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Brain network topology and future development of freezing of gait in Parkinson’s disease: a longitudinal study

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Abstract

Background

Freezing of gait (FOG) is a common disabling gait disturbance in Parkinson’s disease (PD). The objectives of this study were to explore alterations in the topological organization of whole-brain functional networks in patients with PD who will develop FOG.

Methods

We recruited 20 patients with PD who developed FOG (PD-FOGt) during a 5-year follow-up period, 20 patients with PD who did not developed FOG (PD-FOGn) within the follow-up period, and 20 healthy control subjects. Using graph theory approaches, we performed a comparative analysis of the topological organization of whole-brain functional networks among the groups, and further explored their potential relationships with latency to develop FOG.

Results

At baseline, the global topological properties of functional brain networks in PD-FOGt and PD-FOGn showed no abnormalities. Additionally, regarding regional topological properties, compared with PD-FOGn patients, PD-FOGt patients exhibited decreased nodal centrality in the left middle frontal gyrus (MFG). Although there were no significant differences compared with PD-FOGn patients, the PD-FOGt group exhibited the lowest nodal centrality values in the frontal cortex (left gyrus rectus), and visual cortex (bilateral inferior occipital gyrus and left fusiform gyrus), and the highest nodal centrality values in the cerebellum (vermis_6) among the three groups. However, no relationship was found between the nodal centrality in above brain regions and latency to develop FOG.

Conclusion

This study demonstrates the disrupted regional topological organization might contribute to the future development of FOG in PD patients, especially associated with damage to the left MFG.

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Availability of data

Data are available from the corresponding author, upon reasonable request.

Code availability

Not applicable.

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Acknowledgements

The authors would like to thank the patients for their generous participations.

Funding

This work was supported by the National Natural Science Foundation of China (81801272), Sichuan Science and Technology Program (2018HH0077), Fundamental Research Funds for the Central Universities (2018SCU12029), and Post-Doctor Research Project, West China Hospital, Sichuan University (2018HXBH085).

Author information

Authors and Affiliations

  1. Department of Neurology, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, Sichuan, China

    Nannan Li, Jiaxin Peng, Junying Li, Liren Duan, Chaolan Chen & Rong Peng

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

    Du Lei, Xueling Suo & Qiyong Gong

  3. Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA

    Du Lei

Authors
  1. Nannan Li
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  2. Du Lei
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  3. Jiaxin Peng
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  9. Rong Peng
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Contributions

NNL was responsible for the study concept, statistical analysis, and drafting and revision of the manuscript. DL was responsible for the study concept and revision of the manuscript. JXP, XLS, JYL, LRD, and CLC contributed to patient recruitment and data collection. QYG was responsible for the supervision of the study. RP was responsible for the study concept, supervision, and revision of the manuscript. All authors approved the final version of the manuscript for submission.

Corresponding author

Correspondence to Rong Peng.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the Ethics Committee of Sichuan University. Written informed consent was obtained from all participants before enrollment and the study was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Supplementary Information

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415_2021_10817_MOESM1_ESM.tif

Fig. S1 Graphs show that over the defined threshold range, the functional brain networks in the total PD, PD-FOGt, PD-FOGn, and HC groups exhibited a value of γ that was substantially larger than 1 and λ approximately equal to 1, indicating that all groups exhibited typical small-world features. PD Parkinson’s disease, FOG freezing of gait, PD-FOGt group for FOG-transitional PD, PD-FOGn group for FOG-nontransitional PD, HC healthy controls, γ normalized clustering coefficient, λ normalized characteristic path length

415_2021_10817_MOESM2_ESM.tif

Fig. S2 Comparison of the global topological properties of functional brain networks between the total PD and HC groups and among the three groups. PD Parkinson’s disease, FOG freezing of gait, PD-FOGt group for FOG-transitional PD, PD-FOGn group for FOG-nontransitional PD, HC healthy controls, Cp clustering coefficient, Lp characteristic path length, γ normalized clustering coefficient, λ normalized characteristic path length, σ small-worldness, Eglob global efficiency, Eloc local efficiency

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Li, N., Lei, D., Peng, J. et al. Brain network topology and future development of freezing of gait in Parkinson’s disease: a longitudinal study. J Neurol 269, 2503–2512 (2022). https://doi.org/10.1007/s00415-021-10817-x

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