Heady work

Professor Charles Nelson reassures one of the infants
participating in his lab research.

In a small room in Elliott Hall, a baby—let’s call her Harriet—coos happily on her father’s lap. She is only five months old, but already this is Harriet’s second visit to the University of Minnesota’s Nelson Laboratory, where once again a researcher will fit her with a hairnet of brightly colored electrodes to measure how her brain reacts to the things she sees.

On her first visit, she had met a new “face”: a full-sized woman’s head, realistically sculpted out of silicone, plastic, and rubber. The family took it home where it sat in the living room all month. (“We dressed her up as a witch for Halloween,” Harriet’s mother says.) Today’s tests will help show if Harriet will respond to pictures of this now-familiar face in the same way that she does to pictures of, say, her mother.

“We’re interested in how experience influences brain development — the effects of adverse biological or psychosocial experiences.”

Harriet’s “early experience” study is just one example of the College of Education and Human Development’s research in mapping the human brain—its “neural architecture,” as Charles Nelson, the professor who heads up the study, calls it. Faculty members at the college currently run about 30 studies in brain research, many in collaboration with other professors and students across the disciplines. And in the complicated world of interdisciplinary work, Distinguished McKnight University Professor Nelson may well have the most complicated schedule of all.

“I’m always teaching, as a guest lecturer or in seminars, but most of my teaching work is advising,” says Nelson, who also holds the Lindahl Professorship for Excellence in Teaching and Learning. “At the college, I’m in charge of a seminar next summer that cuts across three disciplines.” His appointment at the University is split 75-25 between the college and the medical school across the river, where he is a full professor of pediatrics. He directs the Center for Neurobehavioral Development (CNBD) and runs the Nelson Lab, which bears his name. “We have projects in Chile, Romania, Italy, and London. I flew 100,000 miles last year.”

What ‘normal’ looks like

At the Nelson Lab, and the nearby Institute for Child Development, Nelson and his colleagues study typically developing children, drawing from a registry of volunteer parents and children from the Twin Cities that goes back more than 20 years. Showing what “normal” looks like in the developing brain helps in CNBD’s research, where they work with at-risk children—for example, autistic kids, or children who spent their infancy in orphanages, or children of diabetic mothers. Memory is Nelson’s specialty, and his work has shown, for example, a link between prenatal iron deprivation (common in children whose mothers were diabetic during the pregnancy) and later impairments in memory.

“We’re interested in how experience influences brain development—the effects of adverse biological or psychosocial experiences,” Nelson says. “If you’re put into an institution [like the orphanages in Romania], that’s deprivation on a grand scale.” Such a child, with limited past exposure to new faces, may “process” the faces she sees quite differently from little Harriet, raised with two middle-class parents in an American household.

Such a child also might have trouble paying attention, or regulating her emotions. Megan Gunnar, like Nelson a Distinguished McKnight Professor of child development, just got funding for a five-year study of the neurobehavioral development of children who were adopted internationally by Minnesotans.

“Many [formerly institutionalized] kids don’t show any problems, even with extremely long periods of deprivation, but many others are at risk for attention problems, or for sensory motor problems stemming from long-term institutional care,” Gunnar says. “They might also have deficits in something called ‘theory of mind,’ the ability to understand what other people are thinking in common situations.”

Measuring stress in your spit

But Gunnar, like Nelson, also looks at typically developing children: “what I call ‘Garrison Keillor’ kids,” she says. In another long-term study, she follows children around to see how their stress levels change throughout the day. “I’m looking at the role of social experiences and temperament in how stress-reactive we are—how they affect our stress-hormone production,” Gunnar says. A preschooler who stays at home most of the day typically has a spike in stress hormones in the morning (“You need a certain amount of stress to deal with what’s coming at you,” Gunnar says), which then goes down for the rest of the day. But a child in a day-care center often has a higher measurable stress-hormone level in the afternoon than in the morning. It’s Gunnar’s job to find out how much higher and, maybe, why.

