title: Robust Detection of Impaired Resting State Functional Connectivity Networks in Alzheimer's Disease Using Elastic Net Regularized Regression.
abstract: The large number of multicollinear regional features that are provided by resting state (rs) fMRI data requires robust feature selection to uncover consistent networks of functional disconnection in Alzheimer's disease (AD). Here, we compared elastic net regularized and classical stepwise logistic regression in respect to consistency of feature selection and diagnostic accuracy using rs-fMRI data from four centers of the "German resting-state initiative for diagnostic biomarkers" (psymri.org), comprising 53 AD patients and 118 age and sex matched healthy controls. Using all possible pairs of correlations between the time series of rs-fMRI signal from 84 functionally defined brain regions as the initial set of predictor variables, we calculated accuracy of group discrimination and consistency of feature selection with bootstrap cross-validation. Mean areas under the receiver operating characteristic curves as measure of diagnostic accuracy were 0.70 in unregularized and 0.80 in regularized regression. Elastic net regression was insensitive to scanner effects and recovered a consistent network of functional connectivity decline in AD that encompassed parts of the dorsal default mode as well as brain regions involved in attention, executive control, and language processing. Stepwise logistic regression found no consistent network of AD related functional connectivity decline. Regularized regression has high potential to increase diagnostic accuracy and consistency of feature selection from multicollinear functional neuroimaging data in AD. Our findings suggest an extended network of functional alterations in AD, but the diagnostic accuracy of rs-fMRI in this multicenter setting did not reach the benchmark defined for a useful biomarker of AD.
authors.affiliation: Department of Psychosomatic Medicine, University of RostockRostock, Germany; German Center for Neurodegenerative Diseases, Site Rostock/GreifswaldRostock, Germany.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
authors.affiliation: German Center for Neurodegenerative Diseases, Site Rostock/Greifswald Rostock, Germany.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Grothe
authors.affiliation: Institute of Cognitive Neurology and Dementia Research and Department of Psychiatry and Psychotherapy, Otto von Guericke UniversityMagdeburg, Germany; German Center for Neurodegenerative Diseases, Site MagdeburgMagdeburg, Germany.
authors.forename: Coraline D
authors.initials: CD
authors.lastname: Metzger
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München Munich, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.affiliation: Department of Neuroradiology of Klinikum rechts der Isar, Technische Universität MünchenMunich, Germany; Department of Psychiatry of Klinikum rechts der Isar, Technische Universität MünchenMunich, Germany; TUM-Neuroimaging Center, Technische Universität MünchenMunich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sorg
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ewers
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität Munich, Germany.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Franzmeier
authors.affiliation: Department of Psychiatry, Klinikum der Universität München, Ludwig-Maximilians-Universität Munich, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Meisenzahl
authors.affiliation: Department of Psychiatry and Psychotherapy, Section of Gerontopsychiatry and Neuropsychology, Faculty of Medicine, University of FreiburgFreiburg, Germany; University Hospital of Old Age PsychiatryBern, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Klöppel
authors.affiliation: Leibniz Institute for Neurobiology Magdeburg, Germany.
authors.forename: Viola
authors.initials: V
authors.lastname: Borchardt
authors.affiliation: Leibniz Institute for NeurobiologyMagdeburg, Germany; Department of Psychiatry, University of TübingenTübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Walter
authors.affiliation: German Center for Neurodegenerative Diseases, Site Rostock/Greifswald Rostock, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dyrba
keywords: Alzheimer's disease; diagnostic imaging; feature selection; functional magnetic resonance imaging (fMRI); regularization