title: Depletion of brain functional connectivity enhancement leads to disability progression in multiple sclerosis: A longitudinal resting-state fMRI study.
abstract: The compensatory effect of brain functional connectivity enhancement in relapsing-remitting multiple sclerosis (RRMS) remains controversial.
  
  
  
  To characterize the relationships between brain functional connectivity changes and disability progression in RRMS.
  
  
  
  Long-range connectivity, short-range connectivity, and density of connections were assessed using graph theoretical analysis of resting-state functional magnetic resonance imaging (fMRI) data acquired in 38 RRMS patients (disease duration: 120 ± 32 months) and 24 controls. All subjects were explored at baseline and all patients and six controls 2 years later.
  
  
  
  At baseline, levels of long-range and short-range brain functional connectivity were higher in patients compared to controls. During the follow-up, decrease in connections' density was inversely correlated with disability progression. Post-hoc analysis evidenced differential evolution of brain functional connectivity metrics in patients according to their level of disability at baseline: while patients with lowest disability at baseline experienced an increase in all connectivity metrics during the follow-up, patients with higher disability at baseline showed a decrease in the connectivity metrics. In these patients, decrease in the connectivity metrics was associated with disability progression.
  
  
  
  The study provides two main findings: (1) brain functional connectivity enhancement decreases during the disease course after reaching a maximal level, and (2) decrease in brain functional connectivity enhancement participates in disability progression.
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France/Service de Neurologie, Hôpital d'Instruction des Armées Sainte-Anne, Toulon, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Faivre
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France/Service de Neurologie, Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Robinet
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France/CEMEREM, Pôle d'Imagerie Médicale, APHM, Hôpital de la Timone, Marseille, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Guye
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Celia
authors.initials: C
authors.lastname: Rousseau
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Adil
authors.initials: A
authors.lastname: Maarouf
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Le Troter
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Zaaraoui
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France/Service de Neurologie, Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Rico
authors.affiliation: Service de Neurologie, Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Crespy
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Soulier
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Confort-Gouny
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France/Service de Neurologie, Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: UMR CNRS 5216, GIPSA, Saint Martin d'Hères, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Achard
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Ranjeva
authors.affiliation: CRMBM UMR AMU 7339, Faculté de Médecine, CNRS, Aix-Marseille Université, Marseille, France/Service de Neurologie, Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille, France bertrand.audoin@ap-hm.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Audoin
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D063132:Connectome / Q000379:methods*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012720:Severity of Illness Index
keywords: Multiple sclerosis; disability; functional MRI; functional connectivity; graph theory