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Cerebellar functional abnormalities in early stage drug-naïve and medicated Parkinson’s disease

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Abstract

Parkinson’s disease (PD) is a progressive neurological degenerative disorder characterized by impaired motor function and non-motor dysfunctions. While recent studies have highlighted the role of the cerebellum in PD, our understanding of its role in PD remains limited. In the present study, we used resting-state fMRI to evaluate dysfunctions within the cerebellum in PD patients treated with medication and drug-naïve PD patients. We applied amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) analysis methods. Thirty-one patients with early stage PD (22 drug-naïve and 9 medicated patients) and 31 gender- and age-matched healthy controls were recruited in this study. ALFFs increased in the left cerebellar areas (lobules VI/VIIb/CruI/CruII and the dentate gyrus) and right cerebellar areas (lobules VI/VIIb/VIIIa/CruI/CruII and the dentate gyrus) of all PD patients and in the left and right cerebellar areas (lobules VI/VIIb/CruI and the dentate gyrus) of drug-naive PD patients but were not significantly changed in medicated PD patients. DC increased in the right cerebellar areas of all PD patients and medicated PD patients. All PD patients and all drug-naive PD patients showed significantly weaker functional connectivity (FC) between the left cerebellum and the left medial frontal gyrus. However, FC was significantly stronger between the right cerebellum and the left precentral and right middle occipital gyri in the medicated PD patients than in controls. Furthermore, a correlation analyses revealed that ALFF z scores in the left cerebellum (lobule VI) and right cerebellum (lobule VI/CruI and dentate gyrus) were negatively correlated with Mini-Mental State Examination (MMSE) scores in all PD patients and drug-naive patients. These results indicate that the cerebellum plays an important role in PD, mainly by exerting a compensatory effect in early stage PD. Additionally, antiparkinsonian medication would modified PD-induced changes in local neural activity and FC in PD patients. The results of this study offer novel insights into the roles of the cerebellum in early stage drug-naïve PD.

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Acknowledgements

This research was supported by Grants from the National Natural Science Foundation of China (nos. 81571658 to X. X. Du and 81271302 to J. R. Liu), Shanghai Pujiang Program (18PJD023 to W. Chen), a research innovation project from Shanghai Municipal Science and Technology Commission (no. 14JC1404300 to J. R. Liu), the “Prevention and Control of Chronic Diseases Project” of Shanghai Hospital Development Center (no. SHDC12015310 to J. R. Liu), a project from the SHSMU-ION Research Center for Brain Disorders (no. 2015NKX006 to J. R. Liu), a project from the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (no. 20161422 to J. R. Liu), the Clinical Research Project from Shanghai Jiao Tong University School of Medicine (no. DLY201614 to J. R. Liu), and the Biomedicine Key Program from Shanghai Municipal Science and Technology Commission (no. 16411953100 to J. R. Liu). We thank the patients and their families who participated in the study for their support.

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  1. Shuai Xu and **n-Wei He are equal contributors.

Authors and Affiliations

  1. Shanghai Key Laboratory of Magnetic Resonance and Department of Physics, School of Physics and Materials Science, East China Normal University, 3663 North Zhong-Shan Road, Shanghai, 200062, People’s Republic of China

    Shuai Xu, Zhaoxia Qin, Jilei Zhang, Shiyu Ban, Jianqi Li & **aoxia Du

  2. Department of Neurology and Jiuyuan Municipal Stroke Center, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People’s Republic of China

    **n-Wei He, Rong Zhao, Wei Chen, Ge-Fei Li, Yan-Hui Shi, Yue Hu, Mei-Ting Zhuang, Yi-Sheng Liu, **ao-Lei Shen & Jian-Ren Liu

  3. Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China

    **n-Wei He, Rong Zhao, Ge-Fei Li, Yan-Hui Shi, Yue Hu & Jian-Ren Liu

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  1. Shuai Xu
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Correspondence to Jian-Ren Liu or **aoxia Du.

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This study was carried out in accordance with the recommendations of the East China of Normal University Ethics Committee and the Independent Ethics Committee of Shanghai Ninth People’s Hospital. The study was approved by the East China of Normal University Ethics Committee (HR062-2018) and the Independent Ethics Committee of Shanghai Ninth People’s Hospital (2016-44-T1). All subjects provided signed written informed consent documents approved by the East China of Normal University Ethics Committee and the Independent Ethics Committee of Shanghai Ninth People’s Hospital.

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Xu, S., He, XW., Zhao, R. et al. Cerebellar functional abnormalities in early stage drug-naïve and medicated Parkinson’s disease. J Neurol 266, 1578–1587 (2019). https://doi.org/10.1007/s00415-019-09294-0

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