Altered dynamic functional connectivity of insular subregions could predict symptom severity of male patients with autism spectrum disorder

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by difficulties with social communication and restricted or repetitive patterns of behavior. This disorder was characterized by widespread abnormalities involving distributed brain networks. As one such key network node, the insular cortex has been regarded as a research focus of ASD neuropathology. The insula is a functionally complex brain structure. However, it is not fully clear if dynamic characteristics of resting-state functional magnetic resonance imaging (R-fMRI) signals in insular heterogeneous could be used to depict abnormalities in ASD. To address this question, we investigated dynamic functional connectivity (dFC) of 12 insular subregions. Data were obtained from 44 individuals with ASD and 65 typically developing age-matched controls (TDC). We assessed dFC by sliding-window method and quantified its temporal variability. Multivariable linear regression models were constructed to determine whether dFC support complementary information about symptom severity of individuals with ASD rather than static functional connectivity (sFC). The results showed that individuals with ASD exhibited dFC and sFC alterations in distinct insular subregions. Some brain regions showed only abnormal dFC but not sFC with insular subregions. These abnormal dFC could significantly predict the symptom severity of individuals with ASD. Our findings might advance our knowledge about the potential of insular heterogeneity and dynamic characteristics in understanding the neuropathology mechanism of ASD and in developing neuroimaging biomarkers for clinical applications.