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Freezing of gait depends on cortico-subthalamic network recruitment following STN-DBS in PD patients

  • Gizem Temiz
    Affiliations
    Inserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Institut Du Cerveau et de la Moelle Epinière, F-75013, Paris, France
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  • Marie des Neiges Santin
    Affiliations
    Inserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Institut Du Cerveau et de la Moelle Epinière, F-75013, Paris, France
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  • Claire Olivier
    Affiliations
    Inserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Institut Du Cerveau et de la Moelle Epinière, F-75013, Paris, France

    PANAM core Facility, Paris Brain Institute, Paris, France
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  • Antoine Collomb-Clerc
    Affiliations
    Inserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Institut Du Cerveau et de la Moelle Epinière, F-75013, Paris, France
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  • Sara Fernandez-Vidal
    Affiliations
    Inserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Institut Du Cerveau et de la Moelle Epinière, F-75013, Paris, France
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  • Elodie Hainque
    Affiliations
    Inserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Institut Du Cerveau et de la Moelle Epinière, F-75013, Paris, France
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  • Eric Bardinet
    Affiliations
    Inserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Institut Du Cerveau et de la Moelle Epinière, F-75013, Paris, France
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  • Brian Lau
    Affiliations
    Inserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Institut Du Cerveau et de la Moelle Epinière, F-75013, Paris, France
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  • Chantal François
    Affiliations
    Inserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Institut Du Cerveau et de la Moelle Epinière, F-75013, Paris, France
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  • Author Footnotes
    1 These authors contributed equally.
    Carine Karachi
    Footnotes
    1 These authors contributed equally.
    Affiliations
    Inserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Institut Du Cerveau et de la Moelle Epinière, F-75013, Paris, France

    Neurosurgery Department, AP-HP, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, F-75013, Paris, France
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  • Author Footnotes
    1 These authors contributed equally.
    Marie-Laure Welter
    Correspondence
    Corresponding author. Neurophysiology Department, CHU Rouen, 1 rue de Germont, 76031, Cedex, Rouen, France.
    Footnotes
    1 These authors contributed equally.
    Affiliations
    Inserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Institut Du Cerveau et de la Moelle Epinière, F-75013, Paris, France

    PANAM core Facility, Paris Brain Institute, Paris, France

    Neurophysiology Department, Rouen University Hospital, CHU Rouen, F-76000, Rouen, France
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally.

      Highlights

      • FOG severity partially and variably improved after STN-DBS.
      • More severe FOG correlated with higher right prefrontal VAT connectivity.
      • Less severe FOG correlated with higher right sensorimotor VAT connectivity.

      Abstract

      Introduction

      Subthalamic deep-brain-stimulation (STN-DBS) is an effective means to treat Parkinson's disease (PD) symptoms. Its benefit on gait disorders is variable, with freezing of gait (FOG) worsening in about 30% of cases. Here, we investigate the clinical and anatomical features that could explain post-operative FOG.

      Methods

      Gait and balance disorders were assessed in 19 patients, before and after STN-DBS using clinical scales and gait recordings. The location of active stimulation contacts were evaluated individually and the volumes of activated tissue (VAT) modelled for each hemisphere. We used a whole brain tractography template constructed from another PD cohort to assess the connectivity of each VAT within the 39 Brodmann cortical areas (BA) to search for correlations between postoperative PD disability and cortico-subthalamic connectivity.

      Results

      STN-DBS induced a 100% improvement to a 166% worsening in gait disorders, with a mean FOG decrease of 36%. We found two large cortical clusters for VAT connectivity: one “prefrontal”, mainly connected with BA 8,9,10,11 and 32, and one “sensorimotor”, mainly connected with BA 1-2-3,4 and 6. After surgery, FOG severity positively correlated with the right prefrontal VAT connectivity, and negatively with the right sensorimotor VAT connectivity. The right prefrontal VAT connectivity also tended to be positively correlated with the UPDRS-III score, and negatively with step length. The MDRS score positively correlated with the right sensorimotor VAT connectivity.

      Conclusion

      Recruiting right sensorimotor and avoiding right prefrontal cortico-subthalamic fibres with STN-DBS could explain reduced post-operative FOG, since gait is a complex locomotor program that necessitates accurate cognitive control.

      Keywords

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