Cognitive and subjective acute dose effects of intramuscular ketamine in healthy adults.

Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) antagonist. Given the purported role of the NMDA receptor in long-term potentiation, the primary purpose of the present study was to further understand the dose-related effects of ketamine on memory. The study was also designed to provide information about the relative effects of ketamine on memory versus nonmemory effects and to more fully characterize ketamine's overall pattern and time course of effects. Single intramuscular injections of ketamine (0.2 mg/kg, 0.4 mg/kg) were administered to 18 healthy adult volunteers using a double-blind, placebo-controlled, crossover design. Word lists were used to evaluate episodic memory (free recall, recognition memory, source memory) and metamemory. Working memory, time estimation, psychomotor performance, and subjective effects were assessed repeatedly for 5 hours after drug administration. Ketamine selectively impaired encoding (as measured by free recall) while sparing retrieval, working memory while sparing attention, and digit symbol substitution task speed while sparing accuracy. Ketamine did not significantly impair recognition or source memory, metamemory, or time estimation. There were no hallucinations or increases in mystical experiences with ketamine. Memory measures were less sensitive to ketamine effects than subjective or psychomotor measures. Subjective effects lasted longer than memory and most psychomotor impairments. Ketamine produces selective, transient, dose- and time-related effects. In conjunction with previous studies of drugs with different mechanisms of actions, the observed selectivity of effects enhances the understanding of the pharmacological mechanisms underlying memory, attention, psychomotor performance, and subjective experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Memory and psychomotor effects of oxcarbazepine in healthy human volunteers

Cognitive and psychomotor impairments can be unwanted adverse effects of antiepileptic drugs. The present double-blind, cross-over study with healthy volunteers was designed to assess the effects of two doses of oxcarbazepine (OXCZ) (150 mg b.i.d.; 300 mg b.i.d.) and a placebo, each given over a two week period. Twelve subjects completed a battery of tests before and 4 h after morning doses on days 1, 8 and 15. Results of objective tests indicated that OXCZ improved performance on a focussed attention task and increased manual writing speed. Subjective ratings showed OXCZ increased feelings of altertness, clear-headedness and quickwittedness. OXCZ had no effect on the range of long-term memory processes assessed in this study. It is concluded that at the doses employed, OXCZ has a slightly stimulant effect on some aspects of psychomotor functioning.     

Working memory performance predicts subjective cognitive complaints in HIV infection.

The authors examined the contribution of working memory performance to subjective cognitive complaints in HIV infection beyond the influence of depressive symptoms. Thirty-six adults with HIV infection were administered neuropsychological (NP) tests of working memory, complex psychomotor efficiency, verbal learning, delayed recall, and questionnaires measuring depressive symptoms and cognitive complaints. Working memory performance, depression scores, and complex psychomotor efficiency were most strongly associated with self-reported cognitive complaints, whereas verbal learning scores and simple psychomotor efficiency showed more modest associations. Regression analyses revealed working memory performance to be the strongest NP predictor of self-reported cognitive complaints, comparable with depression scores in the amount of variance explained. These results suggest that working memory performance may be well suited to reflect how patients function in their everyday environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of transdermal nicotine and concurrent smoking on cognitive performance in tobacco-abstinent smokers.

Smokers experience cognitive decrements during tobacco abstinence and boosts in performance on resumption of smoking. Few studies have examined whether smoking cessation treatments such as transdermal nicotine (TN) ameliorate these decrements or attenuate the cognitive effects of smoking. Identifying the effects of nicotine on these tobacco-related changes in performance could guide the development of more efficacious treatments. The purpose of this double-blind, randomized, laboratory study was to use process-specific cognitive tasks to examine the effects of TN and tobacco smoking on attention and working memory in overnight-abstinent smokers (N = 124; 54 women). Each participant completed 4 sessions lasting 6.5 hr corresponding to 0-, 7-, 14-, or 21-mg TN doses, and smoked a single cigarette 4 hr after TN administration. Outcome measures were administered before and after smoking and included tasks measuring attention (alerting, orienting, and executive function), working memory (verbal and spatial), and psychomotor function. Analysis of variance (p     

Effect of some gastrointestinal hormones on antral, small intestinal and caecal myoelectrical activity in the conscious miniature pig

The effect of i.v. infusion of gastrin (CCK-4), cholecystokinin (CCK-8) and pancreatic polypeptide (PP), 20 and 200 ng/kg/min for 1 h, on gastrointestinal electrical activity and arterial pressure was studied in conscious miniature pigs. During infusion of CCK-8 a transient hypertension was observed. In the antrum, the 3 peptides provoked an increase in slow wave activity and a decrease in spike activity. In the intestine, CCK-8 induced an increase in ileal spiking activity, whereas infusion of PP resulted in an increased frequency of long spike bursts in the caecum.     

