title: Abnormalities of voxel-based whole-brain functional connectivity patterns predict the progression of hepatic encephalopathy.
abstract: Resting state functional magnetic resonance imaging (fMRI) is an important tool for understanding the functional reorganization of the brain in cirrhotic patients. Previous studies revealed that functional integration failure were observed in the whole brain. However, the whole-brain functional connectivity analysis methods used in these studies have the limitation that the result relied on a priori definition of network nodes. Moreover, the utility of resting state functional connectivity in the diagnosis and prediction of hepatic encephalopathy (HE) is not well examined. In this study, we recruited 87 subjects consisting of patients without HE, with HE, and healthy controls. We employed a voxel-based, unbiased functional connectivity analysis and the functional connectivity density (FCD) metric to precisely study abnormalities in the intrinsic functional connectivity patterns of cirrhotic patients. FCD analyses showed that hub regions in the brain were less topologically important in cirrhotic patients, whereas non-hub regions became topologically important in the disease state. This trend was more apparent with the progression of cirrhosis severity. Most FCD abnormalities were associated with deficits in psychomotor function, executive control, or visual-spatial abilities (p < 0.05, AlphaSim corrected). FCD alterations in the left inferior parietal lobe and the right hippocampal gyrus/parahippocampal gyrus were significantly correlated with cognitive ability and blood ammonia level (p < 0.05, AlphaSim corrected). A pattern classification analysis indicated that whole-brain FCD differences distinguished cirrhotic patients from healthy controls and predicted disease severity with high accuracies. These findings suggest that voxel-based FCD analysis may be clinically important for the diagnosis and prediction of HE.
authors.affiliation: School of Computer Science and Technology, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Yaguan Road No. 135, Jinnan District, Tianjin, 300350, People's Republic of China.
authors.forename: Gaoyan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Tianjin First Central Hospital, Fukang Road No. 24, Nankai District, Tianjin, 300192, People's Republic of China. chengyue200017076@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: School of Computer Science and Technology, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Yaguan Road No. 135, Jinnan District, Tianjin, 300350, People's Republic of China. liubaolin@tsinghua.edu.cn.|State Key Laboratory of Intelligent Technology and Systems, National Laboratory for Information Science and Technology, Tsinghua University, Beijing, 100084, People's Republic of China. liubaolin@tsinghua.edu.cn.
authors.forename: Baolin
authors.initials: B
authors.lastname: Liu
mesh_terms: D000641:Ammonia / Q000097:blood; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D003071:Cognition; D018450:Disease Progression; D005260:Female; D006501:Hepatic Encephalopathy / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D009483:Neuropsychological Tests; D011379:Prognosis; D012372:ROC Curve; D012146:Rest
chemical_list: D015415:Biomarkers; D000641:Ammonia
keywords: Functional connectivity density; Hepatic encephalopathy; Pattern classification; Resting state fMRI; Voxel-based analysis