Atypical functional connectivity in resting-state networks of individuals with 22q11.2 deletion syndrome: associations with neurocognitive and psychiatric functioning

Abstract

Background22q11.2 deletion syndrome (22q11DS) is a neurogenetic condition associated with deficits in neuropsychological functioning and psychiatric disorders. This deletion confers a high risk for the development of psychosis, as approximately 30–45 % of individuals develop psychosis in adulthood. Previous reports of resting-state functional magnetic resonance imaging (rs-fMRI) functional connectivity patterns in 22q11DS have demonstrated that atypical connectivity is associated with both the emergence and severity of psychotic symptoms. However, due to sample overlap and large age ranges of samples spanning multiple critical periods of brain maturation, more independent studies with samples within the window of time when psychotic symptoms have been shown to emerge (ages 17–26) are needed. Resting-state networks (RSNs) in 22q11DS during this stage of brain development may thus provide insight into the dynamic changes in functional integration that influence the incidence of prodromal symptoms and neurocognitive deficits characteristic of this syndrome.MethodsIndependent component analysis (ICA) was performed to identify RSNs in a combined sample of 55 individuals with 22q11DS (27 males; age range 17–26) and 29 controls (17 males; age range 17–23, consisting of 8 siblings without the deletion and 21 typically developed individuals) from two research sites. We conducted a full factorial analysis to determine group differences between 22q11DS and controls. A Poisson regression analysis was conducted in the 22q11DS group to determine relationships of rs-fMRI network connectivity with psychiatric symptoms based on factors of the 18-item Brief Psychiatric Rating Scale. Nonparametric Spearman correlations were performed to test associations between within-network functional connectivity (FC) and performance on measures of verbal memory (California Verbal Learning Test) and executive function (Behavior Rating Inventory of Executive Function Adult version) in 22q11DS.ResultsBetween-group network connectivity analyses revealed significant differences in 9 RSNs. Decreased network FC in 22q11DS was observed in the following networks: high-level visual processing network (HLVPN), low-level visual processing network (LLVPN), visual/precuneus network, left frontal-parietal network (LFPN), right frontal-parietal network (RFPN), and self-referential network (SRN). In contrast, greater network FC in 22q11DS was observed in subclusters of the LLVPN, visual/precuneus network, limbic network (LN), default mode network (DMN), and visuospatial processing network (VSPN). Increased functional connectivity of the right cuneus (visual/precuneus network) and right superior parietal lobule (DMN) in 22q11DS was positively associated with both thought disturbance and disorganization factors of the Brief Psychiatric Rating Scale (BPRS). Decreased functional connectivity in the left posterior cingulate (LLVPN) was associated with higher thought disturbance scores in 22q11DS. No associations with our neurocognitive measures passed correction fo...

Multimodal investigation of triple network connectivity in patients with 22q11DS and association with executive functions

“…We observed no difference in functional connectivity within the CEN and the SN. This result is in contrast with recent findings in 22q11DS [Mattiaccio et al, 2016], but is in line with previous results from our group . This discrepancy in the results may be due to the use of different acquisition, processing and analysis techniques as well as to different sample characteristics.…”

“…However, few studies showed white matter impairments [Radoeva et al, ] or aberrant functional activation [Gothelf et al, ; Montojo et al, ] associated with executive dysfunctions in patients with the syndrome. On the opposite, in a recent study investigating functional connectivity within resting‐state networks [Mattiaccio et al, ], the authors found no association between altered connectivity and executive functions measures. A number of studies (reviewed in [Scariati et al, ]) further reported an association between impairments in long‐range connections and psychotic symptoms in 22q11DS.…”

“…Contrarily, Mattiaccio et al [2016] compared the activation of spatial CEN and SN maps obtained from ICA. Furthermore, in this study we included patients from 8 to 33 years old, while Mattiaccio et al [2016] mostly included adolescents and young adults (17-26 years old). Given the presence of impaired developmental trajectories in patients with 22q11DS [Gothelf et al, 2007b;Schaer et al, 2009], it is possible that adult patients present a greater pattern of connectivity impairment compared with children.…”

“…This finding was further confirmed by a multimodal investigation [Padula et al, ] showing reduced structural and functional connectivity between medial DMN nodes. Moreover, Mattiaccio et al [] further showed reduced activation of the CEN and the SN. However, no study to date directly investigated connectivity between the three networks in patients with 22q11DS.…”

Large-scale brain network dynamics provide a measure of psychosis and anxiety in 22q11.2 deletion syndrome

“…Despite these promises of dynamic fMRI analysis, functional neuroimaging research in 22q11DS has so far mostly focused on static functional features (17,80,54,84,55), often targeting only specific functional networks such as the DMN (66,85). The studies who explicitly investigated psychotic symptoms in 22q11DS showed correlations of DMN dysconnectivity with prodromal psychotic symptoms (17), as well as successful discrimination between patients at high vs. low risk based whole-brain rs-fMRI (80) and hypoconnectivity of DMN, SN, anterior cingulate cortex (ACC) and frontoparietal network (FPN; 84).…”