Abstract
Background and PurposeLive failure can cause brain edema and aberrant brain function in cirrhotic patients. In particular, decreased functional connectivity within the brain default-mode network (DMN) has been recently reported in overt hepatic encephalopathy (HE) patients. However, so far, little is known about the connectivity among the DMN in the minimal HE (MHE), the mildest form of HE. Here, we combined diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) to test our hypothesis that both structural and functional connectivity within the DMN were disturbed in MHE.Materials and MethodsTwenty MHE patients and 20 healthy controls participated in the study. We explored the changes of structural (path length, tracts count, fractional anisotropy [FA] and mean diffusivity [MD] derived from DTI tractography) and functional (temporal correlation coefficient derived from rs-fMRI) connectivity of the DMN in MHE patients. Pearson correlation analysis was performed between the structural/functional indices and venous blood ammonia levels/neuropsychological tests scores of patients. All thresholds were set at P<0.05, Bonferroni corrected.ResultsCompared to the healthy controls, MHE patients showed both decreased FA and increased MD in the tract connecting the posterior cingulate cortex/precuneus (PCC/PCUN) to left parahippocampal gyrus (PHG), and decreased functional connectivity between the PCC/PCUN and left PHG, and medial prefrontal cortex (MPFC). MD values of the tract connecting PCC/PCUN to the left PHG positively correlated to the ammonia levels, the temporal correlation coefficients between the PCC/PCUN and the MPFC showed positive correlation to the digital symbol tests scores of patients.ConclusionMHE patients have both disturbed structural and functional connectivity within the DMN. The decreased functional connectivity was also detected between some regions without abnormal structural connectivity, suggesting that the former may be more sensitive in detecting the early abnormalities of MHE. This study extends our understanding of the pathophysiology of MHE.
Highlights
Minimal hepatic encephalopathy (MHE) refers to a transitional stage between non-hepatic encephalopathy cirrhotic patients and overt HE (OHE), which is used to classify a subpopulation of cirrhotic patients with no obvious clinical manifestation of HE but can be identified with neuropsychological examination [1,2,3]
We explored the changes of structural and functional connectivity of the default-mode network (DMN) in minimal HE (MHE) patients
The decreased functional connectivity was detected between some regions without abnormal structural connectivity, suggesting that the former may be more sensitive in detecting the early abnormalities of MHE
Summary
Minimal hepatic encephalopathy (MHE) refers to a transitional stage between non-hepatic encephalopathy cirrhotic patients and overt HE (OHE), which is used to classify a subpopulation of cirrhotic patients with no obvious clinical manifestation of HE but can be identified with neuropsychological examination [1,2,3]. HE is reversible with appropriate treatment in the initial phase, e.g., treatment with lactulose [4] or rifaximin [5] may improve cognitive function and health-related quality of life for MHE patients. Imaging plays an important role in detecting structural and functional abnormality of the brain in HE patients. A recent resting-state functional MRI (rs-fMRI) study by Zhang et al reported decreased functional connectivity within the DMN in OHE patients [17]. Decreased functional connectivity within the brain default-mode network (DMN) has been recently reported in overt hepatic encephalopathy (HE) patients. We combined diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) to test our hypothesis that both structural and functional connectivity within the DMN were disturbed in MHE
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