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Abnormal Cerebellar Connectivity Patterns in Patients with Parkinson’s Disease and Freezing of Gait

  • Komal Bharti
  • Antonio Suppa
  • Sara Pietracupa
  • Neeraj Upadhyay
  • Costanza Giannì
  • Giorgio Leodori
  • Francesca Di Biasio
  • Nicola Modugno
  • Nikolaos Petsas
  • Giovanni Grillea
  • Alessandro Zampogna
  • Alfredo Berardelli
  • Patrizia Pantano
Original Paper
  • 104 Downloads

Abstract

In this study, we aimed to evaluate the importance of cerebellum in freezing of gait (FOG) pathophysiology. Due to the fundamental role of the cerebellum in posture and gait control, we examined cerebellar structural and functional connectivity (FC) in patients with PD and FOG. We recruited 15 PD with FOG (PD-FOG), 16 PD without FOG (PD-nFOG) patients, and 16 healthy subjects (HS). The FOG Questionnaire (FOG-Q) assessed FOG severity. Three tesla-MRI study included resting-state functional MRI, diffusion tensor imaging (DTI), and 3D T1-w images. We located seed regions in the cerebellar locomotor region, fastigial, and dentate nucleus to evaluate their FC. DTI parameters were obtained on the superior, middle, and inferior cerebellar peduncles. Global and lobular cerebellum volumes were also calculated. Cerebellar locomotor and fastigial FC was higher in cerebellar and posterior cortical areas in PD-FOG than in HS. FC of the cerebellar locomotor region with cerebellar areas positively correlated with FOG-Q. Dentate FC was lower in the prefrontal and parieto-occipital cortices in PD-FOG than in HS and in the brainstem, right basal ganglia, and frontal and parieto-occipital cortices than in PD-nFOG. DTI parameters in superior and middle cerebellar peduncles were altered in PD-FOG compared with PD-nFOG and significantly correlated with FOG-Q. There were no differences in cerebellar volumes between PD-FOG and either PD-nFOG or HS. Our results suggest that altered connectivity of the cerebellum contributes to the pathophysiology of FOG. FC of the cerebellar locomotor region and white matter (WM) properties of cerebellar peduncles correlate with FOG severity, supporting the hypothesis that abnormal cerebellar function underlies FOG in PD.

Keywords

Resting-state functional magnetic resonance imaging Functional connectivity Parkinson’s disease Freezing of gait Cerebellar locomotor region Fastigial nucleus Dentate nucleus 

Notes

Author Contribution

KB, AS, SP, NU, CG, GL, FDB, NM, NP, GG, and AZ: patient recruitment, patient data collection, patient clinical and neuroradiological evaluation, data analysis, and manuscript preparation.

AB, PP: patient recruitment, patient data collection, patient clinical and neuroradiological evaluation, data analysis, manuscript preparation, critical revision of the manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethics Approval

The study approved by our institutional review board and conformed with the declaration of Helsinki. All participants gave their written informed consent.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Komal Bharti
    • 1
  • Antonio Suppa
    • 1
    • 2
  • Sara Pietracupa
    • 2
  • Neeraj Upadhyay
    • 1
  • Costanza Giannì
    • 1
  • Giorgio Leodori
    • 2
  • Francesca Di Biasio
    • 3
  • Nicola Modugno
    • 2
  • Nikolaos Petsas
    • 2
  • Giovanni Grillea
    • 2
  • Alessandro Zampogna
    • 1
  • Alfredo Berardelli
    • 1
    • 2
  • Patrizia Pantano
    • 1
    • 2
  1. 1.Department of Human NeurosciencesSapienza University of RomeRomeItaly
  2. 2.IRCCS NeuromedPozzilliItaly
  3. 3.Unit of NeurologySan Martino Policlinic Hospital ISTGenoaItaly

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