Journal Article

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

Mun, Jongmin, Namgung, Jong Young, Park, Bo-yong, Kim, Jaeoh, Park, Yeongjun

2024

Overview

•Investigated interaction effects between sex and autism condition.•Sex ratio was matched using the Gaussian mixture model-based oversampling.•Low-dimensional principal functional gradients were generated.•Sex-related effects were linked to gene enrichment in cortex, thalamus, and striatum.•Gradients showed varying associations with symptom severity across sexes. Autism spectrum disorder (ASD) is an atypical neurodevelopmental condition with a diagnostic ratio largely differing between male and female participants. Due to the sex imbalance in participants with ASD, we lack an understanding of the differences in connectome organization of the brain between male and female participants with ASD. In this study, we matched the sex ratio using a Gaussian mixture model-based oversampling technique and investigated the differences in functional connectivity between male and female participants with ASD using low-dimensional principal gradients. Between-group comparisons of the gradient values revealed significant interaction effects of sex in the sensorimotor, attention, and default mode networks. The sex-related differences in the gradients were highly associated with higher-order cognitive control processes. Transcriptomic association analysis provided potential biological underpinnings, specifying gene enrichment in the cortex, thalamus, and striatum during development. Finally, the principal gradients were differentially associated with symptom severity of ASD between sexes, highlighting significant effects in female participants with ASD. Our work proposed an oversampling method to mitigate sex imbalance in ASD and observed significant sex-related differences in functional connectome organization. The findings may advance our knowledge about the sex heterogeneity in large-scale brain networks in ASD.

• Publisher: Elsevier Inc,Elsevier Limited,Elsevier
• Subject: Adolescent / Adult / Association analysis / Autism / Autism spectrum disorder / Autism Spectrum Disorder - diagnostic imaging / Autism Spectrum Disorder - physiopathology / Brain - diagnostic imaging / Brain - physiopathology / Brain architecture / Brain research / Child / Class imbalance / Connectome - methods / Deep learning / Female / Females / Functional gradient / Functional morphology / Gaussian mixture model / Gender differences / Humans / Hypotheses / Hypothesis testing / Integrated software / Magnetic resonance imaging / Magnetic Resonance Imaging - methods / Male / Markov analysis / Neostriatum / Nerve Net - diagnostic imaging / Nerve Net - physiopathology / Neural networks / Neurodevelopmental disorders / Oversampling / Physical sciences / Sample size / Sensorimotor system / Sex Characteristics / Sex difference / Sex differences / Sex ratio / Time series / Transcriptomics / Young Adult