Enhanced motor learning in older adults is accompanied by increased bilateral frontal and fronto-parietal connectivity.

We recently demonstrated that older adults can benefit as much as younger adults from learning skills in an interleaved manner. Here we investigate whether optimized learning through interleaved practice (IP) is associated with changes in inter-regional brain connectivity and whether younger and older adults differ in such brain-behavior correlations. Younger and older adults practiced a set of three 4-element motor sequences in a repetitive or in an interleaved order for 2 consecutive days. Retention of the practiced sequences was evaluated 3 days after practice with functional images acquired simultaneously. A within-subject design was used so that subjects practiced sequences in the other condition (repetitive or interleaved) 2-4 weeks later. Using the psychophysiological interaction (PPI) analysis approach, we found that IP led to higher functional connectivity between the right and left dorsal lateral prefrontal cortex (DLPFC) and between the dorsal premotor cortex (PMd) and inferior parietal lobule (IPL) in older adults. Moreover, increased connectivity between these regions was significantly associated with the learning benefits of IP. In contrast, in younger adults, enhanced learning as a result of IP was associated with increased connectivity between DLPFC and the supplementary motor area (SMA) and the inferior frontal gyrus. These data suggest that though younger and older gain similar behavioral benefits from interleaved training, aging may alter the operation of brain networks underlying such optimized learning.