Sex differences in autism spectrum disorder using class imbalance adjusted functional connectivity.

Area of Science:

• Neuroscience
• Genetics
• Developmental Psychology

Background:

• Autism spectrum disorder (ASD) exhibits a notable sex imbalance in diagnosis.
• Limited understanding exists regarding sex-specific brain connectome organization in ASD.

Purpose of the Study:

• To investigate sex differences in functional brain connectivity in ASD.
• To address the challenge of sex imbalance in ASD research samples.
• To explore the relationship between sex, brain networks, and ASD symptom severity.

Main Methods:

• Employed a Gaussian mixture model-based oversampling technique to balance sex ratios in the study cohort.
• Utilized low-dimensional principal gradients to analyze functional connectivity differences.
• Conducted transcriptomic association analysis to identify potential biological underpinnings.

Main Results:

• Identified significant sex-interaction effects in sensorimotor, attention, and default mode networks.
• Observed associations between sex-related gradient differences and higher-order cognitive control.
• Found differential associations between principal gradients and ASD symptom severity, particularly in females.

Conclusions:

• The proposed oversampling method effectively mitigates sex imbalance in ASD research.
• Significant sex-related differences in functional connectome organization within ASD were observed.
• Findings contribute to understanding sex heterogeneity in large-scale brain networks in autism spectrum disorder.