Aberrant functional connectivity within and across the default mode, central-executive, and salience network in patients with schizophrenia: a resting-state functional magnetic resonance imaging study

Abstract

Objective To explore the neural profile of functional connectivity of default mode network (DMN), central-executive network(CEN) , and salience network (SN) in patients with schizophrenia during a resting-state functional magnetic resonance imaging(rs-fMRI). Methods The SPM8, DPARSFA, CONN softwares combined with data-driven region of interest (ROI) analysis were used to investigate functional connectivity (FC) of the DMN, CEN, and SN in 74 patients with schizophrenia (SZ) and 79 age-and gender-matched normal controls (NC). Medial prefrontal cortex (MPFC) was selected as seed region for identifying the DMN and CEN while right anterior insula (rAI) for the SN. Voxel-wise functional connectivity analyses were performed between MPFC and rAI while pair-wise functional connectivity analyses were conducted across DMN, CEN, and SN. Results Concerning the MPFC, SZ showed increased functional connectivity, comparing with NC, with bilateral dorsolateral prefrontal cortex (left: - 0.02 ± 0.18 vs. - 0.12±0.12, t=4.25, P<0.01; right: -0.02±0.11 vs. -0.10±0.10,t=5.40,P<0.01) and bilateral putamen (left: 0.14± 0.12 vs. 0.04±0.10,t=5.03,P<0.01; right: 0.13±0.11 vs. 0.03±0.98, t=4.96,P<0.01). With regard to rAI, increased functional connectivity between rAI and left middle frontal cortex (-0.05±0.17 vs. -0.07±0.17,t= 4.60,P<0.01) and between rAI and precuneus/posterior cingulate cortex (0.01±0.13 vs. -0.09±0.14,t=4.01, P<0.01) were found in SZ comparison to NC (gaussian random field thaeory-corrected; voxel level P<0.01, cluster level P<0.05). Additionally, SZ also showed enhanced interconnectivity strengths of DMN-CEN and DMN-SN (Bonferroni-corrected, P<0.05). Furthermore, partial correlation analyses showed that the increased functional connectivity between rAI and precuneus/posterior cingulate cortex was significantly correlated with PANSS-positve symptoms (r=0.232,P=0.025). Positive relationships were found between the duration of illness and functional connectivity between rAI and left middle frontal cortex (r=0.288, P=0.007) and between rAI and precuneus/posterior cingulate cortex (r=0.196, P=0.049). Conclusions This study provides evidence for resting state functional connectivity abnormalities of DMN, CEN, and SN in patients with schizophrenia. These aberrant functional connectivities between some key brain regions of three networks may be responsible for certain schizophrenic symptoms, which could contribute to exploring the pathophysiological mechanisms of schizophrenia. Key words: Schizophrenia; Magnetic resonance imaging; Default mode network; Central-executive network; Salience network; Functional connectivity