Autism has long been recognized as a highly diverse condition, but an international study suggests some of those differences may stem from two distinct biological brain patterns.
Researchers have identified two major autism subtypes that appear to be linked to different forms of brain connectivity.
The study was led by scientists from the Italian Institute of Technology, the Child Mind Institute in New York, and the University of Trento.
The research focused on functional connectivity, which refers to how different regions of the brain communicate and coordinate with one another.
After analyzing large amounts of brain imaging data, researchers found two recurring patterns among people on the autism spectrum.
One group showed lower-than-normal communication between brain regions, a pattern known as hypoconnectivity.
The second group displayed the opposite effect, with unusually high levels of communication across brain networks, referred to as hyperconnectivity.
These distinct patterns suggest that autism may not arise from a single biological mechanism but, rather, from multiple underlying pathways.
A Large-Scale Brain Imaging Study
To investigate these differences, scientists combined data from both animal models and human brain scans.
The team studied 20 separate mouse models associated with autism-related traits and compared those findings with brain imaging data from 940 kids and young adults diagnosed with ASD.
Researchers also analyzed scans from more than 1,000 neurotypical individuals for comparison.
By examining both animal and human data, the team was able to identify consistent connectivity signatures that appeared across species.
What Mouse Models Revealed
The mouse studies provided important clues about the biology behind the connectivity patterns.
Researchers paired brain imaging results with genetic and molecular analyses, allowing them to link specific connectivity changes to processes occurring inside the brain.
The hypoconnectivity pattern was associated primarily with biological pathways involving synapses, the specialized connections that allow nerve cells to communicate.
But the hyperconnectivity pattern appeared to be linked to immune-related processes.
These findings suggest that different biological systems may contribute to different forms of autism.
There’s a well-known saying in the autism community: “If you’ve met one autistic person you’ve met one autistic person.”
Connecting Animal Research to Human Brains
Researchers described the mouse models as a valuable tool for decoding the biological meaning behind brain imaging patterns.
Once specific connectivity signatures were identified in animals, the team searched for the same patterns in human brain scans.
The same two connectivity profiles observed in mice also appeared in the human datasets, providing strong support for the existence of distinct biological subgroups within autism.
Additional analyses strengthened the connection between brain activity patterns and biology.
Brain regions associated with reduced connectivity showed increased activity of genes involved in synaptic function.
Meanwhile, areas linked to hyperconnectivity were enriched with genes related to immune system activity.
These genetic signatures closely mirrored the biological pathways identified in the mouse studies.
The study also found that the results remained consistent across multiple independent datasets collected at research centers around the world, increasing confidence in the findings.
Rather than viewing autism as a single condition with varying symptoms, researchers increasingly believe it may consist of multiple biological pathways that produce similar behavioral characteristics.
In the future, identifying those pathways could help doctors develop more targeted diagnostic tools and personalized treatment strategies tailored to an individual’s unique biology.
