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Brain Connectivity Differs in Autism

Teen girl with headphones wearing yellow hoodie, illustrating sensory sensitivity in autism.
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What if brain scans could help detect autism earlier and more precisely?


A new study led by researchers at the University of Fukui, and published in NeuroImage, investigates how white matter connectivity differs in children with autism spectrum disorder (ASD). Using advanced imaging techniques, the researchers found that differences in key neural pathways were linked to core ASD symptoms such as repetitive behaviors and communication difficulties.

The need for better ASD diagnosis and understanding

​ASD is a complex neurodevelopmental condition characterized by challenges in social interaction, communication and repetitive behaviors. Recent estimates indicate that ~1 in 36 children in the United States are diagnosed with ASD, highlighting its growing prevalence and the urgent need for effective diagnostic strategies.

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Early diagnosis is important for implementing interventions that can improve developmental outcomes. However, current diagnostic methods primarily rely on behavioral assessments, which can be subjective and may not detect ASD until behavioral symptoms become evident. This reliance on observable behaviors often delays diagnosis, postponing the initiation of beneficial interventions during critical developmental windows.​


Advancements in neuroimaging have provided insights into the structural and functional differences in the brains of individuals with ASD. Studies have identified alterations in both gray and white matter, as well as atypical functional connectivity patterns. Investigations into the default mode network have revealed decreased connectivity between key regions in individuals with ASD, which may contribute to the social and communicative challenges characteristic of the disorder. ​


Despite these findings, the relationship between brain structure and function in ASD is still not fully understood. While structural and functional abnormalities have been independently documented, integrating these findings to elucidate how structural changes influence functional connectivity – and vice versa – poses a significant challenge.

White matter connectivity in ASD

The new study aimed to overcome these issues using magnetic resonance imaging (MRI). The team employed a novel population-based bundle-to-region connectome approach to uncover how structural brain differences contribute to ASD symptoms. The researchers analyzed MRI scans of 34 children with ASD and 43 typically developing (TD) children, with a focus on examining white matter tracts – bundles of nerve fibers responsible for communication between different regions of the brain – and assessing functional connectivity patterns between these regions.

 

Population-based bundle-to-region connectome approach

The population-based bundle-to-region connectome approach is an advanced neuroimaging method that maps how large-scale white matter tracts (bundles of nerve fibers) connect to specific brain regions across a group of individuals.

 

The results revealed both structural and functional connectivity differences, particularly in the left hemisphere of the brain – a region often associated with language processing and social cognition. Children with ASD exhibited altered organization and density of neural pathways, suggesting disruptions in white matter integrity. Two key white matter tracts stood out in their association with ASD symptoms.


“We observed that superior longitudinal fasciculus was associated with repetitive behaviors, whereas cingulum connectivity correlated more with communication abilities,” said corresponding author Dr. Akemi Tomoda, a professor and director of the Research Center for Child Mental Development at the University of Fukui.

 

Superior longitudinal fasciculus (SLF)

A major white matter tract in the brain that connects regions of the frontal, parietal, occipital and temporal lobes. It plays a role in language, attention and motor coordination.

Cingulum

A white matter bundle that runs along the medial aspect of the brain, connecting areas of the limbic system – which is involved in emotions and memory – to the prefrontal cortex.

 

The observed disruptions in white matter connectivity may indicate developmental delays during the formation of critical brain networks. These delays could play a key role in the emergence of ASD symptoms.


Beyond identifying white matter alterations, the study also examined resting-state functional connectivity to assess how different brain regions interact when the brain is not engaged in a specific task.


Overall, ASD brains exhibited weaker integration between key functional networks, supporting the idea that the condition is not just a disorder of isolated brain regions but one that affects the coordination and integration of multiple networks involved in behavior and cognition.


“These findings highlight the potential of multi-modal imaging in identifying ASD-related brain changes, helping to refine diagnostic criteria and guide the development of targeted interventions,” Tomoda added.

Diagnostic biomarkers for ASD

One of the key implications of the study is the potential for developing MRI-based biomarkers that could support more objective and earlier diagnoses. By measuring white matter integrity researchers may be able to identify specific connectivity patterns associated with ASD symptoms.


“MRI-based biomarkers, such as changes in fractional anisotropy or mean diffusivity in the superior longitudinal fasciculus or cingulum, could help in earlier and more precise ASD diagnosis,” said Tomoda.

 

Fractional anisotropy (FA)

A measure in diffusion tensor imaging (DTI) that quantifies the directionality of water diffusion in white matter tracts. Higher FA suggests more organized and intact white matter, while lower FA can indicate reduced connectivity or damage.

Mean Diffusivity (MD)

Another DTI-based metric that reflects the overall movement of water molecules in tissue. Increased MD in white matter can suggest weakened or less dense neural connections, which has been observed in ASD-related brain differences.

 

Beyond diagnosis, these findings suggest possible directions for therapeutic interventions. By identifying white matter tracts linked to specific ASD traits, researchers can explore approaches aimed at improving connectivity in these regions.


“Our results could inform the design of personalized interventions. Therapeutic approaches, such as neurofeedback or brain stimulation techniques, could be tailored to improve connectivity in specific white matter tracts, potentially addressing repetitive behaviors or enhancing communication abilities in children with ASD as needed,” said Tomoda.


While further research is needed to establish clinical applications, this study contributes to a growing body of work exploring the neural basis of ASD and potential ways to support affected individuals.


Reference: Wang J, Kawata NYS, Cao X, et al. White-Matter fiber tract and resting-state functional connectivity abnormalities in young children with autism spectrum disorder. NeuroImage. 2025;310:121109. doi: 10.1016/j.neuroimage.2025.121109


This article is a rework of a press release issued by the University of Fukui. Material has been edited for length and content.