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.

Keywords: DTI; cognitive functions; large-scale networks; psychotic symptoms; resting-state fMRI; schizophrenia.

Figure 1

Group differences in within‐network structural connectivity. The figure shows the connections within DMN (A), CEN (B), and SN (C) that significantly differed between patients and controls. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Between network structural connectivity. The figure indicates the structural connections that significantly differed between patients and controls after multiple comparisons correction. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Correlation between structural connectivity and cognitive scores. The figures in the left column show the within‐ or between‐network connections that significantly correlated with the executive functions scores in the group of patients with 22q11DS. The plots show the Spearmann correlation between the structural connectivity measures and the specific scores. [Color figure can be viewed at http://wileyonlinelibrary.com]