Eric Courchesne managed to find a positive thing about getting polio: It gave him a clear idea of what he would do when he grew up. Courchesne was stricken in 1953, when he was 4. The infection left his legs so wasted that he couldn’t stand or walk. “My mother had to carry me everywhere,” he says. His parents helped him learn how to move his toes again. They took him to a pool to learn to swim. When he was 6, they took him to a doctor who gave him metal braces, and then they helped him learn to hobble around on them. Doctors performed half a dozen surgeries on his legs, grafting muscles to give him more strength.
Courchesne was 11 when the braces finally came off, and his parents patiently helped him practice walking on his own. “Through their encouragement, I went on to have dreams beyond what you’d expect,” he says. He went to college at the University of California, Berkeley. One day he stopped to watch the gymnastics team practicing, and the coach asked him to try out. Before long Courchesne was on the team, where he won the western U.S. championship in still rings.
When Courchesne wasn’t competing at gymnastics, he was studying neuroscience. “I understood a neurological disorder firsthand, and I wanted to help other children,” he says. Fortunately, the polio outbreak that snared him in 1953 was the last major one in the United States; a vaccine largely eliminated the disease in this country. But in the mid-1980s, as a newly minted assistant professor of neuroscience at the University of California, San Diego, Courchesne encountered a 15-year-old with another kind of devastating neurological disorder: autism.
At the time, Courchesne was investigating how children’s brains respond to new pieces of information. “I encountered a clinical psychologist who studied children with autism,” he says. “She told me, ‘Autistic children aren’t interested in novelty. They’re interested in routine.’ ” Yet the young man Courchesne met showed more range. At first he responded to Courchesne’s questions only with short answers, “but when I talked with him further, I discovered he had a tremendous wealth of knowledge,” the neuroscientist recalls. “He had calendar memory. He just wasn’t interested in being sociable.”
Autism had cut the boy off from the social world, Courchesne realized. “I could see his loneliness, and I could see his parents’ heartache,” he says. He could also see that the boy’s parents refused to give up on him, in the same way his parents had refused. “As they say, that was it,” he says. He swung his entire career toward autism.
In the three decades since, autism has gone from obscurity to painful familiarity. The Centers for Disease Control and Prevention estimates that about 1 in 110 children in the United States are autistic. Yet the disorder remains enigmatic. “Every turn of my research has been about figuring out how this thing began,” Courchesne says. Gradually he built up a picture of the autistic brain from infancy to adulthood, zeroing in on a crucial distinction between those who have autism and those who don’t.
As they develop, autistic brains bloom with an overabundance of neurons, Courchesne finds. It might sound like bad news, implying that autism is rooted in such a fundamental change to the structure of the brain that there’s no hope of undoing it. But Courchesne says his findings could lead to key treatments in years to come.
Back when Courchesne began his work, the notion of a neuroscientist studying autism seemed a bit odd. Many researchers considered the disorder a psychological problem, perhaps the result of bad mothering. “It was a medieval way of thinking,” Courchesne says. As time went on, he became convinced that autism was not only a neurological disorder but more specifically a developmental disease that altered the structure of the nervous system as it matured.
Scientists had done a few anatomical studies on the autistic brain, but the results were ambiguous. Even normal brains can vary enormously in size and structure, so it was hard to see what, if anything, set autistic brains apart. To push past this confusion, Courchesne needed to look at a much larger sample of brains.
In 1988 he sought out parents of autistic children and got their permission to have the children lie in MRI scanners so he could take high-resolution anatomical pictures of their brains. Then he used computers to mark the boundaries of different brain regions and estimate their volume. The subjects spanned a wide range of ages, from adults down to toddlers as young as 2. Courchesne did not scan infants, but he went back through medical records to look at the circumference of the heads of his volunteers since birth.
Courchesne hoped to find something, anything, that set the autistic subjects apart. “We didn’t know what it might be or where it might be found,” he says. “We didn’t know if it would come on in the youngest stages or older. It was wide open.”
Gradually he saw a pattern. At birth, children with autism had normal-size brains. But by the time they were a year old, the brains of most autistic children had grown far beyond average. The average adult human brain weighs 1,375 grams, but Courchesne encountered one 3-year-old autistic boy whose brain weight was estimated at 1,876 grams.
The MRI scans further revealed that only certain parts of the brain became larger. The growth was striking in the prefrontal cortex, the region just behind the eyes that is responsible for language, decisions, and other sophisticated thinking. Courchesne also saw an increase in both the gray matter (consisting of dense clusters of neurons) and the white matter linking different regions of the brain. This explosive neural expansion continued in many autistic children until the age of 5, and then it stopped. Past that age, Courchesne found, the rate of brain growth slowed in autistic children, falling behind that of ordinary children. By the teen years, some brain regions actually started to shrink.
Over the past two decades, Courchesne has replicated these results in three additional sets of brain scans. And he has moved beyond MRI, working with tissue banks at institutions like the National Institutes of Health, which stores donated brains. Working with the brains of six normal children and seven autistic children ages 2 to 16, most of whom died of drowning, Courchesne has studied neurons under the microscope and even counted the number of neural cells in different tissue samples. Last November he reported the first results: On average, autistic brains had many more neurons in some regions than normal brains. In the prefrontal cortex, autistic children had 67 percent more neurons than average.
These results provide insight into the origin of autism. During the second trimester of pregnancy, the precursors to neurons in the brain divide furiously. Then they almost all stop, well before birth. When the brain gets bigger after delivery, all that is happening is that the individual neurons are growing and sprouting branches. The only time autistic children can get their extra neurons, in other words, is while they are in the womb. “We established a time zone,” Courchesne says.
That time zone rules out the old bad-mothering theory of autism, and also the notion that vaccines trigger autism in toddlers. Courchesne suspects that fetal brains become autistic due to a combination of genetic and environmental influences that strike during the second and possibly third trimesters, just as neurons are dividing. It may be no coincidence that many of the genes thought to increase the risk of autism are also involved in the division of cells. It’s possible that an environmental influence--perhaps a virus--can trigger these genes to produce too many neurons.
When autistic children are born, Courchesne’s research suggests, they have an abundance of neurons jammed into an average-size brain. Over the first few years, the neurons get bigger and sprout thousands of branches to join other neurons. The extra neurons in the autistic brain probably send out a vast number of extra connections to other neurons. This overwiring may interfere with normal development of language and social behavior in young children. It would also explain the excess brain size seen in the MRI scans.
For Courchesne, this provocative discovery is just the beginning. His initial results are based on only 13 brains, and he would like to look at more to see if the differences hold up. He also wants to figure out why the early overgrowth in autistic brains is followed by slowed or arrested growth. Perhaps the overgrowth triggers the brain to prune the extra connections, and the pruning becomes just as excessive as the initial burst.
It may take a long time to get those deep answers, but Courchesne’s findings could produce practical benefits much sooner. For one thing, they suggest that the earlier doctors can diagnose autism, the better. Using MRI scans along with blood and behavioral tests, “it might be possible to identify infants at risk at a much younger age, when circuits are just being established,” Courchesne says.
Once children are identified, they could be treated to help their brains develop properly. The treatment might take the form of behavioral therapy or pharmaceuticals that modulate the way the neurons grow. The most targeted drug interventions might not be available for a decade or more. That is quite a while to wait--but Courchesne knows not to give up hope.
Copyright 2012 Carl Zimmer