BY JUDY LIN-EFTEKHAR
UCLA Today Staff
Everybody’s brain is different.
“No two brains are the same,” said
John Mazziotta, Frances Stark Chair of Neurology and head of
the Department of Neurology at UCLA’s David Geffen School
of Medicine. “Their shape. Their size. The way they are
organized.”
|
Arthur
Toga, director of the Laboratory of Neuro Imaging |
All of this makes it difficult to know what
is normal and what is not — is that piece of tissue a
doctor sees on a scan an aberration or just a normal variation?
Brain researchers are frustrated by differences that confound
their attempts to compare data from several subjects.
And for surgeons, the risk is always there that
they may unwittingly slip into dangerous territory. Unable to
actually view the critical areas in a patient’s brain,
neurosurgeons must plot their course via functional magnetic
resonance scans on each individual patient.
“We can point to an area the size of an
egg and say, ‘Somewhere in there is where the center is,’
” said Neil Martin, chief of UCLA’s Division of
Neurosurgery. “When we remove a tumor or a blood-vessel
malformation in the brain, we have to be sure that we can remove
it without damaging the patient’s ability to function,
without impairing his ability to control movement, to read,
write, speak, to comprehend.
“We need a road map to the critically
important functional areas of the brain, the key control centers,”
Martin said.
While anatomical maps of the brain do exist,
Mazziotta noted that “they are typically based on just
one or two brains. So they don’t tell you anything about
its variability.”
But, after nine years of study, a comprehensive
brain atlas is nearing completion at UCLA as a joint project
of the Ahmanson-Lovelace Brain Mapping Center, where Mazziotta
is director, and the Laboratory of Neuro Imaging, headed by
Professor of Neurology Arthur Toga.
 |
John
Mazziotta, director of the Ahmanson-Lovelace Brain Mapping
Center |
When completed next year, these collaborators’
creation will be the world’s largest, most comprehensive,
most high-tech brain atlas ever. In the process, they have established
UCLA as the world’s foremost center on brain imaging and
mapping.
The brain atlas will help surgeons like Martin
pinpoint critical areas within millimeters. “That’s
the precision we need to plan surgery,” he said. “That
will help us determine where we make an opening in the skull
and how we separate the abnormality from the surrounding brain
tissue. It gets us closer to our goal of 100% cure with 0% neurological
impairment.”
In many respects the neuroscience equivalent
of the human genome project, the brain atlas will comprise high-definition
structural maps — from gross anatomy to microscopic detail
— of individual brains based on age, race, gender, educational
background, genetic composition and other distinguishing characteristics.
Layered over the anatomical maps will be brain functions such
as memory, emotion, language and speech.
Within the next two years, brain experts worldwide
will be able to access the atlas online for details on brain
structure and function, descriptions of how the brain changes
as we age and how and where neurological disease occurs —
all viewable in full-color 3-D, much of it computer-animated.
The atlas will be of great assistance to researchers
like Daniel Geschwind, director of the Neuro-genetics Program
in the Department. of Neurology. His research focuses on how
genetics influences brain structure and on cognitive processes
such as language among normal populations as well as those suffering
from neurological disease. Data on gene expression could be
integrated into the three-dimensional structure of the atlas,
he said, “linking genetic information to many other types
of data and giving us the ability to create a dynamic picture
of gene expression over the entire life span in the context
of the 3-D structure of the brain.”
Mazziotta and Toga began with 450 “normals,”
primarily UCLA students and other volunteers between the ages
of 18 and 40 who tested within a typical range on measures such
as blood pressure and pulse and were free of medical or neurological
problems. Under the direction of Mazziotta, who is handling
the project’s data collection at the Brain Mapping Center,
these subjects submitted to magnetic resonance imaging scans,
lying as still as possible for an hour or two inside a donut-shaped
tube while a giant magnet bounced thousands of images of their
brains into a computer. Later, under the direction of Toga,
who is handling data analysis with the aid of a supercomputer,
these “brain slices,” reflecting a broad range of
orientations and depths, will be compiled in three dimensions
to establish the brain’s basic anatomical structure.
The research subjects also ran through a series
of functional tasks, from focusing on a picture of a checkerboard
to responding to auditory tones, while a functional magnetic
resonance scanner recorded details about how and where brain
activity was taking place. Also added to their data was detailed
personal information, from the volunteers’ age and gender
to handedness and diet, as well as samples of their DNA.
Cadaver brains are studied in a cryosectioning
lab near Toga’s office at Reed Neurological Research Center.
Each brain is cut into some 2,500 microscopically thin slices,
mounted on glass slides, stained and digitally photographed.
The slides will provide information at a much closer range than
the scans of living brains: While magnetic resonance scans can
resolve down to 1.5 millimeters, cryosections are 60 microns
thick — about half the thickness of a human hair —
and can be studied under microscopes at such high degrees of
magnification that details like neurons and their constituent
parts can be discerned.
Further adding to data collected at UCLA are
contributions from researchers around the world. The brain atlas
project has evolved to include researchers from six other countries
— Canada, Finland, France, Germany, Japan and the Netherlands
— and UC San Francisco and the University of Texas in
what is now known as the International Consortium for Brain
Mapping. Thus far, this global team has compiled hundreds of
thousands of brain images from some 7,000 live subjects and
cadavers.
Toga’s supercomputer pulls in data from
collaborators around the globe and direct from Mazziotta’s
scanning equipment via high-speed fiber-optic cables running
underground to Toga’s offices. The supercomputer is actually
five networked computers plus a room-size robot behind a windowed
enclosure. The robot sits in the center of a circle of shelves
holding hundreds of cassettes of hard data, some of the 40 terabytes
— the equivalent of 1,000 average office computers —
the computer can store.
Toga’s computer-analysis team consists
of some 60 researchers selected for the project from a wide
range of disciplines campuswide. They have their work cut out
for them in their challenge to capture structural and functional
information about the brain, because the brain is a dynamic
environment, always in flux.
For example, said Toga, “The way in which
we experience a feeling or recollect a memory is a process that
involves a complex circuit that is changing even as we’re
becoming aware of that sensation. When you scan a subject, all
you’ve got is a picture of that moment in time. The next
minute the picture changes.”
What’s more, brain functions are highly
distributed.
“You can’t just point to an area
and say, ‘Here’s the seat of language,’ ”
Mazziotta said. “For example, the brain handles the challenge
of thinking of and initiating a word, and of understanding that
word, differently. Execution of these tasks involves complex
circuitry throughout the brain.”
With a goal of establishing the “average”
brain, the researchers have determined that collecting a massive
amount of data would be their best hope for approaching this
moving target. Mathematics, in the form of “brain-warping”
software that Toga and his team have developed, will help them
unlock the brain’s puzzles.
The software will take the atlas’s tens
of thousands of images of thousands of brains and modify them
to make some number of brains look “the same” to
describe a certain population, such as right-handed females,
for example. Warping the images also will describe the range
of variations between brains.
“It’s incredibly painstaking work,”
said Mazziotta.
“We’re getting closer,” Toga
said. “What we find out about the brain isn’t going
to answer all those ancient and philosophical questions about
the nature of the human mind. Still, our work on this project
is a way in which we can try to understand complex, hard-to-touch
concepts. It is a way to help understand all those odd combinations
of functions that give us our experiential life.”
www.loni.ucla.edu
