A new study published reports that social deficits in children diagnosed with autism spectrum disorder (ASD) correlate with early structural and connectivity traits particularly in the visual circuitry of the brain, in their infant siblings who later go on to develop ASD.

The researchers conducted structural, diffusion, and functional magnetic resonance imaging (MRI) studies on the younger child of 384 sibling pairs at six, twelve, and twenty-four months, where the older child in each pair had been diagnosed with autism, putting the infant sibling at a higher risk for autism. In 89 of the 384 sibling pairs, the younger sibling was eventually diagnosed with ASD.

Jessica Girault, PhD, assistant professor of psychiatry at the University of North Carolina School of Medicine, is the lead author of the study.

Jessica Girault, PhD, assistant professor of psychiatry at the University of North Carolina (UNC) School of Medicine and lead author of the study said, “While it’s well documented that autism is heritable, and that brain development is different during infancy in children later diagnosed with autism, there had been no prior work linking infant brain development to inherited factors. We wanted to understand whether aspects of brain development were linked to family-level genetic factors.”

Girault’s earlier work showed younger infant siblings were more likely to develop autism if their older siblings with autism had severe autistic traits. Girault said, “This suggests that these autistic traits tell us something about the strength of genetic factors for autism within a family. The current study takes our work a step forward.”

This study, conducted as part of the NIH-funded Infant Brain Imaging Study (IBIS) Network and led by scientists at UNC-Chapel Hill and Washington University, was published in an article in the American Journal of Psychiatry titled, “Infant Visual Brain Development and Inherited Genetic Liability in Autism.”

Girault said, “Our results suggest, for the first time, that family markers of inherited genetic liability to autism influence the development of the brain’s visual system during infancy.”

“It is particularly notable that we were able to demonstrate associations between brain findings in infants and the behavior of their older siblings with autism,” said co-senior author John Pruett, Jr., MD, PhD, professor of psychiatry at the Washington University School of Medicine.

Co-senior author Joe Piven, MD, director at the Carolina Institute of Developmental Disabilities (CIDD) added, “Aberrant visual circuitry is a fundamental cog in the cascade of events leading to later autism. This circuitry alters how infants experience the world. How they experience the world alters how their brains subsequently develop. It’s this secondary altered brain development that may result in autism that typically emerges in the latter part of the first and second years of life.”

In addition to measuring the severity of social deficits in the older sibling diagnosed with autism, the investigators in the current study measured the volumes of the cerebral cortex and cerebrospinal fluid, the surface areas of the whole brain and regions involved in vision (occipital cortex), and the white matter microstructure in the splenium, in the younger sibling. In earlier studies, the researchers had shown these parameters to be changed in infants who went on to develop ASD as toddlers.

The splenium is the posterior end of the corpus callossum that connects the two brain hemispheres. In earlier studies, the team had shown the splenium is related to the speed with which infants orient their attention toward visual stimuli in their environments.

In the current study, the researchers showed that changes in the size of the brain, white matter integrity, and functional connectivity of the visual processing systems of six-month-olds are evident well before they show social deficits—the hallmark of autism diagnosis. The team also showed that changes in the visual system are associated with the severity of autism traits in their older siblings.

“We’re beginning to parse differences in infant brain development that might be related to genetic factors,” said Girault. “Using MRI, we studied selected structures of the brain, the functional relationship between key brain regions, and the microstructure of white matter connections between those brain regions. Findings from all three pointed us to the discovery of unique differences in the visual systems of infants who later developed autism.”

Visual perception enables infants to form social bonds in their environment and is crucial for their cognitive and emotional development. The current study indicates the brain’s visual processing is impaired in infants who go on to develop autism.

The researchers found, compared to normal infants who did not develop ASD later,  in six-month-olds who went on to develop ASD at two years, the structure of the visual system differed and the functional connections between brain circuits that linked to the visual system were weaker. The team specifically point out differences in the occipital gyrus that plays a major role in object recognition, and the splenium that is important for inter-hemispheric communication and the speed of redirecting attention to visual stimuli.

Anatomical locations of the splenium (yellow) and right middle occipital gyrus (red) in a representative infant brain. [CIDD at UNC-Chapel Hill]
This study opens new possibilities of behavioral interventions aimed at visual and related brain systems in infants who are at higher risk for autism, based on genetic factors. The team is currently replicating this work in a new cohort of infants.

Pruett noted, “The convergence of brain-wide, data-driven functional connectivity MRI results with the structural and diffusion findings strengthens our confidence in the future replication of these discoveries, which could be tested in the new cohort of 250 high-familial likelihood infants we are presently recruiting.”

Previous articleComorbidities Impact Biomarker Levels to Hinder Alzheimer’s Blood Test Development
Next articleGene Delivery of Brain-Specific Interleukin 2 Protects Mice from Brain Injury