Study of Verbal Working Memory in Patients With Parkinson's Disease.

The authors examined the nature of the working memory deficit in persons with Parkinson's disease (PD). Three hypotheses were tested: a limited storage capacity, an impaired executive component, and a reduction of psychomotor speed. Verbal working memory was assessed in 14 PD patients without dementia and 14 matched control participants. Participants were administered a classical verbal span test, working memory tasks that required either updating or manipulation capacities, and motor and psychomotor speed tasks. Patients' performance was comparable to that of control participants on the verbal span test. However, results on the working memory tasks indicated a deficit in manipulation with normal updating capacities. Motor and psychomotor slowing were found in the patient group, but slowing could not fully account for the impairment observed in the manipulation task. Results indicated that there is a genuine but selective working memory impairment in patients with PD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential deficit in executive control in euthymic bipolar disorder.

Patients with remitted bipolar disorder (BD) have persistent cognitive deficits, but the nature and specificity of this deficit remain unclear. The authors evaluated the executive hypothesis of BD by determining whether (a) patients' executive deficits qualify as differential deficits, that is, that these significantly exceed deficits in other cognitive domains; (b) deficits in particular executive functions are evident, and (c) executive difficulties mediate declarative memory deficits in BD. The cognitive performance of 63 prospectively verified euthymic bipolar patients was compared with controls, using J. Baron and R. Trieman's (1980) method of testing for differences in nonindependent correlations. There were no differential deficits within the executive domain. Patients' generic executive performance was differentially impaired relative to primary verbal memory and retention in declarative memory, but not relative to their declarative recall, recognition, or their psychomotor performance. However, patients' executive deficit was not an artifact of their poor psychomotor performance. Executive performance accounted for all but a trivial portion of the between-group variance in declarative memory. Persistent cognitive difficulties in euthymic bipolar disorder (EBD) are thus usefully characterized as a generic dysexecutive syndrome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transportin: nuclear transport receptor of a novel nuclear protein import pathway

The main purposes of this study were to investigate the best parameter for describing gallbladder emptying and whether gallbladder bile emptying should be induced with a bolus injection or continuous infusion of cholecystokinin-octapeptide (CCK-8). METHODS: Gallbladder emptying was measured by dynamic cholescintigraphy. Twelve healthy subjects and six patients with gallstones were examined twice with CCK-8 infusion cholescintigraphy, 0.3 ng CCK-8 kg per min for 60 min under identical circumstances. Another six healthy subjects randomly received bolus injection (0.04 microgram/kg) and infusion of CCK-8 (0.3 ng/kg per min for 60 min), respectively, during cholescintigraphy on two separate occasions. The choice of bolus dose was based on recommendations from the CCK-8 manufacturer. The infusion dose was chosen to produce plasma CCK concentrations similar to postprandial plasma CCK levels. RESULTS: A parameter of gallbladder emptying, mean ejection fraction (EF), was defined as 100% minus the area under the time-activity curve normalized to 100% and divided by the time interval from maximum to minimum counts per minute. This parameter proved superior to the well known parameters, EFmax. and EF30, in regard to reproducibility in healthy subjects. The slope of the regression line for the mean EF was 0.998 and the intercept value approximately 0% (p = 0.0001). The mean coefficient of variation was 4%. Apart from a higher mean coefficient of variation, similar reproducibility results were seen in the six patients. The measurements of EF30 in healthy subjects scattered more widely around the mean compared to the mean EF and EFmax, which indicates poorer ability to separate normal from abnormal gallbladder emptying. Intravenous bolus injection of CCK-8 resulted in incomplete gallbladder emptying with a mean EF value of 16% (s.d. 9%; range 7%-32%) compared to 49% (s.d. 7%; range 37%-57%) following CCK-8 infusion (p = 0.004). Abdominal discomfort was observed in all subjects after administration of the bolus injection, whereas no complaints were reported during infusion. CONCLUSION: Mean EF is the best parameter for describing gallbladder emptying. Moreover, slow infusion of a physiological dose of CCK-8 is preferable to induce gallbladder emptying because it results in more complete emptying and has no side effects.     

