Smoking and human information processing

There is much evidence which indicates that smoking improves various aspects of human information processing (Wesnes 1987). The aim of the present study was to elucidate the stages of human information processing which are improved after cigarette smoking. Twelve regular smokers were tested on three cognitive tasks using a repeated measures design. Tasks used were: rapid visual information processing (RVIP), digit symbol substitution (DSST), and inspection time (IT). Performance parameters derived from these were intended to index different stages of the information processing sequence. Only those measures which involved a motor component were improved after smoking: response time on the RVIP task (P<0.025) and DSST performance (P<0.1). These findings suggest that central cholinergic pathways are involved in the late, response-related stages of the processing sequence.     

The stage-specific effect of alcohol on human information processing

Rationale Research on the limits of information processing shows that when a dual task is performed in quick succession, performance on the second task is increasingly degraded as the temporal gap between task 1 and task 2 decreases. The carry-over effect on task 2 is assumed to occur because the central cognitive stage of processing must be completed before the processing of task 2 can begin. This creates a bottleneck when the tasks are performed in close succession, but with longer delays task 2 is no longer affected by task 1.Objectives It was predicted that if alcohol disturbs (slows) the central stage of processing, shorter delays between task 1 and task 2 should reveal more intense disruption in the performance of task 2.Methods Two groups (n=16) of healthy male social drinkers performed a baseline test on a dual task. On each trial, task 1 was followed by task 2 at one of four delays (50, 200, 500, and 1100 ms). The groups then received either 0.65 g alcohol/kg or a placebo and performed the task again.Results The RT of the alcohol and placebo groups did not differ on the baseline test. In accord with the hypothesis, the alcohol group performed task 2 more slowly on the treatment test than did the placebo group at the three shortest delays (P<0.02). At the longest delay, the RT of the groups did not differ (P>0.15).Conclusions This pattern of task 2 RTs indicates that a moderate dose of alcohol can significantly impair (slow) the central, cognitive stage of information processing.     

The effects of clonidine and yohimbine on human information processing

The effects of clonidine and yohimbine on human information processing were tested in six normal volunteers ages 18–30 years. Subjects were tested in a pre-post design with sessions conducted at weekly intervals. Three drug conditions were: Placebo (lactose), 0.2 mg clonidine, and 30 mg yohimbine. Two choice reaction time (RT) tasks were used. One was a stimulus evaluation-response selection task (SERS) that has been shown to be sensitive tod-amphetamine, methylphenidate and scopolamine. The other task was to assess stimulus pre-processing and used spatial frequency as a discriminative stimulus. The principle finding was that clonidine slowed RT; this effect was significant for both tasks. In contrast, yohimbine tended to speed RT, but the effects were significant only for the spatial frequency task on some analyses while not for others. RTs to high spatial frequency stimuli were speeded more than for low spatial frequency. The effects of these two NE drugs were compared with findings withd-amphetamine and scopolamine and interpreted within the framework of a serial information processing model proposed by Callaway (1983). Specifically, it is suggested that yohimbine and clonidine affect an early pre-processing stage.     

The separate and combined effects of scopolamine and nicotine on human information processing

Previous work in this and another laboratory has shown that nicotine tablets improve the performance of a rapid information processing task and reduce the Stroop effect, whereas scopolamine has the opposite effects. The purpose of this study was to extend these previous findings by determining whether, when administered together, these two drugs have mutually antagonistic effects on task performance. Two experiments are reported, both using within-subjects double-blind Latin Square designs. In the first, six subjects received single and combined doses of scopolamine 1.2 mg and nicotine 1.5 mg, and there was some evidence that the two drugs had mutually antagonistic effects on the rapid information processing task. In the second experiment 12 subjects received the same doses, but rapid information processing testing was carried out over a longer time period and Stroop testing was introduced at the end of the 2.5 h session. Nicotine was found to counteract the depression of performance produced by scopolamine on both the rapid information task and the Stroop test. These results provide further support for the theory that central cholinergic pathways play a major role in human information processing.     

