Default Mode Network Functional Connectivity: A Promising Biomarker for Diagnosing Minimal Hepatic Encephalopathy

To investigate the contribution of brain default mode network (DMN) in the early diagnosis of the minimal hepatic encephalopathy (MHE), the mildest form of HE from cirrhotic patients by using resting-state functional magnetic resonance imaging (rs-fMRI). This study was approved by the local ethical committee, and a written informed consent was obtained from each participant. A total of 103 cirrhotic patients (34 MHE, 69 non-HE) and 103 matched healthy controls underwent rs-fMRI scanning. The DMN correlation map was acquired by using unbiased seed-based functional connectivity analysis and compared among MHE patients, non-HE patients, and healthy controls with analysis of variance tests. Pearson correlation analysis was performed between the abnormal DMN connectivity and neuropsychological performances. Receiver operator characteristic (ROC) analysis was used to evaluate the contribution of DMN connectivity strength in the differential diagnosis between MHE and non-HE. Compared with the healthy controls, MHE and non-HE patients showed decreased DMN connectivity in medial prefrontal cortex (MPFC), left superior frontal gyrus (SFG), left temporal lobe, and bilateral middle temporal gyri (MTG). The MHE patients showed even more decreased connectivity in MPFC, left SFG, and right MTG when compared with non-HE patients. Pearson correlation analyses revealed that the decreased connectivity strength of some DMN regions correlated with patients' neuropsychological tests scores. Connectivity strength of the MPFC, right MTG, and left SFG could differentiate MHE from non-HE, of which the MPFC had the highest effectiveness (sensitivity = 81.5%, specificity = 70.4%). Cirrhotic patients had gradually reduced DMN functional connectivity from non-HE patients to MHE patients. DMN function, especially the MPFC, might be a useful imaging marker for differentiating MHE from cirrhotic patients.