Journal
NEUROIMAGE-CLINICAL
Volume 2, Issue -, Pages 79-94Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.nicl.2012.11.006
Keywords
Resting-state functional connectivity; Diffusion tensor imaging; Graph theory; Brain networks; Autism spectrum disorders
Categories
Funding
- NICHD [P50 HD055784]
- NIMH [R01HD06528001]
- UCLA Training Program in Neurobehavioral Genetics [T32 MH073526-05]
- UCLA Medical Scientist Training Program [T32 GM008044]
- NIH [R01 AG040060, EB008432, EB007813, HD050735, RR12169, RR13642, RR00865]
- Autism Speaks
- Brain Mapping Medical Research Organization
- Brain Mapping Support Foundation
- Pierson-Lovelace Foundation
- Ahmanson Foundation
- Northern Piedmont Community Foundation
- Tamkin Foundation
- Jennifer Jones-Simon Foundation
- Capital Group Companies Charitable Foundation
- Robson Family
- North-star Fund
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [P50HD055784] Funding Source: NIH RePORTER
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD050735] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR012169, P41RR013642, M01RR000865] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB007813, R01EB008432] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008042] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [T32MH073526] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG040060] Funding Source: NIH RePORTER
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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. (C) 2012 The Authors. Published by Elsevier Inc. Open access under CC BY license.
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