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Exploring atypical spatial-functional coupling in adolescent autism spectrum disorder: insights from neurodevelopment
Jun Pan1, Heng Zhang1, Yiran Zhai1
1College of Electrical Engineering, Sichuan University, Chengdu, China.
Frontiers in Neuroscience
|August 11, 2026
Summary
Autism Spectrum Disorder (ASD) is linked to altered brain network organization. Higher spatial functional heterogeneity in ASD brains correlates with social-affective symptoms and specific gene expression patterns.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Computational Neuroscience
Background:
- Autism Spectrum Disorder (ASD) is characterized by atypical large-scale brain network organization.
- Understanding the relationship between spatial-functional brain properties, clinical manifestations, and molecular underpinnings in ASD is crucial.
Purpose of the Study:
- To quantify spatial functional heterogeneity (Sill) and coherence persistence (Range) in adolescents with and without ASD.
- To investigate the association between these spatial-functional properties and clinical symptoms in ASD.
- To explore the relationship between regional Sill differences and transcriptomic profiles.
Main Methods:
- Resting-state functional magnetic resonance imaging (fMRI) data were analyzed from 162 adolescents with ASD and 175 typically developing (TD) adolescents (aged 12-18).
- Spatial functional heterogeneity (Sill) and coherence persistence (Range) were quantified.
- Cortical gene expression reference data were integrated to identify transcriptomic patterns.
Main Results:
- Adolescents with ASD showed significantly increased Sill in higher-order association networks (e.g., Language, Posterior Multimodal) compared to TD individuals.
- No significant group differences in Range were observed after multiple-comparison correction.
- Elevated Sill within the ASD group was associated with greater social-affective symptom severity, but not restricted and repetitive behaviors.
- Transcriptomic analysis revealed gene enrichment for synaptic signaling, mitochondrial processes, and glial functions in regions with altered Sill.
Conclusions:
- Altered spatial-functional brain organization, specifically increased heterogeneity, is present in adolescents with ASD.
- These spatial-functional alterations are statistically associated with clinical severity and specific molecular pathways, including synaptic signaling and glial functions.
- Findings provide a complementary spatial perspective on the neurobiology of ASD, linking brain organization to molecular profiles.
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