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04/02/93

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RESEARCHERS SEE BRAIN AT WORK WITH NEW TECHNIQUE

STANFORD - At night for the past few months, physicists, psychologists and computer experts have been climbing into the bore of a magnet to take pictures of blood surging through each other's brains.

A discovery in the 1980s of the magnetic properties of blood, along with the development of magnetic resonance imaging, may turn out to make the '90s the decade of the brain, said psychologist Brian Wandell, whose "day job" involves studying how the brain computes colors. For the first time, scientists can watch a person's brain while he or she undertakes different activities, such as watching various objects.

"We do our brainwork at night because that's when we're not busy teaching and have time to get together," said Gary Glover, the director of the Lucas Imaging Center at Stanford Medical School. Glover, a professor of diagnostic radiology and nuclear medicine, is the chief technical expert at fine-tuning the center's magnetic resonance imaging machine for the new work.

The clinical machine is used by day to help doctors diagnose cancer, liver disease and skeletal injuries. At night, the scientists are finding it to be effective also as the highest resolution non-invasive tool for watching the brain at work.

Until now, brain researchers caught only glimpses of human brain activity with positron emission tomography - a technique that involves having someone take radioactive material so that his or her blood contains a radioactive tracer. Sensitive particle detectors show where brain bloodflow is heaviest, which is presumably where the most activity occurs. Because of the limits on safe use of radioactivity, it is not possible to do repeated imaging of the same person's brain.

"We all think this new brain imaging technique is very exciting because it can be widely used on both healthy people and patients to learn more about brain function," said psychologist John Gabrieli, who studies memory with Stanford psychologists David Rumelhart and Barbara Tversky. Also involved in the project are neurobiologist William Newsome, computer imaging specialist David Heeger, neuroscientists Mike Shadlen and Judy Illes, and graduate students Steve Engel and E.J. Chichilnisky.

"If we knew more about which brain regions are active for which kinds of memory, it would help us better understand the normal aging process and severe diseases like Alzheimer's," Gabrieli said. "Right now, it is difficult to tell the difference between the onset of the serious disease and different types of benign memory loss."

Added Wandell: "There's really important stuff to learn about the brain -- about blows to the head, strokes, Alzheimer's and visual prosthetic devices. We've studied brain function in primates, but I can't tell a primate, 'Would you please think about a math problem or read this text while I record activity from your neurons?' "

Most information about the location of human brain activity has come from people who suffered strokes or head wounds that impaired them in one way or another.

"The brain, as a biological object, is really pretty large. It's been a problem of even knowing where to look for localized activity," Wandell said.

Within the past year, magnetic resonance experts at the University of Minnesota and Harvard Medical School demonstrated the potential for using the technique to study brain function. The Stanford team is interested in further developing the technology but more interested in getting on with applying it to the brain problems they have been studying all along, Wandell said.

They have begun by focusing on visual motor activity. The locations of specific vision activity within the brain are "much better worked out in animals than for memory, but both are far less well known in humans," Gabrieli said.

Glover and Wandell explained how the technique works. One of the researchers lies down in the magnet bore, biting down on a mouthpiece to hold his head still. He is asked to close his eyes while the magnetic resonance imaging machine takes a picture of a cross-section of his head - currently an ear-to-ear slice that is roughly perpendicular to the shoulder line. The subject then is asked to look at computer images that have been projected onto a screen in the magnet room. Pictures of his head are taken again while he watches a stationary object and yet again while he is watching a stationary object in a field of moving objects.

The resulting brain pictures actually show magnetism. This can be used to map brain function because hemoglobin with the oxygen molecule attached to it is less magnetic than deoxygenated blood. A section of the cortex that is involved in watching an object will demand slightly more blood than other areas of the brain and therefore should "light up" on the image.

Far more subtle than detecting a brain tumor or lesion in the gray matter of the brain, this search for oxygenated blood requires Glover's exceptional skills at "tuning" the scan with various software knobs, Wandell said.

"The signal differences we are looking for are on the order of several percent," Glover said.

So far, the researchers say, they've clearly seen some things they expected and some they had not. The area thought to be the primary processor of visual stimuli was thought to lie at the back of the head just above the neck, and the magnetic resonance images do not disagree. However, other brain sections are "lighting up" for some types of visual activity, in preliminary results, Wandell said.

"We've been able to successfully measure changes in the brain during motor activity and changes when people look; that is, in vision versus non-vision," he said. "We are now looking for specialized visual pathways in the brain for representing and calculating aspects of moving objects, and we are seeing some evidence of that.

"We also hope to find specialized pathways for color."

Computer screens go berserk in a magnet, however, so the group first must acquire better projection equipment to calibrate color images inside the magnet.

"We're at the stage where there is an explosion of things to be done," Glover said.

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