Saxe and her team tinkered with solutions until 2013 when a firm deadline appeared: Saxe became pregnant. “There is no way I’m missing the chance to scan this baby’s brain,” she recalls thinking.
Her son was born in September of that year; his first fMRI scan took place a month later. “I spent a lot of my maternity leave inside an MRI machine, singing ‘The Wheels on the Bus’ over and over and over again, trying to keep the baby calm and happy,” Saxe says. They used a quiet scanning sequence to lower the risk of hearing damage and a custom infant-sized head coil designed to improve the signal-to-noise ratio.
The first scan that actually worked took place in January 2014, when Saxe’s son was 4 months old. The team captured activity in his visual cortex as he watched short movie clips. Over the next year, they successfully scanned eight more babies between ages 4 and 6 months, three of whom were the children of lab members. A participant’s parent or another lab member lay in the scanner during every scan to check that the infant stayed awake. In 2017, they reported that the infant visual cortex is organized in roughly the same fashion as in adults and contains regions that respond to faces and scenes.
A
round the same time, but before Saxe’s data were published, Turk-Browne and Cameron Ellis, his graduate student at the time, started their own awake infant fMRI program. Instead of collecting data for a single experiment at a time, they decided to design several tasks and switch between them based on what an infant found most appealing. “Rather than putting all of our eggs in one question basket, let’s have multiple baskets and multiple questions and pursue them in parallel rather than sequentially,” says Ellis, who is now assistant professor of psychology at Stanford. They chose four baskets: statistical learning, attention, visual processing and infantile amnesia.
This approach was a “very bright, brilliant idea,” says Dehaene-Lambertz, who is not involved in their work. “Adults, you can make them do boring stuff,” but not so with babies—switching tasks increased the odds that the team could collect usable data for at least one experiment.
Tailoring each imaging session to an individual infant is something that Turk-Browne and his team have stuck with. A participant’s parent joins Turk-Browne in the scanner room—but not in the scanner itself—and lets him know when their child needs a break, snack or diaper change. Infants can also bring a favorite stuffed animal or blanket into the scanner with them. “I’ve held hands with probably 100 babies during these scans,” Turk-Browne says. During one scan in January, he sang songs and played peek-a-boo to soothe one fussy participant in between runs and twice lunged partway into the scanner to return a spit-out pacifier.
“In a way, it’s terrible science because it’s not repeatable. I don’t think I’ve ever had two scans be the same. Which is the opposite of what you normally want—you want to have a protocol that you follow to the letter for everybody so there’s no bias and no confounds,” Turk-Browne says. “But that’s the reality of working with this population: being adaptable and working with each individual kid and family.”
And it works: Turk-Browne’s group collects an average of one usable experiment per imaging session, they reported in a preprint last month. Even though not every scan yields data, “on average, we know that this research program will bear fruit,” Ellis says. In his own lab at Stanford University, Ellis says he also gleans the same average of one usable experiment per scanning session.
“There’s a lot of talk about how impossible it is. And I think we’re showing that it’s not completely impossible,” says Tristan Yates, a postdoctoral research scientist in Nim Tottenham’s lab at Columbia University and former graduate student in Turk-Browne’s lab.
A
fter Turk-Browne and Ellis discovered that—contrary to what was commonly thought—the hippocampus shows signs of activity as early as 3 months old, they started to wonder if other assumptions about the brain region were true.
One computational model suggests that the hippocampus contains separate pathways for episodic memory and statistical learning. And the learning pathway matures earlier than the memory one in nonhuman primates, a 2013 paper showed. This staggered development could explain why babies are good statistical learners yet don’t form memories that can be accessed in adulthood, Turk-Browne says. Without neural evidence, however, it was impossible to pinpoint which part of the infant memory process fails: encoding, storage, retrieval or something else entirely.
So, Yates and Turk-Browne designed an fMRI experiment to fill this gap. They presented a series of images for two seconds each—on top of a moving psychedelic pattern just to hold the infants’ attention—and then showed an old and new image together and tracked which one the infant looked at the most. The infants would likely spend more time looking at an image if they remembered it, the pair predicted.
During memory encoding, the infants had a stronger BOLD signal in their hippocampus while looking at the images they later recognized than for the ones they appeared to forget; the infants with the greatest preference for familiar images showed the strongest difference in signal, the team reported in today’s Science paper. This difference is more pronounced in infants between ages 12 and 24 months than in infants between ages 4 and 9 months.
“It seems that the hippocampus is capable of encoding new individual memories,” Yates says, so potentially something “further down the line” is going awry. This idea jibes with findings in rodents: Stimulating neurons tagged while a mouse encodes a memory in infancy reactivates it in adulthood. In other words, the memory is there; it’s just not typically accessible.
In his ongoing projects, Turk-Browne is exploring how the complexity of representations in the hippocampus changes over the course of development, and when and how retrieval of autobiographical memories encoded during infancy breaks down. “You can’t get that level of granularity of ‘What are the neural representations of an experience?’ with any other method in infants right now,” he says.
And fMRI in awake infants is poised to address other “really big questions that, at the same time, are kind of low-hanging fruit,” says Ellis, who is using the technique to study attention and language. “You can do a relatively simple task and answer something that’s been a mystery for a long time.”
Outside the memory domain, Saxe says she is analyzing data from projects on language lateralization in toddlers and scene-processing in infants; Rhodri Cusack, professor of cognitive neuroscience at Trinity College Dublin, says his team finished scanning 134 2-month-olds last year for a study on the development of the visual system.
A “first generation of young investigators” is also joining the charge, says Vlad Ayzenberg, incoming assistant professor of psychology and neuroscience at Temple University, referring not only to himself but also to Ellis and Yates. Yates created a toddler-scanning program in Tottenham’s lab, which previously imaged only children, and she plans to study the relationship between caregiver-infant bonds and cognition. When Ayzenberg opens his lab later this year, he plans to use fMRI in awake infants to study how cortical and subcortical areas contribute to cognitive abilities at different points in development.
A decade ago, it would have been too risky for a junior faculty member to take on an awake fMRI project, Ayzenberg says. “Now, I think there’s enough evidence that this can work, and enough people have done it successfully, that it doesn’t feel as insane of a prospect.” It’s possible, he says, but “it’ll still be really hard.”
