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.

Frontal dysconnectivity in 22q11.2 deletion syndrome: an atlas-based functional connectivity analysis

“…In individuals with 22q11DS, the DMN has been associated with prodromal symptoms [ 21 ], sustained attention [ 21 ] and reciprocal social behaviors [ 23 ]. It is not clear why we observed increased functional connectivity between these DMN regions, while several other studies [ 23 – 26 ] of 22q11DS have observed decreased functional connectivity between these regions. This may be attributable, in part, to our implementation of measurements within each subject’s native brain space.…”

“…Results of these studies indicate anomalous connectivity in frontal lobe connections [ 20 ] and parieto–occipital connections [ 20 – 22 ]. Decreases in functional connectivity have also been observed, in partially overlapping samples, in the default mode [ 23 – 26 ], salience [ 24 ] and frontal–parietal networks [ 22 , 24 ]. In a modularity analysis of overall functional network organization, Scariati and colleagues [ 27 ] observed increased modular segregation across superior parietal, frontal and inferior temporal lobes in individuals with 22q11DS.…”

Neuropsychiatric mutations delineate functional brain connectivity dimensions contributing to autism and schizophrenia

“…Dysconnectivity of thalamic-hippocampal circuitry 13 has been reported in 22q11.2 deletion carriers, with prominent under-connectivity of the default mode network (DMN), which was predictive of prodromal psychotic symptomatology 14,15 . Impaired connectivity of long-range connections within the DMN has also been reported by other studies 16 . A single 16p11.2 study has showed a decrease in connectivity of fronto-temporal and -parietal connections in deletion carriers 17 .…”

Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia

“…Dysconnectivity of thalamic-hippocampal circuitry 17 has been reported in 22q11.2 deletion carriers, with prominent under-connectivity of the default mode network (DMN), which was predictive of prodromal psychotic symptomatology 18,19 . Impaired connectivity of long-range connections within the DMN has also been reported by other studies 20 . A single 16p11.2 study has shown a decrease in connectivity of frontotemporal and -parietal connections in deletion carriers 21 .…”