The functional brain connectome in isolated rapid eye movement sleep behavior disorder and Parkinson’s disease

Sleep Medicine, vol. 117, pp. 184–191

Abstract

BACKGROUND: Isolated rapid-eye-movement behavior disorder (iRBD) often precedes the development of alpha-synucleinopathies such as Parkinson's disease (PD). Magnetic resonance imaging (MRI) studies have revealed structural brain alterations in iRBD partially resembling those observed in PD. However, relatively little is known about whole-brain functional brain alterations in iRBD. Here, we characterize the functional brain connectome of iRBD compared with PD patients and healthy controls (HC) using resting-state functional MRI (rs-fMRI). METHODS: Eighteen iRBD subjects (67.3 ± 6.6 years), 18 subjects with PD (65.4 ± 5.8 years), and 39 age- and sex-matched HC (64.4 ± 9.2 years) underwent rs-fMRI at 3 T. We applied a graph theoretical approach to analyze the brain functional connectome at the global and regional levels. Data were analyzed using both frequentist and Bayesian statistics. RESULTS: Global connectivity was largely preserved in iRBD and PD individuals. In contrast, both disease groups displayed altered local connectivity mainly in the motor network, temporal cortical regions including the limbic system, and the visual system. There were some group specific alterations, and connectivity changes were pronounced in PD individuals. Overall, however, there was a good agreement of the connectome changes observed in both disease groups. CONCLUSIONS: This study provides evidence for widespread functional brain connectivity alterations in iRBD, including motor circuitry, despite normal motor function. Connectome alterations showed substantial resemblance with those observed in PD, underlining a close pathophysiological relationship of iRBD and PD.

Authors 12

1. Florian Holtbernd Aachen Department of Neurology JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11)

   RWTH Aachen University · Forschungszentrum Jülich · Jülich Aachen Research Alliance

   Affiliation as printed

   RWTH Aachen University, Department of Neurology, Aachen, Germany; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Center GmbH and RWTH Aachen University, Aachen, Germany; Institute of Neuroscience and Medicine (INM-4/INM-11), Juelich Research Center, Juelich, Germany

   Institute of Neuroscience and Medicine (INM-4/INM-11), Juelich Research Center, Juelich, Germany

   JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Center GmbH and RWTH Aachen University, Aachen, Germany

   RWTH Aachen University, Department of Neurology, Aachen, Germany

2. Christian Hohenfeld Aachen Department of Neurology JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11)

   RWTH Aachen University · Jülich Aachen Research Alliance

   Affiliation as printed

   RWTH Aachen University, Department of Neurology, Aachen, Germany; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Center GmbH and RWTH Aachen University, Aachen, Germany

   JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Center GmbH and RWTH Aachen University, Aachen, Germany

   RWTH Aachen University, Department of Neurology, Aachen, Germany

3. Wolfgang Hermann Oertel

   Philipps University of Marburg

   Affiliation as printed

   Department of Neurology, Philipps-University Marburg, Marburg, Germany

4. Susanne Knake

   Philipps University of Marburg · Universitätsklinikum Gießen und Marburg

   Affiliation as printed

   Department of Neurology, Philipps-University Marburg, Marburg, Germany; CMBB, Center for Mind, Brain and Behavior, University Hospital Marburg, Marburg, Germany

   CMBB, Center for Mind, Brain and Behavior, University Hospital Marburg, Marburg, Germany

   Department of Neurology, Philipps-University Marburg, Marburg, Germany

5. Elisabeth Sittig

   Philipps University of Marburg

   Affiliation as printed

   Department of Neurology, Philipps-University Marburg, Marburg, Germany

6. Sandro Romanzetti Aachen Department of Neurology JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11)

   RWTH Aachen University · Jülich Aachen Research Alliance

   Affiliation as printed

   RWTH Aachen University, Department of Neurology, Aachen, Germany; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Center GmbH and RWTH Aachen University, Aachen, Germany

   JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Center GmbH and RWTH Aachen University, Aachen, Germany

   RWTH Aachen University, Department of Neurology, Aachen, Germany

7. Anna Heidbreder

   Innsbruck Medical University · University of Münster · University Hospital Münster · Universität Innsbruck

   Affiliation as printed

   Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Muenster, Germany; Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria

   Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Muenster, Germany

   Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria

8. Imis Dogan Aachen Department of Neurology JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11)

   RWTH Aachen University · Jülich Aachen Research Alliance

   Affiliation as printed

   RWTH Aachen University, Department of Neurology, Aachen, Germany; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Center GmbH and RWTH Aachen University, Aachen, Germany

   JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Center GmbH and RWTH Aachen University, Aachen, Germany

   RWTH Aachen University, Department of Neurology, Aachen, Germany

9. Jörg Bernhard Schulz Aachen Department of Neurology JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11)

   RWTH Aachen University · Jülich Aachen Research Alliance

   Affiliation as printed

   RWTH Aachen University, Department of Neurology, Aachen, Germany; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Center GmbH and RWTH Aachen University, Aachen, Germany

   JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Center GmbH and RWTH Aachen University, Aachen, Germany

   RWTH Aachen University, Department of Neurology, Aachen, Germany

10. Johannes Schiefer Aachen Department of Neurology

    RWTH Aachen University

    Affiliation as printed

    RWTH Aachen University, Department of Neurology, Aachen, Germany

11. Annette Janzen

    Philipps University of Marburg

    Affiliation as printed

    Department of Neurology, Philipps-University Marburg, Marburg, Germany

12. Kathrin Reetz corresponding Aachen Department of Neurology JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11)

    RWTH Aachen University · Jülich Aachen Research Alliance

    Affiliation as printed

    RWTH Aachen University, Department of Neurology, Aachen, Germany; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Center GmbH and RWTH Aachen University, Aachen, Germany. Electronic address: kreetz@ukaachen.de

    JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Center GmbH and RWTH Aachen University, Aachen, Germany

    RWTH Aachen University, Department of Neurology, Aachen, Germany