More flexible brain activation underlies cognitive reserve in older adults.

• Reserve is associated with more activation of the right caudate for high-load. • Caudate activation is linked to a reduced impact of age on working memory. • The activation is found in a region which is part of the fronto-striatal network. • Neural flexibility is a major substrate for cognitive reserve. The goal of this study was to identify the brain mechanisms underlying cognitive reserve using a parametric n-back working memory (WM) task in a sample of healthy older adults. We first identified the WM-related activations associated with years of education and then tested whether these activations mitigated the detrimental impact of age on cognition. Thirty-nine older adults received a magnetic resonance imaging examination while completing an n-back task with different levels of WM load (0-, 1- vs. 2-back). Results show that more education is associated with lower activation of the left medial superior frontal gyrus (BA8) in the 1-back condition and a greater activation of the right caudate nucleus in the 2-back condition. The caudate and frontal activations are task-positive and task-negative regions, respectively. Moderation analyses indicate that the effect of age on performance is less detrimental in participants with higher caudate activation in the 2-back condition. Overall, these results suggest that cognitive reserve is explained by a superior ability to flexibly engage greater or novel activation as cognitive demand increases. [ABSTRACT FROM AUTHOR]