Atypical Flexibility in Dynamic Functional Connectivity Quantifies the Severity in Autism Spectrum Disorder

Resting-state functional connectivity (FC) analyses have shown atypical connectivity in autism spectrum disorder (ASD) as compared to typically developing (TD). However, this view emerges from investigating static FC overlooking the whole brain transient connectivity patterns. In our study, we investigated how age and disease influence the dynamic changes in functional connectivity of TD and ASD. We used resting-state functional magnetic resonance imaging (rs-fMRI) data stratified into three cohorts: children (7–11 years), adolescents (12–17 years), and adults (18+ years) for the analysis. The dynamic variability in the connection strength and the modular organization in terms of measures such as flexiblity, cohesion strength, and disjointness were explored for each subject to characterize the differences between ASD and TD. In ASD, we observed significantly higher inter-subject dynamic variability in connection strength as compared to TD. This hyper-variability relates to the symptom severity in ASD. We also found that whole-brain flexibility correlates with static modularity only in TD. Further, we observed a core-periphery organization in the resting-state, with Sensorimotor and Visual regions in the rigid core; and DMN and attention areas in the flexible periphery. TD also develops a more cohesive organization of sensorimotor areas. However, in ASD we found a strong positive correlation of symptom severity with flexibility of rigid areas and with disjointness of sensorimotor areas. The regions of the brain showing high predictive power of symptom severity were distributed across the cortex, with stronger bearings in the frontal, motor, and occipital cortices. Our study demonstrates that the dynamic framework best characterizes the variability in ASD