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

Alle Meije Wink, Frédéric Bernard, Raymond Salvador, Ed Bullmore, John Suckling

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93 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1395-404
Number of pages10
JournalNeurobiology of aging
Issue number10
Publication statusPublished - Oct 2006


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

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