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

Hum Brain Mapp. 2019 Nov 1;40(16):4657-4668. doi: 10.1002/hbm.24728. Epub 2019 Aug 7.

Abstract

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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / physiology*
  • Algorithms
  • Brain Chemistry / physiology*
  • Causality
  • Female
  • Fluorodeoxyglucose F18
  • Frontal Lobe / growth & development
  • Frontal Lobe / metabolism
  • Healthy Volunteers
  • Humans
  • Image Processing, Computer-Assisted
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • Prefrontal Cortex / growth & development
  • Prefrontal Cortex / metabolism
  • Principal Component Analysis
  • Radiopharmaceuticals
  • Temporal Lobe / growth & development
  • Temporal Lobe / metabolism

Substances

  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18

Grants and funding