Altered Resting-state Brain Functional Connectivities In Minimal Hepatic Encephalopathy And Their Association With Cognitive Impairments

Part one:Functional network-based statistics reveal abnormal resting-state functional connectivity in minimal hepatic encephalopathy Purpose: Whole-brain functional network analysis is an emerging methodology for exploring the mechanisms underlying hepatic encephalopathy(HE).This study aimed to identify the brain subnetwork that is significantly altered within the functional connectome in minimal HE(MHE),the earliest stage of HE.Materials and Methods: The study enrolled 19 cirrhotic patients with MHE and 19 controls who underwent the resting-state functional magnetic resonance imaging and cognitive assessment based on the Psychometric Hepatic Encephalopathy Score(PHES).A whole-brain functional connectivity(FC)matrix was calculated for each subject.Then,network-based statistical analyses of the functional connectome were used to perform group comparisons,and correlation analyses were conducted to identify the relationships between FC alterations and cognitive performance.Results: MHE patients showed significant reduction of positive FC within a subnetwork that predominantly involved the regions of the default-mode network,such as the bilateral posterior cingulate gyrus,bilateral medial prefrontal cortex,bilateral hippocampus and parahippocampal gyrus,bilateral angular gyrus,and left lateral temporal cortex.Meanwhile,MHE patients showed significant reduction of negative FC between default-mode network regions(such as the bilateral posterior cingulate gyrus,medial prefrontal cortex,and angular gyrus)and the regions involved in the somatosensory network(i.e.,bilateral precentral and postcentral gyri)and the language network(i.e.,the bilateral Rolandic operculum).The correlations of FC within the default-mode subnetwork and PHES results were noted.Conclusion: Default-mode network dysfunction may be one of the core issues in the pathophysiology of MHE.Our findings support the notion that HE is a neurological disease related to intrinsic brain network disruption.Part two:Disrupted resting-state functional connectivity of the hippocampus in patients without overt hepatic encephalopathyPurpose: The hippocampus is one of crucially pathological node for minimal hepatic encephalopathy(MHE)and associates with patients' various cognitive impairments such as memory dysfunction,learning defects,and navigation disability.Few studies have specifically investigated how resting-state hippocampal functional connectivity(FC)changes in MHE.We aimed to evaluate hippocampal FC alteration and its association with cognitive decline in MHE.Materials and Methods: Twenty-two cirrhotic patients with MHE,31 cirrhotic patients without MHE(NHE),and 43 healthy controls underwent resting-state functional magnetic resonance imaging and cognition assessment based on Psychometric Hepatic Encephalopathy Score(PHES).Seed-based correlation analysis was used to identify bilateral hippocampal connectivity network.FC within each hippocampal connectivity network was compared across three groups and correlated against PHES index in cirrhotic patients.Results:Globally,the averaged FC strength of bilateral hippocampal connectivity network is significantly decreased in MHE patients.Specifically,MHE patients had deceased FC of left hippocampus to bilateral posterior cingulate gyrus and left angular gyrus.Also,MHE patients showed FC reduction between right hippocampus and bilateral medial frontal cortex.A progressively decreased trend of hippocampal FC was noted from NHE to MHE.The bilateral hippocampal FC strength were positively correlated with PHES index,among the cirrhotic patients.Conclusion: Our results revealed the decreased hippocampal connectivity with the regions primarily involved in default-mode network,suggesting a functional disconnection syndrome in MHE.This alteration may underlie the mechanisms about cognitive deterioration with the disease progression.