This research, led by Jessica Girault, PhD, at the UNC School of Medicine, was conducted as part of the NIH-funded Childhood Brain Imaging Study Network, which used MRI to document crucial differences in the visual processing system in the brains of infants who were subsequently diagnosed with autism.
CHAPEL HILL, NC — For the first time, scientists have found that brain differences in the visual brain systems of infants who are later diagnosed with autism are associated with inherited genetic factors.
Posted in the American Journal of Psychiatry, this research shows that brain changes in size, white matter integrity, and functional connectivity of visual processing systems in six-month-old children are evident long before they show symptoms of autism as toddlers. Additionally, the presence of brain changes in the visual system is associated with the severity of autistic traits in their older siblings.
Led by Jessica Girault, PhD, assistant professor of psychiatry at the UNC School of Medicine, this is the first research to observe that infants with older siblings with autism who develop them -Even autism later as toddlers, have specific biological differences in visual processing regions of the brain, and that these brain features precede the onset of autistic symptoms. The presence of these visual processing differences is linked to the pronunciation of autistic traits in older siblings.
“We are beginning to analyze differences in infant brain development that might be related to genetic factors,” said Girault, who is also a fellow at the Carolina Institute of Developmental Disabilities (CIDD). “Using magnetic resonance imaging (MRI), we studied selected brain structures, the functional relationship between major brain regions, and the microstructure of white matter connections between these brain regions. The findings of all three led us to discover unique differences in the visual systems of infants who later developed autism.
As part of the NIH-funded Infant Brain Imaging Study (IBIS) network, researchers from UNC-Chapel Hill and the University of Washington led this one-of-a-kind study.
Behind baby’s eyes
When parents and babies bond, when they look at each other and discover their world together day after day, it’s not just cute; this is how babies learn to interpret subtle cues from their environment. It’s how babies learn to relate a caregiver’s behaviors to their own. This visual rhythm throughout the first years of life is crucial for cognitive, emotional and social development. In babies who go on to develop autism, this research suggests that something is going wrong in the visual system of the brain, impacting this visual interaction.
In recent years, IBIS network researchers have used MRI to document brain differences in babies who later develop autism in the second year of life. In 2020, Girault’s research showed that younger siblings were much more likely to develop autism if their older autistic siblings had higher levels of autistic traits.
“This suggests that these autistic traits tell us Something on the strength of autism genetic factors within a family,” Girault said. “But we couldn’t say much more beyond that. This current study advances our work.
For this study, researchers from the Infant Brain Imaging Study (IBIS) network recruited 384 pairs of siblings. The oldest child in each pair had previously been diagnosed with autism, which put the sibling as toddlers
to a higher likelihood of developing autism. Next, the researchers used various MRI approaches to study the brains of younger siblings in detail at six, 12 and 24 months of age.
The researchers measured brain volume, the surface area of the brain, in the region of the brain involved in vision (the occipital cortex) – structures that this research team had previously shown to be impaired in babies who developed autism at an early age. They also looked at the microstructure of the white matter of the splenium, a structure the researchers have previously shown to be related to how quickly infants orient to visual stimuli in their environment. At the same time, the researchers documented the level of autistic traits in the older autistic siblings of these infants.
Girault and his colleagues identified brain differences in two parts of the visual processing system – the occipital gyrus, which is important for object recognition, and the splenium, which is important for communication between different hemispheric parts of the visual system. The splenium is also crucial for quickly focusing our attention on the things we see around us.
“It is particularly remarkable that we were able to demonstrate associations between brain findings in infants and the behavior of their older siblings with autism,” said co-lead author John R. Pruett, Jr., MD, PhD, Professor of Psychiatry at the University of Washington School of Medicine. “The convergence of the brain-wide, data-driven cMRI results with the structural and diffusion results strengthens our confidence in the future replication of these findings, which could be tested in the new cohort of 250 infants at high family probability that we are currently recruiting.”
Co-lead author Joe Piven, MD, Director of CIDD, added, “We believe that aberrant visual circuitry is a fundamental cog in the cascade of events leading to later autism. We believe that this circuitry changes the way infants experience the world, and the way they experience the world changes how their brains subsequently develop. It is this secondary impaired brain development that can lead to what we call autism which usually appears in the latter part of the first and second years of life.
More research is needed, but this study points in the direction of behavioral interventions targeting visual and related brain systems during the first year of life in infants with a higher likelihood of developing autism based on factors of hereditary risk. Such interventions would aim to reduce the likelihood of children developing certain more severe autistic traits.
Co-lead authors are Joe Piven, MD, director of CIDD and Thomas E. Castelloe Professor Emeritus of Psychiatry and Pediatrics at UNC School of Medicine; John Constantino, MD, Blanche F. Ittleson Professor of Psychiatry and Pediatrics at Washington University School of Medicine and chief psychiatrist at St. Louis Children’s Hospital; and John R. Pruett, Jr., MD, PhD, professor of psychiatry at Washington University School of Medicine.
This research was supported by grants from the National Institutes of Health (K01-MH122779, R01-HD055741, T32-HD040127, P30-HD003110, R01-MH118362, MH118362-02S1, and P30-NS098577), and the Simons Foundation (140209 ).
The authors are grateful to all the families and children who participated in the Infant Brain Imaging Study (IBIS). The IBIS Network is an NIH-funded Autism Center of Excellence project and consists of a consortium of nine universities in the United States and Canada.
Media contact: Marc Derewicz919-923-0959