An Anesthesiologist Traces the Pathway Back to Consciousness
Even after years in practice, Dr. Alex Proekt still finds it remarkable that anesthesiologists like him can induce a coma-like state, allowing patients to undergo surgery without feeling pain. But Dr. Proekt's amazement doesn't end with putting people under; he's equally awed by how they wake up. As he puts it: With billions of neurons that interconnect in myriad, complex ways, it's astounding that patients regain consciousness and are exactly as they were before. "The total number of activity patterns that the brain can produce is absolutely enormous," Dr. Proekt says. "It's essentially infinite — yet the brain is able to navigate this landscape to find its way back to a normal state. That's not at all trivial."
The process is also far more complicated than previously thought, as a new study that Dr. Proekt spearheaded now proves. Scientists have long assumed that the brain returns to full function in a gradual, linear fashion as anesthetic drugs wear off. Instead, Dr. Proekt's findings, published last summer in the Proceedings of the National Academy of Sciences, reveal that the brain reboots erratically, powering through a series of distinct states to reach wakefulness. "Brain activity doesn't change smoothly — it changes abruptly," Dr. Proekt explains. "And it's not necessarily a direct path."
To understand the strategy that the brain uses to navigate its way back to consciousness, Dr. Proekt and his research team administered the anesthetic isoflurane to rats and then slowly decreased the amount, as is done to humans during a medical procedure. As the rats recovered, the team measured electrical activity in regions of the brain associated with sleeping and waking; recordings of this activity, known as local field potentials, look similar to that of an electroencephalogram. Dr. Proekt and his colleagues found that this neuronal activity happens in clusters, and that the brain transitions from cluster to cluster in unpredictable bursts. Each animal's brain took different routes as it moved from unconsciousness to consciousness — but in all of the rats, researchers identified a few hubs of activity that link otherwise disconnected clusters. In other words, the report concluded, the brain must eventually arrive at these specific hubs in order to awaken.
Dr. Proekt compares the process to the way a metropolitan transit system works, with a set map that restricts the places where one can travel. "There are different stations and you can take different subway lines to get to a destination," he says. "But if you want to change from one train line to the other, you have to go through a hub — like Grand Central Terminal — that connects them."
While the study shows that these so-called hubs exist, it's still unclear why they're there — and researchers don't yet know what prompts the brain to suddenly shift from one state of activity to another. As Dr. Donald Pfaff, head of the Laboratory of Neurobiology and Behavior at The Rockefeller University and a study co-author, puts it: "It's like knowing Mars is out there, but we're just beginning to know what its composition is." Such knowledge could help anesthesiologists pinpoint when a patient is about to wake up; currently, doctors can't know with complete certainty whether someone is fully unconscious. Dr. Proekt says that cases of those who are partially awake during surgery are rare, but "some of those patients who have these conscious experiences go on to be really traumatized."
The study could have great significance, too, for patients with a brain injury or neurological disease. Dr. Proekt says that if scientists can understand why the brain leaves one state of activity and segues to another, perhaps a therapy can be developed for comatose patients. "What this implies is that we might be able to repair the pathway toward consciousness," he says, adding, "Perhaps a person is trapped in a state of depressed consciousness because some of the subway lines, if you will, are blocked."
But to aid such patients, researchers must first determine whether this phenomenon exists in human brains. Dr. Nicholas Schiff, a co-director of the Consortium for the Advanced Study of Brain Injury and the Jerold B. Katz Professor of Neurology and Neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell, hopes to apply Dr. Proekt's methods to human subjects in his own studies. "Out of the large number of configurations in this vast space, Dr. Proekt and his colleagues looked to see if there was a standard path the brain took, like a road in the forest, and found evidence for it," Dr. Schiff says. "Their results suggest a robustness — that there's something consistent in the brain that we could potentially understand from a biological point of view. And that's very exciting."
— Heather Salerno
This story first appeared in Weill Cornell Medicine,Vol. 14, No. 1.