Atypical dynamic neural configuration in autism spectrum disorder and its relationship to gene expression profiles

Although it is well recognized that autism spectrum disorder (ASD) is associated with atypical dynamic functional connectivity patterns, the dynamic changes in brain intrinsic activity over each time point and the potential molecular mechanisms associated with atypical dynamic temporal characteristics in ASD remain unclear. Here, we employed the Hidden Markov Model (HMM) to explore the atypical neural configuration at every scanning time point in ASD, based on resting-state functional magnetic resonance imaging (rs-fMRI) data from the Autism Brain Imaging Data Exchange. Subsequently, partial least squares regression and pathway enrichment analysis were employed to explore the potential molecular mechanism associated with atypical neural dynamics in ASD. 8 HMM states were inferred from rs-fMRI data. Compared to typically developing, individuals on the autism spectrum showed atypical state-specific temporal characteristics, including number of states and occurrences, mean life time and transition probability between states. Moreover, these atypical temporal characteristics could predict communication difficulties of ASD, and states assoicated with negative activation in default mode network and frontoparietal network, and positive activation in somatomotor network, ventral attention network, and limbic network, had higher predictive contribution. Furthermore, a total of 321 genes was revealed to be significantly associated with atypical dynamic brain states of ASD, and these genes are mainly enriched in neurodevelopmental pathways. Our study provides new insights into characterizing the atypical neural dynamics from a moment-to-moment perspective, and indicates a linkage between atypical neural configuration and gene expression in ASD.