title: The connectomics of brain demyelination: Functional and structural patterns in the cuprizone mouse model.
abstract: Connectomics of brain disorders seeks to reveal how altered brain function emerges from the architecture of cerebral networks; however the causal impact of targeted cellular damage on the whole brain functional and structural connectivity remains unknown. In the central nervous system, demyelination is typically the consequence of an insult targeted at the oligodendrocytes, the cells forming and maintaining the myelin. This triggered perturbation generates cascades of pathological events that most likely alter the brain connectome. Here we induced oligodendrocyte death and subsequent demyelinating pathology via cuprizone treatment in mice and combining mouse brain resting state functional Magnetic Resonance Imaging and diffusion tractography we established functional and structural pathology-to-network signatures. We demonstrated that demyelinated brain fundamentally reorganizes its intrinsic functional connectivity paralleled by widespread damage of the structural scaffolding. We evidenced default mode-like network as core target of demyelination-induced connectivity modulations and hippocampus as the area with strongest connectional perturbations.
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 60a, 79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, Schänzlestraße 1, 79104 Freiburg, Germany. Electronic address: neele.huebner@uniklinik-freiburg.de.
authors.forename: Neele S
authors.initials: NS
authors.lastname: Hübner
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 60a, 79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, Schänzlestraße 1, 79104 Freiburg, Germany.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Mechling
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 60a, 79106 Freiburg, Germany.
authors.forename: Hsu-Lei
authors.initials: HL
authors.lastname: Lee
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 60a, 79106 Freiburg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Reisert
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 60a, 79106 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bienert
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 60a, 79106 Freiburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hennig
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 60a, 79106 Freiburg, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: von Elverfeldt
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 60a, 79106 Freiburg, Germany; Laboratory of Engineering, Informatics and Imaging (ICube), Integrative Multimodal Imaging in Healthcare (IMIS), UMR 7357, University of Strasbourg, 4 Rue Kirschleger, 67000 Strasbourg, France; Department of Biophysics and Nuclear Medicine, Hautepierre Hospital, University Hospitals of Strasbourg, 1, Avenue Molière, 67098 Strasbourg Cedex, France. Electronic address: harsan@unistra.fr.
authors.forename: Laura-Adela
authors.initials: LA
authors.lastname: Harsan
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D063132:Connectome; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D005260:Female; D008279:Magnetic Resonance Imaging; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology
chemical_list: D003471:Cuprizone
keywords: Anticorrelated networks; Default mode network; Diffusion tensor imaging; Hippocampal connectivity; Mouse brain connectivity; Resting state functional magnetic resonance imaging