Midazolam amnesia and short-term/working memory processes

Fisher, Julia; Hirshman, Elliot; Henthorn, Thomas K.; Arndt, Jason; Passannante, Anthony N.

doi:10.1016/j.concog.2005.03.004

Cited by 18 publications

(10 citation statements)

References 20 publications

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“…There is evidence that digit span is affected by the speed of rehearsal (Baddeley 1986). Why did Fisher et al (2006) find an effect on the backward digit span task, p<0.05 between the two drug conditions, when they did not in the forward direction? The reverse digit span subject averaged 7 in the midazolam condition and 7.7 in the saline condition.…”

Section: Resultsmentioning

confidence: 96%

“…Nonetheless, it is useful to understand our results in light of previous research that has found an effect of drug on STM. Fisher et al (2006) showed a small, but significant, drop in performance on a traditional digit span task when subjects were required to give back the digits in reverse order. Drug condition did not affect performance when digits were recalled in the forward order.…”

Section: Resultsmentioning

confidence: 97%

“…The literature is mixed on this point. There are studies that indicate no effect of benzodiazepines on working memory (e.g., Blin et al 2001;Ghoneim and Mewaldt 1975;Hennessy et al 1991;Kirkby et al 1995;Knopman 1991;Mallick et al 1993) and several studies that indicate that there is an effect of benzodiazepines on working memory (Fisher et al 2006;Mintzer and Griffiths 2003a,b). Given that many factors can contribute to these different results, including differences in the nature of the task and the pharmacology of the drug, it is useful to try to collect more data to help tease apart what variables affect the conclusions drawn.…”

Section: Study 1: Is Working Memory Affected By Midazolam?mentioning

confidence: 99%

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Midazolam does not inhibit association formation, just its storage and strengthening

et al. 2006

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Rationale-Although there have been many studies examining the effects of benzodiazepines on memory performance, their effects on working memory are equivocal and little is known about whether they affect the efficacy of practice of already learned material.Objectives-The objectives in two experiments were to examine (a) whether midazolam impairs performance on a working memory task designed to minimize mnemonic strategies such as rehearsal or chunking of information to be recalled and (b) the effect of midazolam on repeated practice of paired associates that were learned before drug administration.Materials and methods-Both experiments involved subcutaneous administration of 0.03 mg/ kg of body weight of saline or midazolam in within-subject, placebo-controlled designs, involving 23 subjects in (a) and 31 in (b).Results-The drug had no effect on the ability to recall the digits in serial order even though the encoding task prevented the digits from being rehearsed or maintained in an articulatory buffer. Paired associates that were learned before the injection showed a benefit of subsequent practice under saline but not under midazolam. Conclusions-The results suggest that (a) midazolam does not affect the formation of new associations in short-term memory (STM) provided that the presentation rate is not too fast to form these associations when sedated, despite the evidence that the drug blocks long-term memory (LTM) retention of associations; and (b) the potential for over-learning with practice of learned associations in LTM is adversely affected by midazolam such that repeated exposures do not strengthen new learning. KeywordsBenzodiazepine; Working memory; Memory; Binding; Paired associate learning; Practice; MODS task; Midazolam; Over-learning; Digit span Researchers concerned with understanding human memory have sometimes relied on studies of patients with anterograde amnesia to provide insights and constraints on theories of memory mechanisms (Milner 2005). Although this research on patients with amnesia can use accidents

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 97%

Section: Study 1: Is Working Memory Affected By Midazolam?mentioning

confidence: 99%

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Midazolam does not inhibit association formation, just its storage and strengthening

et al. 2006

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“…Another study using the same task found that midazolam affected perceptual learning, particularly the learning of repeated displays (Park et al, 2004). However, the effects of midazolam are not limited to the hippocampus (Taguchi et al, 1989;Veselis et al, 1997), and they also extend to hippocampusindependent cognitive functions (Polster et al, 1993;Hirshman et al, 1999;Fisher et al, 2006). Accordingly, it is difficult to reach conclusions about hippocampus-dependent memory and awareness in studies involving midazolam.…”

