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Parkinson's disease patients show reduced cortical-subcortical sensorimotor connectivity

Authors

  • Michael Sharman PhD,

    Corresponding author
    1. CENIR, ICM, Hôpital Pitié-Salpêtrière, Paris, France
    • UMR-S975, CRICM-INSERM-UPMC Paris 6, Paris, Île-de-France, France
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  • Romain Valabregue PhD,

    1. UMR-S975, CRICM-INSERM-UPMC Paris 6, Paris, Île-de-France, France
    2. CENIR, ICM, Hôpital Pitié-Salpêtrière, Paris, France
    3. UMR 7225, CNRS, Paris, France
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  • Vincent Perlbarg PhD,

    1. UMR-S678, INSERM-UPMC Paris 6, LIF, Paris, France
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  • Linda Marrakchi-Kacem PhD,

    1. Neurospin, CEA, Gif-Sur-Yvette, France
    2. IFR49, UPMC Paris 6, Paris, France
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  • Marie Vidailhet MD, PhD,

    1. UMR-S975, CRICM-INSERM-UPMC Paris 6, Paris, Île-de-France, France
    2. UMR 7225, CNRS, Paris, France
    3. IFR49, UPMC Paris 6, Paris, France
    4. ICM—Institut du Cerveau et de la Moelle epiniere, Hôpital Pitié-Salpêtrière, Paris, France
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  • Habib Benali PhD,

    1. UMR-S678, INSERM-UPMC Paris 6, LIF, Paris, France
    2. IFR49, UPMC Paris 6, Paris, France
    3. Unité de Neuroimagerie Fonctionnelle, CRIUGM, Université de Montréal, Montréal, Quebec, Canada
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  • Alexis Brice MD,

    1. UMR-S975, CRICM-INSERM-UPMC Paris 6, Paris, Île-de-France, France
    2. UMR 7225, CNRS, Paris, France
    3. ICM—Institut du Cerveau et de la Moelle epiniere, Hôpital Pitié-Salpêtrière, Paris, France
    4. Département de Génétique et Cytogénétique, Hôpital Pitié-Salpêtrière, Paris, France
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  • Stephane Lehéricy MD, PhD

    1. UMR-S975, CRICM-INSERM-UPMC Paris 6, Paris, Île-de-France, France
    2. CENIR, ICM, Hôpital Pitié-Salpêtrière, Paris, France
    3. UMR 7225, CNRS, Paris, France
    4. IFR49, UPMC Paris 6, Paris, France
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  • Funding agencies: This study was supported by European Union (EU) Framework Project 6–GENEPARK: Genomic Biomarkers for Parkinson's Disease, Action Line: LIFESCIHEALTH Life sciences, genomics and biotechnology for health, and LSH-2005-1.2.2.2—Development of innovative methods for diagnosis of nervous system disorders.

  • Relevant conflicts of interest/financial disclosures: Alexis Brice received honoraria from the Wolfson Foundation for reviewing the scientific project, as well as research support from the French Agency for Research and the European Union.

  • Full financial disclosures and author roles may be found in the online version of this article.

Correspondence to: Dr. Michael Sharman, CENIR, ICM, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France; michael.sharman@etu.upmc.fr

Abstract

Reduced dopamine input to cortical and subcortical brain structures, particularly those in the sensorimotor network, is a hallmark of Parkinson's disease (PD). The extent to which dopamine dysfunction affects connectivity within this and other brain networks remains to be investigated. The purpose of this study was to measure anatomical and functional connectivity in groups of PD patients and controls to determine whether connectivity deficits within the cortico–basal ganglia thalamocortical system could be attributed to PD, particularly in sensorimotor connections. A neuroimaging paradigm involving diffusion-weighted magnetic resonance imaging (MRI) and resting-state functional MRI was implemented in a large cohort of PD patients and control subjects. Probabilistic tractography and functional correlation analyses were performed to map connections between brain structures and to derive indices of connectivity that were then used to compare groups. Anatomical connectivity deficits were demonstrated in PD patients, specifically for sensorimotor connections. Functional deficits were also found in some of the same connections. In addition, functional connectivity was found to increase in associative and limbic connections in PD patients compared with controls. This study lends support to findings regarding the dysfunction of the sensorimotor circuit in PD. As deficits in anatomical and functional connectivity within this circuit were in some cases concordant in PD patients, a possible link between brain structure and function is suggested. Increases in functional connectivity in other cortico–basal ganglia thalamocortical circuits may be indicative of compensatory effects in response to system deficits elsewhere. © 2012 Movement Disorder Society

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