like a “fingerprint” to identity a person.
However, Luppi and colleagues found that, under anaesthesia, individual brains became less “unique” and more similar to one another. Intriguingly, the anaesthetised human brain also became less distinguishable from the brains of other primates, suggesting that the regions of the human brain that are most affected by anaesthesia are those that are most evolutionarily recent.
Luppi believes that a key signature of anaesthesia is that it stops disparate regions of the brain from talking to one another. During wakefulness, regions can interact even if they are not directly connected. However, this is very rare in the anaesthetised brain, where only regions that are directly linked to one another appear to “talk”.
“During wakefulness, the stream of consciousness guides the sequence of brain patterns that we visit,” Luppi wrote in a 2024 commentary. Instead, under anaesthesia brain activity is rudderless, he explained.
Luppi’s findings fit with the idea that consciousness does not result from activity in a specific brain region. Instead, it’s a network – it emerges from the coordination of different hubs. Like shutting down a government by crashing a country’s communications systems.
Luppi also believes that general anaesthetics could shine a light on how psychedelics such as LSD and psilocybin (“magic mushrooms”) alter consciousness. While anaesthetics dampen communication between different brain regions, psychedelics appear to do the opposite – they induce the brain to open new lines of communication.
Ultimately though, there’s still a lot to learn about where consciousness resides in the human brain.
“Our understanding of consciousness is pretty rudimentary,” says Boris Heifets, associate professor of anaesthesiology, perioperative and pain medicine at Stanford University, California.
“So I think if you can find someone to explain how conscious experience works, please let me know. I would love to talk to them.”
* All content within this article is provided for general information only, and should not be treated as a substitute for the medical advice of health care professionals.
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