Cholinergic modulation of visual working memory during aging: A parametric PET study

Age-related differences in the regional recruitment of prefrontal cortex (PFC) during cognitive tasks suggests that aging is associated with functional reorganization. Cholinergic enhancement with physostigmine reduces activity in the PFC regions selectively recruited during working memory (WM) and increases activity in visual processing areas, suggesting that augmenting cholinergic function reduces task effort by improving the visual representation of WM stimuli. Here, we investigated how cholinergic enhancement influenced PFC and visual cortical activity in young and older subjects as WM difficulty was altered. Regional cerebral blood flow (rCBF) was measured using (H2O)-O-15-PET in 10 young and 10 older volunteers during a parametrically varied face WM task, following an i.v. infusion of saline and physostigmine. Reaction time decreased during physostigmine relative to placebo in both groups. Prefrontal brain regions selectively recruited in each age group that responded differentially to task demands during placebo, had no significant activity during physostigmine. Medial visual processing areas showed task-selective increases in activity during drug in both groups, while lateral regions showed decreased activity in young and increased activity in older participants at longer task delays. These results are consistent with our previous findings, showing that the modulatory role of the cholinergic system persists during aging, and that the effects of cholinergic enhancement are functionally specific rather than anatomically specific. Moreover, the use of the parametric design allowed us to uncover group specific effects in lateral visual processing areas where increasing cholinergic function produced opposite effects on neural activity in the two age groups. (C) 2009 Elsevier Inc. All rights reserved.