Age and cholinergic effects on hemodynamics and functional coherence of human hippocampus

Neurobiol Aging. 2006 Oct;27(10):1395-404. doi: 10.1016/j.neurobiolaging.2005.08.011. Epub 2005 Sep 30.

Abstract

Aging is normally associated with increased predictability of neurophysiological processes. To test the related prediction of age-related increase in the Hurst exponent, H, of functional MRI time series, and its possible cholinergic mechanisms, two groups of healthy participants (old [mean age = 65 years]; young [mean age = 22 years]; N = 11 per group) were scanned twice at rest, following placebo and a muscarinic receptor antagonist, scopolamine 0.3 mg. Older age was associated with significant increase in H of fMRI time series in bilateral hippocampus. Similarly, scopolamine was associated with increased H in left hippocampus; and there was an age-by-drug interaction in medial temporal lobe whereby older participants specifically had increased H following scopolamine. Scopolamine also enhanced fronto-hippocampal low-frequency coherence, and this could be correlated with its effect on hippocampal H. Thus, increased persistence of hippocampal dynamics in older subjects is demonstrable by resting fMRI; scopolamine mimics these effects, especially in older subjects, implying a cholinergic mechanism for age-related change; and cholinergic effects on hippocampal dynamics are associated with enhanced functional connectivity between frontal cortex and hippocampus.

Publication types

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

MeSH terms

  • Acetylcholine / metabolism*
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Adult
  • Aged
  • Aging / physiology*
  • Brain Mapping
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology*
  • Double-Blind Method
  • Electroencephalography
  • Female
  • Hippocampus / blood supply*
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage*
  • Placebo Effect
  • Scopolamine / administration & dosage

Substances

  • Muscarinic Antagonists
  • Scopolamine
  • Acetylcholine