Altered functional and structural brain network organization in autism

J.D Rudie,S.Y Bookheimer,J.A Brown,M Dapretto,L.M Hernandez,D Beck-Pancer,E.L Dennis,P.M Thompson

doi:10.1016/j.nicl.2012.11.006

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.

Highlights

Autism spectrum disorders (ASD) are increasingly prevalent neurodevelopmental disorders (Kim et al, 2011) characterized by atypical social behavior, including deficits in receptive and expressive language, theory of mind, and mental flexibility
High-functioning children with autism spectrum disorders (ASD) had a prior clinical diagnosis of autism based on criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM IV), which was confirmed with the Autism Diagnostic Observation Scale (ADOS-G; Lord et al, 2000) and/or Autism Diagnostic Interview (ADI-R; Lord et al, 1994)
We found that the ASD group had 1.6 times as many connections with lower Fractional Anisotropy (FA) (67 typically developing (TD)> ASD vs. 41 ASD>TD) and 6.2 times as many connections with higher mean diffusivity (MD) (112 ASD> TD vs. 18 ASD > TD; Fig. 5D)

Summary

Introduction

Autism spectrum disorders (ASD) are increasingly prevalent neurodevelopmental disorders (Kim et al, 2011) characterized by atypical social behavior, including deficits in receptive and expressive language, theory of mind, and mental flexibility. Findings of functional underconnectivity between brain regions in individuals with ASD relative to matched controls have been reported as they perform a variety of cognitive tasks (see Schipul et al, 2011, for review). Multiple studies have found that task-independent (i.e., intrinsic) functional connectivity, including interhemispheric (Anderson et al, 2011a) and default mode. ⁎ Corresponding author at: Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, 660 Charles E. Further supporting an underconnectivity theory, diffusion tensor imaging (DTI) studies have found reductions in structural white matter integrity across most major tracts (see Vissers et al, 2012, for review). Functional brain networks become simultaneously more integrated and segregated during typical development (e.g., Fair et al, 2009) and white matter integrity increases during development (e.g., Lebel et al, 2012), suggesting that brain networks in ASD may reflect ‘immature’ or aberrant developmental processes

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