Dr. Marcus Raichle

The insight that “the brain is never really at rest” has a long history in science and the arts, Raichle noted. Roman playwright Seneca in the first century, philosopher Immanuel Kant in 1781, psychologist/philosopher William James in 1890, neuroscientist Rodolfo Llinas in 2001—all have weighed in with variations on this theme.

Raichle, who is professor of radiology and neurology at Washington University in St. Louis, helped launch the field whose most iconic image is the brain map—brightly colored in areas of measurable activity (as determined by oxygen use or increased blood flow) and dark elsewhere.

It is those “dark” areas that have claimed Raichle’s attention in recent years. He and colleagues have begun to wonder about what he calls the brain’s “intrinsic activity,” which can be defined as what the brain is doing that’s not directly related to the task of a given moment, or experiment.

They were led to an interest in the brain’s intrinsic activity by a number of clues, including that no matter what measure of brain activity is used for imaging—blood flow, glucose utilization, oxygen utilization or oxygen availability—“ the changes that you see in the brain are exceedingly small—they represent a small incremental cost to the system.” What other activity, as yet unseen, consumes the rest of the brain’s “energy budget?”

Physiologists have long known that the human brain has an outsize appetite for energy— while it accounts for only 2 percent of body weight, it consumes a hefty 20 percent of the body’s energy.

Most imaging studies that have emerged since the discovery of computed tomography in 1972, the development of PET in 1974 and the refinements of functional magnetic resonance imaging first pioneered in 1992 are based on “evoked” activity. In other words, someone in a white coat measures brain activity in response to some kind of stimulus—a word, a sound, a blink. Before and after images show the brain’s response. What Raichle has found is that the areas that “light up” offering evidence of some activity cost the brain very little compared to so-called “dark” areas. Furthermore, viewed as an economic model, more of the brain’s energy is spent on intrinsic rather than evoked activity.

“Evoked changes in neural activity represent a small fraction (less than 10 percent) of functionally relevant, ongoing brain activity as measured in terms of brain energy consumption,” Raichle notes, on his lab’s web page, “while intrinsic functional activity consumes more than 50 percent of the brain’s energy budget. Thus, intrinsic functional activity must be at least as important to an understanding of brain function as the task-related or evoked responses that have been traditionally studied.”

He continues, “This perspective has shifted our view of the brain from that of a system simply responding to changing contingencies to one operating on its own, intrinsically, with sensory information modulating rather than determining the operation of the system, a view which has both historical and experimental support.”

“The images showing changes in activity within the brain can be deceptive,” warned Raichle in his NIH talk. “We think that what is ‘subtracted’ is of greater interest than what is shown.”

Images yield “only part of the agenda” of what the brain is actually up to while devoted to a task, he said.

“Most of the [burgeoning] scientific literature is about task…but how do you interrogate the state of the brain when the mind is wandering and the patient is just laying there?” he asked. It isn’t known, he said, what the “baseline” physiological state of the brain is.

How to study intrinsic activity? “It’s not a trivial problem,” said Raichle, who reviewed a host of the scientific challenges involving cell biology and physics. Potential payoffs are enormous, however, ranging from how to treat cognitive and performance deficits associated with a range of diseases to managing the growing number of head injuries sustained during blasts in the Iraq war, he said.

“We are also interested in the brain’s fundamental organizational structure—to know that would be very helpful. We also might discover how the brain works.

“I am convinced,” he concluded, “that the brain’s intrinsic activity will more than equal task-evoked activity in importance, when all is known.”

Musing on the brain’s fundamental nature during Q and A at the end of his talk, Raichle noted the importance of memory and reminiscence, and stated, “I would submit that the brain is in the prediction business,” which confers an obvious survival benefit. “The thing to remember is that the brain is always on—it doesn’t get turned on.”