Section: Discussionmentioning

confidence: 99%

Experience-Dependent Eye Movements, Awareness, and Hippocampus-Dependent Memory

Smith¹,

Hopkins²,

Squire³

2006

J. Neurosci.

119

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We asked what kind of memory is operating when eye movements change as the result of experience. Participants viewed scenes that were either novel, repeated, or manipulated (i.e., a change was introduced in one region of the scene). Eye movements differed depending on the past viewing history of each scene. Participants made fewer fixations and sampled fewer regions when scenes were repeated than when scenes were novel. When scenes were altered, participants made more fixations in the altered region, spent more time looking at the altered region, and made more transitions into and out of the altered region than in unchanged (matched) regions in the repeated scenes. Importantly, these effects occurred only when individuals were aware that a change had occurred. Participants who were unaware that the scene had been altered looked at the changed scenes in the same way that they looked at repeated scenes. Thus, there was no indication that eye movements could reveal an unaware (unconscious) form of memory. Instead, eye movements reflected conscious memory of whether the scene was repeated or manipulated. The findings were the same when awareness was assessed after viewing all the scenes (experiment 1) and when awareness was assessed after each scene was presented (experiment 2). In experiment 3, memory-impaired patients with damage limited to the hippocampus were impaired at deciding whether scenes were novel, repeated, or manipulated. Thus, the ability to consciously recollect recent encounters with scenes reflects a form of hippocampus-dependent memory. The findings show that experience-dependent eye movements in response to altered scenes reflect conscious, declarative memory, and they support the link between aware memory, declarative memory, and hippocampus-dependent memory.

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“…GABA is the primary inhibitory neurotransmitter in the mammalian central nervous system and the GABA A receptors are expressed in cerebral cortex, hippocampus, basal ganglia, thalamus, cerebellum, and brainstem (Young and Chu, 1990). Midazolam, like benzodiazepines in general, promotes transient anterograde amnesia (Bulach et al, 2005; Fisher et al, 2006; Merritt et al, 2005; Reder et al, 2006a) and as such, provides a promising tool for studying human memory that finesses problems inherent in patient populations. Some of our previous work has suggested that midazolam-induced memory effects occur by inhibiting the formation of new associations (Park et al, 2004; Reder et al, 2007; 2009).…”

Section: Introductionmentioning

confidence: 99%

Using arterial spin labeling perfusion MRI to explore how midazolam produces anterograde amnesia

Liang

Manelis

Liu

et al. 2012

Neuroscience Letters

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While our previous work suggests that the midazolam-induced memory impairment results from the inhibition of new association formation, little is known about the neural correlates underlying these effects beyond the effects of GABA agonists on the brain. We used arterial spin-labeling perfusion MRI to measure cerebral blood flow changes associated with the effects of midazolam on ability to learn arbitrary word-pairs. Using a double-blind, within-subject cross-over design, subjects studied word-pairs for a later cued-recall test while they were scanned. Lists of different word-pairs were studied both before and after an injection of either saline or midazolam. As expected, recall was severely impaired under midazolam. The contrast of MRI signal before and after midazolam administration revealed a decrease in CBF in the left dorsolateral prefrontal cortex (DLPFC), left cingulate gyrus and left posterior cingulate gyrus/precuneus. These effects were observed even after controlling for any effect of injection. A strong correlation between the midazolam-induced changes in neural activity and memory performance was found in the left DLPFC. These findings provide converging evidence that this region plays a critical role in the formation of new associations and that low functioning of this region is associated with anterograde amnesia.

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Midazolam amnesia and short-term/working memory processes

Cited by 18 publications

References 20 publications

Midazolam does not inhibit association formation, just its storage and strengthening

Midazolam does not inhibit association formation, just its storage and strengthening

Experience-Dependent Eye Movements, Awareness, and Hippocampus-Dependent Memory

Using arterial spin labeling perfusion MRI to explore how midazolam produces anterograde amnesia

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