Differential effects of scopolamine and lorazepam on working memory maintenance versus manipulation processes

Abstract

argued that, like neuropsychological studies of brain-damaged patients, which have played a critical role in advancing the understanding of normal and abnormal memory mechanisms, investigation of drug-induced amnesia can also be a powerful tool for elucidating memory mechanisms. In fact, investigation of drug-induced amnesia has several distinct advantages over traditional studies of amnesic patients. Most importantly, unlike the memory deficits found in amnesic patients, effects of drugs on memory processes are reversible and can be empirically manipulated in controlled laboratory experiments with large numbers of healthy volunteers. Furthermore, the quantitative dosing properties of drugs can be exploited to produce a graded amnesic effect in a dose-effect design. Findings of selective effects of drugs on particular aspects of memory performance but not others, or of dissociations between drugs, can provide converging evidence with data from nonpharmacological studies for the dissociability of specific processes or subcomponents (see Hirshman, Fisher, Henthorn, Arndt, & Passannante, 2002;Hirshman et al., 2001;Mintzer, 2003;Mintzer & Griffiths, 2001b). In addition, comparison of memory-impairing drugs with distinct neurochemical or pharmacological mechanisms of action can elucidate the brain mechanisms underlying specific cognitive processes.The present experiment was designed to compare the acute effects of the benzodiazepine lorazepam and the anticholinergic scopolamine on working memory processes. Benzodiazepines facilitate the action of gammaaminobutyric acid (GABA) by acting as agonists at specific sites on the GABA A receptor complex (Mohler & Okada, 1977;Squires & Braestrup, 1977), whereas scopolamine inhibits the action of acetylcholine by acting as an antagonist at muscarinic cholinergic receptors (Ketchum, Sidell, Crowell, Aghajanian, & Haines, 1973). Working memory refers to the temporary maintenance and online manipulation of a limited amount of information in the service of current behavioral goals (Baddeley, 1986(Baddeley, , 1992; for recent reviews, see D'Esposito, 2001; Smith & Jonides, 1998). The concept of working memory was originally introduced by Baddeley (1986) and replaced earlier conceptualizations of a unitary, passive, short-term storage system (Atkinson & Shiffrin, 1968). In Baddeley's model, working memory is a multicomponent system consisting of a number of limited-capacity (Miller, 1956), material-specific "slave systems" (e.g., the phonological loop for verbal material and the visuospatial sketchpad for visual material) involved in temporarily maintaining Differential effects of scopolamine and lorazepam on working memory maintenance versus manipulation processes MIRIAM Z. MINTZER AND ROLAND R. GRIFFITHS Johns Hopkins University, Baltimore, MarylandBetween-study comparisons of benzodiazepine and anticholinergic drugs on working memory suggest that anticholinergics may produce greater impairment in maintenance processes, whereas benzodiazepines may produce greater impairment in man...

Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers

“…The two working memory tasks are variants of the classic Sternberg task (Sternberg 1969) and were administered using procedures similar to those described by Mintzer and Griffiths (2007). During each experimental session, standardized instructions were read to the participants before each task (each block of the modified Sternberg manipulation task; see below), and practice trials were presented before the experimental trials to ensure that the participants understood and performed the tasks correctly.…”

“…The order of presentation of trials from the three conditions was random and the probed digit represented the correct position of the probed letter on half of the trials. Dependent measures included the accuracy of the response (i.e., yes or no) and reaction time from the onset of the probe to a participant’s response (see Mintzer and Griffiths 2007 for further detail).…”

“…Maintenance requirements were held constant using a consistent delay (0 s) and memory set size (five stimuli) across trials. The order of three separate 15-trial blocks in each of the three conditions (position, alphabetize, alphabetize and rotate; a total of 45 trials) was counterbalanced across all participants (see Mintzer and Griffiths 2007 for further detail).…”

Does neuroimaging research examining the pathophysiology of posttraumatic stress disorder require medication-free patients?

“…In addition, some of the studies, most of which had small sample sizes, may have lacked the power to detect a potential medication effect. This is particularly relevant for the studies discussed above that examined PTSD patients who were taking benzodiazepines or antidepressants at the time of the study, because it has been clearly demonstrated that these drugs can affect memory performance 17,18 as well as emotional processing. 19 In addition to memory, psychomotor functioning and concentration are the cognitive domains most commonly affected by commonly used prescription medications.…”

Encoding of rat working memory by power of multi-channel local field potentials via sparse non-negative matrix factorization

“…Working memory refers to a brain system that provides temporary storage and manipulation of information, supporting human thought processes by providing an interface between perception, long-term memory and action [1][2][3] . Studies have suggested that working memory is mediated by the continuous activity of prefrontal cortex (PFC) neurons [4,5] , and the PFC plays an important role in working memory [6,7] .…”