Cholinergic enhancement improves performance on working memory by modulating the functional activity in distinct brain regions: A positron emission tomography regional cerebral blood flow study in healthy humans

Previously, we have shown that physostigmine, an acetylcholinesterase inhib itor, improved performance on a working memory for faces task, as reflected by reduced reaction time (RT), and reduced task-specific regional cerebral blood flow (rCBF) in right prefrontal cortex and, further, that these redu ctions in RT and right frontal rCBF were significantly correlated. Here we investigated the relation between the effects of physostigmine on task perf ormance and task-specific functional brain response throughout the cortex b y examining correlations between physostigmine-related changes in rCBF in a ll brain areas and changes in RT, In subjects who received an infusion of p hysostigmine, reduced RT correlated (p < 0.001) positively with reduced rCB F in right frontal cortex, left temporal cortex, anterior cingulate, and le ft hippocampus; and correlated with increased rCBF in medial occipital visu al cortex, In subjects who received a placebo infusion of saline, no signif icant correlations between changes in RT and cortical rCBF were observed. T he results show that cholinergically induced improvements in working memory performance are related to alterations in neural activity in multiple cort ical regions, including increased neural activity in regions associated wit h early perceptual processing and decreased neural activity in regions asso ciated with attention, memory encoding, and memory maintenance. (C) 2000 El sevier Science Inc.