title: Brain networks disconnection in early multiple sclerosis cognitive deficits: an anatomofunctional study.
abstract: Severe cognitive impairment involving multiple cognitive domains can occur early during the course of multiple sclerosis (MS). We investigated resting state functional connectivity changes in large-scale brain networks and related structural damage underlying cognitive dysfunction in patients with early MS. Patients with relapsing MS (3-5 years disease duration) were prospectively assigned to two groups based on a standardized neuropsychological evaluation: (1) cognitively impaired group (CI group, n = 15), with abnormal performances in at least 3 tests; (2) cognitively preserved group (CP group, n = 20) with normal performances in all tests. Patients and age-matched healthy controls underwent a multimodal 3T magnetic resonance imaging (MRI) including anatomical T1 and T2 images, diffusion imaging and resting state functional MRI. Structural MRI analysis revealed that CI patients had a higher white matter lesion load compared to CP and a more severe atrophy in gray matter regions highly connected to networks involved in cognition. Functional connectivity measured by integration was increased in CP patients versus controls in attentional networks (ATT), while integration was decreased in CI patients compared to CP both in the default mode network (DMN) and ATT. An anatomofunctional study within the DMN revealed that functional connectivity was mostly altered between the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in CI patients compared to CP and controls. In a multilinear regression model, functional correlation between MPFC and PCC was best predicted by PCC atrophy. Disconnection in the DMN and ATT networks may deprive the brain of compensatory mechanisms required to face widespread structural damage.
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UMR-S975, Paris, F-75013, France; Inserm, U975, Paris, F-75013, France; CNRS, UMR 7225, Paris, France; AP-HP, Hôpital de la Salpêtrière, Hôpital Tenon, F-75020, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Louapre
authors.forename: Vincent
authors.initials: V
authors.lastname: Perlbarg
authors.forename: Daniel
authors.initials: D
authors.lastname: García-Lorenzo
authors.forename: Marika
authors.initials: M
authors.lastname: Urbanski
authors.forename: Habib
authors.initials: H
authors.lastname: Benali
authors.forename: Rana
authors.initials: R
authors.lastname: Assouad
authors.forename: Damien
authors.initials: D
authors.lastname: Galanaud
authors.forename: Léorah
authors.initials: L
authors.lastname: Freeman
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bodini
authors.forename: Caroline
authors.initials: C
authors.lastname: Papeix
authors.forename: Ayman
authors.initials: A
authors.lastname: Tourbah
authors.forename: Catherine
authors.initials: C
authors.lastname: Lubetzki
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lehéricy
authors.forename: Bruno
authors.initials: B
authors.lastname: Stankoff
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology*; D038524:Diffusion Magnetic Resonance Imaging; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology* / Q000503:physiopathology*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012146:Rest; D055815:Young Adult
keywords: MRI; cognition; default mode network; multiple sclerosis; resting state