Identifying Diagnostic Biomarkers for Autism Spectrum Disorder From Higher-order Interactions Using the PED Algorithm.

In the field of neuroimaging, more studies of abnormalities in brain regions of the autism spectrum disorder (ASD) usually focused on two brain regions connected, and less on abnormalities of higher-order interactions of brain regions. To explore the complex relationships of brain regions, we used the partial entropy decomposition (PED) algorithm to capture higher-order interactions by computing the higher-order dependencies of all three brain regions (triads). We proposed a method for examining the effect of individual brain regions on triads based on the PED and surrogate tests. The key triads were discovered by analyzing the effects. Further, the hypergraph modularity maximization algorithm revealed the higher-order brain structures, of which the link between right thalamus and left thalamus in ASD was more loose compared with the typical control (TC). Redundant key triad (left cerebellum crus 1 and left precuneus and right inferior occipital gyrus) exhibited a discernible attenuation in interaction in ASD, while the synergistic key triad (right cerebellum crus 1 and left postcentral gyrus and left lingual gyrus) indicated a notable decline. The results of classification model further confirmed the potential of the key triads as diagnostic biomarkers.