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The bar for normal

Medicine | IN THE LAB

As a landmark study on healthy children's brains forges ahead, researchers look forward--finally--to having a benchmark for identifying neurological disorders.

July 16, 2007|Eric Jaffe | Special to The Times

NEWBORNS sleep about 16 hours a day. When infants reach a year, they stand on their own, or at least wobble. At age 4, many children can tell stories -- and in the decade that follows, motor skills become bike rides; memory skills become math solutions; language skills turn into back talk -- as the brain prunes its billions of nerve cells and refines its trillions of connections.

And once they're 18, they may again sleep 16 hours a day.

This path into adulthood is well worn, but developmental scientists know very little about the mental changes that guide the way -- limiting their ability to identify and understand many disorders that crop up en route.

Soon, however, a group of researchers will complete a major study of normal brain growth -- the first of its kind -- that will fill in this map of child development.

The National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development, an encyclopedic and unprecedented project, will track the growth and structural changes of healthy children's brains as they develop from birth to late adolescence -- providing developmental researchers and pediatricians with a benchmark, finally, of what is "normal."

"When you're trying to study anything about brain abnormality, the assumption is you know what normal is," says Alan C. Evans, professor of neurology and neuroscience at McGill University in Montreal, who is head of data collection for the project. "In fact -- we don't."

Once this project is complete and they do know, he adds, it will be possible to compare any number of psychiatric and cognitive disorders with the normal plot of brain development -- ADHD, autism, bipolar disorder, schizophrenia -- and have a better idea of just what goes wrong in the brain, and when.

"We can see what normal variation looks like, which we don't really know," says Deborah Waber, a psychology professor at Harvard Medical School and Children's Hospital Boston. "We might be able to see how a brain veers off course."

Such understanding, in turn, may guide researchers as they search for treatments and therapies that may prevent or mitigate the disorders.

The project, which began in 1999, involves researchers at six centers across the country and about 500 children. When most of the studies conclude this August, the scientists will have examined each child several times during the course of the study, compiling results from a battery of psychological and brain-imaging tests performed on children from 7 days to 18 years old. As findings emerge, so will a portrait of normalcy.

"We are very, very close to getting a true understanding of how the brain develops," says C. Robert Almli, director of the developmental neuropsychobiology lab at Washington University in St. Louis School of Medicine.

The picture is already getting clearer. In mid-May, a group of researchers led by Waber published the results of behavioral tests on participants age 6 to 18 in the Journal of the International Neuropsychological Society -- the first paper based on data from the project.

The children took more than a dozen tests, assessing verbal fluency, memory, motor skills and general intelligence.

Even at these young ages, low-income children scored worse than middle- and high-income children on IQ tests -- a finding supported by prior research that may be the result of environmental factors.

But surprisingly, Waber notes, this gap was smaller than it had been in previous studies. In addition, children of different socioeconomic groups showed no difference on certain verbal exams and on organization tests.

The newer findings may well be more accurate because the data are so thorough and the children screened so rigorously for clean health.

Taken together, Waber says, these results suggest that a lot of disparity on cognitive tests disappears when all subjects are healthy, regardless of income.

Among the other conclusions: proficiency in most tasks improved greatly between ages 6 to 10 and then leveled off. Tests of verbal fluency (which in the past have favored girls) and calculation (which in the past have favored boys) showed no sex-related differences across all ages, a finding that Waber says is difficult to explain.

The first wave of results appeared on the project's online database in late June, and researchers can now apply to access the information. Eventually -- perhaps in 2008 -- all the data will be made available to researchers looking for a sizable control group to compare with brains, or behavioral tests, of children who have disorders, or to clinicians wondering whether something they notice during a brain scan of a patient falls within the realm of normal.

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