How does Gunnar get her stress-hormone samples? If you’re imagining scary hypodermic needles, relax. “I’m the spit lady,” Gunnar laughs, explaining that, although this stress hormone does circulate in the blood, its biologically active part is secreted in saliva. Children lick a cotton ball that’s been dipped in sugar crystals. “Most kids like it,” she says.

Over at the Center for Magnetic Resonance Research, Kathleen Thomas, assistant professor of child psychology, uses a rather more exotic technique for looking at the hidden recesses of children’s brains: the magnetic resonance imager, or MRI. Functional MRI lets her see which part of the brain is involved when the child is engaged in specific tasks. She is especially interested in an area deep in the brain called the caudate nucleus, which lights up (as it were) both when you’re forced to pay attention to something, and when you’re engaged in what Thomas calls unaware or “implicit” learning—when, say, you pick up cues or follow a pattern you didn’t consciously memorize.

Attention and implicit learning

“Very few people have looked at implicit learning in normally developing children,” Thomas says. “But we know even less about how that learning develops in different disorders like ADHD,” attention deficit hyperactive disorder. Since the caudate nucleus is compromised in children with ADHD, they have trouble keeping their attention focused, and Thomas’s preliminary data in one study suggests that they may have difficulties with implicit learning as well.

“MRI is one of the few methods, maybe the only method, for actually seeing the brain and its structure, and how it changes.”

The adults Thomas studies—“we always run our studies first with adults, then with children,” she says—have a very different reaction to the MRI scanner than the children. Thomas has her subjects performing a mental task, like identifying pictures on a screen, while the functional MRI scans the brain from the narrow tube the subject is lying in. Adults don’t mind holding still, but many hate the scanner’s small space. Children, surprisingly, are almost never claustrophobic. “They like the tunnel,” Thomas says. “They really like to see pictures of their brain, and they like the games. But they don’t like to lie still. You put a child with ADHD into a scanner, and they don’t suddenly become calm.”

But even with this drawback, functional MRI (the “functional” refers to the fact that, unlike a standard MRI, this technique shows not just a static picture of your brain, but which parts of your brain are active during different tasks) returns rich data. At the Nelson Lab, most of the data is drawn from EEGs (electroencephalograms), which, as Nelson explains it, show when something is happening in the brain, but not where. A functional MRI can show within millimeters exactly what structure in the brain is engaged during a task, using the fact that mental activity requires more oxygenated blood. In the MRI, “your oxygenated blood looks different from your deoxygenated blood,” Thomas says.

What's alarming: fear or neutral?

Thomas is collaborating on Nelson's diabetic-pregnancy study, examining how the hippocampus functions when children are having to constantly update their memories (is that a new picture on the screen, or one they've seen already?). In another series of studies, she's looking at how the amygdala, a structure sometimes called the "reptile brain" because its lineage stretches so far back into human evolution, reacts to different facial expressions.

"The amygdala seems to be important in determining what to be afraid of," Thomas says, "but it doesn't work the same way in children as in adults." In adults, the amygdala shows most activity when shown a fearful face; one where you can't tell why the actor might be afraid; in children, interestingly, it responds more to neutral faces, ones where you can't tell whether the person is mad or not. Thomas is exploring why neutral faces may be more important in childhood than in adulthood.

Yet another technique for studying the brain—eye movements—is the specialty of Canan Karatekin, associate professor of child development. “I’m interested in the nature of cognitive impairments,” she says—studying children and adolescents with either ADHD or schizophrenia spectrum disorders. Children with these disorders often have trouble with small-motor skills, but they have the same ability to move their eyes as their “normal” peers. This gives Karatekin an advantage.

Making inferences about the brain

“It’s hard to find an intact system, especially in schizophrenia,” Karatekin says. “Studying eye movements allows me to make cleaner inferences, since certain types of eye movements have been linked to certain brain functions.” She will, for instance, ask a child to look away from an object, then see how long it takes them to move their eyes.

“We might find that ADHD kids are fine when asked to look at something, but they have longer reaction times when they are asked to look away from something,” she says. “I don’t look directly at the brain, but I make inferences about the brain.”

