title: Improvement of spasticity following intermittent theta burst stimulation in multiple sclerosis is associated with modulation of resting-state functional connectivity of the primary motor cortices.
abstract: Intermittent theta burst stimulation (iTBS) of the primary motor cortex improves transiently lower limbs spasticity in multiple sclerosis (MS). However, the cerebral mechanisms underlying this effect have never been investigated.
  
  
  
  To assess whether modulation of spasticity induced by iTBS is underlined by functional reorganization of the primary motor cortices.
  
  
  
  A total of 17 patients with MS suffering from lower limbs spasticity were randomized to receive real iTBS or sham iTBS during the first half of a 5-week indoor rehabilitation programme. Spasticity was assessed using the Modified Ashworth Scale and the Visual Analogue Scale at baseline, after the stimulation session and at the end of the rehabilitation programme. Resting-state functional magnetic resonance imaging (fMRI) was performed at the three time points, and brain functional networks topology was analysed using graph-theoretical approach.
  
  
  
  At the end of stimulation, improvement of spasticity was greater in real iTBS group than in sham iTBS group ( p = 0.026). iTBS had a significant effect on the balance of the connectivity degree between the stimulated and the homologous primary motor cortex ( p = 0.005). Changes in inter-hemispheric balance were correlated with improvement of spasticity (rho = 0.56, p = 0.015).
  
  
  
  This longitudinal resting-state fMRI study evidences that functional reorganization of the primary motor cortices may underlie the effect of iTBS on spasticity in MS.
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France/APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Boutière
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France/APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rey
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Zaaraoui
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Le Troter
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France/APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Rico
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France/APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Crespy
authors.affiliation: CNRS, Grenoble Image Parole Signal Automatique (GIPSA), Grenoble, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Achard
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France/APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Reuter
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France/APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.
authors.forename: Fanelly
authors.initials: F
authors.lastname: Pariollaud
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wirsich
authors.affiliation: Clinique Saint Martin, Marseille, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Asquinazi
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Confort-Gouny
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Soulier
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France/APHM, Hôpital de la Timone, Pôle d'Imagerie médicale, CEMEREM, Marseille, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Guye
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France/APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Ranjeva
authors.affiliation: CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France/APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Audoin
mesh_terms: D000328:Adult; D063132:Connectome / Q000379:methods*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex; D009103:Multiple Sclerosis / Q000150:complications / Q000628:therapy*; D009128:Muscle Spasticity / Q000209:etiology / Q000628:therapy*; D017063:Outcome Assessment, Health Care; D013826:Theta Rhythm / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
keywords: Multiple sclerosis; connectivity; intermittent theta burst stimulation; primary motor cortex; resting state fMRI; spasticity