USC study maps brain wiring differences in youth with autism

Researchers at the Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC have uncovered new insights into how brain wiring differs in children and young adults with autism, pointing to more precise ways of understanding the condition.

The study, published in Cerebral Cortex, analyzed brain scans from 365 participants between the ages of 5 and 24. Using advanced imaging and informatics methods, the team mapped tiny structural differences in the brain’s white matter, the “communication highways” that connect different regions of the brain.

“These pathways are essential for everything from language and social interaction to sensory processing,” said Katherine Lawrence, PhD, assistant professor of research neurology and senior author of the study. “By examining these pathways segment by segment, we could pinpoint where the wiring looks different in autism. Instead of treating an entire connection as one unit, our approach lets us see subtle changes along its length, revealing patterns that earlier methods would have blurred or missed.”

Traditional imaging studies have suggested differences in white matter in autism, but results have been inconsistent. To address this, the team applied new computational tools that allow for fine-scale mapping along individual fiber bundles. They found that, on average, autistic participants showed localized changes across many major tracts that link the brain’s hemispheres and connect regions involved in language, social behavior, and sensory processing.

“These findings highlight the importance of developing new methods to better understand the brain using existing data,” said Gaon Kim, a doctoral student working with Lawrence and first author of the study. “Rather than implicating a single region, autism appears to involve widespread differences concentrated within specific parts of affected brain areas.”

The work builds on the Stevens INI’s global leadership in large-scale brain mapping and advanced imaging analytics.

“Autism is highly diverse, and no two individuals are alike,” said Arthur W. Toga, PhD, director of the Stevens INI. “These results underscore that brain differences in autism are not uniform but localized and complex. Understanding these patterns brings us closer to identifying meaningful biological markers and, ultimately, more personalized approaches to care.”

The study is one of the largest and most detailed of its kind, combining data from multiple cohorts and applying refined imaging methods developed at USC. The researchers note that future work will examine how these structural differences relate to language, social function, and sensory processing, as well as how they evolve across development. The team is currently pursuing funding to further advance this work.

About the study

In addition to Lawrence and Kim, the study’s other authors are Bramsh Q. Chandio, Sebastian M. Benavidez, Yixue Feng, and Paul M. Thompson.

This research was supported by the National Institutes of Health (K01MH135160 and RF1AG057892), the Momental Foundation (Mistletoe Research Fellowship), and the Asan Foundation (Biomedical Science Scholarship). Research reported in this publication was also supported by the Office of the Director of the National Institutes of Health under Award Number S10OD032285.