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

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

doi:10.1016/j.neurobiolaging.2005.08.011

« Previous Next »Neurobiology of Aging
Volume 27, Issue 10 , Pages 1395-1404, October 2006

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

Alle Meije Wink
- Brain Mapping Unit and Wolfson Brain Imaging Centre, University of Cambridge, Departments of Psychiatry and Clinical Neurosciences, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
- These authors contributed equally to this work.
Frédéric Bernard
- Brain Mapping Unit and Wolfson Brain Imaging Centre, University of Cambridge, Departments of Psychiatry and Clinical Neurosciences, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
- These authors contributed equally to this work.
Raymond Salvador
- Brain Mapping Unit and Wolfson Brain Imaging Centre, University of Cambridge, Departments of Psychiatry and Clinical Neurosciences, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
- Sant Joan de Déu—Serveis de Salut Mental, C/Antoni Pujadas, 42. 08830, St. Boi de Llobregat, Barcelona, Spain
Ed Bullmore
- Brain Mapping Unit and Wolfson Brain Imaging Centre, University of Cambridge, Departments of Psychiatry and Clinical Neurosciences, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
- Corresponding author. Tel.: +44 1223 336583; fax: +44 1223 336581.
John Suckling
- Brain Mapping Unit and Wolfson Brain Imaging Centre, University of Cambridge, Departments of Psychiatry and Clinical Neurosciences, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK

Received 10 May 2005; received in revised form 25 July 2005; accepted 2 August 2005. published online 04 October 2005.

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 0.3mg. 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.