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Disrupted topological organization of resting-state functional brain networks in Parkinson’s disease patients with glucocerebrosidase gene mutations

  • Functional Neuroradiology
  • Published:
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Abstract

Purpose

The mutations of the glucocerebrosidase (GBA) gene are the greatest genetic risk factor for Parkinson’s disease (PD). The mechanism underlying the association between GBA mutations and PD has not been fully elucidated.

Methods

Using resting-state functional magnetic resonance imaging and graph theory analysis to investigate the disrupted topological organization in PD patients with GBA mutation (GBA-PD). Eleven GBA-PD patients, 11 noncarriers with PD, and 18 healthy controls (HCs) with a similar age and sex distribution were recruited. Individual whole-brain functional connectome was constructed, and the global and nodal topological disruptions were calculated among groups. Partial correlation analyses between the clinical features of patients with PD and topological alterations were performed.

Results

The GBA-PD group showed prominently decreased characteristic path length (Lp) and increased global efficiency (Eg) compared to HCs at the global level; a significantly increased nodal betweenness centrality in the medial prefrontal cortex (mPFC) and precuneus within the default mode network, and precentral gyrus within the sensorimotor network, while a significantly decreased betweenness centrality in nodes within the cingulo-opercular network compared to the noncarrier group at the regional level. The altered nodal betweenness centrality of mPFC was positively correlated with fatigue severity scale scores in all patients with PD.

Conclusion

The preliminary pilot study found that GBA-PD patients had a higher functional integration at the global level. The nodal result of the mPFC is congruent with the potential fatigue pathology in PD and is suggestive of a profound effect of GBA mutations on the clinical fatigue in patients with PD.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

The authors thank the patients and their families for their participation in the study.

Funding

The present study was supported by the National Key Research and Development Program of China (Grant No. 2021YFC2501203 to FHS); and the Sichuan Science and Technology Program (Grant No. 2022ZDZX0023 to FHS).

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Authors and Affiliations

  1. Department of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

    Yanbing Hou, Fei Feng, Lingyu Zhang, Ruwei Ou, Junyu Lin & Huifang Shang

  2. Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

    Qiyong Gong

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  1. Yanbing Hou
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Contributions

Yanbing Hou: conception and design of the study, statistical analysis, interpretation of data, and drafting of manuscript

Fei Feng: data collection and statistical analysis

Lingyu Zhang: data collection and statistical analysis

Ruwei Ou: data collection

Junyu Lin: data collection

Qiyong Gong: study design, analysis and interpretation, and revision of the manuscript

Huifang Shang: study design, analysis and interpretation, and revision of the manuscript

Corresponding authors

Correspondence to Qiyong Gong or Huifang Shang.

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The authors declare no competing interests.

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Approval was received from the West China Hospital of Sichuan University Clinical trials and Biomedical ethics committee.

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Written informed consent was obtained from all participants in the study.

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Hou, Y., Feng, F., Zhang, L. et al. Disrupted topological organization of resting-state functional brain networks in Parkinson’s disease patients with glucocerebrosidase gene mutations. Neuroradiology 65, 361–370 (2023). https://doi.org/10.1007/s00234-022-03067-9

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  • DOI: https://doi.org/10.1007/s00234-022-03067-9

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