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Altered dynamic functional connectivity in the default mode network in patients with cirrhosis and minimal hepatic encephalopathy

  • Functional Neuroradiology
  • Published:
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Abstract

Purpose

Abnormal brain intrinsic functional connectivity (FC) has been documented in minimal hepatic encephalopathy (MHE) by static connectivity analysis. However, changes in dynamic FC (dFC) remain unknown. We aimed to identify altered dFC within the default mode network (DMN) associated with MHE.

Methods

Resting-state functional MRI data were acquired from 20 cirrhotic patients with MHE and 24 healthy controls. DMN seed regions were defined using seed-based FC analysis (centered on the posterior cingulate cortex (PCC)). Dynamic FC architecture was calculated using a sliding time-window method. K-means clustering (number of clusters = 2–4) was applied to estimate FC states.

Results

When the number of clusters was 2, MHE patients presented weaker connectivity strengths compared with controls in states 1 and 2. In state 1, decreased FC strength was found between the PCC/precuneus (PCUN) and right medial temporal lobe (MTL)/bilateral lateral temporal cortex (LTC); left inferior parietal lobule (IPL) and right MTL/left LTC; right IPL and right MTL/bilateral LTC; right MTL and right LTC; and medial prefrontal cortex (MPFC) and right MTL/bilateral LTC. In state 2, reduced FC strength was observed between the PCC/PCUN and bilateral MTL/bilateral LTC; left IPL and left MTL/bilateral LTC/MPFC; and left LTC and right LTC. Altered connectivities from state 1 were correlated with patient cognitive performance. Similar findings were observed when the number of clusters was set to 3 or 4.

Conclusion

Aberrant dynamic DMN connectivity is an additional characteristic of MHE. Dynamic connectivity analysis offers a novel paradigm for understanding MHE-related mechanisms.

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Abbreviations

MHE:

minimal hepatic encephalopathy

HE:

hepatic encephalopathy

FC:

functional connectivity

DMN:

default mode network

dFC:

dynamic functional connectivity

HCs:

healthy controls

PHES:

psychometric hepatic encephalopathy score

MNI:

Montreal Neurological Institute

PCC:

posterior cingulate cortex

FWE:

family-wise error

ROI:

region of interest

PCC/PCUN:

posterior cingulate cortex/precuneus

MPFC:

medial prefrontal cortex

IPL:

inferior parietal lobule

MTL:

medial temporal lobe

LTC:

lateral temporal cortex

ICA:

independent component analysis

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Authors and Affiliations

  1. Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China

    Hua-Jun Chen & Hai-Long Lin

  2. School of Information Science and Engineering, Central South University, Changsha, 410083, China

    Qiu-Feng Chen & Peng-Fei Liu

Authors
  1. Hua-Jun Chen
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  2. Hai-Long Lin
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Corresponding author

Correspondence to Hua-Jun Chen.

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Funding

This work was funded by a grant from the National Natural Science Foundation of China (No. 81501450) and a project funded by the China Postdoctoral Science Foundation (No. 2015M580452).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in the studies involving human participants were in accordance with the ethical standards of the Medical Research Ethics Committee of Fujian Medical University Union Hospital and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Supplementary Figure 1

The common states (matrix) of functional connectivity within the DMN, which was extracted using the K-means clustering method (with the number of clusters = 3 and the window size = 40s) and the visualized network pattern of the common functional connectivity states at a threshold of 0.35. The line sizes indicate functional connectivity strength in the states. (GIF 1526 kb)

High resolution image (TIFF 4613 kb)

Supplementary Figure 2

The common states (matrix) of functional connectivity within the DMN, which was extracted using the K-means clustering method (with the number of clusters = 4 and the window size = 40s) and the visualized network pattern of the common functional connectivity states at a threshold of 0.35. The line sizes indicate functional connectivity strength in the states. (GIF 2078 kb)

High resolution image (TIFF 6114 kb)

Supplementary Figure 3

The two-sample t-tests results from comparing subject-specific states between the 2 groups (with the number of clusters = 3 and the window size = 40s) and the visualized aberrant connectivities for states 1, 2, and 3. The line sizes indicate significance of between-group differences in functional connectivity. A significant reduction of functional connectivity was found during states 1, 2, and 3, while no increased connectivity was observed in MHE patients. The “*” denotes significantly decreased connectivity (P < 0.05, uncorrected) in the patient group. (GIF 1520 kb)

High resolution image (TIFF 5168 kb)

Supplementary Figure 4

The two-sample t-tests results from comparing subject-specific states between the 2 groups (with the number of clusters = 4 and the window size = 40s) and the visualized aberrant connectivities for states 1, 2, 3, and 4. The line sizes indicate significance of between-group differences in functional connectivity. A significant reduction of functional connectivity was found during states 1, 2, 3, and 4, while no increased connectivity was observed in MHE patients. The “*” denotes significantly decreased connectivity (P < 0.05, uncorrected) in the patient group. (GIF 1998 kb)

High resolution image (TIFF 6560 kb)

Supplementary Figure 5

The common states of functional connectivity within the DMN, which were extracted using the K-means clustering method (with the number of clusters = 2 and the window size = 100 s) and the visualized network pattern of the common functional connectivity states at a threshold of 0.35. The line sizes indicate functional connectivity strength in the states. (GIF 365 kb)

High resolution image (TIFF 4322 kb)

Supplementary Figure 6

The two-sample t-tests results from comparing subject-specific states between the 2 groups (with the number of clusters = 2 and the window size = 100 s) and the visualized aberrant connectivities for states 1 and 2. The line sizes indicate significance of between-group differences in functional connectivity. A significant reduction of functional connectivity was found during states 1 and 2 (P < 0.05, uncorrected), while no increased connectivity was observed in MHE patients. (GIF 365 kb)

High resolution image (TIFF 4329 kb)

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Chen, HJ., Lin, HL., Chen, QF. et al. Altered dynamic functional connectivity in the default mode network in patients with cirrhosis and minimal hepatic encephalopathy. Neuroradiology 59, 905–914 (2017). https://doi.org/10.1007/s00234-017-1881-4

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  • DOI: https://doi.org/10.1007/s00234-017-1881-4

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