Researchers look at what happens in the brain during general anesthesia.
Pamela Ferdinand
If you have ever experienced general anesthesia, you may recall feeling as if your brain was temporarily switched off. You plunged into unconsciousness and woke up, seemingly seconds later, without any memories of having undergone a painful procedure.
What changes happen in the brain during general anesthesia have long been a mystery. But preliminary results from an ongoing study at Massachusetts General Hospital—where anesthesia was first successfully demonstrated 160 years ago—suggest that the neurophysiological process of “going under” is more nuanced than simply a shutdown of the brain.
Emery Brown, a professor of computational neuroscience and anesthesia at Harvard and MIT and director of MGH’s neuroscience statistics research laboratory, is using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to capture how a commonly used general anesthetic called propofol produces loss of consciousness in the human brain.
Other researchers have studied the brains of patients after the drug has taken effect and have suggested various mechanisms of anesthesia across multiple brain regions.
Brown and his multidisciplinary team, however, are watching the human brain as it transitions from the awake, conscious state to the anesthetized, unconsciousness state. With this approach, “we can look to see when we have a certain drug level, what patterns we see on the EEG, and how the activity in the relevant brain regions change,” says Brown.
This way, researchers may be able to correlate drug levels with brain activity, which could lead to the development of target-specific anesthetic agents and more fine-tuned delivery methods that minimize the side effects and lower the risk of complications of general anesthesia. While it’s a routine and generally safe procedure, general anesthesia can have side effects, from nausea and anxiety to rare complications such as cardiac arrthymias and brain damage.
The study of anesthesia could also help researchers learn more about pain processing, memory formation, and the neuroscience of sleep, not to mention the larger question of consciousness itself.
“By studying anesthesia, we’ll learn as much about how the brain works as we will about how to make better anesthetics,” says Bruce MacIver, a professor of anesthesia at the Stanford University School of Medicine.
Selective effects
So far, four subjects have undergone Brown’s experiment. The researchers obtain EEG recordings and do fMRI scans on the subjects as they are slowly injected with increasing doses of propofol. As the drug takes effect, the researchers monitor the subjects’ level of consciousness by asking them to perform simple tasks in response to auditory sounds. They continue to probe for activity in the brain’s auditory pathways even after the subject has stopped responding to the sounds.
According to Brown, his early results suggest that propofol is selective in stopping, dampening, or scrambling specific signals in certain parts of the brain. The findings so far are consistent with previous positron emission tomography (PET) studies of human subjects under general anesthesia, he says. These studies showed that the subjects had less communication between the cerebral cortex and thalamocortical systems in the brain, which are considered critical to maintaining consciousness.
“We don’t have to necessarily have things shut down. All you have to do is just change the way regions [of the brain] communicate,” Brown says. “And it doesn’t have to be the same way all the time. It may be just altering pathways and turning off some key areas that have to do with the integration of information.”
If that’s the case, anesthetic agents could be designed to disconnect only specific regions of the brain that allow you to, for example, sense pain or to be aware, says Warren Zapol, chief of anesthesia and critical care at MGH. “Why treat the whole body if you could focus on the place in the brain where the key wires for consciousness are?”