Subdissociative dose ketamine produces a deficit in manipulation but not maintenance of the contents of working memory - PubMed (original) (raw)

Clinical Trial

Subdissociative dose ketamine produces a deficit in manipulation but not maintenance of the contents of working memory

Rebekah A E Honey et al. Neuropsychopharmacology. 2003 Nov.

Abstract

We investigated the effects of subdissociative dose ketamine on executive processes during a working memory task. A total of 11 healthy volunteers participated in a double-blind, placebo-controlled, randomized, within-subjects study. They attended on three occasions, receiving intravenous infusions of placebo, a lower ketamine dose, and a higher ketamine dose. On each occasion, they underwent a series of tasks engaging working memory function in verbal and visuo-spatial domains. Further tasks explored aspects of long-term memory, planning, attention, and perceptual processing. With respect to working memory/executive function, a highly specific pattern of impairment was observed. Impairments were seen only at the higher dose of ketamine and restricted to a subgroup of the verbal working memory tasks: While visuo-spatial working memory showed no evidence of impairment, and while simple maintenance processes during verbal working memory were also unimpaired, higher dose ketamine produced a significant impairment in the manipulation of information within working memory. This process-specific effect of ketamine was reflected in a drug-by-task interaction. The specificity of this ketamine effect suggests that the earliest effect of NMDA receptor blockade is in higher order control of executive function rather than in more basic maintenance processes.

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Figures

Figure 1

Figure 1

Timeline demonstrating the timing of tasks, ketamine infusion, and blood samples during the study.

Figure 2

Figure 2

Mean scores (± S.E. mean) of digit span and verbal working memory for placebo, 50 ng/ml ketamine, and 100 ng/ml ketamine conditions.

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