The effect of methylphenidate on information processing

Models of information processing currently popular in cognitive psychology divide the reaction process into a series of discrete separable stages. The distinction between one stage and another is verified by the additive factors method (AFM) as defined by Sternberg (1969). Task factors that do not interact with each other are inferred to affect different stages. The distinction between stimulus evaluation stages and response selection stages has been supported by brain event related potential (ERP) studies. The latency of the P300 component of the ERP is sensitive to changes in stimulus complexity but not to to changes in response complexity. The focus of this research is to determine the effects of stimulant drugs on stages of information processing using both reaction time (RT) and P300 latency within an AFM framework. four doses of methylphenidate (MP) were used in a within-subjects design to examine the effects of MP on stimulus and response processing. We found that MP speeds RT, and that this effect does not interact with the effect of stimulus complexity on RT. MP dose interacts with response complexity, the dose for optimal speeding varying with the level of complexity. The latency of P300 is increased by stimulus complexity, and not by response complexity, nor is it affected by MP. These results show that the stimulant drug acts on processes involved in response selection, rather than in stimulus evaluation. Individual differences in drug response are dose dependent, but also point to an effect on response processing.     

Effects of scopolamine and nicotine on human rapid information processing performance

In the first experiment, after a 10-min baseline test on a rapid information processing task, subjects received oral doses of either placebo, methscopolamine 1.2 mg, scopolamine 0.6 mg or scopolamine 1.2 mg, and 1 h later performed the task again for a 20-min period. Following scopolamine 1.2 mg, correct detections were significantly lower over the 20-min period, whereas no such decrement was observed in the other three conditions. In the second experiment a similar design was used to study the effects of nicotine 0.5 mg, 1.0 mg and 1.5 mg and placebo, except that post-drug testing was carried out 10 min after baseline due to the faster absorption of nicotine. Nicotine helped prevent both the decline in detections and the increase in reaction time which occurred over time in the placebo condition. These findings indicate that compounds with opposite effects on central cholinergic pathways produce opposite effects on the performance of a task involving rapid information processing, and are consistent with previous findings from this laboratory.     

Effects of d-amphetamine in human models of information processing and inhibitory control

Although stimulants are generally associated with enhanced information processing, reports of stimulant effects on behavioral functions that rely on inhibitory processes have been inconsistent. The present research tested the joint effects of d-amphetamine on information processing and inhibitory control in healthy adults (N = 22) with no reported history of illicit stimulant use or drug dependence. Information processing was measured by a rapid information processing (RIP) task and inhibitory control was measured using a stop-signal task. Performance was measured in response to 15 mg/70 kg, 7.5 mg/70 kg, and 0 mg/70 mg (placebo) doses of d-amphetamine, administered double-blind in a randomized, within-subjects design. Results showed that d-amphetamine improved information processing in a dose-dependent manner. By contrast, no enhancement of response inhibition was observed. Stimulant effects were also observed in physiological and subjective effects measures. The findings indicate that a stimulant drug can enhance aspects of cognitive functioning without producing a concomitant improvement in inhibitory control of behavior. The findings highlight the complex nature of stimulant effects on human behavior and the utility of performance tasks as models of complex behavioral and cognitive functions.     

Alcohol and information processing

Three experiments are reported which investigate the effects of acute alcohol intoxication (average blood alcohol concentration 100 mg-%) on some aspects of human information processing. The results are interpreted within the framework of a general information processing model (Smith, 1968), using the Sternberg (1969b) additive-factor method of analysis. Alcohol consistently impaired information outputting operations (i.e., response selection-organization), rather than information inputting operations (i.e., stimulus preprocessing and encoding).This study was supported in part by the Office of the Surgeon General, Department of the Army, Research Contract No. DADA-17-73-C-3157 and by USPHS Research Grant No. AA00212-06. Part of the data were reported at the 20th International Institute on the Prevention and Treatment of Alcoholism in Manchester, England.We thank Lawrence C. Cowden, Sharolyn Lentz, Judy Smith, Joe Gold, Jan Staat and Cindy Coulter for their technical assistance, management of subjects and analysis of data.     

Tolcapone improves cognition and cortical information processing in normal human subjects.

Prefrontal cortical dopamine (DA) regulates various executive cognitive functions, including attention and working memory. Efforts to enhance prefrontal-related cognition, which have focused on catecholaminergic stimulant drugs, have been unsatisfactory. Recently, the demonstration that a functional polymorphism in the catecholamine-O-methyltransferase (COMT) gene impacts prefrontal cognition raises the possibility of a novel pharmacological approach for the treatment of prefrontal lobe executive dysfunction. To explore in a proof of concept study the effects of tolcapone, a CNS penetrant specific COMT inhibitor, we performed a randomized, double blind, placebo controlled, and crossover design of this drug in normal subjects stratified by COMT (val158met) genotype. COMT enzyme activity was determined in peripheral blood. Forty-seven normal volunteers with no family history of psychiatric disorders underwent neuropsychological testing and 34 of those subjects underwent physiological measurement of prefrontal information processing assessed by blood oxygen level-dependent functional magnetic resonance imaging (fMRI). We found significant drug effects on measures of executive function and verbal episodic memory and a significant drug by genotype interaction on the latter, such that individuals with val/val genotypes improved, whereas individuals with met/met genotypes worsened on tolcapone. fMRI revealed a significant tolcapone-induced improvement in the efficiency of information processing in prefrontal cortex during a working memory test. This study demonstrates enhancement of prefrontal cortical function in normal human subjects with a nonstimulant drug having COMT inhibitory activity. Our results are consistent with data from animal studies and from computational models of the effects of selective enhancement of DA signaling in the prefrontal cortex.     

