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Revealing the brain's mysteries

Using souped-up versions of conventional brain imaging machines, scientists can now peer into the workings of the human brain, making movies of changes that occur as the mind thinks, talks, listens, dreams and imagines.

This is a breakthrough, researchers say, that may lead to quantum leaps in psychiatry and neurosciences _ perhaps allowing answers to some great unanswered questions. What is different about the brain of a poet? Or of a gifted mathematician? Do artists see differently? How do male and female brains compare? Do cultures affect the way brains are organized?

"This is the wonder technique we've all been waiting for," said Dr. Hans Breiter, a psychiatrist and postdoctoral fellow at Massachusetts General Hospital in Boston where the technique was first demonstrated. "At last we can see inside the human brain."

Dr. Walter Schneider, a psychologist who is using the technique to map human vision at the University of Pittsburgh, said, "We have, in a single afternoon, been able to replicate in humans what took 20 years to do in nonhuman primates."

Dr. Kamil Urgubil, director of the Center for Magnetic Resonance Research at the University of Minnesota School of Medicine in Minneapolis, said: "It allows us to study how the human mind is organized.

"Most neuroscience research is conducted at the cellular level. But if you are interested in the human brain, you have to study patterns at the organizational level _ what groups of neurons are activated and how they interact with each other during the performance of any complex task."

The tool making that possible is called functional magnetic resonance imaging, or fast MRI. Conventional MRI machines employ strong magnets and radio waves to make sectional images of the brain's anatomy. Most functional MRI machines are clinical machines that have been fitted with special hardware to speed the imaging process and advanced computer programs that can turn the static images into movies.

Fast MRI exploits the fact that activated brain cells use more oxygen as fuel than cells at rest. When a network of cells is called upon to carry out a task, such as recognizing a face or imagining a picture, those cells release a chemical that summons oxygenated blood from tiny arteries in the brain. As the blood gives up its oxygen, it moves past the brain cells to hook up with tiny veins that will carry it back to the lungs. The MRI machine is able to detect the motion of this blood flow because deoxygenated blood carries a faint magnetic signal distinct from oxygenated blood.

The fast MRI machine locates these faint signals and, through computer enhancement techniques, produces movies of the activated brain networks, Schneider said.

A research team at Yale University has one of the first published papers on these experiments, which appeared in a recent issue of The Proceedings of the National Academy of Sciences. It is about spoken language in the brain and confirms results from other imaging techniques.

A baseline image is taken of a subject lying passively in the machine, said Dr. Robert G. Shulman, a professor of molecular biophysics and biochemistry at Yale. Then researchers say a noun and ask the subject to speak the first verb that pops into mind.

The region for generating spoken verbs is in the left frontal cortex, in back of the left eyeball, deep down, Shulman said. It is about the size of a pencil eraser.

At the University of Minnesota, Urgubil's team asks subjects to silently imagine faces and move imaginary objects through space. Different areas of the brain light up, he said, depending on what is imagined.

Schneider's group is confirming decades of research carried out on monkeys to understand human vision.

Fast MRI, Schneider said, can distinguish cell groups one millimeter apart and is ideally suited to mapping vision in the human brain. So far, he said, the areas for detecting fine lines are identical in monkeys and humans, but the regions for seeing motion vary somewhat.

Applications in medicine

The new technique will find immediate applications in medicine, said Dr. Gregory McCarthy, an associate professor of neurosurgery at Massachusetts General Hospital in Boston. For example, patients undergoing surgery for intractable epilepsy must now submit to a highly invasive brain mapping procedure using implanted electrodes done to spare critical brain areas from the surgeon's knife. Fast MRI can do the same much more simply.

But it is in psychiatry where the more fascinating challenges lie. The human brain has distributed networks of neurons involved in various functions sitting in a bath of chemicals, Breiter said. "Change the balance of chemicals and you get a different set of processes out of a neural network," he said. Change the anatomy of the network from birth or early childhood experience, he said, and abnormal processes can result.

For example, patients with obsessive compulsive disorder may have an altered brain circuit for coping with dangerous, primitive thoughts. Instead of being filtered from consciousness, anxious thoughts invade everyday life. Some people wash constantly to avoid imagined germs.

When Breiter puts such obsessive compulsive disorder patients into the fast MRI machine and hands them a dirty pillow, they obsess. He watches their brain circuits light up. "Their circuits are different from normals," he said.

Similarly, Breiter and other psychiatrists plan to study patients suffering from schizophrenia and dementia to trace their altered brain circuits. This work is just getting under way, as is research on the effects of addictive drugs in the brain.

A principal obstacle in such MRI research is that the technique does not measure nerve-cell activity directly, but rather the enhanced blood flow to a region of the brain where nerve cells are active.

"We've seen some really neat things," said Dr. Bruce Rosen, a radiologist at Massachusetts General Hospital. "But what do they mean? Is hemodynamics a good surrogate for brain function?" Nerves fire in milliseconds, Rosen said, yet the blood flow takes a second or more to occur.

Difficulties with technique

"This is the brain-vein debate," said Dr. Brian Wendell, a psychologist in Stanford University's neuroscience program.

"Everyone wonders, if a tiny vein lights up, is that because there is neural activity right there? Or might the activity be taking place somewhere else? Maybe a couple of places drain into the same vein."

Also, it is difficult for subjects _ even highly motivated brain scientists _ to hold dead still inside the torpedo-shaped, loudly clanking MRI machines for up to two hours. Any tiny movement can blur the image and foil an experiment.

Nevertheless, scientists in the fledgling field of fast MRI tend to have supreme confidence in their findings.

The future of brain imaging is spectacular, said Dr. William Orrison, a neuroradiologist at the University of New Mexico School of Medicine who is working closely with supercomputer experts at Los Alamos and Sandia National Laboratories. There, fast MRI and another technique, MEG, or magnetoencephalography, are being combined to produce high-resolution, high-speed movies of the human brain with the aim of helping stroke victims and spinal cord patients.

PICTURES OF HUMAN THOUGHT: Computer-enhanced images using magnetic resonance imaging (MRI) are beginning to capture mental processes in the brain. This image shows in color the brain activity generated when a person was asked to generate verbs to match a noun, such as "cake" inspiring the word "eat." The MRI image then is overlaid on an anatomical image.

Brainpower

Our brain makes up only 2 percent of our total body weight but uses about 20 percent of the oxygen used by the entire body when it's at rest. There are three main divisions of the brain.

1. Cerebrum: Receives messages from the body's sense organs, sends out impulses to control skeletal movements and processes and stores information, making thinking, speaking and remembering possible. The cerebrum is divided into right and left hemispheres and is covered by the cortex.

2. Brain stem: Controls many involuntary muscles such as those of heartbeat and breathing.

3. Cerebellum: Controls balance, posture and unconcious movements such as eating or walking.

Mapping the cerebrum's cortex

The cortex is a layer of cell bodies that covers the cerebrum. Different parts of the cortex control various functions of the body. Diagram shows the left cortex indicates some of these functions.

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