Selective Impairments of Resting-State Networks in Minimal Hepatic Encephalopathy

Rongfeng Qi,Huafu Chen,Guangming Lu,Long Jiang Zhang,Jianhui Zhong,Qing Jiao,Shengyong Wu,Qiang Xu,Yuan Zhong,Zongjun Zhang,Yijun Liu,Zhiqiang Zhang,Wei Liao,Xingjiang Wu,Xinxin Fan,Ling Ni,Kewei Chen

doi:10.1371/journal.pone.0037400

Abstract

BackgroundMinimal hepatic encephalopathy (MHE) is a neuro-cognitive dysfunction characterized by impairment in attention, vigilance and integrative functions, while the sensorimotor function was often unaffected. Little is known, so far, about the exact neuro-pathophysiological mechanisms of aberrant cognition function in this disease.Methodology/Principal FindingsTo investigate how the brain function is changed in MHE, we applied a resting-state fMRI approach with independent component analysis (ICA) to assess the differences of resting-state networks (RSNs) between MHE patients and healthy controls. Fourteen MHE patients and 14 age-and sex-matched healthy subjects underwent resting-state fMRI scans. ICA was used to identify six RSNs [dorsal attention network (DAN), default mode network (DMN), visual network (VN), auditory network (AN), sensorimotor network (SMN), self-referential network (SRN)] in each subject. Group maps of each RSN were compared between the MHE and healthy control groups. Pearson correlation analysis was performed between the RSNs functional connectivity (FC) and venous blood ammonia levels, and neuropsychological tests scores for all patients. Compared with the healthy controls, MHE patients showed significantly decreased FC in DAN, both decreased and increased FC in DMN, AN and VN. No significant differences were found in SRN and SMN between two groups. A relationship between FC and blood ammonia levels/neuropsychological tests scores were found in specific regions of RSNs, including middle and medial frontal gyrus, inferior parietal lobule, as well as anterior and posterior cingulate cortex/precuneus.Conclusions/SignificanceMHE patients have selective impairments of RSNs intrinsic functional connectivity, with aberrant functional connectivity in DAN, DMN, VN, AN, and spared SMN and SRN. Our fMRI study might supply a novel way to understand the neuropathophysiological mechanism of cognition function changes in MHE.

Highlights

Hepatic encephalopathy (HE) is a common and serious neurocognitive dysfunction in patients with acute and chronic hepatic dysfunction, which is characterized by a wide spectrum of clinical manifestations, ranging from alterations of psychometric performance to stupor and coma [1,2]
Spatial pattern of resting-state networks (RSNs) in each group The results of one-sample t-tests revealed typical spatial patterns in each RSN of both Minimal hepatic encephalopathy (MHE) and control groups, as illustrated in Aberrant RSNs in patients with MHE The results obtained from the two-sample t test clearly showed significant difference of functional connectivity (FC) between the MHE and healthy controls, setting at a corrected threshold of P,0.05 (Fig. 2)
Within six RSNs, the dorsal attention network (DAN) showed decreased FC; the default mode network (DMN), auditory network (AN), and the visual network (VN) displayed a bidirectional change of FC; while the sensorimotor network (SMN) and the self-referential network (SRN) were unchanged

Summary

Introduction

Hepatic encephalopathy (HE) is a common and serious neurocognitive dysfunction in patients with acute and chronic hepatic dysfunction, which is characterized by a wide spectrum of clinical manifestations, ranging from alterations of psychometric performance to stupor and coma [1,2]. The term minimal hepatic encephalopathy (MHE) is used to classify a subpopulation of cirrhotic patients with no obvious clinical manifestation but can be identified with neuropsychological examination, such as the number connection test and the digit symbol test [3,4]. MHE was found to prominently affect the cognition function in the domain of attention, vigilance and integrative functions, while the sensorymotor areas were often unaffected [7,9]. The exact pathophysiological mechanisms of these cognition function changes in MHE patients remain unclear so far. Two prior task-state blood oxygenation level dependent (BOLD) functional MRI (fMRI) studies showed that the MHE patients exhibit abnormal brain activation when performing the task. Minimal hepatic encephalopathy (MHE) is a neuro-cognitive dysfunction characterized by impairment in attention, vigilance and integrative functions, while the sensorimotor function was often unaffected. About the exact neuro-pathophysiological mechanisms of aberrant cognition function in this disease

Methods

Results

Conclusion