The impact of age on prefrontal cortex integrity during spatial working memory retrieval

• Older adults show lower dorsolateral prefrontal activation than younger adults.
• Older adults show lower dorsolateral prefrontal connectivity than younger adults.
• Prefrontal activation and functional connectivity modulate performance accuracy.
• Older low-performers show reduced anterior and dorsolateral prefrontal activation.
• Older low-performers show reduced dorsolateral prefrontal connectivity.

Healthy aging is accompanied by a decline in spatial working memory that is related to functional cerebral changes within the spatial working memory network. In the last decade, important findings were presented concerning the location (e.g., prefrontal), kind (e.g., ‘underactivation,’ ‘overactivation’), and meaning (e.g., functional deficits, compensation) of these changes. Less is known about how functional connections between specific brain regions are affected by age and how these changes are related to behavioral performance. To address these issues, we used functional magnetic resonance imaging to examine retrieval-related brain activation and functional connectivity in 18 younger individuals and 18 older individuals. We assessed working memory with a modified version of the Corsi Block-Tapping test, which requires the storage and reproduction of spatial target sequences. Analyses of group differences in brain activation and functional connectivity included comparisons between younger individuals, older individuals, older high-performers, and older low-performers. In addition, we conducted a functional connectivity analysis by using a seed region approach. In comparison to younger individuals, older individuals showed lower right-hemispheric dorsolateral prefrontal activation and lower functional connectivity between the right dorsolateral prefrontal cortex and the bilateral orbitofrontal cortex. Older high-performers showed higher right dorsolateral and anterior prefrontal cortex activation than older low-performers, as well as higher functional connectivity between these brain regions. The present results suggest age-related reductions of prefrontal activation during spatial working memory retrieval. Moreover, task-related functional connectivity appears to be lower in older adults. Performance accuracy in older adults is associated with right dorsolateral and anterior prefrontal cortex activation, and with the functional connection between these regions.