Functional fractionation of default mode network in first episode schizophrenia

A disruption in the connectivity between brain regions may underlie the core pathology in schizophrenia. One of the most consistent observations in human functional imaging is a network of brain regions referred to as the default network (DMN) that contains core subsystem, the dorsomedial prefrontal cortex (dMPFC) subsystem and the medial temporal lobe (MTL) subsystem, with differential contributions. The goal of this study was to examine abnormalities of different DMN subsystems in first episode schizophrenia and associations between these abnormalities and individual psychopathology. We recruited 203 patients and 131 healthy controls. A seed-based resting-state functional connectivity (RSFC) analysis on the 2D surface was conducted. Individual DMN functional connectivity matrices were then obtained by calculating spatial correlations between pairs of RSFC maps, characterizing the functional fractionation of the DMN. Patients showed patterns similar to controls but markedly reduced strength of DMN fractionation, with the degree centrality of the MTL subsystem significantly reduced, including the posterior inferior parietal lobule (pIPL), parahippocampal cortex (PHC) and lateral temporal cortex (LTC). Patients also exhibited hypo-connectivity within the MTL subsystem and between the MTL and dMPFC subsystems. Clinical symptoms were negatively correlated with degree centrality of LTC, pIPL and PHC in patients. Hyper-fractionation of different DMN components implied that communication and coordination throughout the dissociated components of the DMN are functionally over-segregated in schizophrenia. The associations between the hyper-fractionation with clinical symptoms suggest a role of the high fractionation in the DMN in the abnormal neuropathology observed in schizophrenia.