r Human Brain Mapping 32:1125–1140 (2011) r Increasing Measurement Accuracy of Age-Related BOLD Signal Change: Minimizing Vascular Contributions by Resting-State-Fluctuation-of-Amplitude Scaling

In this report we demonstrate a hemodynamic scaling method with resting‐state fluctuation of amplitude (RSFA) in healthy adult younger and older subject groups. We show that RSFA correlated with breath hold (BH) responses throughout the brain in groups of younger and older subjects which RSFA and BH performed comparably in accounting for age‐related hemodynamic coupling changes, and yielded more veridical estimates of age‐related differences in task‐related neural activity. BOLD data from younger and older adults performing motor and cognitive tasks were scaled using RSFA and BH related signal changes. Scaling with RSFA and BH reduced the skew of the BOLD response amplitude distribution in each subject and reduced mean BOLD amplitude and variability in both age groups. Statistically significant differences in intrasubject amplitude variation across regions of activated cortex, and intersubject amplitude variation in regions of activated cortex were observed between younger and older subject groups. Intra‐ and intersubject variability differences were mitigated after scaling. RSFA, though similar to BH in minimizing skew in the unscaled BOLD amplitude distribution, attenuated the neural activity‐related BOLD amplitude significantly less than BH. The amplitude and spatial extent of group activation were lower in the older than in the younger group before and after scaling. After accounting for vascular variability differences through scaling, age‐related decreases in activation volume were observed during the motor and cognitive tasks. The results suggest that RSFA‐scaled data yield age‐related neural activity differences during task performance with negligible effects from non‐neural (i.e., vascular) sources. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.