AUTISM’S PUZZLE IS COMING TOGETHER
Brain scans may one day give researchers, and parents, a jump on the complex, growing problem
PHILADELPHIA — Nicole May sits in a dimly lit hospital room, cradling her 2-year-old son on her lap, rhythmically rocking him to sleep. She smiles into Nicholas’ wide blue eyes, brushing back his soft brown curls.
One by one, Nicky’s fingers loosen their grip on his bottle of milk, the muscles of his round face relax and his eyelids droop.
Carefully, May carries her sleeping boy to a loudly humming MRI scanner, laying him gently on the machine’s long, white platform. She makes a thumbs-up signal to the researchers and technicians watching from the other side of a glass window.
In an adjacent room, researchers from the Children’s Hospital of Philadelphia watch as black-andwhite images of Nicky’s brain flash onto a monitor.
Across the country, researchers are scanning the brains of hundreds of autistic children like Nicky, looking for insights into a condition that has proved frustratingly hard to understand. Autism, which now afflicts more than 1 million children in the USA, is associated with a spectrum of disabilities, including repetitive behaviors and problems socializing and communicating.
The quest to unravel the mystery — and get children and families the help they need — has become more urgent as autism has become more widely diagnosed. The condition now affects one in 88 children, according to a report last month from the Centers for Disease Control and Prevention.
Yet researchers today also say they’re beginning to make progress, perhaps for the first time, in understanding the autistic brain. Thanks to children such as Nicky and babies far younger, scientists are getting a glimpse of what might go wrong in early brain development, says Sarah Paterson, a developmental psychologist at
Children’s Hospital who works closely with the May family.
And while some of the field’s most exciting discoveries have come only in the past year or two, researchers such as Paterson say the findings could soon make a real difference for toddlers like Nicky. A decade from now, she expects doctors to diagnose the condition earlier and treat it more effectively, at least for children whose family history singles them out as high-risk.
Autism brain science “has moved stunningly fast,” says Kevin Pelphrey, an associate professor of child psychiatry at the Yale School of Medicine’s Child Study Center. “We’ve fundamentally moved around a corner where we will move much faster now.”
Pelphrey knows parents are impatient; they desperately need help today. Yet, as the father of an autistic child, Pelphrey says, the latest research also gives him hope for therapies that can reshape children’s brains, not just as babies but into adolescence. “Treatment can have effects even very late,” he says. “It’s not a lost cause at all.”
Parents have helped make some of the advances possible by pushing for funding that is now bearing fruit, says Robert Schultz, director of the Center for Autism Research at Children’s Hospital. Technological advances in imaging, stem cell science, gene sequencing and computing have opened doors as well. In only a few years, it will be cheaper to sequence an autistic child’s genetic blueprint than to perform an intensive, one-onone behavioral examination now performed when diagnosing the condition, Schultz says.
Not one puzzle but many
Yet mapping the autistic brain — like everything about autism — has been difficult, says Thomas Insel, director of the National Institutes of Mental Health. Researchers often describe autism as a puzzle with countless pieces, none of which yet fit together to form a recognizable picture. Yet to hear Insel talk, the condition might be even more complex. Insel says autism is now commonly regarded not as a single condition but as a group of related disorders with similar symptoms but different causes. Trying to make progress against autism, then, is not so much like putting together one puzzle but a dozen, whose pieces are mixed together in one box.
“It would be great if there were a grand unified theory of autism, but we’re far from that right now,” says David Amaral, research director at the University of California-davis MIND Institute.
Parents often ask to see their children’s brain images, hoping to learn what’s going on in the minds of youngsters who have trouble speaking for themselves, says neurologist Sarah Spence of Children’s Hospital Boston. But, Insel notes, “even when you look at a child who has no language, who is self-injuring, who’s had multiple seizures, you would be amazed at how normal their brains look. It’s the most inconvenient truth about this condition.”
So doctors are zooming in, looking not simply at the whole brain but at the “wiring” between brain regions and the spaces between cells, where chemical messages are sent, Spence says.
Research suggests the brains of autistic children may indeed be “wired” differently “right from the beginning,” Paterson says. A popular theory among researchers holds that autistic people have an abundance of “local connections,” in one specific part of the brain, but not enough “longdistance connections” to coordinate complex tasks among various parts of the brain, such as interpreting emotions, says Geraldine Dawson, chief science officer for the advocacy group Autism Speaks.
