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Hum Brain Mapp. 2019 Aug 7. doi: 10.1002/hbm.24728. [Epub ahead of print]

Interregional causal influences of brain metabolic activity reveal the spread of aging effects during normal aging.

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Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey.
School of Life Sciences and Technology, University of Electronic Science and Technology of China, Chengdu, China.
Clinical Affective Neuroimaging Laboratory (CANLAB), Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
Department for Behavioral Neurology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.


During healthy brain aging, different brain regions show anatomical or functional declines at different rates, and some regions may show compensatory increases in functional activity. However, few studies have explored interregional influences of brain activity during the aging process. We proposed a causality analysis framework combining high dimensionality independent component analysis (ICA), Granger causality, and least absolute shrinkage and selection operator regression on longitudinal brain metabolic activity data measured by Fludeoxyglucose positron emission tomography (FDG-PET). We analyzed FDG-PET images from healthy old subjects, who were scanned for at least five sessions with an averaged intersession interval of 1 year. The longitudinal data were concatenated across subjects to form a time series, and the first-order autoregressive model was used to measure interregional causality among the independent sources of metabolic activity identified using ICA. Several independent sources with reduced metabolic activity in aging, including the anterior temporal lobe and orbital frontal cortex, demonstrated causal influences over many widespread brain regions. On the other hand, the influenced regions were more distributed, and had smaller age-related declines or even relatively increased metabolic activity. The current data demonstrated interregional spreads of aging on metabolic activity at the scale of a year, and have identified key brain regions in the aging process that have strong influences over other regions.


Granger causality; LASSO regression; aging; anterior temporal lobe; metabolic connectivity; orbitofrontal cortex


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