Aging and brain activation with working memory tasks: an fMRI study of connectivity.

BACKGROUND White matter changes in aging and neuropsychiatric disorders may produce disconnection of neural circuits. Temporal correlations in regional blood oxygen level dependent (BOLD) signals may be used to assess effective functional connectivity in specific circuits, such as prefrontal cortex (PFC) circuits supporting working memory (WM) tasks. We hypothesized healthy older subjects would show lower connectivity than younger subjects. METHODS Healthy younger (n = 9, 25.9 (SD 6.0) years) and older adults (n = 11, 68.3 (4.9) years) performed WM tasks during functional MRI. Subjects viewed images and were instructed to label them, either simultaneously or after a delay; BOLD responses with and without delay were contrasted to assess differential WM activation and connectivity. Two tasks were used: a semantic task, with line drawings categorized as 'alive' or 'not living', and an emotional task, with emotive faces as stimuli and subjects selecting the better emotional description. RESULTS In both tasks, older subjects activated larger regions and had greater inter-individual variability in extent of activation. In the semantic task, connectivity was lower in the older subjects for the amygdala/orbital PFC circuit (p = 0.04). Contrary to our predictions, older subjects exhibited higher connectivity than younger subjects in the circuit linking orbital and dorsolateral PFC in both semantic (p = 0.04) and emotional (p = 0.02) tasks. CONCLUSIONS Healthy subjects exhibited age-dependent differences in connectivity in working memory circuits, but this may reflect effects of aging on white matter, compensatory mechanisms, and other factors. Volumetric determination of white matter hyperintensities in future studies may clarify the functional importance of structural damage.