Dysconnectivity of Large-Scale Functional Networks in Early Psychosis: A Meta-analysis

Abstract

Objective: Increasingly, studies have identified abnormalities in the functional connectivity (FC) of large-scale neural networks in early psychosis, but the findings thus far have been inconclusive. Therefore, the aim of this study was to identify robust alterations in FC of the default mode (DMN), salience (SN), and central executive networks (CEN), in patients with first-episode psychosis (FEP) using a meta-analytic approach.

Methods: Included studies were required to be resting-state, seed-to-whole brain, FC neuroimaging studies, comparing FEP patients to healthy controls (HC), with seeds within the boundaries of the region-of-interest networks. Peak effect coordinates and peak t, z, or p values were meta-analyzed using Seed-based d Mapping software.

Results: The DMN seeds primarily displayed within-network hypoconnectivity (largest clusters including the middle orbital gyrus; and ventral anterior cingulate gyrus). The SN seeds displayed hypoconnectivity with regions in the DMN and CEN (largest clusters located in the bilateral middle temporal gyri). Review of the limited CEN data revealed hypo- and hyperconnectivity across the networks. Negative symptoms were positively correlated with all DMN FC abnormalities in the FEP group. Antipsychotic-treated patients displayed greater hypoconnectivity than antipsychotic-naïve patients between both the DMN/SN seeds and prefrontal regions.

Conclusions: These findings provide substantial evidence of widespread resting-state FC abnormalities of the DMN, SN, and CEN in early psychosis; particularly implicating DMN and SN dysconnectivity as a core deficit underlying the psychopathology of psychosis. Additionally, we highlight the importance of disentangling connectivity abnormalities resulting from disease processes, from those that result from antipsychotic treatment.

Keywords: connectivity; dysconnectivity; first episode; functional connectivity; networks; psychosis.

Fig. 1.

PRISMA flow-chart depicting the study selection process, and the number of studies either included or excluded at each stage.

Fig. 2.

Results of the meta-analysis of (A) DMN to whole-brain functional connectivity, and (B) SN to whole-brain functional connectivity, in FEP individuals, relative to controls. Brain regions that showed significant differences in functional connectivity with (A) the DMN seed network, and (B) the SN seed network, in individuals with first-episode psychosis (FEP), relative to healthy controls (HC). MNI z coordinates are displayed at the top of the figure. Peaks appear from left to right in the (A) left cerebellum (P = .0026); right inferior semi-lunar cerebellar lobule (P = .00033); medial orbital gyrus (P = .00048); left superior temporal gyrus (P = .0026); ventral anterior cingulate gyrus (P = .00077); the inferior frontal gyrus (P = .0027); and the dorsal anterior cingulate gyrus (P = .0018); (B) cerebellum/culmen (P = .0033); right middle temporal gyrus (P = .000015); left planum polare (P = .0029); left middle temporal gyrus (P = .000034); middle frontal gyrus (P = .0011); superior temporal gyrus (P = .00038) and posterior transverse temporal gyrus (P = .00068); occipital gyrus (P = .0004); left superior frontal gyrus (P = .0027); right superior frontal gyrus (P = .00054). For color, please see the figure online.