title: The Whole-Brain "Global" Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism.
abstract: The evolution of functional magnetic resonance imaging to resting state (R-fMRI) allows measurement of changes in brain networks attributed to state changes, such as in neuropsychiatric diseases versus healthy controls. Since these networks are observed by comparing normalized R-fMRI signals, it is difficult to determine the metabolic basis of such group differences. To investigate the metabolic basis of R-fMRI network differences within a normal range, eyes open versus eyes closed in healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro-deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was observed in the eyes open state. Variance-based metrics calculated from R-fMRI did not match the baseline shift in FDG. Functional connectivity density (FCD)-based metrics showed a shift similar to the baseline shift of FDG, however, this was lost if R-fMRI "nuisance signals" were regressed before FCD calculation. Average correlation with the mean R-fMRI signal across the whole brain, generally regarded as a "nuisance signal," also showed a shift similar to the baseline of FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation may reflect changes in baseline brain metabolism. Conversely, variance-based metrics may remain similar between states due to inherent region-to-region differences overwhelming the differences between normal physiological states. As most previous studies have excluded the spatial means of R-fMRI metrics from their analysis, this work presents the first evidence of a potential R-fMRI biomarker for baseline shifts in quantifiable metabolism between brain states.
authors.affiliation: 1 Magnetic Resonance Research Center (MRRC), Yale University , New Haven, Connecticut.|2 Department of Radiology and Biomedical Imaging, Yale University , New Haven, Connecticut.
authors.forename: Garth J
authors.initials: GJ
authors.lastname: Thompson
authors.affiliation: 3 Department of Neuroradiology, Technische Universität München , München, Germany .|4 Department of Nuclear Medicine, Technische Universität München , München, Germany .|5 Neuroimaging Center, Technische Universität München , München, Germany .
authors.forename: Valentin
authors.initials: V
authors.lastname: Riedl
authors.affiliation: 5 Neuroimaging Center, Technische Universität München , München, Germany .|6 Department of Psychiatry, Technische Universität München , München, Germany .
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.affiliation: 7 Nuclear Medicine , Uniklinikum, Koeln, Germany .
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.affiliation: 1 Magnetic Resonance Research Center (MRRC), Yale University , New Haven, Connecticut.|2 Department of Radiology and Biomedical Imaging, Yale University , New Haven, Connecticut.|8 Quantitative Neuroscience with Magnetic Resonance (QNMR) Core Center, Yale University , New Haven, Connecticut.
authors.forename: Peter
authors.initials: P
authors.lastname: Herman
authors.affiliation: 1 Magnetic Resonance Research Center (MRRC), Yale University , New Haven, Connecticut.|2 Department of Radiology and Biomedical Imaging, Yale University , New Haven, Connecticut.|8 Quantitative Neuroscience with Magnetic Resonance (QNMR) Core Center, Yale University , New Haven, Connecticut.|9 Department of Biomedical Engineering, Yale University , New Haven, Connecticut.
authors.forename: Fahmeed
authors.initials: F
authors.lastname: Hyder
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography
chemical_list: D015415:Biomarkers; D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: baseline state; default mode; energy metabolism; functional connectivity; neuronal activity; resting state