Schizophrenia is considered a disorder characterized of improper functional integration. The aims of this dissertation are to investigate the improper functional integration during rest in schizophrenia, and to explore its patophysiological significance. Firstly, for the first time, we investigated the resting-state functional connectivity pattern of the dorsolateral prefrontal cortex (DLPFC) in patients with first-episode schizophrenia (FES) and their matched controls by selecting DLPFC as a region of interest. We found that the bilateral DLPFC showed reduced or enhanced functional connectivities to many regions in FES patients. Our results suggest that the improper functional integrity also exist in resting brain of FES patients, which may be related to the disturbed intrinsic brain activity. Then, we investigated the low frequency fluctuation (LFF) of the regions with the intrinsic brain functional organization pattern by computing the amplitude of LFF (ALFF) in patients with schizophrenia and their matched healthy controls. We found that the regions related to “self” showed decreased ALFF, as well as the regions associated with mentalizing and attention demonstrated increased ALFF in patients with schizophrenia. The split of ignoring self, over-mentalizing and excessively sensitive to the environmental changes provides additional evidence for the improper functional integration observed in schizophrenia. In order to explore the neural correlates of the abnormality in resting-state functional connectivity in schizophrenia, we combined fMRI and diffusion tensor imaging (DTI) to investigate the anatomical and resting-state functional connectivities of hippocampus in patients with paranoid schizophrenia and their matched healthy controls. We found that the bilateral hippocampi showed reduced functional connectivities as well as damaged integrity of the fornix in patients with schizophrenia. Furthermore, the lateralized (left side) vulnerability was found in both resting-state functional connectivity and DTI measure in patients. Our findings therefore suggest that the damage of the integrity of white matter may partially explain the reduced resting-state functional connectivities of the hippocampus in schizophrenia, and provide a multidisciplinary approach to investigate underlying mechanism of the abnormality of resting-state functional connectivity in disease state
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