An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome.

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State: Public
Version: Final published version
Serval ID
serval:BIB_1B1E1B72497A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome.
Journal
NeuroImage. Clinical
Author(s)
Váša F., Griffa A., Scariati E., Schaer M., Urben S., Eliez S., Hagmann P.
ISSN
2213-1582 (Electronic)
ISSN-L
2213-1582
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
10
Pages
239-249
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Chromosome 22q11.2 deletion syndrome (22q11DS) is a genetic disease known to lead to cerebral structural alterations, which we study using the framework of the macroscopic white-matter connectome. We create weighted connectomes of 44 patients with 22q11DS and 44 healthy controls using diffusion tensor magnetic resonance imaging, and perform a weighted graph theoretical analysis. After confirming global network integration deficits in 22q11DS (previously identified using binary connectomes), we identify the spatial distribution of regions responsible for global deficits. Next, we further characterize the dysconnectivity of the deficient regions in terms of sub-network properties, and investigate their relevance with respect to clinical profiles. We define the subset of regions with decreased nodal integration (evaluated using the closeness centrality measure) as the affected core (A-core) of the 22q11DS structural connectome. A-core regions are broadly bilaterally symmetric and consist of numerous network hubs - chiefly parietal and frontal cortical, as well as subcortical regions. Using a simulated lesion approach, we demonstrate that these core regions and their connections are particularly important to efficient network communication. Moreover, these regions are generally densely connected, but less so in 22q11DS. These specific disturbances are associated to a rerouting of shortest network paths that circumvent the A-core in 22q11DS, "de-centralizing" the network. Finally, the efficiency and mean connectivity strength of an orbito-frontal/cingulate circuit, included in the affected regions, correlate negatively with the extent of negative symptoms in 22q11DS patients, revealing the clinical relevance of present findings. The identified A-core overlaps numerous regions previously identified as affected in 22q11DS as well as in schizophrenia, which approximately 30-40% of 22q11DS patients develop.

Keywords
Adolescent, Adult, Brain/pathology, Connectome, DiGeorge Syndrome/pathology, Diffusion Magnetic Resonance Imaging/methods, Female, Humans, Image Processing, Computer-Assisted, Male, White Matter/pathology, Young Adult, Connectomics, Graph theory, Negative symptoms, Schizophrenia, Structural connectivity, Velo-cardio-facial syndrome
Pubmed
Web of science
Open Access
Yes
Create date
20/02/2016 17:01
Last modification date
20/08/2019 12:51
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