Schizophrenia is characterized by the distributed dysconnectivity of resting-state multiple brain networks. However, the abnormalities of intra- and inter-network functional connectivity (FC) in schizophrenia and its relationship to symptoms remain unknown. The aim of the present study is to compare the intra- and inter-connectivity of the intrinsic networks between a large sample of patients with schizophrenia and healthy controls. Using the Region of interest (ROI) to ROI FC analyses, the intra- and inter-network FC of the eight resting state networks [default mode network (DMN); salience network (SN); frontoparietal network (FPN); dorsal attention network (DAN); language network (LN); visual network (VN); sensorimotor network (SMN); and cerebellar network (CN)] were investigated in 196 schizophrenia and 169-healthy controls. Compared to the healthy control group, the schizophrenia group exhibited increased intra-network FC in the DMN and decreased intra-network FC in the CN. Additionally, the schizophrenia group showed the decreased inter-network FC mainly involved the SN-DMN, SN-LN and SN-CN while increased inter-network FC in the SN-SMN and SN-DAN (p < 0.05, FDR-corrected). Our study suggests widespread intra- and inter-network dysconnectivity among large-scale RSNs in schizophrenia, mainly involving the DMN, SN and SMN, which may further contribute to the dysconnectivity hypothesis of schizophrenia.

Past researches have suggested that in regard to working memory-induced dorsolateral prefrontal cortex (DLPFC) activation and connectivity differences between patients with schizophrenia and healthy controls have not reached a consistent result. The functional integration perspective further suggests that working memory performance also modulates group differences in functional interactions of the DLPFC between patients and controls. To explore this possibility, forty-five healthy controls and forty-five patients with schizophrenia were recruited to perform a 2-back task during functional magnetic resonance imaging (fMRI). Each group was further divided into two subgroups based on task performance in order to examine the modulatory effect of performance on functional interactions of the DLPFC, as measured via psychophysiological interaction (PPI) analyses. We observed that, in patients with schizophrenia who exhibited impaired working memory capacity and decreased brain activation/deactivation, functional interactions between the right/left DLPFC and angular cortex were decreased relative to those of healthy controls. More importantly, we observed an interaction effect of working memory performance and diagnosis on functional connectivity between the right/left DLPFC seed region and posterior regions such as the angular cortex, fusiform gyrus, and middle occipital gyrus. This interaction effect was mainly driven by the negative correlation between functional connectivity and performance in healthy controls but by the positive correlation in patients with schizophrenia. These results demonstrate the differential effects of inter-individual differences in working memory performance on the functional interaction between the DLPFC and posterior regions in patients with schizophrenia compared to healthy controls, which may shed new light on the neural basis of working memory. Keywords: Schizophrenia, N-back, fMRI, Psychophysiological Interaction (PPI), Dorsolateral Prefrontal Cortex (DLPFC), Fusiform Gyrus, Inferior Parietal Lobule (IPL)

Schizophrenia and depression are psychiatric disorders with overlapping clinical and biological features. This study aimed to identify common and distinct neuropathological mechanisms in schizophrenia and depression patients using resting-state functional magnetic resonance imaging (fMRI). The study included 28 patients with depression (DEP), 29 patients with schizophrenia (SCH), and 30 healthy control subjects (HC). Intrinsic connectivity contrast (ICC) was used to identify functional connectivity (FC) changes at the whole-brain level, and significant ICC differences were found in the bilateral orbitofrontal cortex (OFC) across all three groups. Further seed-based FC analysis indicated that compared to the DEP and HC groups, the FC between bilateral OFC and medial prefrontal cortex (MPFC), right anterior insula, and right middle frontal gyrus were significantly lower in the SCH group. Additionally, the FC between right OFC and left thalamus was decreased in both patient groups compared to the HC group. Correlation analysis showed that the FC between OFC and MPFC was positively correlated with cognitive function in the SCH group. These findings suggest that OFC connectivity plays a critical role in the pathophysiology of schizophrenia and depression and may provide new insights into the potential neural mechanisms underlying these two disorders.

Background: Theory of Mind (ToM) is an ability to infer the mental state of others, which plays an important role during social events. Previous studies have shown that ToM deficits exist frequently in schizophrenia, which may result from abnormal activity in brain regions related to sociality. However, the interactions between brain regions during ToM processing in schizophrenia are still unclear. Therefore, in this study, we investigated functional connectivity during ToM processing in patients with schizophrenia, using functional magnetic resonance imaging (fMRI). Methods: A total of 36 patients with schizophrenia and 33 healthy controls were recruited to complete a ToM task from the Human Connectome Project (HCP) during fMRI scanning. Psychophysiological interaction (PPI) analysis was applied to explore functional connectivity. Results: Patients with schizophrenia were less accurate than healthy controls in judging social stimuli from non-social stimuli (Z = 2.31, p = 0.021), and displayed increased activity in the right inferior frontal gyrus and increased functional connectivity between the bilateral middle temporal gyrus and the ipsilateral parahippocampal gyrus during ToM processing (AlphaSim corrected p < 0.05). Conclusions: Here, we showed that the brain regions related to sociality interact more with the parahippocampal gyrus in patients with schizophrenia during ToM processing, which may reflect a possible compensatory pathway of ToM deficits in schizophrenia. Our study provides a new idea for ToM deficits in schizophrenia, which could be helpful to better understand social cognition of schizophrenia.