Effects of aging on cerebral blood flow, oxygen metabolism, and blood oxygenation level dependent responses to visual stimulation

Abstract

Calibrated functional magnetic resonance imaging (fMRI) provides a noninvasive technique to assess functional metabolic changes associated with normal aging. We simultaneously measured both the magnitude of the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) responses in the visual cortex for separate conditions of mild hypercapnia (5% CO(2)) and a simple checkerboard stimulus in healthy younger (n = 10, mean: 28-years-old) and older (n = 10, mean: 53-years-old) adults. From these data we derived baseline CBF, the BOLD scaling parameter M, the fractional change in the cerebral metabolic rate of oxygen consumption (CMRO(2)) with activation, and the coupling ratio n of the fractional changes in CBF and CMRO(2). For the functional activation paradigm, the magnitude of the BOLD response was significantly lower for the older group (0.57 +/- 0.07%) compared to the younger group (0.95 +/- 0.14%), despite the finding that the fractional CBF and CMRO(2) changes were similar for both groups. The weaker BOLD response for the older group was due to a reduction in the parameter M, which was significantly lower for older (4.6 +/- 0.4%) than younger subjects (6.5 +/- 0.8%), most likely reflecting a reduction in baseline CBF for older (41.7 +/- 4.8 mL/100 mL/min) compared to younger (59.6 +/- 9.1 mL/100 mL/min) subjects. In addition to these primary responses, for both groups the BOLD response exhibited a post-stimulus undershoot with no significant difference in this magnitude. However, the post-undershoot period of the CBF response was significantly greater for older compared to younger subjects. We conclude that when comparing two populations, the BOLD response can provide misleading reflections of underlying physiological changes. A calibrated approach provides a more quantitative reflection of underlying metabolic changes than the BOLD response alone.

Figure 1

Functional changes in the blood oxygen level dependent (BOLD) and cerebral blood flow (CBF) response in the VC for mild hypercapnia and functional activation. The panels show average response curves and standard errors for the CBF activated voxels within healthy younger (n = 10) and older (n = 10) subjects. (A) Fractional changes in the CBF responses to hypercapnia, (B) Changes in the BOLD responses to hypercapnia, (C) Fractional changes in the CBF responses to activation, and (D) Changes in the BOLD responses to activation. A significant increase in the fractional changes in the CBF response to hypercapnia was seen in older subjects compared to younger subjects leading to a decrease in the M value for older subjects. For the functional activation task the BOLD response was greater for younger compared to older subjects. For all panels the solid bars indicate stimulus presentation. For all time series data the error bars are presented at every other time point that was sampled. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 2

Covariance of calculated and measured parameters. (A) Fractional changes in CBF as a function of CMRO₂ showing a similar slope, n, for both younger and older subjects. (B) Comparison of n with baseline CBF, showing no significant correlation. Younger subjects did have a significantly higher mean baseline CBF than older subjects. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 3

Single block averaged dynamics of the BOLD and CBF responses for older and younger subjects. A signal averaged block of 80 s (20 s of rest, 20 s of stimulus, and 40 s of rest) was assessed for both older and younger subjects. (A) The magnitude of the CBF response was similar for both groups. (B) A significant decrease in the magnitude of the BOLD response was seen in older compared to younger subjects. (C) In contrast, the undershoot period for the CBF response was significantly different. (D) However, a similar BOLD poststimulus undershoot was seen for both groups. For panels (A) and (B) the solid black bars indicate stimulus presentation. For each figure the standard errors are shown and are presented at every other time point sampled for time series data. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]