A meta-analysis of cognitive flexibility in aging: Perspective from functional network and lateralization.

Cognitive flexibility, the ability to switch between mental processes to generate appropriate behavioral responses, is reduced with typical aging. Previous studies have found that age-related declines in cognitive flexibility are often accompanied by variations in the activation of multiple regions. However, no meta-analyses have examined the relationship between cognitive flexibility in aging and age-related variations in activation within large-scale networks. Here, we conducted a meta-analysis employing multilevel kernel density analysis to identify regions with different activity patterns between age groups, and determined how these regions fall into functional networks. We also employed lateralization analysis to explore the spatial distribution of regions exhibiting group differences in activation. The permutation tests based on Monte Carlo simulation were used to determine the significance of the activation and lateralization results. The results showed that cognitive flexibility in aging was associated with both decreased and increased activation in several functional networks. Compared to young adults, older adults exhibited increased activation in the default mode, dorsal attention, ventral attention, and somatomotor networks, while displayed decreased activation in the visual network. Moreover, we found a global-level left lateralization for regions with decreased activation, but no lateralization for regions with higher activation in older adults. At the network level, the regions with decreased activation were left-lateralized, while the regions with increased activation showed varying lateralization patterns within different networks. To sum up, we found that networks that support various mental functions contribute to age-related variations in cognitive flexibility. Additionally, the aging brain exhibited network-dependent activation and lateralization patterns in response to tasks involving cognitive flexibility. We highlighted that the comprehensive meta-analysis in this study offered new insights into understanding cognitive flexibility in aging from a network perspective.