The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults
Version of Record online: 27 FEB 2015
© 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Human Brain Mapping
Volume 36, Issue 6, pages 2248–2269, June 2015
How to Cite
Tsvetanov, K. A., Henson, R. N. A., Tyler, L. K., Davis, S. W., Shafto, M. A., Taylor, J. R., Williams, N., Cam-CAN and Rowe, J. B. (2015), The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults. Hum. Brain Mapp., 36: 2248–2269. doi: 10.1002/hbm.22768
- Issue online: 28 APR 2015
- Version of Record online: 27 FEB 2015
- Manuscript Accepted: 5 FEB 2015
- Manuscript Revised: 4 FEB 2015
- Manuscript Received: 27 OCT 2014
- Biotechnology and Biological Sciences Research Council . Grant Number: BB/H008217/1
- UK Medical Research Council Programme . Grant Number: MC-A060-5PR10
- Wellcome Trust . Grant Number: 088324
- cerebral vascular reactivity;
- signal variability;
- resting state;
- fluctuation amplitude
In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood-oxygenation level-dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting-state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath-hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age-related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population-based Cambridge Centre for Ageing and Neuroscience cohort (Cam-CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task-based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects of age on task-based activation studies with fMRI do not survive correction for changes in vascular reactivity, and are likely to have been overestimated in previous fMRI studies of ageing. The results from the mediation analysis demonstrate that RSFA is modulated by measures of vascular function and is not driven solely by changes in the variance of neural activity. Based on these findings we propose that the RSFA scaling method is articularly useful in large scale and longitudinal neuroimaging studies of ageing, or with frail participants, where alternative measures of vascular reactivity are impractical. Hum Brain Mapp 36:2248–2269, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.