title: Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls.
abstract: The emergence of resting-state functional connectivity (rsFC) analysis, which examines temporal correlations of low-frequency (<0.1 Hz) blood oxygen level-dependent signal fluctuations between brain regions, has dramatically improved our understanding of the functional architecture of the typically developing (TD) human brain. This study examined rsFC in Down syndrome (DS) compared with another neurodevelopmental disorder, Williams syndrome (WS), and TD. Ten subjects with DS, 18 subjects with WS, and 40 subjects with TD each participated in a 3-Tesla MRI scan. We tested for group differences (DS vs. TD, DS vs. WS, and WS vs. TD) in between- and within-network rsFC connectivity for seven functional networks. For the DS group, we also examined associations between rsFC and other cognitive and genetic risk factors. In DS compared with TD, we observed higher levels of between-network connectivity in 6 out 21 network pairs but no differences in within-network connectivity. Participants with WS showed lower levels of within-network connectivity and no significant differences in between-network connectivity relative to DS. Finally, our comparison between WS and TD controls revealed lower within-network connectivity in multiple networks and higher between-network connectivity in one network pair relative to TD controls. While preliminary due to modest sample sizes, our findings suggest a global difference in between-network connectivity in individuals with neurodevelopmental disorders compared with controls and that such a difference is exacerbated across many brain regions in DS. However, this alteration in DS does not appear to extend to within-network connections, and therefore, the altered between-network connectivity must be interpreted within the framework of an intact intra-network pattern of activity. In contrast, WS shows markedly lower levels of within-network connectivity in the default mode network and somatomotor network relative to controls. These findings warrant further investigation using a task-based procedure that may help disentangle the relationship between brain function and cognitive performance across the spectrum of neurodevelopmental disorders.
authors.affiliation: 1 Neuroscience Graduate Program, Center for Cognitive Medicine, Vanderbilt University , Nashville, Tennessee.|2 Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University School of Medicine , Nashville, Tennessee.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Vega
authors.affiliation: 3 Department of Molecular Physiology & Biophysics, Vanderbilt Genetics Institute, Vanderbilt University School of Medicine , Nashville, Tennessee.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Hohman
authors.affiliation: 4 Interdisciplinary Studies in Neuroimaging of Neurodevelopmental Disorders, The Graduate School, Vanderbilt University , Nashville, Tennessee.|5 Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University , Nashville, Tennessee.|6 Vanderbilt University Institute of Imaging Science, Vanderbilt University , Nashville, Tennessee.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Pryweller
authors.affiliation: 2 Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University School of Medicine , Nashville, Tennessee.|5 Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University , Nashville, Tennessee.|7 Department of Psychology and Human Development, Vanderbilt University , Nashville, Tennessee.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Dykens
authors.affiliation: 3 Department of Molecular Physiology & Biophysics, Vanderbilt Genetics Institute, Vanderbilt University School of Medicine , Nashville, Tennessee.|5 Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University , Nashville, Tennessee.|6 Vanderbilt University Institute of Imaging Science, Vanderbilt University , Nashville, Tennessee.
authors.forename: Tricia A
authors.initials: TA
authors.lastname: Thornton-Wells
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001288:Attention / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D032882:Comprehension / Q000502:physiology; D063132:Connectome / Q000379:methods; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology*; D018980:Williams Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D001057:Apolipoproteins E
keywords: APOE; Down syndrome; Williams syndrome; fMRI; resting state functional connectivity