Neuropsychological functioning in HIV-positive African-American women with a history of drug use

This preliminary investigation examined neuropsychological performance in a sample of human immunodeficiency virus (HIV)-positive and HIV-negative African-American women with a history of drug use. The study population was comprised of 10 HIV-negative, 9 asymptomatic HIV-positive, 13 symptomatic HIV-positive, and 10 acquired immunodeficiency virus (AIDS) patients. A neuropsychological battery designed to assess attention, psychomotor processing, verbal memory, and visual memory was administered to participants. No evidence of HIV-related cognitive impairment was found in patients in the early stages of HIV infection. Multivariate analyses of variance revealed significant deficits in psychomotor processing and verbal recall in persons with AIDS. These individuals showed greater difficulty in tasks requiring maintained attention and performed poorly on measures of immediate and delayed verbal recall. In contrast, HIV status was not related to visual memory, verbal recognition, or the number of errors made during a verbal recall task. The pattern of cognitive deficits observed in persons with AIDS resembles that commonly associated with subcortical pathology. The cognitive deficits observed were not related to depression or recentness of drug use.     

Indications and dangers of osteosynthesis in childhood

The relationship between long-term occupational styrene exposure and disturbances in psychological functions was studied. The exposed group consisted of 98 male workers exposed to styrene in the manufacture of polyester plastic products, and the comparison group comprised 43 concrete reinforcement workers. The duration of exposure in years and the mean mandelic acid concentration in urine (five determinations during 5 weeks before the clinical examination) and the cumulative dose of exposure were used as the indicators of exposure. The psychological functions studied were intelligence, visuomotor speed, visuomotor accuracy, memory, vigilance, and psychomotor performance. Some personality test variables were also included. In a group comparison two variables (visuomotor inaccuracy and poor psychomotor performance) out of 20 showed statistically significant differences and characterized the styrene exposed group. These findings were confirmed when workers with low and high styrene exposure were compared. One variable measuring visuomotor speed and another measuring visual memory were related to the duration of exposure (R = 0.28, p less than 0.05). In a multiple regression analysis disturbances in visuomotor accuracy, poor psychomotor performance, and lowered vigilance proved to have some connection with a high mandelic acid concentration (R = 0.49, p less than 0.01). In addition workers with disturbances in visuomotor accuracy and slight disturbances in virumotor speed had higher mandelic acid concentrations when compared with those workers without any deterioration. The results indicate that disturbances in visuomotor accuracy and, to a lesser degree, in psychomotor performance are the main findings measured by test methods used in this study and related to one indicator of styrene exposure, mandelic acid concentration. The psychological methods used revealed subclinical symptoms related to exposure, and they should aid in making group diagnoses, e.g., when additional information is needed for the determination of the threshold limit value. The deterioration found in visuomotor accuracy could be related to lowered safety in work and traffic.     

Lorazepam and scopolamine: A single-dose comparison of effects on human memory and attentional processes.

This placebo-controlled, double-blind, double-dummy, independent groups study directly compared effects of the benzodiazepine, lorazepam (2.0 mg/70 kg orally administered), and the anticholinergic scopolamine (0.6 mg/70 kg subcutaneously administered) on memory and attentional measures hypothesized to differentiate the drugs. At the studied doses, lorazepam and scopolamine produced similar decrements in psychomotor performance, free recall, and overall sensitivity in distinguishing between studied and nonstudied items on a recognition memory test. However, the drugs differed with respect to effects on working memory, response bias, metacognition, subjective awareness, and selective attention. In addition to providing information about the cognitive psychopharmacological profiles of drugs with distinct neurochemical and pharmacological mechanisms of action, this study also informs the understanding of memory and attentional processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of confounding variables in the assessment of neurobehavioural effects of chronic solvent exposure

An issue in the assessment of toxic effects on neurobehavioural function in occupational or environmental settings is the presence and relative contribution of confounding variables. Factors such as education level and alcohol use are well-known to exert effects on the performance of neurobehavioural tests. In a prospective study of a cohort of vehicle spray painters, measures of neurobehavioural function, demographic characteristics, daily habits including alcohol-use and general health status were taken from the onset of their exposure on four occasions for three full years. This study provided the opportunity to assess the relative contribution of confounding variables and the study factor, solvent exposure, on neurobehavioural function in a study design which limits the heterogeneity of the study sample. In such a design the effects of confounding would expected to be reduced. Multiple linear regression analysis was used with three confounding variables, education level, alcohol use and occupational experience as well as solvent exposure as predictor variables of neurobehavioural test performance. Although the level of solvent exposure was considerably less than the composite threshold limit value for the solvent mixtures encountered, the results indicated that psychomotor performance deteriorated with increasing solvent exposure, but only on the hand steadiness test. The confounding variables showed even greater influences on performance. Education level affected performance on both psychomotor and cognitive tests in the expected direction. Occupational experience also influenced test performance but only for psychomotor tests. With increasing time in the trade, spray painters showed significantly superior performance on reaction time, hand steadiness and visual pursuit tests. Since training in spray painting focuses on psychomotor coordination, this result would be expected. Alcohol use was associated with mixed effects on neurobehavioural function. Painters who reported using greater amounts of alcohol showed significantly poorer performance on the visual test, critical flicker fusion, but better performance on the short term memory and learning measures of the paired associates test so supporting the findings of previous studies of facilitating effects of lower levels of alcohol on memory. These findings reinforce the importance of separating effects due to confounders from effects due to toxic exposures in studies of neurobehavioural function. They emphasise the dilemma of test selection, choosing tests that are sensitive enough to detect effects due to toxic exposure but which are not affected by confounding variables.     

