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Brain activity during lower limb movements in Parkinson’s disease patients with and without freezing of gait

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Abstract

In this study, we assessed brain functional MRI (fMRI) activity during a foot movement task in Parkinson’s disease patients with (PD-FoG) and without freezing of gait (PD-noFoG). Twenty-seven PD patients (17 PD-FoG) and 18 healthy controls (HC) were recruited. PD-FoG cases were divided into nine with mild and eight with moderate FoG according to the FoG questionnaire. Patients underwent motor and neuropsychological evaluations. Both patients and controls performed an fMRI task consisting of alternate dorsal/plantar foot flexion movements according to an auditory stimulus of 0.5 Hz. PD-FoG and PD-noFoG patients were similar for all motor variables (except for the presence of FoG). PD-FoG patients performed worse in executive, attention and working memory, visuospatial, language and memory cognitive tests relative to HC and in executive and language functions compared with PD-noFoG patients. While PD-noFoG patients showed an increased recruitment of the fronto-striatal circuit relative to HC during the fMRI task, PD-FoG subjects showed an increased activity of the parieto-occipital and cerebellar areas compared with HC and a reduced basal ganglia activity when compared with PD-noFoG patients. Within the PD-FoG group, patients with more severe FoG scores showed a decreased recruitment of fronto-parietal areas relative to less severe cases. fMRI modifications correlated with FoG severity and with executive-attentive and visuospatial deficits in PD-FoG patients. This study revealed the presence of two different patterns of brain activity during a foot movement task in PD-FoG and PD-noFoG patients, suggesting a possible compensatory role of parieto-occipital networks to overcome the fronto-striatal failure in PD-FoG cases.

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Acknowledgements

The authors thank the patients and their families for the time and effort they dedicated to the research.

Funding

This study was partially supported by the Jacques and Gloria Gossweiler Foundation. The funding source had no role in the conduct of the research and/or preparation of the article.

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Authors and Affiliations

  1. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy

    Noemi Piramide, Federica Agosta, Elisabetta Sarasso, Elisa Canu & Massimo Filippi

  2. Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Maria Antonietta Volontè & Massimo Filippi

  3. Vita-Salute San Raffaele University, Milan, Italy

    Federica Agosta & Massimo Filippi

  4. Laboratory of Movement Analysis, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Elisabetta Sarasso

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  1. Noemi Piramide
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  2. Federica Agosta
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Contributions

NP and FA helped in study concept/design, analysis/interpretation of data and drafting the manuscript for content. ES, EC and MAV contributed to acquisition of data, analysis/interpretation of data and revising the manuscript for content. MF helped in study concept/design, interpretation of data, revising the manuscript for content, study supervision and coordination and obtaining funding.

Corresponding author

Correspondence to Massimo Filippi.

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Conflicts of interest

N. Piramide, E. Sarasso and M.A. Volontè report no disclosures. F. Agosta is Section Editor of NeuroImage: Clinical; has received speaker honoraria from Biogen Idec, Novartis and Philips and receives research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), and the European Research Council. M. Filippi is Editor-in-Chief of the Journal of Neurology, received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Ethical standards

This study was approved by the Local Ethical Committees on human studies and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All subjects’ parents provided written informed consent prior to study participation.

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Piramide, N., Agosta, F., Sarasso, E. et al. Brain activity during lower limb movements in Parkinson’s disease patients with and without freezing of gait. J Neurol 267, 1116–1126 (2020). https://doi.org/10.1007/s00415-019-09687-1

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  • DOI: https://doi.org/10.1007/s00415-019-09687-1

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