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

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Psychiatry

Background:

• Resting-state functional connectivity (FC) studies reveal atypical brain connectivity in autism spectrum disorder (ASD) compared to typically developing (TD) individuals.
• Previous research primarily focused on static FC, potentially overlooking dynamic connectivity patterns crucial for understanding brain function.

Purpose of the Study:

• To investigate age- and disease-related dynamic changes in functional connectivity within TD and ASD populations.
• To characterize differences in dynamic connectivity variability, modular organization (flexibility, cohesion, disjointness), and their relationship with ASD symptom severity.

Main Methods:

• Utilized resting-state functional magnetic resonance imaging (rs-fMRI) data from children, adolescents, and adults across TD and ASD groups.
• Analyzed dynamic variability in connection strength and modular organization metrics like flexibility, cohesion strength, and disjointness for each subject.
• Explored the relationship between dynamic connectivity measures, symptom severity, and brain region organization (core-periphery).

Main Results:

• ASD individuals exhibited significantly higher inter-subject dynamic variability in connection strength compared to TD individuals, correlating with symptom severity.
• Whole-brain flexibility correlated with static modularity only in TD individuals.
• A core-periphery organization was observed, with sensorimotor and visual regions forming a rigid core, and default mode network (DMN) and attention areas in the flexible periphery. ASD showed increased flexibility in core regions and disjointness in sensorimotor areas, both correlating with symptom severity.

Conclusions:

• Dynamic functional connectivity provides a more comprehensive framework for understanding brain variability in ASD than static analyses.
• Altered dynamic connectivity patterns, particularly hyper-variability and disrupted modular organization, are key features of ASD.
• Brain regions in the frontal, motor, and occipital cortices show high predictive power for ASD symptom severity, highlighting potential targets for intervention.