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Hippocampal atrophy and functional connectivity disruption in cirrhotic patients with minimal hepatic encephalopathy
Hua-Jun Chen1, Zhongshuai Zhang2, and Tian-Xiu Zou1

1Fujian Medical University Union Hospital, Fuzhou, China, 2Siemens Healthcare, Fuzhou, China

Synopsis

The hippocampus is a crucial pathological node for minimal hepatic encephalopathy (MHE) and it is associated with various cognitive impairments. We assessed hippocampal FC alterations in relation to regional volume and their associations with PHES results of cirrhotic patient and reached the following findings. (i) Hippocampal volume is significantly lower in MHE. (ii) A disruption of hippocampal connectivity to the default-mode network was observed in the MHE patients. (iii) The bilateral hippocampal FC strength (but not hippocampal volume) was positively correlated with the PHES results of the cirrhotic patients and aggravate with HE progression. Our findings revealed that both structural and functional abnormalities of the hippocampus are involved in the mechanism underlying cognitive deterioration with disease progression.

Purpose

The hippocampus is a crucial pathological node for minimal hepatic encephalopathy(MHE) and it is associated with various cognitive impairments. Investigations on alterations involving hippocampal morphology and functional connectivity (FC) in MHE are limited. This study aimed to simultaneously evaluate hippocampal volume and FC alterations and their association with cognitive decline in MHE.

Materials and Methods

Data were collected on a MAGNETOM Prisma 3.0T scanner (Siemens Healthcare, Erlangen, Germany) with a 64-channel head coil. Twenty-two cirrhotic patients with MHE, 31 cirrhotic patients without MHE (NHE), and 43 healthy controls underwent high-resolution T1-weighted imaging, resting-state functional magnetic resonance imaging, and cognition assessment based on Psychometric Hepatic Encephalopathy Score (PHES). The structural images were preprocessed using a voxel-based morphometry method, during which hippocampal volume was measured. The hippocampal connectivity network was identified using seed-based correlation analysis. Hippocampal volume and FC strength were compared across the three groups and correlated against the PHES results of the cirrhotic patients.

Results

Compared to the controls, MHE patients exhibited a significantly lower bilateral hippocampal volume. A slight decrease in hippocampal volume was obtained from NHE to MHE, but it did not reach statistically significance. In addition, the average FC strength of the bilateral hippocampal connectivity network was significantly lower in the MHE patients. In particular, the MHE patients showed a decrease in FC involving the left hippocampus to bilateral posterior cingulate gyrus and left angular gyrus. The MHE patients also showed FC reduction between the right hippocampus and bilateral medial frontal cortex. A progressive reduction in hippocampal FC from NHE to MHE was also observed. The bilateral hippocampal FC strength (but not hippocampal volume) was positively correlated with the PHES results of the cirrhotic patients.

Conclusion

Our assessment of MHE patients revealed decreased hippocampal volume, which suggests regional atrophy, and reduced hippocampal connectivity with regions that are primarily involved in the default-mode network, thereby suggesting a functional disconnection syndrome. These alterations reveal the mechanisms underlying cognitive deterioration with disease progression.

Acknowledgements

This study was funded by the grants from the National Natural Science Foundation of China (No.81501450), Fujian Provincial Science Fund for Distinguished Young Scholars (No. 2018J06023), Fujian Provincial Program for Distinguished Young Scholars (No.2017B023), and Fujian Provincial Health Commission Project for Scientific Research Talents (2018-ZQN-28).

References

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Figures

The hippocampal volume of the three study groups. MHE, minimal hepatic encephalopathy; NHE, patients without MHE; HCs, healthy controls. The markers * and †respectively indicate the significant difference (P<0.05) between MHE/NHE and HC.

The pattern of hippocampal functional connectivity among the three groups. MHE, minimal hepatic encephalopathy; NHE, patients without MHE; HCs, healthy controls.

The averaged functional connectivity strength (indicated by Z value) of global hippocampal connectivity network. One-way ANOVA and post hoc comparisons show a significantly lower mean Z value in MHE patients compared to the NHE patients and HCs. Moreover, a progressive decrease in hippocampal functional connectivity was observed from NHE to MHE. MHE, minimal hepatic encephalopathy; NHE, patients without MHE; HCs, healthy controls; FC, functional connectivity. The markers * and †indicate significant differences (P<0.05) in FC strength between the MHE/NHE and HC groups.

Group differences in the left hippocampal functional connectivity (FC). ANOVA analysis shows significant differences in FC of the left hippocampus (LHP) to bilateral posterior cingulate gyrus (PCC) and left angular gyrus (LAG) among the three study groups. The bar graphs present the findings of post hoc comparisons between every two groups. A reduction in the left hippocampal FC was noted during progression from NHE to MHE. The markers *, †, and # respectively represent significant differences in FC strength between MHE vs. HC, NHE vs. HC, as well as MHE vs. NHE.

Group differences in the right hippocampal functional connectivity (FC). ANOVA analysis shows significant differences in FC of the right hippocampus (RHP) to bilateral medial frontal cortex (MFC) among the three study groups. The bar graphs present the findings of post hoc comparisons between every two groups. A reduction in the right hippocampal FC was noted during progression from NHE to MHE. The markers *, †, and # respectively represent the significant difference in FC strength in MHE vs. HC, NHE vs. HC, and MHE vs. NHE.

Scatterplots of the extracted Z values (that represent the hippocampal connectivity strength) and neurocognitive performances (PHES result) of the cirrhotic patients. LHP, left hippocampus; LAG, left angular gyrus; RHP, right hippocampus; RMFC, right medial frontal cortex; PHES, psychometric hepatic encephalopathy score; FC, functional connectivity.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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