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Biomedicine

Inside the Premature Brain

Part 3 of our magazine story on advanced MRI looks at efforts by Columbia University researchers to map brain abnormalities in preterm newborns.

This article was a feature story in Technology Review’s December 2005/January 2006 print issue. It has been divided into three parts for presentation online. This is part 3; part 1 appeared on Monday, January 23, and part 2 on Tuesday, January 24.

Parts 1 and 2 discussed the work of John Port, a neuroradiologist at the Mayo Clinic who is using MRI to explore the parts of the brain that may be involved in bipolar disorder.

Diagnosing Development

The techniques Port is studying, if they prove successful, will be used in diagnosing people already showing signs of mental illness. But what about others who are predisposed to problems but have not yet begun to exhibit symptoms? Can the MRI technology help to find these people so that they can be helped before symptoms appear?

At Columbia, Peterson is trying to answer that question. He and collaborators are among the first to scan the brains of premature infants – sometimes within days of their birth. The aim is to catalogue the types of brain abnormalities they discover and to devise ways to intervene earlier than ever before to try to correct or compensate for them.

Peterson first became interested in the complications of premature birth about 10 years ago, when he was beginning his psychiatric research at Yale University. He had discovered something very unusual in the brains of people with Tourette’s syndrome. Most of us have asymmetries in our brains – the left side doesn’t exactly match the right. Most of us also have one eye that’s bigger than the other (as portrait photographers will point out) and other minor asymmetries.

But the brains of people with Tourette’s syndrome were different. “In the Tourette’s brain, there seemed to be an absence of asymmetry,” Peterson says. A similar absence of asymmetry had been observed in animals that survived complicated births. Peterson decided to look at children who had been born prematurely. Like Port, he is using the newest MRI technologies to try to obtain information that hasn’t been available before.

There was a reason for his interest. Children born prematurely are at greater risk for learning disabilities and even psychiatric illnesses. Understanding how their brains are different should lead to new ways to help them.

As it happened, Laura Rowe Ment, a pediatric neurologist at Yale, was following a group of 500 premature children born between 1989 and 1992 as part of an ongoing study. Peterson and Ment set up a collaboration. “There were imaging reports suggesting various kinds of problems in the brain – in terms of brain development. But they were uncontrolled, the numbers were small – they were impressionistic,” says Peterson.

Even given their smaller body size, premature kids tend to have disproportionately small heads. “The guess was that brain size would be reduced” later in life, says Peterson. Researchers also speculated that there would be damage to the white matter. Ment’s kids, who were then about eight years old, were especially useful because she and her colleagues had documented everything that had happened to them since they were born.

The first thing Peterson did was use the MRI scanner to determine the size of the eight-year-old children’s brains. The guess was right – their brains were smaller than normal. But the decrease in size occurred only in certain brain regions – the parts of the cortex that govern movement, vision, language, memory, and visual and spatial reasoning. “These regions were dramatically smaller,” Peterson says. The other parts of their brains were normal size, or close to it.

The second guess – about damage to white matter – also proved accurate. There was less white matter in the motor regions of the children’s brains, meaning there were relatively few wiring connections there. And the reduction in volume correlated with IQ scores. “The bigger the abnormality – the more abnormal it was in all these regions – the lower their IQ was,” Peterson says.

The question then was, Did these abnormalities arise at or before birth or sometime later? Peterson started scanning normal and premature infants. The scans of premature newborns showed that they had the same brain abnormalities as the eight-year-olds. “It was so distinctive, the pattern of abnormalities, it’s almost impossible to look at a scan and not be able to tell this is a premature child,” Peterson says.

One of the most salient differences was in the size of the tiny cavities in the brain known as ventricles. “The ventricles are massively dilated, about four times larger in the prematurely born kids than in the term children,” Peterson says. “We saw that in eight-year-olds and in the infants. The tissue around those ventricles is really damaged….It suggests that these babies are having problems in development even before they’re born.” Peterson followed the newborns for two years and then tested them with a kind of IQ test meant for toddlers. The earlier they were born, the more immature their brains were at birth. And the more immature their brains, the lower their intelligence scores.

To neuroscientists, the discovery that premature kids had brain abnormalities made sense. Much of the brain’s growth and development occurs during the last half of pregnancy. Neurons begin life clumped near the center of what will become the brain but soon start to migrate outward. Glial cells, which help neurons communicate, go through a period of explosive growth, accounting for most of the brain’s increase in weight. The neurons extend meandering tentacles, seeking connections with other cells. Billions of connections are made during the last weeks of pregnancy. The axons then develop their coats of white, fatty insulation. By this time, the brain is massively overdeveloped, with far too many wires and connections. So it begins cutting back. It’s as if each connection is tested, to determine its value. The useful circuits are kept; the others are trimmed away, leaving a sleek, efficient machine.

Premature birth likely disrupts these processes – the migration of the nerve cells, the growth of glial cells and white matter, and the trimming. Premature kids have most of the neurons they will carry with them into adult life, but it’s possible they’re not in the right places or properly connected or tested. Researchers, says Peterson, are “intensively testing” these possibilities.

Peterson’s research offers the hope of helping children compensate for whatever brain-related peculiarities they might have. “We want to use imaging to predict who’s going to have particularly difficult problems in the course of development, so we can intervene more effectively,” he says. That intervention might consist of specially designed education programs or physical therapy and other treatments to compensate for physical and emotional difficulties.

When Peterson began this work, his interest was professional. But now he has a personal interest as well. Two years ago, his daughter was born four weeks premature. While she shows no ill effects, he says he watches her, and he worries.

Brainstorming

When Peterson scanned me, he found nothing wrong or worrisome. If I’d had a brain tumor or some prominent abnormality, he would have spotted it. But that’s about all the clinically useful information he could get from a quick scan. If Peterson had put me through the sophisticated scans he uses with the premature infants, perhaps he could have detected some quirk in the way my brain behaves. But because of the large variability in normal brain structure and function, he would not have been able to conclude much specifically about how my brain differs from those of other people.

In the coming years, however, as the technology continues to improve, it may become possible for any of us, with or without obvious illnesses or neurological problems, to learn much more about the state of our brains, our perceptions, and our thinking. “The bad news is that although these techniques are very powerful, they are not where we need to be,” says MIT’s Desimone. “We need to use these MRI magnets in ways they haven’t been used before.”

Desimone’s McGovern Institute has just inaugurated the Martinos Imaging Center. One room at the center houses a state-of-the-art MRI scanner. Beside it is another room that, for the time being, will remain empty. “We have it sitting there for a new device,” Desimone says. He doesn’t yet know what that device will be. “That’s our challenge – to invent it here. The idea is to go beyond where we are now, to the technology of the future.”

Paul Raeburn’s most recent book is Acquainted with the Night, a memoir of raising children with depression and bipolar disorder.

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