Her colleague, Tonya White, assistant professor in pediatric psychiatry, works with the same group using diffusion tensor imaging, “a kind of MRI that, instead of looking at different regions of the brain, looks at connectivity—how efficiently different parts of the brain talk to each other,” Karatekin says.

It is highly unusual for one place like the University to have so much research focused on brain structures in children. Nelson estimates that his lab is one of only six around the world, including his own recently developed Institute for Child Development in Bucharest, Romania, that does EEGs on babies; Thomas says that very few do functional MRIs on children, although it is catching on. “It’s one of the safest medical procedures known,” she says.

None of this research comes cheap. The EEG nets that the Nelson Lab uses on children cost nearly $2,000 each and must be replaced every year; the machine that reads the data they provide costs $100,000. Nelson estimates that it costs the CNBD $500 per hour to do MRI testing on a volunteer subject. Even the heads on which children like Harriet are testing their memory for faces run $5,000 apiece; Nelson has seven of them in all, each specially made in Sweden a year and a half ago.

But the potential benefits to children and adults everywhere are enormous.

The beginning and end of the lifespan

Assistant Professor Kathleen
Thomas gets ready to test brain
function in an MRI machine.

The strides being made by college brain researchers are among the main reasons underlying the establishment of the President’s Initiative on Brain Development and Vitality Across the Lifespan. It is one of eight initiatives that University of Minnesota President Robert Bruininks has identified to help set priorities for the University. The possibilities that current research has highlighted makes it a field ripe for important developments.

“MRI is one of the few methods, maybe the only method, for actually seeing the brain and its structure, and how it changes,” Thomas says. “It’s exciting to think how we could use it to, for instance, actually follow children through adolescence.”

Gunnar agrees. Neuroscience is fascinating, she says, for what it reveals about the connection between early biological programming and late-onset diseases—such as the so-called Barker hypothesis that has shown that babies with low birth weight, if they rapidly gain weight after birth, are more susceptible to cardiovascular disease when they’re older.

“The beginning and end of the lifespan seem to be better connected than we thought,” Gunnar says. “The ideology of what we thought were late-life disorders have their initial organization in the fetal and early-childhood years.” Many researchers, for instance, think there’s a link between early-childhood stress and later cognitive deterioration—not Alzheimer’s, specifically, but simply memory loss.

The trouble is getting a true picture of a human lifespan. “Humans tend to live longer than the researchers,” Gunnar says wryly, “and the National Institutes of Mental Health”—the source of the grants that fund most of these studies—“tend to fund things in five-year spans.”

Beyond babies and Mozart

With their investment in students, equipment, and professors, the college and the University are gathering unique neurological data—data that professors like Gunnar fervently hope can eventually inform public policy. “It is sad that we need concrete evidence, not just behavioral evidence, to inform the debates about the importance of providing for young children’s health and well-being,” Gunnar says. “Neither Chuck [Nelson] nor I are really pointing to much beyond what’s being said from a behavioral standpoint, but there’s no question that biological evidence”—like data from an EEG or functional MRI—“just energizes the discussion. It seems more quantifiable, less murky, even though of course it’s not.”

Understanding neurobiology seems to be key in getting lawmakers to fund initiatives that truly help children, and keep them from spending money on “solutions” that do nothing. As an example, Gunnar points to the state of Florida’s expensive decision, a year or so ago, to buy classical tapes for parents of newborns, “even though no research supports the idea that listening to Mozart makes babies smart.”

On the other hand, hard data, even on such ordinary activities as attention and memory, brings us closer to being able to treat heartbreaking illnesses like schizophrenia and autism.

“Understanding how development works in the brain, and how it goes wrong, brings us closer to targeting how we might use interventions in children,” Thomas says. “We might also begin to understand how the brain learns from experience in a healthy way.”

She pauses.

“That’s just astounding to me: With all the things that could possibly go wrong in the brain, how often it goes right.”

—Rebecca Ganzel