Recent Imaging Study Shows How Cholinesterase Inhibitor Improves Working Memory
Scientists from the National Institute of Mental Health (NIMH) have used functional brain imaging to show how visual working memory may be affected by cholinesterase inhibitors currently being used--with modest effectiveness--to improve cognitive functioning in some patients with Alzheimer s Disease (AD). Working memory refers to short-term memory of information that is temporarily maintained for immediate use, for example, remembering a phone number until it is dialed or the location of cars you see in the rearview mirror while driving. In working memory, a widely distributed set of brain areas acquires the new information through perception (encoding), holds that information in an active representation (maintenance), and uses the information to perform a task (recall).
Research results from Cholinergic Enhancement and Increased Selectivity of Perceptual Processing During Working Memory appear in the December 22, 2000, issue of Science magazine. In the study s experiments, functional magnetic resonance imaging (fMRI) was used to measure second-to-second changes in brain activity as well as visual working memory performance of 7 normal, young subjects both during infusion of the cholinesterase inhibitor physostigmine and during infusion of a placebo. The researchers findings suggest that the subjects working memory may have been more efficient when they were on physostigmine, and brain images showed that the cholinesterase inhibitor had a selective effect on activity in visual processing areas at the time when new memories were acquired. Physostigmine had no effect on activity in these same areas when when the subjects were looking at nonsense patterns during a control task.
The results of the study indicate that the way cholinesterase inhibitors may improve memory is by enhancing the selectivity of perceptual processing that is to be remembered. Enhanced perception produces more vivid memories, and thus simplifies the processing demands for memory maintenance and retrieval.
Although physostigmine is not currently being used to treat AD (because it clears so fast from the blood), other cholinesterase inhibitors are being used to prevent the breakdown of the neurotransmitter acetylcholine, which is known to play an important role in learning and memory. This latest research suggests that the memory-enhancing effect of cholinesterase inhibitors in AD patients may be attributable to a clearer perception of newly acquired information.