title: Longitudinal reproducibility of default-mode network connectivity in healthy elderly participants: A multicentric resting-state fMRI study.
abstract: To date, limited data are available regarding the inter-site consistency of test-retest reproducibility of functional connectivity measurements, in particular with regard to integrity of the Default Mode Network (DMN) in elderly participants. We implemented a harmonized resting-state fMRI protocol on 13 clinical scanners at 3.0T using vendor-provided sequences. Each site scanned a group of 5 healthy elderly participants twice, at least a week apart. We evaluated inter-site differences and test-retest reproducibility of both temporal signal-to-noise ratio (tSNR) and functional connectivity measurements derived from: i) seed-based analysis (SBA) with seed in the posterior cingulate cortex (PCC), ii) group independent component analysis (ICA) separately for each site (site ICA), and iii) consortium ICA, with group ICA across the whole consortium. Despite protocol harmonization, significant and quantitatively important inter-site differences remained in the tSNR of resting-state fMRI data; these were plausibly driven by hardware and pulse sequence differences across scanners which could not be harmonized. Nevertheless, the tSNR test-retest reproducibility in the consortium was high (ICC=0.81). The DMN was consistently extracted across all sites and analysis methods. While significant inter-site differences in connectivity scores were found, there were no differences in the associated test-retest error. Overall, ICA measurements were more reliable than PCC-SBA, with site ICA showing higher reproducibility than consortium ICA. Across the DMN nodes, the PCC yielded the most reliable measurements (≈4% test-retest error, ICC=0.85), the medial frontal cortex the least reliable (≈12%, ICC=0.82) and the lateral parietal cortices were in between (site ICA). Altogether these findings support usage of harmonized multisite studies of resting-state functional connectivity to characterize longitudinal effects in studies that assess disease progression and treatment response.
authors.affiliation: Center for Mind/Brain Sciences (CIMEC), University of Trento, Rovereto, Italy. Electronic address: jorge.jovicich@unitn.it.
authors.forename: Jorge
authors.initials: J
authors.lastname: Jovicich
authors.affiliation: Center for Mind/Brain Sciences (CIMEC), University of Trento, Rovereto, Italy; Scientific Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Ludovico
authors.initials: L
authors.lastname: Minati
authors.affiliation: LENITEM Laboratory of Epidemiology, Neuroimaging, & Telemedicine, IRCCS San Giovanni di Dio-FBF, Brescia, Italy.
authors.forename: Moira
authors.initials: M
authors.lastname: Marizzoni
authors.affiliation: Center for Mind/Brain Sciences (CIMEC), University of Trento, Rovereto, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Marchitelli
authors.affiliation: Department of Psychiatry and Clinical Psychobiology, Universitat de Barcelona and IDIBAPS, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Sala-Llonch
authors.affiliation: Department of Psychiatry and Clinical Psychobiology, Universitat de Barcelona and IDIBAPS, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Bartrés-Faz
authors.affiliation: LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Essen, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Arnold
authors.affiliation: LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Essen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Benninghoff
authors.affiliation: LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Essen, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Fiedler
authors.affiliation: Department of Neuroradiology, IRCSS San Martino University Hospital and IST, Genoa, Italy; Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Roccatagliata
authors.affiliation: Department of Neuroscience, Ophthalmology, Genetics and Mother-Child Health (DINOGMI), University of Genoa, Genoa, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Picco
authors.affiliation: Department of Neuroscience, Ophthalmology, Genetics and Mother-Child Health (DINOGMI), University of Genoa, Genoa, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Nobili
authors.affiliation: Pharmacology, Assistance Publique, Hôpitaux de Marseille, Aix-Marseille University, CNRS, UMR 7289, Marseille, France.
authors.forename: Oliver
authors.initials: O
authors.lastname: Blin
authors.affiliation: Univ. Lille, INSERM, CHU Lille, U1171 - Degenerative and Vascular Cognitive Disorders, Lille, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bombois
authors.affiliation: Univ. Lille, INSERM, CHU Lille, U1171 - Degenerative and Vascular Cognitive Disorders, Lille, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Lopes
authors.affiliation: Univ. Lille, INSERM, CHU Lille, U1171 - Degenerative and Vascular Cognitive Disorders, Lille, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
authors.affiliation: CRMBM-CEMEREM, UMR 7339, Aix Marseille Université, CNRS, Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Sein
authors.affiliation: CRMBM-CEMEREM, UMR 7339, Aix Marseille Université, CNRS, Marseille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Ranjeva
authors.affiliation: APHM, CHU Timone, Service de Neurologie et Neuropsychologie, Marseille, France; Aix Marseille Université, Inserm, INS UMR_S 1106, 13005 Marseille, France.
