Investigation of sex-related functional connectivity alterations in autism using class imbalance mitigation approach

Autism spectrum disorder is primarily diagnosed in males, leading to the lack of understanding of brain disorganization in female individuals with autism. To fill the gap, we applied a Gaussian mixture model-based oversampling technique to the functional connectivity data to adjust for the sex imbalance in autism. Leveraging a dimensionality reduction technique, we generated a low-dimensional principal component (i.e., gradient) and assessed its between-group differences between the sexes. We observed significant sex-related differences in sensorimotor, attention, and default mode networks, which were associated with higher-order cognitive control processes. Transcriptomic association analysis provided a potential biological underpinning, specifying gene enrichment in the cortex, thalamus, and striatum. Finally, symptom severity prediction analysis suggested that the functional gradient was only associated with symptoms in female individuals with autism.