title: Multimodal investigation of triple network connectivity in patients with 22q11DS and association with executive functions.
abstract: Large-scale brain networks play a prominent role in cognitive abilities and their activity is impaired in psychiatric disorders, such as schizophrenia. Patients with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing schizophrenia and present similar cognitive impairments, including executive functions deficits. Thus, 22q11DS represents a model for the study of neural biomarkers associated with schizophrenia. In this study, we investigated structural and functional connectivity within and between the Default Mode (DMN), the Central Executive (CEN), and the Saliency network (SN) in 22q11DS using resting-state fMRI and DTI. Furthermore, we investigated if triple network impairments were related to executive dysfunctions or the presence of psychotic symptoms. Sixty-three patients with 22q11DS and sixty-eighty controls (age 6-33 years) were included in the study. Structural connectivity between main nodes of DMN, CEN, and SN was computed using probabilistic tractography. Functional connectivity was computed as the partial correlation between the time courses extracted from each node. Structural and functional connectivity measures were then correlated to executive functions and psychotic symptom scores. Our results showed mainly reduced structural connectivity within the CEN, DMN, and SN, in patients with 22q11DS compared with controls as well as reduced between-network connectivity. Functional connectivity appeared to be more preserved, with impairments being evident only within the DMN. Structural connectivity impairments were also related to executive dysfunctions. These findings show an association between triple network structural alterations and executive deficits in patients with the microdeletion, suggesting that 22q11DS and schizophrenia share common psychopathological mechanisms. Hum Brain Mapp 38:2177-2189, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of medicine, Geneva, Switzerland.
authors.forename: Maria C
authors.identifier: 0000-0001-8280-4683
authors.initials: MC
authors.lastname: Padula
authors.affiliation: Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of medicine, Geneva, Switzerland.|Stanford Cognitive and Systems Neuroscience Laboratory, Stanford University School of Medicine, Stanford, California.
authors.forename: Marie
authors.initials: M
authors.lastname: Schaer
authors.affiliation: Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of medicine, Geneva, Switzerland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Scariati
authors.affiliation: Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of medicine, Geneva, Switzerland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Maeder
authors.affiliation: Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of medicine, Geneva, Switzerland.|Center for Contextual Psychiatry, Department of Neuroscience, KU Leuven, Belgium.
authors.forename: Maude
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of medicine, Geneva, Switzerland.|Department of Genetic Medicine and Development, University of Geneva School of Medicine, Geneva, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Eliez
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D002648:Child; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000150:complications*; D002892:Chromosomes, Human, Pair 22; D003072:Cognition Disorders / Q000235:genetics* / Q000473:pathology*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000473:pathology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: DTI; cognitive functions; large-scale networks; psychotic symptoms; resting-state fMRI; schizophrenia