Brush strokes painted on baby Aspen’s arm – both directly on the skin and again with the pictured plastic barrier – will give UVA researchers insight into how stimulation affects mental growth. (Photos by Erin Edgerton, University Communications)
If you’re looking for a touching story about babies, you’re in the right place. And this one starts the way every newborn’s tale begins: with drooling.
Baby Aspen – tiny, drowsy, with big eyelashes – and new mom Mara Roman were asked to make a donation, collected in tubes like those used for COVID-19 saliva testing.
“Just do your best to get the bubbles above the line,” the student lab assistant encouraged the mom. Aspen, only weeks old, needed some extra help getting her sample into the tube, of course.
The drool was meant to help develop some baselines. Specifically, the researchers are tracking a genetic marker called the oxytocin receptor gene, which is expressed throughout the body. Scientists think oxytocin is a major driver behind how we develop an understanding of social cues, learn to regulate emotions, and begin to process information and connect with others.
But the Developmental Neuroanalytics Lab at the University of Virginia is about more than just spit. It’s about cuddles and strokes. It’s about sounds and lights. It’s about play.
Foremost, though, it’s about the initial steps human beings take mentally.
“We’re looking at how genes influence human behavior over time,” explained Meghan Puglia, a UVA research assistant professor of neurology who directs the lab and its investigation into the role of touch and other stimuli in infant neurological development.
The ultimate goal of her study is to create a universal autism screening for babies, she said.
“Right now, the only way we can diagnose autism is by looking at a child’s behavior. The earliest age we can diagnose is shortly before 2 years, but a child often isn’t diagnosed until age 5 or older. By waiting so long, we’re missing out on critical periods of development. Our hope is to develop a quick and easy tool that can identify babies that may not be processing social information in an optimal manner.”
‘Like Dimmer Switches’ – Touch and Play
Just as every newborn these days tends to get hearing and heel-prick tests before leaving the hospital, insights from Puglia’s lab, part of the UVA Center for Healthy Brain Development, could lead to a first-of-its-kind autism test.
Autism is more common than either deafness or blood disorders in newborns, with about one in every 44 children eventually being diagnosed as being on the spectrum.
Puglia and other neurologists believe that autism falls within a category of conditions that may be influenced by interactions between individuals’ genes and their early life experiences, such as exposure to stimuli – or, alternately, deprivation from it.
She said the process of helping babies could involve creating new social development growth charts.
“Most babies enter the world ‘primed’ to attend to social information – like their mother’s face,” Puglia said. “If we know a baby is not processing this information in an optimal way, we can find ways to help them attend to this information so their brains can set up the critical experience-dependent networks that become the foundation for later, advanced social skills.”
“We’re not trying to cure autism, but we want everyone on a path to a fulfilling life.”
Infant screening could lead to novel therapies that help neurodiverse children reach their fullest potential.
“Early intervention gives individuals with autism the best start possible when their young brains are still ‘plastic’ and developing,” she said. “We’re not trying to cure autism, but we want everyone on a path to a fulfilling life.”
Touch and play are thought to be part of the answer for healthy development. They influence what’s known as epigenetics. While one’s genetics are locked in, a person’s epigenetics – influenced by behaviors and environment – are more flexible. Epigenetics influence how DNA sequences are read – loudly, quietly or not at all.
“Epigenetic changes are like dimmer switches getting bumped up or bumped down,” Puglia said. “They tend to be more sensitive in early development and more stable in adults. They can be regulated one way or the other, based on early life experiences.”
Roman, Aspen’s mom, was asked to engage in a little mother-daughter playtime after they gave the saliva samples. The researchers left the room, but monitored the interactions via a camera on each wall and a four-way split screen.
Mara Roman plays with daughter Aspen as researchers watch behind the scenes in a split-screen view.
“Tummy time,” meant to strengthen baby’s arms and prepare her to crawl, was on the agenda, as was reading. Aspen rested on her side as her mommy touched her shoulder and shared the contents of a soft-bound book.
“For this, we’re really just interested in the baby’s overt behaviors,” Puglia said. “How does baby respond when mom touches her and speaks to her? Is mom more talkative or reticent? Is mom switching between tasks or is the baby driving? Is it a loving touch or more operational?”
She added, “We’re capturing five minutes of play, but hopefully it’s representative more or less of the experiences the baby has in daily life.”
Like the saliva, it’s another baseline. A survey about home life will fill in other details.
What’s Going in Their Little Heads?
After the play time, the researchers fitted Aspen with an EEG receptor cap. Even scientists don’t tend to say the mouthful “electroencephalography,” which measures electrical activity in different parts of the brain.
Using a warmed-up gel squirted into the reservoirs for each of 32 metal contacts, the researchers changed the LED lights on the skullcap, one at a time, from red to green – green meaning a connection was made. Aspen’s temporary lack of hair made the process quicker.
Then, in another room, mom held Aspen as the researchers synched the baby with their computers.
Research assistants prepare the electrodes on a tiny EEG cap.
After marking a 3-centimeter space on Aspen’s arm, an assistant donned a pair of headphones and wielded a high-tech brush developed by the UVA School of Engineering. The brush can pick up multiple forms of touch data, such as how much force is used.
On the other side of the partition, a second assistant made adjustments. A display showed the wavy lines indicating Aspen’s brain at work.
With each one-second tick of the metronome sounding, the assistant with the headphones and black wand gave the baby one stroke. The motion activated the infant’s natural sensors, where hair follicles are beginning to sprout.
The auditory ticking translated visually to tick marks on the computer display, containing 32 bands of oscillating lines. Puglia said that allows her to detect fine biological changes.
