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Solving the Mysteries of Anesthesia

New brain imaging studies could explain how certain drugs lull our brains into an unconscious state that pain cannot enter.
November 29, 2006

The doctor tells you to count backward from 100, and you’re out like a light by 97, then you wake up an hour or two later devoid of wisdom teeth or an appendix. That’s all most people can remember of general anesthesia–a drug-induced state of unconsciousness that has revolutionized surgery.

Emery Brown, a neuroscientist at MIT and an anesthesiologist at Massachusetts General Hospital, is using different brain-imaging technologies simultaneously to get an in-depth view of the brain as people go under anesthesia.

While doctors have used anesthesia for about 160 years, little is known about how the drugs affect the brain and render the patient immune to pain. But that may soon change, thanks to Emery Brown, a neuroscientist and anesthesiologist at MIT. Brown, who has been a practicing anesthesiologist at Massachusetts General Hospital for the past 17 years, uses different brain-imaging technologies simultaneously to get an in-depth view of the brain as people sink through the levels of anesthesia.

Brown spoke with Technology Review about how his studies could lead to safer drugs and better monitoring technologies, as well as to a better understanding of some of the brain’s deepest mysteries, such as sleep and consciousness.

Technology Review: What happens when someone goes under anesthesia?

Emery Brown: They don’t feel pain, they don’t remember, and they don’t move. But it remains a black box–we only know what we see clinically. No one really knows how the brain produces that state.

TR: Why is it important to understand the brain changes that underlie anesthesia?

EB: Anesthesia is not just the drug; it’s the whole process. We administer the drug. We make sure heart rate and breathing and blood pressure are okay. And we adjust levels of the drug if they’re not. But we’ve arrived at the current practice of anesthesia through total empiricism. We can’t definitely say when the pain center or the memory center is shut off. That’s what I’d like to know.

If we had a way to understand where the drugs are acting, we could develop new ways of monitoring people. Or we could develop very specific drugs that only target those areas. Maybe we could develop a drug that can shut down the brain regions that feel pain and remember, but leave the breathing center intact. That would be much safer.

Understanding anesthesia could also help us understand things like consciousness, sleep, and meditation. Sleep, for example, is a change in your arousal state. You’re no longer aware of what’s going on around you, but you’re still breathing, and your physiology is stable. If I understood sleep, could I use that to design better paradigms for anesthesia? And understanding anesthesia might tell us something about sleep.

Very practiced meditators can put themselves in impressive states. When you look at their physiology, it’s quite stable, and the metabolic demands of the body are reduced. Since meditation is something we can control, is there something we can learn from that and mimic with drugs? We think it’s important not only to pose these relationships, but eventually to try to link them. Maybe our work will generate some insight into how those conditions are generated.

TR: How do you study anesthesia?

EB: We give volunteers anesthetic drugs over a controlled period of time. As they get more drug, they go deeper into anesthesia. We can see how the brain changes as this occurs using fMRI and EEG. [FMRI, or functional magnetic resonance imaging, measures changes in blood flow to specific parts of the brain and is very spatially precise. EEG, or electroencephalogram, measures the electrical activity of the brain and is very temporally precise.]

We know from previous studies the EEG patterns that correspond to different depths of anesthesia. By combining this with fMRI, we might be able to see something in the brain that gives an idea of the origin of those EEG patterns.

Up until relatively recently, doing combined EEG and fMRI was impossible. The MRI magnet produced large currents in the EEG wires that could potentially burn people. And the MR signal created wide signal distortions. But my colleagues at Mass General worked out a safe way to record brain activity in the magnet and developed signal-processing techniques that help minimize distortions.

TR: Is it difficult to study anesthesia in people?

EB: Most anesthesia drugs stop you from breathing: patients are put to sleep and then given a breathing tube. But because we want to study the transitions in anesthesia, including when a patient stops breathing, we study a special set of volunteers: people who have had tracheostomies, a surgical opening at the neck to aid breathing after cancer or injury. If these people stop breathing as they fall off to sleep, you can help them breathe.

TR: How do you see your research changing the practice of anesthesia?

EB: It will give us a way of tracking what the brain is doing under anesthesia. Let’s say I completed my study and know what brain regions are shut down during different stages of anesthesia, and I know what EEG patterns those changes are associated with. We could put an EEG on the patient in the operating room and say, “I see pattern A, so I know brain region X is shut down, but not region Y, so maybe we shouldn’t start the surgery yet.”

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