Studying the brain is far more challenging than other organs, of course. There are relatively few brains from autistic children available for autopsies. And because doctors rarely biopsy the brain, they can’t easily study brain tissue in labs, as they can with colon cancers or leukemia cells.
Researchers such as Ricardo Dolmetsch may have found a way around that problem. He and others have “created” brain cells in the lab by transforming ordinary skin from autistic children into stem cells, then coaxing them to morph again into neurons. The approach allows doctors to examine the microscopic spaces between brain cells, called synapses, where chemical messages are transmitted.
Game-changing technology
“This is the very beginning of a revolution,” says Dolmetsch, an associate professor of neurobiology at Stanford University.
Dolmetsch says his team is still a long way from identifying a safe drug to correct some problems he has found in autistic brain cells. Still, Insel singles out Dolmetsch’s work as some of the most exciting in the field. “You’re creating a disease in a dish,” Insel says. “This approach could be a game-changer.”
Sophisticated new imaging technology, like the tests given to Nicky, also is picking up subtle differences in the brains of autistic children.
The changes lie not in the brain cells themselves but in the pathways that transmit messages between brain regions, Paterson says. These pathways aren’t visible to the naked eye. But scientists can get a sense of these bundles of nerve fibers with technology that traces the path of water through the brain.
Structural changes in these fiber tracts are evident in the brains of children later diagnosed with autism, even as young as 6 months old. That’s six months to a year before autistic children typically begin to show any outward signs of their condition, says Joseph Piven, a researcher at the University of North CarolinaChapel Hill. Researchers focused on “high-risk” infants like Nicky — those with at least one older autistic sibling, who have a much higher risk of developing the condition.
“A lot of the kids in this study, they looked pretty good socially at 6 months,” Piven says, which suggests “there is a period of time of normal development. . . . But by 12 months, it was almost as if someone had pulled the curtain down.”
Additional imaging research may also shed light into why autistic children are less likely than others to make eye contact. British scientists used a specialized type of EEG, or electroencephalogram, to measure babies’ brain responses to videos of faces, says study co-author Mark Johnson, director of the Centre for Brain and Cognitive Development at the University of London.
In most babies, researchers could see their brains “light up” in response to eye contact, as if a person’s direct gaze piqued their interest far more than the image of someone looking away. The brains of babies later diagnosed with autism, however, didn’t react any differently to images of eyes moving toward the viewer than they did to those of people whose eyes were looking away, Johnson says. Significantly, those changes were also noticeable from around 6 months.
Paterson and others are eager to begin scanning babies even earlier, such as by age 3 months, to see when the first signs of autism emerge. These early tests aren’t yet ready to be used to screen babies, Paterson says. But if the scans could be refined and proven accurate, doctors might be able to use them on the younger siblings of autistic children.
That could allow doctors the chance to get high-risk babies into therapy very early, before symptoms even appear, and when they might even be prevented. “The hope,” Dawson says, “is that you could change the course of brain development.”
Indeed, the brain might be far more capable of repair than scientists once recognized, Pelphrey says. In some cases, the brains of people with an underlying genetic vulnerability to autism appear to “compensate” for whatever deficits they were born with by forming new brain pathways, Pelphrey says. He came to that striking conclusion by using functional MRIS to compare autistic kids with their healthy siblings, as well as a control group of unrelated healthy children.
Researchers weren’t surprised to see that the brains of autistic children responded differently to watching videos. The surprise came from the autistic children’s healthy brothers and sisters. Their MRIS showed a mix of brain patterns: some similar to those of other healthy kids, others closer to their autistic siblings, and a third group of unique patterns found in neither of the other groups, Pelphrey says.
“There may be people who have a genetic risk for autism . . . but their brains compensate by recruiting new brain structures to handle social information,” Pelphrey says. “They must have a set of genes that ‘code’ for resilience. If you understood how that happened, . . . could you create a treatment to teach children to use those other brain regions?”
Bringing Nicky back
Though Nicky has a long way to go, clinicians at Children’s Hospital say he has improved since beginning therapy a few months ago. Nicky, who turned 2 Monday, still doesn’t respond to his name.
Yet he has no trouble showing love for his mom. In the hospital waiting room, May picks Nicky up and hugs him, face to face. He grabs her long brown hair and pulls it toward him, as if closing a curtain around the two of them, creating a private space only they share.
“The goal is not to let him go into his world,” May says later. “When he starts to space out, to bring him back.”