Dr. Emery Brown wants to solve a medical mystery: How does general anesthesia work? Anesthetic drugs debuted 164 years ago and help about 60,000 people per day in the U.S. undergo surgery. Yet, no one knows how those drugs render patients unconscious and impervious to pain.

“How can we better understand how general anesthesia controls the arousal circuits in the brain? It’s a fascinating question in neuroscience,” says Brown, an anesthesiologist, MIT professor of computational neuroscience and health sciences and technology, and member of the Institute of Medicine. His work could not only improve general anesthesia, but also open a new window on consciousness, sleep, coma, and certain brain disorders.

Brown recently co-authored a review article in the prestigious New England Journal of Medicine that, for the first time ever, defines general anesthesia — its clinical and neurophysiological features and their relation to sleep and coma. It does so in part through data from electroencephalogram (EEG), which measures electrical activity in the brain; functional magnetic resonance imaging (fMRI), which measures oxygen-dependent blood flow; and positron emission tomography (PET), which measures brain metabolic activity.

“Anesthesiologists say ‘sleep’ when describing general anesthesia to patients, but it’s not. It’s really a coma” — albeit a reversible, drug-induced one, he says. “One of the things I wanted to do for my colleagues is give them some feel for what these states mean, because we don’t typically look at the EEG when we’re in the operating room. But there’s a lot of information there.”

General anesthesia is safe but not without side effects, including nausea, vomiting, temporary cognitive deficits in many older patients and apoptosis, or programmed cell death, which could be detrimental to still-developing children. Brown uses tools from systems neuroscience — EEG, fMRI, multielectrode recordings, mathematical modeling and signal processing algorithms — to obtain a systemic view of how anesthetics work on neural circuitry in the brain and spinal cord. This could lead to new drugs that target only the relevant sites in the central nervous system and better ways to monitor brain states under general anesthesia.

His work, which the National Institutes of Health recognized with a $2.5 million Pioneer Award in 2007, is also helping to challenge assumptions about general anesthesia. For example, while anesthetics appear to shut down the brain, many of them actually rewire it; the brain is unconscious, but its circuitry is, paradoxically, active. This phenomenon could suggest therapeutics that target the neural circuitry of comatose patients and aid people with depression and other disorders stemming perhaps from faulty wiring, Brown says.

“What I want anesthesiologists to realize is that we have a very interesting set of phenomena happening in front of us.”