Selective Impairments of Resting-State Networks in Minimal Hepatic Encephalopathy

Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu Province, China.
PLoS ONE (Impact Factor: 3.23). 05/2012; 7(5):e37400. DOI: 10.1371/journal.pone.0037400
Source: PubMed


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. Little is known, so far, about the exact neuro-pathophysiological mechanisms of aberrant cognition function in this disease.
To 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.
MHE 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.


Available from: Wei Liao
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    • "Many functional MRI (fMRI) studies have been performed to clarify the pathophysiological mechanisms of MHE. Some fMRI studies focus on the analysis of regional brain networks, supporting that the regional functional connectivity modules (e.g., cognitive, motor control, and concentration attention) of cirrhotic patients were impaired [19] [20] [21]. Different from those studies based on regional brain networks, Zhang et al. investigated patterns of whole-brain functional connectivity in cirrhotic patients with MHE and found widespread cortical and subcortical network connectivity changes, suggesting that not only functional connectivities within regions but also those between functional modules were impaired in MHE patients [22]. "
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    ABSTRACT: Minimal hepatic encephalopathy (MHE) is associated with changes in functional connectivity. To investigate the patterns of modular changes of the functional connectivity in the progression of MHE, resting-state functional magnetic resonance imaging was acquired in 24 MHE patients, 31 cirrhotic patients without minimal hepatic encephalopathy (non-HE), and 38 healthy controls. Newman's metric, the modularity Q value, was maximized and compared in three groups. Topological roles with the progression of MHE were illustrated by intra- and intermodular connectivity changes. Results showed that the Q value of MHE patients was significantly lower than that of controls (P < 0.01) rather than that of non-HE patients (P > 0.05), which was correlated with neuropsychological test scores rather than the ammonia level and Child-Pugh score. Less intrasubcortical connections and more isolated subcortical modules were found with the progression of MHE. The non-HE patients had the same numbers of connect nodes as controls and had more hubs compared with MHE patients and healthy controls. Our findings supported that both intra- and intermodular connectivity, especially those related to subcortical regions, were continuously impaired in cirrhotic patients. The adjustments of hubs and connector nodes in non-HE patients could be a compensation for the decreased modularity in their functional connectivity networks.
    BioMed Research International 06/2014; 2014(2, part 2):727452. DOI:10.1155/2014/727452 · 1.58 Impact Factor
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    • "Our finding of disconnections in DAN, VAN, and DMN is consistent with previous reports about MHE [15], [16]. Qi and the colleagues have reported decreased FC in DAN [15]; while disruption of default-mode connectivity has been also found in MHE [14], [16]. "
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    ABSTRACT: Attention deficit is an early and key characteristic of minimal hepatic encephalopathy (MHE) and has been used as indicator for MHE detection. The aim of this study is to classify the cirrhotic patients with or without MHE (NMHE) and healthy controls (HC) using the resting-state attention-related brain network analysis. Resting-state fMRI was administrated to 20 MHE patients, 21 NMHE patients, and 17 HCs. Three attention-related networks, including dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN), were obtained by independent component analysis. One-way analysis of covariance was performed to determine the regions of interest (ROIs) showing significant functional connectivity (FC) change. With FC strength of ROIs as indicators, Linear Discriminant Analysis (LDA) was conducted to differentiate MHE from HC or NMHE. Across three groups, significant FC differences were found within DAN (left superior/inferior parietal lobule and right inferior parietal lobule), VAN (right superior parietal lobule), and DMN (bilateral posterior cingulate gyrus and precuneus, and left inferior parietal lobule). With FC strength of ROIs from three networks as indicators, LDA yielded 94.6% classification accuracy between MHE and HC (100% sensitivity and 88.2% specificity) and 85.4% classification accuracy between MHE and NMHE (90.0% sensitivity and 81.0% specificity). Our results suggest that the resting-state attention-related brain network analysis can be useful in classification of subjects with MHE, NMHE, and HC and may provide a new insight into MHE detection.
    PLoS ONE 03/2014; 9(3):e89684. DOI:10.1371/journal.pone.0089684 · 3.23 Impact Factor
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    • "Chen et al. showed that the decreased functional connectivity between some regions within the DMN still persisted after clinical recovery from previous episodes of overt HE [17]. Qi et al. also found that MHE patients had selective impairments of RSNs, with aberrant dorsal attention network, DMN, visual and auditory network, and spared sensorimotor network and self-referential network [18]. However, to the best of our knowledge, the resting functional networks of deep gray matter structures, such as the thalamus, have little been investigated in HE. "
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    ABSTRACT: Background and purpose: Little is known about the role of thalamus in the pathophysiology of minimal hepatic encephalopathy (MHE). The purpose of this study was to investigate whether the thalamic functional connectivity was disrupted in cirrhotic patients with MHE by using resting-state functional magnetic resonance imaging (rs-fMRI). Materials and methods: Twenty seven MHE patients and twenty seven age- and gender- matched healthy controls participated in the rs-fMRI scans. The functional connectivity of 11 thalamic nuclei were characterized by using a standard seed-based whole-brain correlation method and compared between MHE patients and healthy controls. Pearson correlation analysis was performed between the thalamic functional connectivity and venous blood ammonia levels/neuropsychological tests scores of patients. Results: The ventral anterior nucleus (VAN) and the ventral posterior medial nucleus (VPMN) in each side of thalamus showed abnormal functional connectivities in MHE. Compared with healthy controls, MHE patients demonstrated significant decreased functional connectivity between the right/left VAN and the bilateral putamen/pallidum, inferior frontal gyri, insula, supplementary motor area, right middle frontal gyrus, medial frontal gyrus. In addition, MHE patients showed significantly decreased functional connectivity with the right/left VPMN in the bilateral middle temporal gyri (MTG), temporal lobe, and right superior temporal gyrus. The venous blood ammonia levels of MHE patients negatively correlated with the functional connectivity between the VAN and the insula. Number connecting test scores showed negative correlation with the functional connectivity between the VAN and the insula, and between the VPMN and the MTG. Conclusion: MHE patients had disrupted thalamic functional connectivity, which mainly located in the bilateral ventral anterior nuclei and ventral posterior medial nuclei. The decreased connectivity between thalamus and many cortices, and basal ganglia indicated reduced integrity of thalamic RSN in MHE.
    European journal of radiology 01/2013; 82(5). DOI:10.1016/j.ejrad.2012.12.016 · 2.37 Impact Factor
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