For neuroscientist Karen Pierce and her husband Eric Courchesne, their painstaking efforts to get kids to sleep didn’t cease when their own babies grew up. Such tasks have become an essential part of their research.

Researchers take pains to study kids in scanners to understand how neurological diseases progress and how a theory of mind develops, the aim of the study pictured here. Image courtesy of Hilary Richardson and Rebecca Saxe (McGovern Center for Brain Research, Massachusetts Institute of Technology, Cambridge, MA).

Together, the two scientists direct the Autism Center of Excellence at the University of California, San Diego, where they study brain development in infants at risk for developing the disorder. “We really need to understand autism from the beginning, imaging the brain at the youngest ages you could possibly do it,” says Pierce. But whereas adults and even older children can stay still for the 30 minutes or so needed to get a clear brain scan, babies and toddlers up to five-years-old tend to be extremely squirmy. One strategy: imaging the kids’ brains at night while they snooze.

Coaxing babies to sleep is just one of several low-tech and high-tech solutions that neuroscientists are using, as they use magnetic resonance imaging (MRI) scanners to examine the brain at earlier and earlier time points in hopes of finding clues to the progression of neurological disorders. MRI study of the developing brain is a growing area of interest, says developmental neuroscientist Helen Tager-Flusberg at Boston University in Massachusetts. “It’s far less active than studies of adults, in part because of the limitations of the tools so far,” she notes. “But there’s growing awareness that even disorders that seem to appear later in life may start very early in development.”

By taking on the challenge of scanning the brains of infants and young children, many researchers hope to understand how brain networks and their activity patterns mature, and how they change in the case of conditions such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Such insights could eventually help diagnose brain disorders, predict symptoms, and deliver early interventions.

Working Past Bedtime Conducting scans on children—even sleeping ones—is no easy task. In the early days of their project, around 2007, Pierce and Courschesne would put their own babies to bed, and then take turns heading into the laboratory on alternate nights, sometimes until 2 o’clock in the morning. “I just remember feeling very sleep-deprived during those early years,” says Pierce. Because studies suggest that newborns are primed to start processing language right away (1, 2), and because language problems are a common feature in many ASD cases, the researchers focus on the babies’ neural responses to stories and other spoken stimuli. They’re looking, in part, to explain why different subtypes of ASD are associated with better or worse language development. To prepare for the team’s studies, parents keep their children awake and active all day (with no naps allowed) until one hour past the babies' normal bedtimes. These tuckered-out tots often nod off on their way to the laboratory, and can usually be whisked carefully into the scanner. But even while wearing miniature noise-reducing headphones, some babies wake up midscan. If this happens, the researchers pause the session, and try again after parents lull the babies back to sleep in a nearby rocking chair. The team is able to collect enough data this way from about half of the babies that come in. Fussier infants may have to return two or three nights in a row before the researchers can obtain sufficient data. To date, the researchers have scanned well over 100 sleeping kids between 12 and 48 months of age, tracking their development, diagnoses, and symptoms over time. Consistent with studies of older children and adults with ASD, Pierce and Courchesne have found that young ASD toddlers show relatively strong responses to language in the right hemisphere—especially in the temporal cortex—instead of the left-hemisphere dominance that takes shape in typically developing toddlers (3). The team has also found abnormally weak synchronization between language centers in the two hemispheres, similar to changes that have been reported later in ASD (4). In one area in particular, the superior temporal cortex, the researchers found that weak activity predicted those toddlers who eventually developed ASD with the most severe language deficits (5). Pierce hopes that by combining early functional MRI with behavioral testing, researchers can understand more about how and when neurological changes begin in ASD. Eventually, the research could help design targeted interventions that can be administered early, when the affected cortical circuits are still highly malleable.

Eyes Wide Open Others have made inroads into studying how infants’ brains work while they’re awake. At the Institut National de la Santé et de la Recherche Médicale in Gif-sur-Yvette, France, Ghislaine Dehaene-Lambertz studies how babies develop the brain circuitry and activity patterns to support language, math, and other cognitive abilities. In a seminal 2002 paper, Dehaene-Lambertz showed that in healthy infants, left-hemisphere specialization for speech processing, especially in the temporal lobe, appears as early as three months, well before babies begin speaking (2). To get active, alert youngsters to play along, Dehaene-Lambertz has rigged a system of mirrors to allow the children to see both the experimenter and a set of visually captivating displays (2). When children see pictures of faces or see toys the experimenter presents, they often become enthralled and stop moving; some remain almost hypnotized for as much as 20 minutes. This allows the researchers to examine how the babies’ brains respond to the sound of children’s stories being read aloud. But some babies will only stay still for one or two minutes—not enough to yield good data—and many babies fall asleep before the study is over. If any infants start crying or fussing, the researchers will stop the experiment. “You never know,” says Dehaene-Lambertz. “Sometimes we have very patient babies, and sometimes we have the machine for the whole afternoon and get no data.” Older children have a much easier time staying still and awake, and they typically have no problem following basic instructions. But even so, practice and preparation are key ingredients to a smooth scanning experience. In Rebecca Saxe’s laboratory at the Massachusetts Institute of Technology in Cambridge, researchers provide an instructional booklet for families to read with their kids ahead of time. The book shows pictures of the equipment and experimenters, and outlines the procedures children will encounter in the laboratory, all with the aim of coaching kids to stay still, relaxed, and attentive. Once in the laboratory, researchers first introduce children to a mock scanner, which has a bed with wheels and a tunnel that plays recordings of noises that the MRI machine makes. Graduate student Hilary Richardson studies how children between the ages of three and seven years develop theory of mind, or the ability to infer what other people are thinking. Saxe’s previous work with adults suggests a key role for the temporoparietal junction, which preferentially responds to stories about a character’s mental states, compared with stories that describe people’s physical attributes, or stories about nonhuman objects (6). In particular, the right temporoparietal junction appears to be attuned to descriptions of a person’s beliefs and desires, rather than to descriptions of a person’s social background (7).