N-methyl-d-aspartate receptors and information processing: human choice reaction time under a subanaesthetic dose of ketamine Yves Guillermain a , Joe È lle Micallef b , Camille-Aime  PossamaõÈ a , Olivier Blin b , Thierry Hasbroucq a,c, * a Centre de Recherches en Neurosciences Cognitives, Centre National de la Recherche Scienti®que, 13402 Marseille Cedex 20, France b Centre de Pharmacologie Clinique et d'E  valuations The  rapeutiques and Laboratoire de Pharmacologie Clinique, Centre Hospitalier Universitaire de la Timone, Marseille, France c Institut de Me  decine Navale du Service de Sante  des Arme Âes, Toulon, France Received 30 May 2000; received in revised form 28 February 2001; accepted 2 March 2001 Abstract Ketamine is an N-methyl-d-aspartate antagonist that induces cognitive dysfunctions. The purpose of the present study was to investigate the effects of a subanesthetic dose of ketamine on human information processing, using the additive factor method. During perfusion of a subanesthetic dose of ketamine (0.5 mg/kg over 60 min) or a placebo (randomized double-blind, cross-over design), eight adults (aged 22±33, mean  27) performed a two-choice visual reaction time (RT) task. Signal intensity, stimulus±response mapping, and foreperiod duration were manipulated. The effects of these three variables were found to be additive on RT, indicating that three independent stages ± namely, stimulus preprocessing, response selection and motor selection- were manipulated. Ketamine altered RT performance in a speci®c way: it interacted with foreperiod duration but its effect was additive with those of signal intensity and stimulus±response mapping. These results show that ketamine speci®cally affects the stage of motor adjustment, which suggests that the glutamatergic system plays an important role in motor processes. q 2001 Published by Elsevier Science Ireland Ltd. Keywords: N-methyl-d-aspartate; Ketamine; Reaction time; Glutamate A widely-held assumption in cognitive psychology is that information processing can be reduced to a series of stages [2], a stage being a functional set of elementary operations. This conception is supported by numerous results obtained using the additive factor method (AFM), [23]. In essence, the AFM relies upon the analysis of the pattern of statistical effects of factorially manipulated variables: if the effects on reaction time (RT) are additive, this means that the variables affect different stages; conversely, if the effects interact, the variables affect at least one common stage. Van der Molen et al. [24] for example, proposed a six-stage decomposition of information processing: three perceptual stages (stimulus preprocessing, feature analysis, and stimulus identi®cation), a central, response-selection stage, and two motor stages (motor programming and motor adjustment). The present experiment was designed to determine which information processing stages are mediated by the glutama- tergic system. About 30% of the afferent sensory and motor ®bre to the cerebral cortex stem from the thalamic nuclei. All these connections are reciprocal and most of the excita- tory ones are glutamatergic (for reviews, see Refs. [1,7]). Glutamate (GLU) pathways can therefore be expected to play an important role in sensorimotor processing. Among the GLU targets, the N-methyl-d-aspartate (NMDA) recep- tors are widely distributed throughout the brain, although primarily in telencephalic regions. One way to study their functional role consists of characterizing the behavioral effects of ketamine, a non-competitive NMDA glutamate receptor antagonist that is a clinically-available anaesthetic agent known to induce different behavioral dysfunctions and cognitive de®cits [3,14,26]. The purpose of the present study was to investigate the role played by the NMDA receptors in human information processing, using the AFM [23], in an attempt to decipher which sensorimotor operations are altered by a subanesthetic dose of ketamine. We chose to manipulate three task factors whose effects on choice RT are well known: visual signal intensity, stimu- lus±response compatibility, and foreperiod duration. Choice Neuroscience Letters 303 (2001) 29±32 0304-3940/01/$ - see front matter q 2001 Published by Elsevier Science Ireland Ltd. PII: S0304-3940(01)01695-0 www.elsevier.com/locate/neulet * Corresponding author. Tel.: 133-04-91164307; fax: 133-04- 914938. E-mail address: thierry@lnf.cnrs-mrs.fr (T. Hasbroucq).