Karen Y. Sirocco

NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers.

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 subjects 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 schizophremia are discussed.

Monitoring the source of memory in detoxified alcoholics

The ability to monitor the source of remembered information and related reflective cognitive processes was examined in normal volunteers and detoxified alcoholics. Normal volunteers were very accurate judges of whether remembered events were presented as stimuli or were self-generated, even when memory was tested 2 days later. In contrast, a subgroup of otherwise cognitively unimpaired alcoholics demonstrated impairments in the ability to track the source of remembered knowledge and were also less able to inhibit intrusion errors in recalling information from memory. These findings provide preliminary evidence of an impairment in cognitive control functions in certain alcoholics. This conclusion is supported by associated findings indicating that, among alcoholics, performance on explicit memory tasks that required reflective cognitive operations were positively correlated with glucose utilization rates in left prefrontal, temporal, and posterior orbital frontal cortical regions.

Comparison of the spectrum of cognitive effects of alprazolam and adinazolam after single doses in healthy subjects

Single doses of alprazolam (0, 0.5, 1.5 mg) or adinazolam mesylate sustained release tablets (SR) (0, 15, 45 mg) were administered to separate groups of 12 healthy men in a crossover design. Psychomotor performance was assessed by digit symbol substitution (DSST), and memory was assessed using a test battery which reflects various aspects of memory, including attention/working memory, explicit memory (recall of categorically related words), semantic memory (fragmented picture recognition, generation of category exemplars), and implicit memory (time saved in resolving fragmented pictures on the second exposure). Maximal psychomotor performance and memory decrements for the highest active doses were significantly different from placebo for all tasks at some time after dosing. The maximum decrement in DSST was not significantly different between drugs at the high dose (P=0.288). Maximum attention/working memory decrements were significantly different between the high doses of the active compounds (P=0.031), and the difference in maximum category recall decrement was marginally significant (P=0.067). Access to knowledge memory was not significantly altered by these drugs; these results are similar to those obtained for other benzodiazepines. Both drugs exhibited slight effects on implicit memory. The results suggest that the sedative and memory effects of these triazolobenzodiazepines may not be closely related and suggest that adinazolam has a somewhat different spectrum of cognitive effects relative to alprazolam.

Dissociations in the expression of the sedative effects of triazolam

Fifteen normal volunteers were administered 0.250, 0.375, and 0.500 mg of triazolam and placebo in a double-blind repeated measures cross-over design. Subjects demonstrated dose-dependent impairments in free recall, a test of explicit memory requiring awareness and reflection, and sedation as assessed by objective behavioral measures (the digit symbol substitution task) and subjective visual analogue scales. The sedative drug response did not account for the impairment in free recall. Differences in performance of the two tests of sedation indicated that the effect of this drug on reflective processes accounts for impairment in episodic memory and the inability to track the sedative effects of this drug at the higher doses tested in this study.

Introduction to special section: ADHD, impulsivity, and alcohol abuse.

The goal of this special section is to highlight progress made and primary research reports on the relation between Attention Deficit Hyperactivity Disorder (ADHD), impulsivity, and alcohol use disorders (AUDs) utilizing a diverse range of methods. The four papers examine various psychological processes underlying the broad construct of impulsivity that are related largely to impairments in inhibitory control. The section addresses the influences of reward sensitivity, working memory/attention control, and social functioning in the development and persistence of AUDs among individuals with ADHD. These papers are important because they approach the relation between ADHD and AUDs, and the role of impulsivity, from varied perspectives.