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Brain Connect. 2016 Jul;6(6):435-47. doi: 10.1089/brain.2015.0394. Epub 2016 May 2.

The Whole-Brain "Global" Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism.

Thompson GJ1,2, Riedl V3,4,5, Grimmer T5,6, Drzezga A7, Herman P1,2,8, Hyder F1,2,8,9.

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1 Magnetic Resonance Research Center (MRRC), Yale University , New Haven, Connecticut.
2 Department of Radiology and Biomedical Imaging, Yale University , New Haven, Connecticut.
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 .
6 Department of Psychiatry, Technische Universität München , München, Germany .
7 Nuclear Medicine , Uniklinikum, Koeln, Germany .
8 Quantitative Neuroscience with Magnetic Resonance (QNMR) Core Center, Yale University , New Haven, Connecticut.
9 Department of Biomedical Engineering, Yale University , New Haven, Connecticut.


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.


baseline state; default mode; energy metabolism; functional connectivity; neuronal activity; resting state

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