Age-related changes in regional activation during working memory in young adults: an fMRI study

Several lines of evidence suggest that working memory diminishes with advancing age, with concomitant functional changes in associated neuronal activation in frontal cortical regions and hippocampi. No studies to date, however, have investigated age-related changes in neuronal activation in these regions during performance of a working memory task in younger subjects without working memory deficits. In this study, we utilized fMRI to examine changes in brain activation with increasing age in specific regions-of-interest. Eleven healthy subjects performed a "two-back" working memory task and a matched "zero-back" attention task during fMRI. There was no association between age and performance on either task. Left hippocampal activation significantly correlated with age (P = 0.01) and right hippocampal activation showed an association with age (P = 0.09). This study demonstrates that increasing age is associated with increased activation of hippocampus even in young patients without evidence of working memory deficits and suggests that functional changes may precede overt evidence of working memory deficits.