title: Altered functional and structural brain network organization in autism.
abstract: 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, network level organization has not been carefully examined in ASD. Here we used resting-state functional MRI (n = 42 ASD, n = 37 typically developing; TD) to show that children and adolescents with ASD display 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 and higher-order visual regions. Using graph theoretical methods, we show that 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, generated from diffusion tensor MRI derived fiber tracts (n = 51 ASD, n = 43 TD), displayed lower levels of white matter integrity yet higher numbers of fibers. 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. Overall, our findings suggest that modeling the brain as a complex network will be highly informative in unraveling the biological basis of ASD and other neuropsychiatric disorders.
authors.affiliation: Brain Mapping Center, UCLA, Los Angeles, CA, USA ; Interdepartmental Neuroscience Program, UCLA, Los Angeles, CA, USA ; David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Rudie
authors.forename: J A
authors.initials: JA
authors.lastname: Brown
authors.forename: D
authors.initials: D
authors.lastname: Beck-Pancer
authors.forename: L M
authors.initials: LM
authors.lastname: Hernandez
authors.forename: E L
authors.initials: EL
authors.lastname: Dennis
authors.forename: P M
authors.initials: PM
authors.lastname: Thompson
authors.forename: S Y
authors.initials: SY
authors.lastname: Bookheimer
authors.forename: M
authors.initials: M
authors.lastname: Dapretto
keywords: Autism spectrum disorders; Brain networks; Diffusion tensor imaging; Graph theory; Resting-state functional connectivity