Sex Differences in Functional Gradients and Dynamic Functional Connectivity in Preschool-Aged Children With ASD
Guangrong Wu1, Linfeng Song1, Guomin Zhang1
1Department of Radiology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, Guizhou, China.
Insights
Autism spectrum disorder (ASD) shows sex differences in brain network organization in young children. These findings highlight the complexity of ASD and offer new insights into its neuroimaging mechanisms.
Area of Science:
- Neuroscience
- Developmental Psychology
- Biomedical Engineering
Background:
- Autism spectrum disorder (ASD) prevalence is higher in males, but its etiology is unclear.
- Investigating sex differences in brain network organization in preschool-aged children with ASD is crucial.
Purpose of the Study:
- To examine multi-scale brain network reorganization in preschool-aged boys and girls with ASD.
- To assess the impact of these network differences on clinical symptoms.
- To explore sex-specific neuroimaging mechanisms in ASD.
Main Methods:
- Functional gradient analysis and dynamic functional connectivity were employed.
- Compared brain functional networks in 54 children with ASD and 44 typically developing (TD) children (ages 2-6).
- Machine learning models evaluated classification performance for distinguishing ASD from TD.
Main Results:
- ASD groups showed functional gradient abnormalities across multiple brain networks.
- Boys with ASD exhibited abnormalities in attention, limbic, and default mode networks (DMN).
- Girls with ASD showed primary abnormalities mainly in the DMN, with distinct secondary and third gradient patterns.
Conclusions:
- Significant sex differences exist in functional gradients and dynamic functional connectivity in preschool-aged children with ASD.
- These findings underscore the heterogeneity of ASD and provide a novel framework for understanding its neuroimaging basis.
Background:
The prevalence of autism spectrum disorder (ASD) is significantly higher in males than in females; although the underlying etiology remains unclear. This study aimed to investigate the multi-scale reorganization of brain networks in preschool-aged boys with ASD and their impact on clinical symptoms.
Methods:
A total of 54 children with ASD (40 boys and 14 girls) and 44 typically developing (TD) children (28 boys and 16 girls), aged between 2 and 6 years, were recruited for this study. Functional gradient analysis and dynamic functional connectivity were used to examine differences in the hierarchical organization of brain functional networks between preschool-aged boys and girls with ASD compared to their corresponding typically developing peers. Subsequently, multiple machine learning models were applied to evaluate the classification performance of the identified abnormal features in distinguishing ASD from TD.
Results:
The results showed that the ASD group exhibited functional gradient abnormalities in multiple brain networks: (1) In boys with ASD, primary gradient abnormalities were identified in the dorsal attention network, limbic network, ventral attention network, and default mode network (DMN), whereas in girls with ASD, primary gradient abnormalities were only found in the DMN; (2) Secondary gradient abnormalities in boys with ASD were found in the sensorimotor network (SMN), ventral attention network, and DMN, while in girls with ASD, secondary gradient abnormalities were restricted to the DMN and SMN; (3) Third gradient abnormalities in boys with ASD were observed only in the visual network, whereas in girls with ASD, abnormalities were present in the limbic network, SMN, and visual network; (4) Enhanced dynamic functional connectivity was detected in boys with ASD only in state 1.
Conclusion:
Preschool-aged boys and girls with ASD exhibit significant sex differences in functional gradients and dynamic functional connectivity, underscoring the complexity and heterogeneity of ASD. These findings provide a novel theoretical framework for understanding the neuroimaging mechanisms underlying ASD.
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