| Part Ⅰ. Altered Regional Homogeneity in patients with Cirrhosis-An fMRI StudyObjective:To evaluate the evolution pattern of spontaneous brain activities from non-hepatic encephalopathy (non-HE) to minimal HE (MHE) using resting-state fMRI with a regional homogeneity (ReHo) method.Mete rials and Methods:Resting-state fMRI data were acquired in47cirrhotic patients (minimal HE [MHE], n=20, and non-HE, n=27) and25age-and sex-matched healthy controls. The regional homogeneity maps were compared with ANOVA tests among MHE, non-HE, and healthy control groups and t-tests between each pair in a voxel-wise way. Correlation analyses were performed to explore the relationships between regional ReHo values and Child-Pugh scores, number connection test type A (NCT-A), digit symboltest (DST) scores, venous blood ammonia levels.Results:Compared with healthy controls, both MHE and non-HE patients showed decreased ReHo in the bilateral frontal, parietal and temporal lobes and increased ReHo in the bilateral caudate. Compared with the non-HE, MHE patients showed decreased ReHo in the bilateral precuneus, cuneus and supplementary motor area (SMA). The NCT-A of cirrhotic patients negatively correlated with ReHo values in the anterior cingulate cortex (ACC), precuneus and cuneus, and positively correlated with ReHo values in the caudate. DST scores positively correlated with ReHo values in the cuneus, precuneus and the medial frontal gyrus, and negatively correlated with ReHo values in the bilateral caudate (P<0.05, AlphaSim corrected).Conclusion:Diffused abnormal homogeneity of baseline brain activity was nonspecific for MHE, and only the progressively decreased ReHo in the SMA and the cuneus, especially for the latter, might be associated with the development of MHE. The ReHo analysis may be potentially valuable for detecting the development from non-HE to MHE. Part II. Study of Working Memory and resting-state Functional Connectivity in patients with Cirrhosis-An fMRI StudyObjective:The purpose of this study was to investigate the patterns of brain activation in hepatic cirrhotic patients under n-back working memory condition, and the functional connectivity differences among the three groups under resting-state by using fMRI.Meterials and Methods:Twenty four patients (MHE=10, non-HE=14) and sixteen normal subjects underwent functional MRI examination with Siemens Magnetom Trio3T MR scanner at resting-state and n-back working memory block-designed task condition. During resting state,250scans of whole brain were performed. Control blocks (0-back) and task blocks (1,2-back) ran alternately, each session constitus150scans. The fMRI data were processed by SPM based on MATLAB.(1) Single sample t-test based on random effect model was used to analyze the brain activation pattern of three groups under different tasks, the brain activation was compared with ANOVA tests among MHE, non-HE, and healthy control groups and t-tests between each pair in a voxel-wise way. Correlation analyses were performed to explore the relationships between brain activation and the accurancy and reaction time.(2) The significant altered brain region under2-back was selected as"seed" pixel. The correlation of "seed" pixel and other pixels in whole brain under resting state was analyzed using Pearson correlation. Single sample t-test based on random effect model was used to analyze the positive-related brain areas and the negative-related brain areas to MidFQ the functional connectivity was compared with ANOVA tests among MHE, non-HE, and healthy control groups and t-tests between each pair in a voxel-wise way. Correlation analyses were performed to explore the relationships between functional connectivity and the Child-Pugh scores, NCT-A, DST and venous ammonia.Results:(1) The MHE group, non-HE group and the control group showed activation of frontal-parietal networks, including the prefrontal cortex, bilateral parietal lobe, bilateral premotor cortex and the supplementary motor area under the n-back task. Under the1-back task, the patients manifested as an increase in related brain activation, while the compensation in MHE was weakened than non-HE. Under the2-back task, the patients showed reduced brain activation, MHE group showed more reduction than non-HE group, which indicated that the impairment in MHE was more serious than in non-HE. The left middle frontal gyrus of cirrhotic patients was closely related to2-back accurancy.(2) The brain areas positively correlated with middle frontal gyrus were mainly located in the dorsal attention network, while negative related brain areas were mainly located in the default mode network. The functional connectivity with left middle frontal gyrus in hepatic cirrhotic patients was similar with that in healthy controls, but the positive correlation network in patients was lower than that in the control group, and the negative correlation network was higher than that in the control group. The functional connectivity with left middle frontal gyrus was negatively correlated with, Child-Pugh scores and blood ammonia, the functional connectivity with super temporal gyrus was negatively correlated with NCT-A.Conclusion:The hepatic cirrhotic patients showed impaired semantic working memory related brain regions, although the behavior data was not significantly different with healthy controls, there was already potential working memory related brain regions impairment. The patients mainly manifested as a compensatory mechanism under1-back condition, but the compensation in MHE was weakened than non-HE. The2-back condition was beyond the compensation limit, mainly manifested as a reduction of brain activation, and the impairment in MHE was more serious than non-HE. The functional connectivity with left middle frontal gyrus in hepatic cirrhotic patients was similar with that in healthy controls, but the positive correlation network in patients was lower than that in the control group, and the negative correlation network was higher than that in the control group. The alteration tendency of functional connectivity in several brain regions under resting-state was in line with the alteration tendency of brain activation under task state, indicating that the functional connectivity alterations under resting state may be basis of the brain activation alterations under the task state. |
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