title: Impairment of movement-associated brain deactivation in multiple sclerosis: further evidence for a functional pathology of interhemispheric neuronal inhibition.
abstract: Motor control demands coordinated excitation and inhibition across distributed brain neuronal networks. Recent work has suggested that multiple sclerosis (MS) may be associated with impairments of neuronal inhibition as part of more general progressive impairments of connectivity. Here, we report results from a prospective, multi-centre fMRI study designed to characterise the changes in patients relative to healthy controls during a simple cued hand movement task. This study was conducted at eight European sites using 1.5 Tesla scanners. Brain deactivation during right hand movement was assessed in 56 right-handed patients with relapsing-remitting or secondary progressive MS without clinically evident hand impairment and in 60 age-matched, healthy subjects. The MS patients showed reduced task-associated deactivation relative to healthy controls in the pre- and postcentral gyri of the ipsilateral hemisphere in the region functionally specialised for hand movement control. We hypothesise that this impairment of deactivation is related to deficits of transcallosal connectivity and GABAergic neurotransmission occurring with the progression of pathology in the MS patients. This study has substantially extended previous observations with a well-powered, multicentre study. The clinical significance of these deactivation changes is still uncertain, but the functional anatomy of the affected region suggests that they could contribute to impairments of motor control.
authors.affiliation: Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Manson
authors.forename: C
authors.initials: C
authors.lastname: Wegner
authors.forename: M
authors.initials: M
authors.lastname: Filippi
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.forename: C
authors.initials: C
authors.lastname: Beckmann
authors.forename: O
authors.initials: O
authors.lastname: Ciccarelli
authors.forename: N
authors.initials: N
authors.lastname: De Stefano
authors.forename: Christian
authors.initials: C
authors.lastname: Enzinger
authors.forename: F
authors.initials: F
authors.lastname: Fazekas
authors.forename: F
authors.initials: F
authors.lastname: Agosta
authors.forename: A
authors.initials: A
authors.lastname: Gass
authors.forename: J
authors.initials: J
authors.lastname: Hirsch
authors.forename: H
authors.initials: H
authors.lastname: Johansen-Berg
authors.forename: L
authors.initials: L
authors.lastname: Kappos
authors.forename: T
authors.initials: T
authors.lastname: Korteweg
authors.forename: C
authors.initials: C
authors.lastname: Polman
authors.forename: L
authors.initials: L
authors.lastname: Mancini
authors.forename: F
authors.initials: F
authors.lastname: Manfredonia
authors.forename: S
authors.initials: S
authors.lastname: Marino
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
authors.forename: X
authors.initials: X
authors.lastname: Montalban
authors.forename: J
authors.initials: J
authors.lastname: Palace
authors.forename: M
authors.initials: M
authors.lastname: Rocca
authors.forename: S
authors.initials: S
authors.lastname: Ropele
authors.forename: A
authors.initials: A
authors.lastname: Rovira
authors.forename: S
authors.initials: S
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Thompson
authors.forename: J
authors.initials: J
authors.lastname: Thornton
authors.forename: T
authors.initials: T
authors.lastname: Yousry
authors.forename: J A
authors.initials: JA
authors.lastname: Frank
authors.forename: P M
authors.initials: PM
authors.lastname: Matthews
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000503:physiopathology*; D003337:Corpus Callosum / Q000503:physiopathology*; D005260:Female; D006225:Hand / Q000294:innervation / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000502:physiology; D009069:Movement Disorders / Q000209:etiology / Q000503:physiopathology*; D009103:Multiple Sclerosis / Q000150:complications / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D009415:Nerve Net / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000503:physiopathology; D011446:Prospective Studies; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000172:deficiency
chemical_list: D005680:gamma-Aminobutyric Acid