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My boy's big giant head

Posted Oct 01 2008 8:03pm
Clues to autism’s mysteries
By Sandra Blakeslee The New York Times
Thursday, February 10, 2005

NEW YORK There comes a point in every great mystery when a confusing set of clues begins to narrow. For scientists who study autism, that moment may be near, thanks to a combination of new tools for examining brain anatomy and of old-fashioned keen observation.

Within the last year, several laboratories have reported finding important new clues about the mysterious syndrome that derails normal childhood brain development. For the first time, they say, a coherent picture is emerging.

In autism, subtle brain abnormalities are present from birth. Infants and toddlers move their bodies differently. From 6 months to 2 years, their heads grow much too fast. Parts of their brain have too many connections, while other parts are underconnected.

Moreover, their brains show signs of chronic inflammation in the same areas that show excessive growth. The inflammation appears to last a lifetime.

‘‘Autism is still a confusing disorder, but one thing is now clear,’’ said Pat Levitt, a neuroscientist who is the director of the Kennedy Center for Research on Human Development at Vanderbilt University. ‘‘There is a specific disruption of circuitry in brain development.’’

To that end, Levitt and two dozen leading brain researchers held a three-day ‘‘autism summit’’ in Malibu, California, sponsored by the Cure Autism Now Foundation, to discuss this emerging view and to plan collaborative studies. The meeting ended Sunday.

People with autism have great difficulty with social interaction. Some cannot speak. Many are clumsy. A common trait is obsessive attention to certain details. Symptoms can be severe to mild.

Diagnoses of the disorder have increased in recent years, although no one knows why. Researchers agree that an unknown number of genes interact with unidentified environmental factors to produce the disorder. The new clues focus on brain development and circuitry, and especially on the brain’s white matter. White matter contains fibers that connect neurons in separate areas of the brain, whereas gray matter contains the neurons themselves. ‘‘You can think of this distinction as analogous to that between cables, or white matter, and circuit boards, or gray matter, inside a computer,’’ said Matthew Belmonte, an autism researcher at the University of Cambridge in England. ‘‘Even though each individual circuit board may be intact, if the cables are disrupted then the computer can’t function.’’

Using a new technique called morphometric analysis, in which post-mortem brain tissue is divided into tiny parcels and examined, Martha Herbert, a pediatric neurologist at Harvard Medical School, found an anomaly in the white matter of autistic brains — it is asymmetrical.

In autism, white matter grows normally until 9 months, Herbert said. Then it goes haywire. By 2 years, excessive white matter is found in the frontal lobes, the cerebellum and association areas, where higher-order processing occurs.

Another clue was reported last year by Eric Courchesne, a neuroscientist at the University of California, San Diego. Using a simple tape measure, he found that newborns who later developed autism had smaller head circumferences than average. From 1 to 2 months of age, their brains suddenly begin to grow rapidly. Another spurt occurs between 6 months and 2 years, giving rise to exceptionally large heads.

The rate of brain growth gradually slows from 2 to 4 years, reaching a peak a year later. A 5-year-old with autism has the same size brain as a normal 13-year-old. But by mid-adolescence, when normally developing children catch up, the autistic child’s brain is again comparatively smaller.

Ruth Carper, who works with Courchesne, went on to show that the frontal lobes, the slowest and latest brain region to develop, have the biggest size increase of all. But the nerve cells in this region, which is responsible for social reasoning and decision making, are actually much smaller than normal and ‘‘underpowered,’’ Carper said.

A third clue, from the laboratory of Marcel Just, a neuroscientist at Carnegie Mellon University, reaffirms the odd circuitry in autism. In a study published in November, he found that people with autism remembered letters of the alphabet in a part of the brain that ordinarily processes shapes.

‘‘Distinct brain areas work independently,’’ Just said. ‘‘People with autism are good at details but bad at conceiving the whole.’’

Skewed brain wiring could explain a fourth clue: clumsiness. Philip Teitelbaum, an expert on human movement patterns at the University of Florida, studies how babies with autism learn to roll over, sit up, crawl and walk. By looking at videotapes of their early months, before their disorders are diagnosed, he finds that autistic children use unusual strategies for locomotion. It is as if the parts of their brains that control movements are not properly connected.
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