We Finally Know How General Anesthesia Knocks You Out

If you’ve ever had a medical procedure that required general anesthesia, you know it’s a trippy experience. One moment you’re wide awake and the next you’re simply out, only to come to in a groggy state where you have no idea what just happened. Putting patients under has a long history that stretches back over 200 years, but exactly how the drugs work has been a mystery.

A team of MIT neuroscientists may have unlocked the answer in the case of propofol. Propofol has been commonly used since the 1980s to put and keep patients in a state of unconsciousness. The new research indicates that it works by interfering with a brain’s “dynamic stability”—a state where neurons can respond to input, but the brain is able to keep them from getting too excited. 

To find out how propofol achieves that disruption, the MIT team looked at electrical recordings from parts of the brain tied to vision, sound processing, spatial awareness, and executive function in animals that had been dosed with the drug. They then compared those measurements to some that were taken before propofol was administered. 

They found that the conscious animal brains showed increased neural activity after input like a sound or a new sight and then returned to a baseline level. But under the effects of propofol, the brain did some odd things. Previous research has shown that animals given the drug lose consciousness but maintain cognition and brain activity—basically, your brain can still process things like sound and smell, even if you’re not aware of it. The team, which published their findings on Monday in the journal Neuron, found that this effect may be due to the brain taking longer to return to its baseline after a sensory input while on the anesthetic, sending brain activity “into chaos,” as one neuroscientist put it.

When the researchers tried to recreate the experiment on a digital model of a brain’s neural network, they found they could reproduce propofol’s destabilizing effect by futzing with certain nodes in the virtual brain. 

“We looked at a simple circuit model of interconnected neurons, and when we turned up inhibition in that, we saw a destabilization. So, one of the things we’re suggesting is that an increase in inhibition can generate instability, and that is subsequently tied to loss of consciousness,” said MIT graduate student and study co-author Adam Eisen in a press release.

“The brain has to operate on this knife’s edge between excitability and chaos. It’s got to be excitable enough for its neurons to influence one another, but if it gets too excitable, it spins off into chaos,” said study author and MIT professor Earl K. Miller in the release. “Propofol seems to disrupt the mechanisms that keep the brain in that narrow operating range.”

It’s unclear if other anesthetics work the same way as propofol, but the team plans to explore that in future research, which could lead to doctors being able to be more exacting in how they put patients under.