Cortico-striatal disconnection within the cingulo-opercular network in schizophrenia revealed by intrinsic functional connectivity analysis: A resting fMRI study

The cingulo-opercular network (CON) is a newly defined control network responsible for various cognitive processes that have been consistently found to be impaired in schizophrenia. The aim of this study was to use functional connectivity magnetic resonance imaging (fcMRI) to test the hypothesis that schizophrenia is associated with functional disconnection within the CON. Thirty subjects with schizophrenia and thirty healthy controls were enrolled in the study. Each subject received resting fMRI scanning, clinical evaluations and cognitive examinations. The CON of each subject was derived by calculating the functional connectivity map of a seed in the dorsal anterior cingulate (dACC). A between-group comparison was performed using a random effect analysis. Further network analyses with multiple regions of interest (ROIs) were performed to characterize the pattern of functional disconnection within the entire CON. Using the dACC seed in healthy controls, we derived the CON, which includes the following anatomical structures: the dACC; the bilateral anterior prefrontal, inferior parietal and anterior insular cortices; the putamen; the thalamus; and the cerebellum. Compared with healthy controls, schizophrenic patients showed significantly reduced functional connectivity in the bilateral putamens. Further network analysis demonstrated widespread cortico-striatal disconnection within the CON of schizophrenic patients. The disconnections correlated with negative symptom severity. Behavioral regression revealed that cortico-striatal functional connectivity predicted 2-back working memory performance in healthy controls, but not in schizophrenic patients. Our findings suggest that schizophrenia is associated with cortical-striatal disconnection within the CON. The result provides a network basis for the cortico-striatal disconnection hypothesis of schizophrenia. (C) 2011 Elsevier Inc. All rights reserved.