Altered Functional and Structural Brain Network Organization in Autism

Background: Structural and functional underconnectivity have been reported for multiple brain regions, functional systems, and white matter tracts in individuals with autism spectrum disorders (ASD). Although recent developments in complex network analysis have established that the brain is a modular network exhibiting small-world properties, little work has been done to characterize network level properties of functional and structural brain organization in ASD. 

Objectives: Here we investigated functional and structural brain network organization in children and adolescents with ASD compared to matched typically-developing (TD) controls.

Methods: We used resting-state functional MRI (N=42 ASD, N=37 TD) and diffusion tensor MRI derived fiber tracts (N=51 ASD, N=43 TD) in a 264-region whole-brain parcellation to examine pairwise differences in functional and structural connectivity as well as differences in higher-level network properties using graph theoretical methods. Additionally, we examined the correspondence between structural and functional connectivity and the relationship between network properties and chronological age.

Results: Children and adolescents with ASD displayed reduced short and long-range connectivity within functional systems (i.e., reduced functional integration) and stronger connectivity between functional systems (i.e., reduced functional segregation), particularly in default mode network and higher-order visual regions. Pairwise group differences in functional connectivity are reflected in network level reductions in modularity and clustering (local efficiency), but shorter characteristic path lengths (higher global efficiency). Structural networks displayed lower levels of white matter integrity yet higher numbers of fibers in children with ASD. TD and ASD individuals exhibited similar levels of correlation between raw measures of structural and functional connectivity (N=35 ASD, N=35 TD). However, a principal component analysis combining structural and functional network properties revealed that the balance of local and global efficiency between structural and functional networks was reduced in ASD, positively correlated with age, and inversely correlated with ASD symptom severity.

Conclusions: Our findings suggest that complex network modeling of structural and functional brain organization will yield a better understanding of the neural basis of ASD and other neuropsychiatric disorders. Ultimately, a more cohesive framework for understanding brain alterations in ASD may inform the design of more sophisticated diagnostic tools and targeted interventions.

Rudie J.D., Brown J.A., Beck-Pancer D., Hernandez L.M., Dennis E.L., Thompson P.M., Bookheimer S.Y., Dapretto M., (In Revision). Altered Functional and Structural Brain Network Organization in Autism. Neuroimage Clinical.