The importance of being variable

Abstract

New work suggests that blood oxygen level-dependent (BOLD) signal variability can be a much more powerful index of human age than mean activation, and that older brains are actually less variable than younger brains. However, little is known of how BOLD variability and task performance may relate. In the current study, we examined BOLD variability in relation to age, and reaction time speed and consistency in healthy younger (20-30 years) and older (56-85 years) adults on three cognitive tasks (perceptual matching, attentional cueing, and delayed match-to-sample). Results indicated that younger, faster, and more consistent performers exhibited significantly higher brain variability across tasks, and showed greater variability-based regional differentiation compared with older, poorer-performing adults. Also, when we compared brain variability- and typical mean-based effects, the respective spatial patterns were essentially orthogonal across brain measures, and any regions that did overlap were largely opposite in directionality of effect. These findings help establish the functional basis of BOLD variability, and further support the statistical and spatial differentiation between BOLD variability and BOLD mean. We thus argue that the precise nature of relations between aging, cognition, and brain function is underappreciated by using mean-based brain measures exclusively.

Figure 1.

a, b, Correlations (Pearson r) between age, mean_RT, and ISD_RT across tasks and SD_BOLD (a) and mean_BOLD (b). Both model effects resulted from the first latent variable from separate task PLS model runs (one for SD_BOLD and one for mean_BOLD). Error bars represent bootstrapped 95% confidence intervals. Although our sample did not consist of middle-aged adults, analyzing age as either a continuous or dichotomous variable (young vs old) made little difference in our PLS model runs. R² values were within 1.4% across relations involving brain, age, and performance, with no differences in permuted p-values. Thus, we elected to maintain the use of age as a continuous measure, just as we did to evaluate initial bivariate relations (see Notes).

Figure 2.

PLS brain patterns and overlay plots. a, Blue regions indicate greater and yellow/red regions indicate lesser brain variability with younger age, and faster and more consistent RT performance. b, Blue regions indicate greater and yellow/red regions indicate lesser mean brain activity with younger age, and faster and more consistent RT performance. In both a and b, all robust areas surpassed a thresholded bootstrap ratio (salience/SE) of ≥ 3.00 (for yellow/red regions) or ≤−3.00 (for blue regions). Darker colors indicate greater robustness. c, Overlay plot highlighting differences between SD_BOLD and mean_BOLD spatial patterns. Red, Greater SD_BOLD with younger age and better performance, but no mean_BOLD effect; yellow, lesser SD_BOLD with younger age and better performance, but no mean_BOLD effect; cyan, greater mean_BOLD with younger age and better performance, but no SD_BOLD effect; blue, lesser mean_BOLD with younger age and better performance, but no SD_BOLD effect. d, Overlay plot highlighting overlap between SD_BOLD and mean_BOLD spatial patterns. Red, Greater SD_BOLD and lesser mean_BOLD with younger age and better performance. All images represent every other slice in z-direction.

Figure 3.

Levels of brain variability in robust blue and yellow regions from our SD_BOLD PLS analysis. Blue and yellow regions refer to those in Figure 2a (we label yellow/red in Fig. 2a as yellow here). Fast and slow refer to ≤1 and ≥1 SD from the sample mean_RT across tasks; consistent and inconsistent refer to ≤ 1 and ≥1 SD from the sample average ISD_RT across tasks. Blue areas represent 84% and yellow areas represent 16% of robust brain voxels identified in the PLS SD_BOLD analysis. Thus, the group difference noted here for blue regions is much more prominent in brain than is the difference noted for yellow regions. Unsurprisingly, a separate analysis of overall brain variability (i.e., SD_BOLD of all robust voxels, regardless of whether blue or yellow) also revealed a strong group difference, F_(1,31) = 21.77, p < 0.0001, partial η² = 0.41; younger, faster, more consistent adults exhibited 25% more brain variability than older, slower, more inconsistent adults across tasks.