A rapidly growing body of preclinical data has implicated the glutamatergic N-methyl-d-aspartate (NMDA) receptor in memory and other cognitive processes. There is comparatively less information about this receptor system in human cognition. We examined the effects of subanesthetic doses of ketamine, a noncompetitive NMDA receptor antagonist, on two forms of memory, free recall and recognition, as well as attention and behavior in a double-blind, placebo-controlled, 1-hour infusion in 15 healthy volunteers. Ketamine produced decrements in free recall, recognition memory, and attention. In addition, ketamine induced a brief psychosis in our healthy volunteers marked by thought disorder and withdrawal-retardation. Ketamine-induced memory impairments were not accounted for by changes in subject's attention and were not significantly related to psychosis ratings. These data suggest that the NMDA receptor plays a direct role in two types of explicit memory. The implications of these data for the pathophysiology of schizophrenia are discussed.

We have reviewed the evidence that processes and functions related to perception and expression of emotions are represented asymmetrically in the cerebral hemispheres. The literature describes three possible aspects of emotional lateralization: that emotions are better recognized by the right hemisphere; that control of emotional expression and related behaviors takes place principally in the right hemisphere; and that the right hemisphere is specialized for dealing with negative emotions, while the left is specialized for dealing with positive emotions. Evidence for the three hypotheses derives from methodologically diverse studies in unimpaired, brain-lesioned, and mood-disordered populations. Relatively little of the work has been precisely replicated, and conclusions rest on parallel lines of evidence from diverse sources. The present level of knowledge suggests a model of emotional control based on interactive inhibition between a right negatively biased and left positively biased hemisphere. However, the details of such a model, including the precise conditions under which emotion-related functions are lateralized, and the mechanisms of such lateralization have yet to be elucidated.

The behavioral, cognitive, and electrophysiological effect of a single dose of dextroamphetamine (0.5 milligram per kilogram of body weight) or placebo was examined in 14 normal prepubertal boys (mean age, 10 years 11 months) in a double-blind study. When amphetamine was given, the group showed a marked decrease in motor activity and reaction time and improved performance on cognitive tests. The similarity of the response observed in normal children to that reported in children with "hyperactivity" or minimal brain dysfunction casts doubt on pathophysiological models of minimal brain dysfunction which assume that children with this syndrome have a clinically specific or "paradoxical" response to stimulants.

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In the first study to examine direct nicotinic augmentation of central cholinergic functioning in Alzheimer's disease, six patients were studied in an intensive pilot study with three doses (0.125, 0.25, and 0.5 microgram/kg/min) of intravenous nicotine and placebo. Cognitive tests showed a decrease in intrusion errors on the middle (0.25 microgram) dose. Prominent behavioral effects were noted, with significant dose-related increases in anxiety and depressive affect. These results suggest that central nicotinic cholinergic stimulation deserves further investigation as a treatment in Alzheimer's disease and that nicotine may also be a useful investigative tool in other populations as a probe of central cholinergic function, especially in regard to the modulation of affect.