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Associations between resting-state functional connectivity changes and prolonged benefits of writing training in Parkinson’s disease

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Abstract

Background

Our earlier work showed that automaticity and retention of writing skills improved with intensive writing training in Parkinson’s disease (PD). However, whether this training changed the resting-state networks in the brain and how these changes underlie retention of motor learning is currently unknown.

Objective

To examine changes in resting-state functional connectivity (rs-FC) and their relation to behavioral changes immediately after writing training and at 6 week follow-up.

Methods

Twenty-five PD patients underwent resting-state fMRI (ON medication) before and after 6 weeks writing training. Motor learning was evaluated with a dual task paradigm pre- and post-training and at follow-up. Next, pre-post within-network changes in rs-FC were identified by an independent component analysis. Significant clusters were used as seeds in ROI-to-ROI analyses and rs-FC changes were correlated with changes in behavioral performance over time.

Results

Similar to our larger cohort findings, writing accuracy in single and dual task conditions improved post-training and this was maintained at follow-up. Connectivity within the dorsal attentional network (DAN) increased pre-post training, particularly with the right superior and middle temporal gyrus (rS/MTG). This cluster also proved more strongly connected to parietal and frontal areas and to cerebellar regions. Behavioral improvements from pre- to post-training and follow-up correlated with increased rs-FC between rS/MTG and the cerebellum.

Conclusions

Training-driven improvements in dual task writing led to functional reorganization within the DAN and increased connectivity with cerebellar areas. These changes were associated with the retention of writing gains and could signify task-specific neural changes or an inability to segregate neural networks.

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Acknowledgements

We are grateful to all participants in this study. We thank Dr. Bruno Bergmans (AZ Sint-Jan, Bruges) for his help in recruitment of participants and Ir. Marc Beirinckx for development of the tablet and for providing technical support.

Funding

The Research Foundation Flanders (FWO) [grant number G.0906.11 and G0A5619N] and the King Baudouin Foundation (Fund Druwé-Eerdekens 2018) supported this work. EN is a postdoctoral fellow funded by the Research Foundation Flanders (FWO) [grant number 12F4719N]. JDV is a doctoral fellow funded by the Research Foundation Flanders (FWO) [grant number 11N5622N].

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Author notes

  1. J. De Vleeschhauwer and E. Nackaerts contributed equally for this work.

Authors and Affiliations

  1. Department of Rehabilitation Sciences, Research Group for Neurorehabilitation (eNRGy), KU Leuven, Tervuursevest 101, Box 1500, 3001, Leuven, Belgium

    Joni De Vleeschhauwer, Evelien Nackaerts, Nicholas D’Cruz, Britt Vandendoorent, Letizia Micca & Alice Nieuwboer

  2. Department of Neurology, University Hospitals Leuven, Herestraat 49, Leuven, Belgium

    Wim Vandenberghe

  3. Laboratory for Parkinson Research, Department of Neurosciences, KU Leuven, O&N IV, Herestraat 49, Box 602, Leuven, Belgium

    Wim Vandenberghe

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  1. Joni De Vleeschhauwer
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  2. Evelien Nackaerts
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  7. Alice Nieuwboer
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Contributions

All authors contributed to the final manuscript of this study. Conceptualization, methodology and data collection were completed by EN. Formal data analysis and investigation were performed by JDV and EN. EN wrote the first draft of the manuscript. Review and editing of the manuscript were carried out by all co-authors. AN was responsible for the overall supervision.

Corresponding author

Correspondence to Joni De Vleeschhauwer.

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The authors declare that they have no relevant financial or non-financial interests to disclose.

Ethics approval

The study was approved by the local Ethics Committee Research UZ /KU Leuven (S54132) in accordance with the Declaration of Helsinki (1967).

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A written informed consent was obtained from all individual participants included in the study, after detailed explanation of the protocol and before the start of the study.

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De Vleeschhauwer, J., Nackaerts, E., D’Cruz, N. et al. Associations between resting-state functional connectivity changes and prolonged benefits of writing training in Parkinson’s disease. J Neurol 269, 4696–4707 (2022). https://doi.org/10.1007/s00415-022-11098-8

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