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Making sense of babies’ brains

Newborn infant. Image courtesy of Elizabeth Hillman

Newborn infant. Image courtesy of Elizabeth Hillman

Newborn babies don’t walk like adults, talk like adults, or interact with others like adults. But do baby brains, at their most basic level of functioning, work the same way as adult brains? Most scientists have assumed so—the cellular mechanism of how neurons in the brain send messages is the same, at least. But a new PNAS Early Edition paper concludes that there are drastic differences between the way infant and adult brains use and control blood. The finding helps explain why researchers studying baby brain development have been stumped in the past by curious results that don’t resemble what they consistently see in adults.

If you want to know what area of the brain is active when a person listens to music, buys a product, tells a lie, or reads an article, the go-to method to answer such questions is a specialized type of brain scan called functional magnetic resonance imaging (fMRI). fMRI data reflects patterns of blood flow throughout the brain—when an area of the brain is activated, local blood flow changes. These blood flow changes lead to altered levels of oxygen in the blood, and fMRI can follow these changes by tracking hemoglobin, the molecule that carries oxygen. In adults, they can spot brain activity by watching for an increase in hemoglobin molecules that aren’t carrying oxygen cargo, called deoxyhemoglobin.

As fMRI has become a key tool in neuroscience over the past two decades, developmental biologists have attempted to apply the technique to newborns and young children to study how their brains change over time and how they differ from adults. But instead of seeing increases in deoxyhemoglobin use in babies’ brains when they were exposed to a new sight, sound, or feeling, scientists often only saw decreases in oxygen use—the opposite of what’s observed in a healthy adults brain.

“There were all these studies saying there was an upside down response,” first author Elizabeth Hillman of Columbia University told me when I asked her about the discrepancies. “But then there were just as many saying they saw a normal, adult-like response.”

Those in the field were puzzled, she said. Did the method just not work in babies? Were some people doing it wrong? Was there something fundamentally different about young brains?

Hillman’s team wanted to get a grasp on what was going on, so in their new work they compared the brains of young and old rats using fMRI. The rats ranged in age from 12 to 80 days, roughly equivalent to human newborns and adults, and are seen as a good model for human brain development. The researchers measured the response of the brain, using fMRI, to small shocks to the rat’s paws.

When they used a small stimulus, they observed the “upside down” response that some researchers had seen in the past. The results pointed toward decreases in blood flow, rather than increases, in specific areas of the brain. And the response of blood vessels to the stimulus was slower than seen in adults.

“The adult brain is very finely tuned. It knows exactly when and where it has to immediately increase blood flow to respond to a stimulus,” Hillman said. “But the newborn brain seems to be completely taken by surprise every single time.”

The observation doesn’t necessarily mean that there is no area of increased brain activity when infants are exposed to stimuli, however. It could mean that babies’ neurons can fire without increased blood flow and oxygen. In fact, Hillman said, this could be an adaptation to the low amounts of oxygen that a fetus is able to get before birth. Oxygen levels and blood flow patterns may simply be decoupled from neuron activity at this stage of development.

As the rats grew older, Hillman’s team found that their response began to become more adult-like in the fMRI experiments. Oxygen levels increased, rather than decreased, in discrete areas of the brain when stimulus was applied. “It’s as if the brain learned the physical response and gradually became more responsive,” said Hillman.

In the paper, the researchers describe one more observation that could explain why previous studies have seen such varied results. When they applied a strong stimulus, rather than a relatively weak one, to the paws of the infant rats, their blood pressure increased drastically and led to more blood flow into the entire brain, flooding the areas in which they’d seen blood flow decreases in the other experiments. On paper, it looked like a typical adult fMRI response, with an increase in oxygen. But it wasn’t caused by the brain’s local regulation of blood, they showed. Instead, it was an artifact of young rats—and likely human infants—having poor blood pressure regulation overall. In previous papers, Hillman says, researchers may have increased the strength of a stimulus in order to see the positive response they wanted, simply ignoring or overlooking the negative response seen at lower stimuli.

But the new findings now offer a direction forward for future fMRI studies. Performing a similar series of fMRI experiments on human babies as they age could offer a starting place to study how the brain response to stimuli matures, and a baseline from which to compare children with brain development disorders.

“Although our research suggests that you could get really funky results using fMRI in infants, that doesn’t mean you should stop doing those studies,” Hillman said. “You just might need to rethink how you interpret your data.”

Categories: Neuroscience
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