Performance Level and Cortical Atrophy Modulate the Neural Response to Increasing Working Memory Load in Younger and Older Adults.

There is evidence that the neural response to increasing working memory (WM) load is modulated by age and performance level. For a valid interpretation of these effects, however, it is important to understand, whether and how they are related to gray matter atrophy. In the current work, we therefore used functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM) to examine the association between age, performance level, spatial WM load-related brain activation and gray matter volume in 18 younger high-performers (YHP), 17 younger low-performers (YLP), 17 older high-performers (OHP), and 18 older low-performers (OLP). In multiple sub regions of the prefrontal cortex (PFC), load-related activation followed a linear trend with increasing activation at increasing load in all experimental groups. Results did not reveal differences between the sub groups. Older adults additionally showed a pattern of increasing activation from low to medium load but stable or even decreasing activation from medium to high load in other sub regions of the PFC (quadratic trend). Quadratic trend related brain activation was higher in older than in younger adults and in OLP compared to OHP. In OLP, quadratic trend related brain activation was negatively correlated with both performance accuracy and prefrontal gray matter volume. The results suggest an efficient upregulation of multiple PFC areas as response to increasing WM load in younger and older adults. Older adults and particularly OLP additionally show dysfunctional response patterns (i.e., enhanced quadratic trend related brain activation compared to younger adults and OHP, respectively) in other PFC clusters being associated with gray matter atrophy.