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Mapping the Brain's Mysteries: At the forefront of today's imaging revolution, mind explorers use a futuristic atlas to discover how healthy and diseased brains work

MacReady, Norra

Brain Imaging: Special Section

Mind explorers are leading a worldwide neuroimaging revolution to discover through hi-tech scans how healthy and diseased brains work

Norra MacReady is a book author whose health and medical articles have appeared in The Economist and Nast Traveler.

The brain hangs in midair, changing continuously. One moment the cortex is large and robust. A few seconds later it's shrunken considerably, devoured by some inexorable demon. Then, suddenly, it's back to normal, and the cycle starts over.

This is the devastation of Alzheimer's disease — an implacable wave of tissue loss that stunned even the investigators who created the images — made real before your eyes. Developed at the University of California–Los Angeles, this three-dimensional rendition represents data taken from thousands of brains at various stages of the disease spanning two years.

Welcome to the hub of the International Consortium for Brain Mapping, which was formed in 1993 to develop a reference system for the human brain. Using data gathered from 7,000 brains at labs around the world, the investigators are assembling a comprehensive brain atlas that can show the ravages of Alzheimer's, autism, schizophrenia and other conditions with breathtaking detail and clarity. The result: new insight into brain functions and dysfunctions.

“We are surprised every day by what we're discovering,” says John Mazziotta, M.D., Ph.D., director of UCLA's Ahmanson Lovelace Brain Mapping Center and principal investigator of the International Consortium for Brain Mapping.

And if this leading expert is constantly surprised by the discoveries afforded by the cutting-edge imaging and analytical capabilities, that's a good indication of how fast the technology is advancing. And how far. The brain atlas released this year provides a repository for the flood of information exploding from the recent proliferation of scans.

“With thousands and thousands of brain images to draw upon, our ability to detect an abnormality is extremely high,” says Dr. Mazziotta.



Through high-resolution MRI (magnetic resonance imaging), for instance, UCLA investigators discovered abnormalities in brain regions governing attention and impulse control in children — a finding that sheds new light on attention deficit hyperactivity disorder.

By providing a virtual map of how brains function, the atlas enables physicians and researchers around the world to compare its data with the scans of their own patients and study participants.

The atlas is unique for several reasons, Dr. Mazziotta says. First, it uses data from thousands of brains, while other labs compile data from a hundred at most. Second, by taking individual variations into account, it is very sensitive to subtle differences other atlases might miss. And third, by relying on such advanced imaging and biochemical techniques, it lets researchers see changes occurring at the level of individual cells.

“This atlas is population-based,” says Arthur Toga, Ph.D., director of UCLA's Laboratory of Neuro Imaging (LONI), where it was developed. “Some labs will take a slice or a scan of a single brain, describe it in detail and call it an atlas. But everyone is different, so we said, Let's develop something that shows the probability of certain features occurring in certain types of brains, so we can study different sub-populations.' For example, now we can take a very specific group, like left-handed women with early Alzheimer's disease, and compare them to healthy left-handed women of the same age, or some other group.”

THOUGH THE ATLAS project began over a decade ago, LONI's state-of-the-art headquarters opened just this spring after 31/2 years of construction and $15 million in funding.

Dr. Toga greets visitors at an entrance that's simultaneously high-tech and low-key, with flat-screen wall monitors flashing posters and videos showing the lab's latest research. Dr. Toga, a professor in the UCLA neurology department chaired by Dr. Mazziotta, takes his guests past a warren of offices like those in universities everywhere. Then he shows them into a chamber with room-sized computers that literally hum with activity. This is the heart of LONI: 850 processors crammed into 500 square feet of space, maintaining a constant crosstalk as they analyze data from the images sent to them from investigators all over the world.



From the information in the brain images they receive, the computers develop sophisticated mathematical formulas. Those formulas in turn are used to generate detailed pictures of a brain in various circumstances — for example, under the influence of methamphetamine, or in the grip of dementia.

LONI's supercomputer has the storage capacity of one petabyte — the equivalent of a million gigabytes, or 250 billion printed pages.

“We are harnessing the horsepower of these very large computer databases and putting it in the hands of neuroscientists,” Dr. Toga says.

From the computer room, he leads the way to his favorite part of the laboratory: a theater he nicknamed “The DIVE,” an acronym for Data Immersive Visualization Environment. If the processors are the heart of LONI, this is its mind. It's here that the information processed by the computers is reconstructed into visual images revealing anatomical relationships and changes wrought by age or illness, like the 3D image of the Alzheimer's-ravaged brain. “We wanted an environment where you could almost climb into the data,” says Dr. Toga. And indeed, viewing the brain through special goggles, it's hard to control the impulse to reach out and grab it. A dense thicket of neurons resembles the underwater kelp forests that dwell off the shores of Catalina Island near L.A.





This spectacular imagery is allowing researchers to draw new conclusions about the brain. Take, for example, their recent finding that the frontal lobes of a normal brain continue developing until relatively late in life. “This is a unique and extremely important advance, and will make us sensitive to subtle differences” in brain structure, Dr. Toga says. Already, LONI investigators have produced the first time-lapse images showing a normally developing brain through childhood, and are now comparing them to images of brains of patients with childhood-onset schizophrenia and bipolar disorder.

“For the first time,” Dr. Toga says, “we are able to assemble and integrate large quantities of data that will allow us to start developing a comprehensive picture of the human brain.”

Thus is the brain atlas providing the roadmap for all other brain studies to come.

“Brain imaging is a huge growth industry,” Dr. Mazziotta says, “and we are poised to become the central repository for this burgeoning field.”

From its UCLA hub at his Brain Mapping Center and LONI, the International Consortium for Brain Mapping (which also comprises core research sites on three continents) allows labs worldwide to interactively exchange data.

Their ability to analyze brain activity is among the most promising recent breakthroughs toward treating and eventually curing neurological diseases.

But the applications extend beyond studying diseases to exploring health. Already, scientists are using these images to analyze what goes on in the brain during everyday activities and through a full range of emotions. The images, in other words, are showing us what it means to be human.



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