Brain Imaging Study Identifies Two Distinct Biological Forms of Autism

Autism may not be a single condition with one underlying biology. A major international study has found evidence for at least two distinct brain-based autism subtypes, each marked by a different pattern of communication between brain regions.

Published in Nature Neuroscience, the research analyzed brain imaging data from 940 children and young adults with autism and compared it with scans from more than 1,000 neurotypical individuals. Scientists also examined 20 different mouse models to investigate the biological mechanisms behind these brain patterns.

The study identified two consistent autism subtypes. One group showed reduced communication between brain regions, known as hypoconnectivity, while the other displayed increased communication, or hyperconnectivity. Together, these two subtypes accounted for about one-quarter of the autistic individuals included in the research.

Researchers found that each subtype appeared to be linked to different biological processes. The hypoconnectivity pattern was associated with genes involved in synapses, the structures that allow nerve cells to communicate. In contrast, the hyperconnectivity subtype was linked to immune-related biological pathways.

To uncover these connections, scientists first identified brain connectivity signatures in mouse models and then searched for the same patterns in human brain scans. The matching results across both species provided strong evidence that distinct biological mechanisms may contribute to different forms of autism.

The findings were further supported by gene expression analyses. Brain regions showing lower connectivity were enriched with synaptic genes, while regions with higher connectivity showed greater activity of immune-related genes.

Scientists say the discovery could help move autism research toward more personalized approaches to diagnosis and treatment. Rather than viewing autism as a single condition, future care strategies may be tailored to underlying biological subtypes. The researchers also believe additional autism subtypes may emerge as larger datasets and more advanced analytical tools become available.

REFERENCE: Marco Pagani, Valerio Zerbi, Silvia Gini, Filomena Grazia Alvino, Abhishek Banerjee, Andrea Barberis, M. Albert Basson, Yuri Bozzi, Alberto Galbusera, Jacob Ellegood, Michela Fagiolini, Jason P. Lerch, Michela Matteoli, Caterina Montani, Davide Pozzi, Giovanni Provenzano, Maria Luisa Scattoni, Nicole Wenderoth, Ting Xu, Michael V. Lombardo, Michael P. Milham, Adriana Di Martino, Alessandro Gozzi. Autism subtypes identified using cross-species functional connectivity analyses. Nature Neuroscience, 2026; DOI: 10.1038/s41593-026-02287-z