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Alterations in white matter network topology contribute to freezing of gait in Parkinson’s disease

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Abstract

Freezing of gait (FOG) is a common symptom in advanced Parkinson’s disease (PD). Despite current advances, the neural mechanisms underpinning this disturbance remain poorly understood. To this end, we investigated the structural organisation of the white matter connectome in PD freezers and PD non-freezers. We hypothesized that freezers would show an altered network architecture, which could hinder the effective information processing that characterizes the disorder. Twenty-six freezers and twenty-four well-matched non-freezers were included in this study. Using diffusion tensor imaging, we investigated the modularity and integration of the regional connectome by calculating the module degree z score and the participation coefficient, respectively. Compared to non-freezers, freezers demonstrated lower participation coefficients in the right caudate, thalamus, and hippocampus, as well as within superior frontal and parietal cortical regions. Importantly, several of these nodes were found within the brain’s ‘rich club’. Furthermore, group differences in module degree z scores within cortical frontal and sensory processing areas were found. Together, our results suggest that changes in the structural network topology contribute to the manifestation of FOG in PD, specifically due to a lack of structural integration between key information processing hubs of the brain.

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Acknowledgements

We thank the patients and their families who contribute to our research at the Parkinson’s Disease Research Clinic. This research was supported by Sydney Informatics Hub, funded by the University of Sydney. JMH is supported by a Western Sydney University Postgraduate Research Award; JMS is supported by a National Health and Medical Research Council CJ Martin Fellowship (1072403); KAEM is supported by a Parkinson Canada Fellowship; MG is supported by a University of Sydney International Scholarship; SJGL is supported by National Health and Medical Research Council-Australian Research Council Dementia Fellowship (#1110414) and this work was supported by funding to Forefront, a collaborative research group dedicated to the study of non-Alzheimer disease degenerative dementias, from the National Health and Medical Research Council of Australia program grant (#1037746 and #1095127). KMB, JYYS, CCW, and AAM have no funding source to disclose.

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Authors and Affiliations

  1. School of Social Sciences and Psychology, Western Sydney University, Milperra, NSW, 2214, Australia

    Julie M. Hall & Ahmed A. Moustafa

  2. Brain and Mind Centre, University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia

    Julie M. Hall, James M. Shine, Kaylena A. Ehgoetz Martens, Moran Gilat, Kathryn M. Broadhouse, Jennifer Y. Y. Szeto, Courtney C. Walton & Simon J. G. Lewis

  3. MARCS Institute, Western Sydney University, Milperra, NSW, 2214, Australia

    Ahmed A. Moustafa

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  1. Julie M. Hall
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Hall, J.M., Shine, J.M., Ehgoetz Martens, K.A. et al. Alterations in white matter network topology contribute to freezing of gait in Parkinson’s disease. J Neurol 265, 1353–1364 (2018). https://doi.org/10.1007/s00415-018-8846-3

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