authors.forename: Mira
authors.initials: M
authors.lastname: Didic
authors.affiliation: INSERM, UMR 825 Imagerie Cérébrale et Handicaps Neurologiques, F-31024 Toulouse, France; Université Toulouse 3 Paul Sabatier, UMR 825 Imagerie Cérébrale et Handicaps Neurologiques, F-31024 Toulouse, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Gros-Dagnac
authors.affiliation: INSERM, UMR 825 Imagerie Cérébrale et Handicaps Neurologiques, F-31024 Toulouse, France; Université Toulouse 3 Paul Sabatier, UMR 825 Imagerie Cérébrale et Handicaps Neurologiques, F-31024 Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Payoux
authors.affiliation: Department of Neuroradiology, General Hospital, Verona, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Zoccatelli
authors.affiliation: Department of Neuroradiology, General Hospital, Verona, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Alessandrini
authors.affiliation: Department of Neuroradiology, General Hospital, Verona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Beltramello
authors.affiliation: Department of Neuroradiology and Magnetic Resonance Image Core Facility, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Bargalló
authors.affiliation: Department of Neuroscience Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti, Italy; Institute for Advanced Biomedical Technologies (ITAB), University "G. d'Annunzio" of Chieti, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferretti
authors.affiliation: Department of Neuroscience Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti, Italy; Institute for Advanced Biomedical Technologies (ITAB), University "G. d'Annunzio" of Chieti, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Caulo
authors.affiliation: IRCCS SDN, Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Aiello
authors.affiliation: IRCCS SDN, Naples, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cavaliere
authors.affiliation: IRCCS SDN, Naples, Italy; University of Naples Parthenope, Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Soricelli
authors.affiliation: Section of Neurology, Centre for Memory Disturbances, University of Perugia, Perugia, Italy.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Parnetti
authors.affiliation: Medical Physics Unit, Perugia General Hospital, Perugia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Tarducci
authors.affiliation: Neuroradiology Unit, Perugia General Hospital, Perugia, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Floridi
authors.affiliation: 3rd Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: Interbalkan Medical Center of Thessaloniki, Thessaloniki, Greece.
authors.forename: Manos
authors.initials: M
authors.lastname: Constantinidis
authors.affiliation: Interbalkan Medical Center of Thessaloniki, Thessaloniki, Greece; Department of Radiology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Drevelegas
authors.affiliation: Dept. Geriatrics, Neuroscience & Orthopaedics, Catholic University, Policlinic Gemelli, Rome, Italy; IRCCS S.Raffaele Pisana, Rome, Italy.
authors.forename: Paolo Maria
authors.initials: PM
authors.lastname: Rossini
authors.affiliation: Center for Neuropsychological Research, Catholic University, Rome, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Marra
authors.affiliation: Department of Psychiatry, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schönknecht
authors.affiliation: Department of Psychiatry, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Hensch
authors.affiliation: Department of Neuroradiology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Karl-Titus
authors.initials: KT
authors.lastname: Hoffmann
authors.affiliation: Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Kuijer
authors.affiliation: Alzheimer Centre and Department of Neurology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands; Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Pieter Jelle
authors.initials: PJ
authors.lastname: Visser
authors.affiliation: Alzheimer Centre and Department of Neurology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: LENITEM Laboratory of Epidemiology, Neuroimaging, & Telemedicine, IRCCS San Giovanni di Dio-FBF, Brescia, Italy; Memory Clinic and LANVIE, Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016477:Artifacts; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D003627:Data Interpretation, Statistical; D006179:Gyrus Cinguli / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D009434:Neural Pathways / Q000502:physiology; D015203:Reproducibility of Results; D059629:Signal-To-Noise Ratio
keywords: Default Mode Network; Functional connectivity; Multi-center; Multi-site MRI; Reproducibility