title: Disrupted global metastability and static and dynamic brain connectivity across individuals in the Alzheimer's disease continuum.
abstract: As findings on the neuropathological and behavioral components of Alzheimer's disease (AD) continue to accrue, converging evidence suggests that macroscale brain functional disruptions may mediate their association. Recent developments on theoretical neuroscience indicate that instantaneous patterns of brain connectivity and metastability may be a key mechanism in neural communication underlying cognitive performance. However, the potential significance of these patterns across the AD spectrum remains virtually unexplored. We assessed the clinical sensitivity of static and dynamic functional brain disruptions across the AD spectrum using resting-state fMRI in a sample consisting of AD patients (n = 80) and subjects with either mild (n = 44) or subjective (n = 26) cognitive impairment (MCI, SCI). Spatial maps constituting the nodes in the functional brain network and their associated time-series were estimated using spatial group independent component analysis and dual regression, and whole-brain oscillatory activity was analyzed both globally (metastability) and locally (static and dynamic connectivity). Instantaneous phase metrics showed functional coupling alterations in AD compared to MCI and SCI, both static (putamen, dorsal and default-mode) and dynamic (temporal, frontal-superior and default-mode), along with decreased global metastability. The results suggest that brains of AD patients display altered oscillatory patterns, in agreement with theoretical premises on cognitive dynamics.
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Aldo
authors.initials: A
authors.lastname: Córdova-Palomera
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kaufmann
authors.affiliation: Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.|Department of Geriatric Medicine, The Memory Clinic, Oslo University Hospital, Norway.
authors.forename: Karin
authors.initials: K
authors.lastname: Persson
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Dag
authors.initials: D
authors.lastname: Alnæs
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Nhat Trung
authors.initials: NT
authors.lastname: Doan
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Torgeir
authors.initials: T
authors.lastname: Moberget
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Martina Jonette
authors.initials: MJ
authors.lastname: Lund
authors.affiliation: Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.|Department of Geriatric Medicine, The Memory Clinic, Oslo University Hospital, Norway.
authors.forename: Maria Lage
authors.initials: ML
authors.lastname: Barca
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.|Department of Medicine, Diakonhjemmet hospital, Oslo, Norway.
authors.forename: Andreas
authors.initials: A
authors.lastname: Engvig
authors.affiliation: Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.|Department of Geriatric Medicine, The Memory Clinic, Oslo University Hospital, Norway.|Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Brækhus
authors.affiliation: Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.|Department of Geriatric Medicine, The Memory Clinic, Oslo University Hospital, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Engedal
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.|Centre for Old Age Psychiatric Research, Innlandet Hospital Trust, Ottestad, Norway.
authors.forename: Geir
authors.initials: G
authors.lastname: Selbæk
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.|Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: Lars T
authors.initials: LT
authors.lastname: Westlye
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D060825:Cognitive Dysfunction / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology