Age dependence of hemodynamic response characteristics in human functional magnetic resonance imaging

Abstract

Functional magnetic resonance imaging (fMRI) studies of cognitive aging have generally compared the amplitude and extent of blood oxygen level-dependent (BOLD) signal increases evoked by a task in older and younger groups. BOLD is thus used as a direct index of neuronal activation and it is assumed that the relationship between neuronal activity and the hemodynamic response is unchanged across the lifespan. However, even in healthy aging, differences in vascular and metabolic function have been observed that could affect the coupling between neuronal activity and the BOLD signal. Here we use a calibrated fMRI method to explore vascular and metabolic changes that might bias such BOLD comparisons. Though BOLD signal changes evoked by a cognitive task were found to be similar between a group of younger and older adults (e.g., 0.50 ± 0.04% vs. 0.50 ± 0.05% in right frontal areas), comparison of BOLD and arterial spin labelling (ASL) responses elicited in the same set of structures by a controlled global hypercapnic manipulation revealed significant differences between the 2 groups. Older adults were found to have lower responses in BOLD and flow responses to hypercapnia (e.g., 1.48 ± 0.07% vs. 1.01 ± 0.06% over gray matter for BOLD and 24.92 ± 1.37% vs. 20.67 ± 2.58% for blood flow), and a generally lower maximal BOLD response M (5.76 ± 0.2% vs. 5.00 ± 0.3%). This suggests that a given BOLD response in the elderly might represent a larger change in neuronal activity than the same BOLD response in a younger cohort. The results of this study highlight the importance of ancillary measures such as ASL for the correct interpretation of BOLD responses when fMRI responses are compared across populations who might exhibit differences in vascular physiology.

Arterial Spin Labeling Perfusion of the Brain: Emerging Clinical Applications

“…Because fMRI does not directly measure neuronal activation but the indirect vascular response, alterations of the neurovascular coupling might influence the resulting fMRI BOLD signal, for example already in normal aging (33,128).…”

Acute caffeine administration impact on working memory-related brain activation and functional connectivity in the elderly: A BOLD and perfusion MRI study

“…To date, no study explored the effects of caffeine on brain activation patterns during highly demanding cognitive tasks in elderly cohorts. However, recent contributions pointed to significant agerelated changes of fMRI activation patterns including higher BOLD signal variability and lower maximal BOLD and flow responses during aging (D'Esposito et al, 2003;Kannurpatti et al, 2010Kannurpatti et al, , 2011Gauthier et al, 2013). In combination with the observation that caffeine has a more pronounced effect on psychomotor and cognitive function in older versus younger participants (Rees et al, 1999), we hypothesized that that caffeinerelated modifications of the BOLD response might be even more pronounced in ageing.…”

The BOLD cerebrovascular reactivity response to progressive hypercapnia in young and elderly

“…These parameters define the BOLD contrast and are known to change during normal ageing. Although conflicting reports using various imaging modalities have evoked some controversy (for more information see (Sachdev, 2003)), previous MRI studies have shown that baseline CMRO 2 (Peng et al, 2014) and CBF (De Vis et al, 2015;Gauthier et al, 2013) generally decrease with age. Variability in these baseline hemodynamic parameters will have implications for BOLD-CVR measurements, since hypercapnia induced changes in the BOLD signal are expressed in terms of percent signal changes (%ΔBOLD) from baseline BOLD signal.…”