The sleeping brain
Sorting, moving, arranging, mixing—there's a lot going on while you snooze. Tufts School of Medicine graduate Jeffrey Ellenbogen is working to figure it all out.
Sleep is the great unknown sea where we go diving for one third of our lives. It has generally been considered a dormant period, an essential time-out for our bodies and minds during which nothing much happens. Historically, from a medical perspective, sleep has been viewed much the same way, as a resetting of our internal clocks, or a random string of z-z-zs, or a nullity between waking hours. But that perception is starting to change. Based in part on research conducted by Jeffrey Ellenbogen, M'00, a pioneering neurologist in the Boston area, sleep is being reconsidered as a time of essential brain activity that, silently and beyond our knowing, enables us to make sense of the world we inhabit.
"This is a very exciting time for the study of sleep," says Ellenbogen when tracked down in his small, neat office at Massachusetts General Hospital, where he works as an assistant in neurology and director of the Sleep Medicine Program. "In the last five or 10 years, we've seen a lot of data suggesting that the old idea that sleep is an inactive state represents an obsolete concept. We have learned that the brain is doing lots of things during sleep, including consolidating memory."
Ellenbogen views sleep as one of the last big medical frontiers—in effect, a field as tantalizing, vast and unplumbed as stars in the night sky. "We don't know why people sleep at all, let alone why they do it so long," he points out. Contrast the depth of that mystery, he continues, with the easy medical comprehension afforded other body functions like the beating of our hearts. "We understand the heart perfectly," Ellenbogen argues. "No one says, 'Why does our heart beat, or why do we have skin?' We take that knowledge for granted. That's not to say that there aren't plenty of exciting things to learn in cardiology or dermatology. But the big-picture questions are not enigmatic in the way that sleep is."
A number of obvious difficulties have hindered sleep research. The brain, where the work of sleep goes on, is virtually inaccessible to examination. It's tucked inside the cranium and susceptible to grievous damage if not handled just so. Then there's the irreducible complexity of the wrinkled mass itself. Ellenbogen notes that the human brain contains approximately 100 billion neurons, with each neuron containing tens of thousands of interconnections. As he remarks, with a look of mild wonderment, "It's a pretty complicated place."
It wasn't until the 1950s that scientists discovered that there were different kinds of sleep, including REM and non-REM phases. These were the barest outlines of the mystery of the sleeping brain. More recently, the tools of functional magnetic resonance imaging (fMRI), PET scans and electrocephalography (EEG) have been used to give researchers a glimpse into the cognitive activity that occurs whenever we hit the hay. At this point, the research is more suggestive than it is complete. Even so, enough has come to light to demand that the old notion of sleep as a mental blank period be replaced with something new—something more akin to a cocktail party than a heavy snow.
A dynamic process
In a recent test at the University of Arizona that was reported in Science, a colony of rats gave the first hint of how focused and relentless the mind can be when the body is sound asleep.
The experiment was simple. With electrodes attached directly to their brains, rats were placed in a maze and closely observed. Their brains gave off a distinctive electrical firing pattern as they sought to navigate the maze. Later that day, when the rats were asleep, the hippocampus portion of their brains kept firing in exactly the same pattern, over and over again. It was as though the rats were studying the maze in their sleep in order to master it, Ellenbogen says.
One of the first signs of some comparable "off-line" activity occurring in humans came about in tests of motor skills—what are known as procedural memories—conducted by Matt Walker, Ph.D., a sleep researcher at Boston's Beth Israel Deaconess Medical Center. In one experiment, Walker would ask his subjects to learn a finger-tapping sequence by practicing it in segments and then combining the parts as best they could into a single rhythm. These performances were generally choppy. "But when you brought the subjects back after a night of sleep," Walker reports, "it was as though those problem points had been smoothed out." By implication, the benefits of a good night's sleep would likely accrue to pianists attempting to master a tricky passage in a concerto, baseball players struggling to hit a curveball or kids learning how to ride a bike.
Declarative memories, or memories about facts and events that can generally be put into words, pose another kind of challenge for the human brain. Ellenbogen examined this phenomenon last year, when he was a fellow in sleep medicine at Brigham and Women's. The results were published in the July 11, 2006 issue of Current Biology. Before this study, no one had been able to show definitively that sleep promotes the strengthening of declarative memories in humans. (continued)
Profile written by Bruce Morgan, editor of Tufts Medicine.
Photo of Ellenbogen by Graham Ramsey
This story ran online on January 14, 2008. It originally appeared in the Winter 2008 edition of Tufts Medicine.