Age and cholinergic effects on hemodynamics and functional coherence of human hippocampus.
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.
Wink
Alle Meije
AM
Brain Mapping Unit and Wolfson Brain Imaging Centre, University of Cambridge, Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
Bernard
Frédéric
F
Salvador
Raymond
R
Bullmore
Ed
E
Suckling
John
J
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
D018727:Muscarinic Antagonists; D012601:Scopolamine; D000109:Acetylcholine