CHOLINERGIC STIMULATION ALTERS PERFORMANCE AND TASK-SPECIFIC REGIONALCEREBRAL BLOOD-FLOW DURING WORKING-MEMORY

Modulation of the cholinergic neurotransmitter system results in chang es in memory performance, including working memory (WM), in animals an d in patients with Alzheimer disease, To identify associated changes i n the functional brain response, we studied performance measures and r egional cerebral blood flow (rCBF) using positron emission tomography (PET) in healthy subjects during performance of a WM task, Eight. cont rol subjects received an infusion of saline throughout the study and 1 3 experimental subjects received a saline infusion for the first 2 sca ns followed by a continuous infusion of physostigmine, an acetylcholin esterase inhibitor, for the subsequent 8 scans, rCBF was measured usin g (H2O)-O-15 and PET in a sequence of 10 PET scans that alternated bet ween rest and task scans. During task scans, subjects performed the WM task for faces, Physostigmine both improved WM efficiency, as indicat ed by faster reaction times, and reduced WM task-related activity in a nterior and posterior regions of right midfrontal gyrus, a region show n previously to be associated with WM. Furthermore, the magnitudes of physostigmine-induced change in reaction time and right midfrontal rCB F correlated, These results suggest that enhancement of cholinergic fu nction can improve processing efficiency and thus reduce the effort re quired to perform a WM task, and that activation of right prefrontal c ortex is associated with task effort.