1. ¹Department of Psychiatry, University of Cambridge, Cambridge, UK
2. ²Department of Anesthesiology, Harborview Medical Center, University of Washington, Cambridge, UK
3. ³Department of Experimental Psychology, University of Cambridge, Cambridge, UK

Correspondence: Dr PC Fletcher, Department of Psychiatry, University of Cambridge, Box 255, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. Tel: +44 1223 336 988; Fax: +44 1223 336 581; E-mail: pcf22@cam.ac.uk

Received 29 January 2003; Revised 11 April 2003; Accepted 6 June 2003; Published online 30 July 2003.

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.