The role of the arousal system in age-related differences in cortical functional network architecture

Hum Brain Mapp. 2022 Feb 15;43(3):985-997. doi: 10.1002/hbm.25701. Epub 2021 Oct 29.

Abstract

A common finding in the aging literature is that of the brain's decreased within- and increased between-network functional connectivity. However, it remains unclear what is causing this shift in network organization with age. Given the essential role of the ascending arousal system (ARAS) in cortical activation and previous findings of disrupted ARAS functioning with age, it is possible that age differences in ARAS functioning contribute to disrupted cortical connectivity. We test this possibility here using resting state fMRI data from over 500 individuals across the lifespan from the Cambridge Center for Aging and Neuroscience (Cam-CAN) population-based cohort. Our results show that ARAS-cortical connectivity declines with age and, consistent with our expectations, significantly mediates some age-related differences in connectivity within and between association networks (specifically, within the default mode and between the default mode and salience networks). Additionally, connectivity between the ARAS and association networks predicted cognitive performance across several tasks over and above the effects of age and connectivity within the cortical networks themselves. These findings suggest that age differences in cortical connectivity may be driven, at least in part, by altered arousal signals from the brainstem and that ARAS-cortical connectivity relates to cognitive performance with age.

Keywords: ascending arousal system; fMRI; functional networks; neurocognitive aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Arousal / physiology*
  • Brain Stem / diagnostic imaging
  • Brain Stem / physiology*
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiology*
  • Cognitive Aging / physiology*
  • Connectome*
  • Default Mode Network / diagnostic imaging
  • Default Mode Network / physiology*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiology*
  • Young Adult