“The stroking activates a type of receptor associated with calming and social forms of touch,” she said. “A mom or any social partner uses it to soothe. Every time my research assistant strokes her arm, we’re looking to see if the baby’s brain fires the same way or if there’s a little bit of variability. You actually want to have some fluctuation and variability. But too much, and you can’t do things like learn from patterns. Too little, and you might get stuck in a developmental rut.”
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As a counterpoint to the effects of touch, the researchers also did the brush test with a piece of medical-grade plastic wrap. The plastic created a barrier between the brush and Aspen’s skin that kept her touch receptors from firing.
Overall, the sessions can take up to an hour and a half, depending on how many timeouts moms and children need. The babies are tested both in their mothers’ arms and in bassinets. The screening includes creative audio and visual stimulus for the children: words, water sounds, faces.
The children are studied from birth to 2 months, then again at 4, 8, 12 and 16 months of age – “and ideally at some point when they’re a toddler,” Puglia said.
Sound effects that could be straight out of a video game help to keep the babies alert and focused. Puglia said most of the newborns sleep through the process, as Aspen did, but that’s OK. Their brains process the touches and sounds regardless.
Baby Aspen rouses after receiving a 3-centimeter brush stroke to the skin.
For her part, Aspen’s mom was still very much engaged.
“I was super-interested in this research,” said Roman, who works at UVA Medical Center. Her specialty is keeping children’s hearts stable during surgery. “I’m also interested in getting my daughter’s results and seeing where she stands for her age.”
Throughout the study, Aspen showed signs of being a healthy, normally developing baby, Puglia said.
Pre-term babies (also referred to as “premature”), born before 37 weeks of pregnancy, are at risk for a number of health and developmental concerns. Their risk of autism is 10-fold that of their peers.
The Newborn Intensive Care Unit at UVA Medical Center works to keep pre-term children alive during those crucial first months, while putting them on a track to thrive. Puglia is partnering with the NICU to do the same research on the “preemies” as she performs on babies carried to term.
One mother participating in the study shared the story of a frenzied trip to the hospital on the day she was supposed to have her baby shower.
Baby Piper, a guest of UVA’s NICU, is in good health now and also participating in the study.
“We had had a really long day at work,” said Kayla, who asked that her family’s last name be withheld. “It was the end of the month. We had done inventory and it was really crazy that day. I came home, and we were prepping the house for her arrival, and I realized at about 10:30 I hadn’t felt her move and it terrified me. So I called my husband, we rushed to the hospital, and we decided it was time for her to make her entrance.”
Piper was born on July 30. At under 5 pounds, her birth weight was low. But she now shows signs of good health, such as finishing her bottles. Puglia only conducts her research when the newborns are in the clear health-wise.
The 2½-week-old kept her eyes closed as her mom told their story. Like her mom, she didn’t seem to mind participating in the study – despite sticking out her lower lip occasionally. A pair of headphones for the hearing portion of the test looked like a gigantic set of Princess Leia curls on either side of her little pink face.
“Knowing that we could help future parents and children get a head start on learning and preparing is a great thing,” Kayla said. “Any way that we can help that’s not invasive, that’s what we want to do.”
Meghan Puglia checks Piper’s EEG readout.
While one might think parents with at-risk babies might be reluctant to participate in the research, Puglia said she hasn’t found that to be the case.
“A lot of families are really excited and want to be involved,” she said. “Plus, their child gets a little extra attention.”
Puglia is a mother herself, so she tries to be extra-sensitive to the needs of parents and their small children while conducting her research. In fact, her 22-month-old daughter has been a special helper in that regard.
“She’s definitely our pilot for every study,” Puglia said. “I wouldn’t do something on a baby in my lab that I wouldn’t feel comfortable doing on my own child.”
Puglia is performing her research as part of a career development grant from the National Institutes of Health. In total, about 30 undergraduate and graduate students, and two full-time staff members, assist her with the research.
One of her grad students, Cabell Williams, is conducting an offshoot study using magnetic resonance imaging, or MRI, scanners (the ones in which a person lies flat inside a giant tube). The images captured are helping to map developmental brain activity.
In addition, the NICU portion of the collaboration extends beyond the hospital. Researchers across Grounds are taking the data Puglia’s team produces and using it for related projects.
Puglia is forging research collaborations across Grounds. (UVA Neurology photo)
The collective study contributes to the University’s $75 million Grand Challenges research in neuroscience, which aims to enlighten perplexing conditions such as Alzheimer’s disease and autism, as well as how the brain functions over a lifespan.
“I was really excited when I learned that the Grand Challenges chose neuroscience as a key area,” Puglia said.
She added that she hopes Challenge funding can help her expand her research to home visits, which would allow families who can’t travel to participate, increasing diversity and inclusion in the study.
The current research builds off Puglia’s doctoral research, which demonstrated that the number of neural states an infant can access, as indicated by those 32 EEG sensors, is partly explained by epigenetic modification to the oxytocin receptor gene.
Funded by a National Science Foundation grant, the study involved speech, sounds and images of faces for the infants to interpret, similar to the current study. The new research incorporates the touch element.
Puglia earned both her master’s and doctorate in cognitive psychology from UVA, in 2015 and 2019, respectively.
“We are absolutely delighted that Dr. Puglia has chosen UVA’s Department of Neurology and the Brain Institute as the home base for her field-leading, ground-breaking research,” said renowned autism researcher Kevin Pelphrey, the Harrison-Wood Jefferson Scholars Foundation Professor at UVA and a parent of a child with autism.
Pelphrey lauded Puglia for forging meaningful collaborations with the School of Medicine (NICU, Neurology, Radiology), Arts & Sciences (Psychology and Engineering), the School of Education and Human Development, and the School of Data Science.
“She is conducting truly transformational, translational developmental neuroscience,” he said. “The results from this work will help save infant lives, optimize healthy brain development and provide unprecedented training opportunities for UVA students.”
