Abstract
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.
Highlights
Minimal hepatic encephalopathy (MHE) is a frequent cognitive complication of hepatic cirrhosis, diagnosed in up to 80% of patients with cirrhosis [1]
We aimed to demonstrate the association between these changes in functional connectivity (FC) patterns and cognitive decline in MHE patients
Very similar results were obtained from these analyses; we only show the result of networkbased statistics” (NBS) analysis with the median cluster-defining threshold (t = 3.1) in this article
Summary
Minimal hepatic encephalopathy (MHE) is a frequent cognitive complication of hepatic cirrhosis, diagnosed in up to 80% of patients with cirrhosis [1]. Based on whole-brain functional connectivity (FC) analysis at the region of interest (ROI)wise level, Zhang et al [8] demonstrated widespread cortical and subcortical network connectivity alterations in MHE patients, disrupted basal ganglia–thalamocortical FC and abnormal intracortical FC (predominantly in the form of decreased connectivity). While the existing whole-brain functional network studies have helped expand our knowledge of the neural substrates underlying MHE, these studies have only examined whole-brain FC with a single seed region or via pairwise coupling. These approaches may fail to elucidate the role of the connections within the larger network; they do not provide insight into how MHE is related to the restructuring of functional networks, at the connectome level
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