Effects of caffeine withdrawal on humans living in a residential laboratory.

Caffeine withdrawal was examined in caffeine-dependent humans living in a residential laboratory. Ten men and 2 women who reported daily caffeine consumption participated in a 17-day study. From 1000–1700, participants worked on computerized tasks assessing memory, vigilance, and psychomotor skills, with a 1-hr break for lunch. From 1700–2330, participants engaged in private or social, recreational activities. Subjective-effects measures were completed 10 times per day. Participants were maintained on caffeine (100 mg 3 times a day at 0945, 1345, and 1745), except on days 5–6 and 12–13, when caffeine was replaced by placebo. Caffeine abstinence selectively influenced subjective effects without altering social behavior or performance on tasks assessing memory, vigilance, and psychomotor skills. Furthermore, the effects of caffeine on food intake were enhanced after 2 days of caffeine abstinence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dimensions of everyday memory in age-associated memory impairment.

A battery of tests that uses computer and laser disk technology to simulate learning and memory tasks of everyday life, such as recalling names after introduction and remembering items on a grocery list, is described. The performance of 110 persons suffering Age-Associated Memory Impairment was factor analyzed and yielded everyday memory dimensions of verbal memory, visual memory, psychomotor speed, attention, and vigilance. These computerized performance dimensions are associated with relevant standard clinical measures of memory performance, such as the Benton Visual Retention Test and the Wechsler Memory Scale Paired-Associated Learning and Logical Memory subtests. The clinical and research utility of the computerized measures and the new diagnostic category of Age-Associated Memory Impairment are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of experimentally imposed noise on task performance of Black children attending day care centers near elevated subway trains.

Investigated whether an experimentally imposed 80 db (A) noise differentially affected the psychomotor, serial memory words and pictures, incidental memory, visual recall, paired associates, perceptual learning, and coding performance of 109 predominantly Black, low socioeconomic status (SES) 5-yr-old children attending daycare centers near and far from elevated subways. Ss were administered psychomotor tasks at the beginning and end of a noisy or quiet play condition and cognitive and perceptual tasks during a noisy or quiet test condition. Factorial analyses revealed that only psychomotor performance was significantly impaired by the 80 db (A) noise. A significant interaction between daycare center environmental noise level and test was found on the coding task, with Ss from relatively noisy daycare centers performing best under noisy test conditions and their counterparts under quiet conditions. Findings suggest that noise does not have a universal effect on children's performance, but the effects vary as a function of the nature of the task and previous exposure to noise. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alprazolam and DN-2327 (Pazinaclone) in humans: Psychomotor, memory, subjective, and reinforcing effects.

The psychomotor, memory, subjective, and reinforcing effects of DN-2327 (DN), a novel partial agonist at benzodiazepine receptors, were compared with those of alprazolam (AL) in 14 men with histories of sedative drug abuse. Placebo, DN (8, 16, and 32 mg), and AL (0.5, 1.0, and 2.0 mg) were administered orally in a randomized, double-blind, cross-over design. DN and AL produced similar maximal impairment on psychomotor and memory performance. AL produced greater increases in participant ratings of sedation and a variety of somatic symptoms that were absent following DN. Abuse liability measures showed both drugs increased liking and good effects and were categorized by participants as sedative-hypnotics; however, 2 of 3 indirect and 1 direct measure of drug reinforcement were greater with AL than with DN. The dissociation between psychomotor-memory performance effects and various subjective effects demonstrates a novel pharmacological profile of DN. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serial analysis of the effects of methimazole therapy on circulating B cell subsets in Graves'' disease

