title: Age and cholinergic effects on hemodynamics and functional coherence of human hippocampus.
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.
authors.affiliation: Brain Mapping Unit and Wolfson Brain Imaging Centre, University of Cambridge, Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
authors.forename: Alle Meije
authors.initials: AM
authors.lastname: Wink
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bernard
authors.forename: Raymond
authors.initials: R
authors.lastname: Salvador
authors.forename: Ed
authors.initials: E
authors.lastname: Bullmore
authors.forename: John
authors.initials: J
authors.lastname: Suckling
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004311:Double-Blind Method; D004569:Electroencephalography; D005260:Female; D006624:Hippocampus / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D015990:Placebo Effect; D012601:Scopolamine / Q000008:administration & dosage
chemical_list: D018727:Muscarinic Antagonists; D012601:Scopolamine; D000109:Acetylcholine