Acetylcholine (ACh) systems have been widely shown to be important for memory. In particular, ACh hippocampal neurons are critical for memory formation, though ACh innervation of other areas such as the nucleus accumbens may also be important. There has also been increasing interest in ACh and dopaminergic (DA) interactions with regard to short-term spatial memory. In a series of studies, we have found that ACh and DA agonists and antagonists given systemically interact to influence memory. The critical neural loci of these interactions are not currently known. In the present study, we used local infusion techniques to examine the role of ACh and DA transmitter systems in the nucleus accumbens and the ventral hippocampus on radial-arm maze (RAM) working memory performance. Into the nucleus accumbens of rats, we infused the nicotinic ACh agonist nicotine, the nicotinic ACh antagonist mecamylamine, the DA agonist apomorphine, or the DA antagonist haloperidol. Into the ventral hippocampus, we infused nicotine, mecamylamine, the muscarinic ACh agonist pilocarpine, or the muscarinic ACh antagonist, scopolamine. The nicotinic ACh and DA interaction was tested by a hippocampal infusion of mecamylamine alone or together with the DA D2 agonist quinpirole given via subcutaneous injection. The results confirmed that both nicotinic and muscarinic ACh receptors in the ventral hippocampus play a significant role in spatial working memory. Blockade of either nicotinic or muscarinic ACh receptors caused significant impairments in RAM choice accuracy. However, infusion of either nicotinic or muscarinic agonists failed to improve choice accuracy. The interaction of DA D2 systems in different with hippocampal nicotinic blockade than with general nicotinic blockade. Systemic administration of quinpirole potentiated the amnestic effect of mecamylamine infused into the ventral hippocampus, whereas it was previously found to reverse the amnestic effect of systemically administered mecamylamine. In contrast to the significant effects of mecamylamine in the hippocampus, no effects were found after infusion into the nucleus accumbens. Nicotine also was not found to have a significant effect on memory after intra-accumbens infusion. Neither the DA agonist apomorphine nor the DA antagonist haloperidol had a significant effect on memory after infusion into the nucleus accumbens. This study provides support for the involvement of nicotinic and muscarinic receptors in the ventral hippocampus in memory function. Ventral hippocampal nicotinic systems have significant interactions with D2 systems, but these differ from their systemic interactions. In contrast, nicotinic ACh and DA systems in the nucleus accumbens were not found in the current study to be important for working memory performance in the RAM.     

Interrelationships among everyday memory tests: Stability of factor structure with age.

Conducted an experiment in which 158 normal adults (aged 18–77 yrs) completed a battery of tests employing computer and laser-disk technology to simulate learning and memory tasks encountered in daily life. The tests were based on different experimental paradigms and were designed to assess multiple variables related to memory performance across the adult age span. Principal components analyses yielded factors of general memory, attention, and psychomotor speed. The factors remained essentially unchanged when scores were residualized to account for differences in performance related to age. Clinical and research applications of the battery are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Working memory is more sensitive than declarative memory to the acute effects of corticosteroids: A dose–response study in humans.

The effects of various doses (40 μg/kg/hr, 300 μg/kg/hr, 600 μg/kg/hr or placebo) of hydrocortisone on tasks assessing working and declarative memory function were measured in 4 groups of 10 young men. During the infusion, participants were given an item-recognition working memory task, a paired-associate declarative memory task, and a continuous performance task used to control possible concomitant effects of corticosteroids on vigilance. The results revealed significant acute effects of the highest dose of hydrocortisone on working memory function, without any significant effect on declarative memory function or arousal–vigilance performance. These results suggest that working memory is more sensitive than declarative memory to the acute elevations of corticosteroids, which could explain the detrimental effects of corticosteroids on acquisition and consolidation of information, as reported in the literature. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dose effects of triazolam and alcohol on cognitive performance in healthy volunteers.

Benzodiazepines and alcohol are widely used psychoactive substances that have performance-impairing effects. Research suggests that the impairment profiles for benzodiazepines and alcohol differ, although few cognitive psychopharmacological studies have directly compared these drugs. This double-blind, double-dummy, placebo-controlled, repeated measures study directly compared the acute dose effects of triazolam (0.125, 0.25 mg/70 kg) and alcohol (0.40, 0.80 g/kg) in 20 social drinkers. At doses that produced comparable psychomotor impairment, triazolam was more likely to impair several objective measures of cognitive performance (e.g., episodic memory, divided attention) and to slow performance across several measures. However, only alcohol impaired accuracy on the digit symbol substitution and semantic memory tasks. In addition to objective measures, both drugs impaired awareness of performance impairments (i.e., metacognition) such that participants overestimated impairment, and the magnitude of this effect was generally larger for alcohol. Only triazolam impaired other measures of metacognition (e.g., error detection on a choice reaction time task). Future research might examine the clinical implications of the performance impairments reported here given the widespread use of benzodiazepines and alcohol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)