The impact of ergotamine-induced headache and ergotamine withdrawal on information processing

Ergotamine abuse and subsequent ergotamine-induced headache is a common problem in the pharmacological treatment of migraine and other headache types; often, withdrawal therapy is necessary. This study investigated whether ergotamine abuse affects information processing and whether withdrawal therapy can lead to an improvement of information processing. We designed a standardized neurophysiological retrospective (ergotamine abuse) and prospective (ergotamine withdrawal) study in a supraregional headache outpatient clinic. Seventy-one patients abusing ergotamine derivatives with subsequent daily headache were enrolled and compared to 36 migraine patients without ergotamine intake and 36 healthy subjects. Information processing was evaluated by latencies and amplitudes of visually evoked event-related potentials (ERP) before and after ergotamine withdrawal therapy. P3 latency of the ERP was significantly increased in ergotamine abuse (442 ± 45 ms) versus migraine (415 ± 40 ms) and healthy subjects (410 ± 33 ms), there was no difference between ergotamine tartrate and dihydroergotamine abuse. The migraine specific loss of habituation in information processing as measured by P3 latency could not be observed in migraine patients with ergotamine abuse. After successful withdrawal therapy in 36 patients, the abnormally prolonged P3 latency was significantly shortened (452 ± 47 ms versus 433 ± 30 ms; P < 0.004). Our findings imply that information processing is impaired by ergotamine abuse and can be improved but not normalized after withdrawal therapy. Furthermore, our data provide strong evidence that ergotamine, besides its peripheral effects, has a central mode of action. Received: 16 March 1998/Final version: 27 July 1998     

The effect of caffeine use on a visual information processing task

Past caffeine studies have shown that differences in task performance may be due to differences in habitual caffeine consumption levels of individuals. No study has yet investigated this caffeine user effect alone without confounding it with the administration of caffeine. The present study used a visual search/detection task to test whether high caffeine users have an enhanced resource capacity and therefore show higher baseline performance than low and moderate caffeine users. A three-way interaction between caffeine user (low, moderate, and high caffeine user), automaticity (automatic and non-automatic), and task difficulty (low and high) was predicted, with user effect significant for the non-automatic portion of the task. The three-way interaction was not significant, suggesting that user effect is not dependent on resource capacity. Several interpretations, based on theoretical, empirical, methodological, and statistical viewpoints, are discussed as to the non-significant caffeine user effect.     

Resource-limited information processing in alcoholism.

A concurrent-task paradigm was utilized to examine the availability of limited-capacity information-processing resources in long-term chronic alcoholism. Normal control subjects and detoxified long-term alcoholics did not differ in their performance of a primary task that required an assessment of the meaning of foveally-presented words. However, reaction time measures indicated that the abstinent alcoholics were relatively impaired in their ability to concurrently perform a secondary task that required them to detect randomly-occurring and spatially-distributed visual probe stimuli. This impairment is interpreted as reflecting an abnormal limitation in the attentional resources abstinent alcoholics have available for task performance. The relationship between this deficit and the types of biological abnormalities and neuropsychological impairments commonly observed in alcoholism is discussed.     

The effects of cigarettes of varying yield on rapid information processing performance

The purpose of this study was to determine the effects of four cigarettes having a range of covarying nicotine and tar yields on the performance of a rapid information processing task. Twenty five smokers were tested on different days with each of the cigarettes and in a non-smoking control condition. The order of testing was counterbalanced over days using a 5×5 Latin Square Design. Not only did smoking help to prevent the decrease in speed and accuracy which occurred over time in the non-smoking conditions, but it actually improved performance over baseline levels. Furthermore, the greatest improvements were found with the higher nicotine yielding cigarttes. These objectively measured effects of the cigarettes on performance matched the subjective evaluations of the effects of the cigarettes outside the laboratory, and are discussed in relation to other questionnaire studies and a survey of smoking at work.     

Cysteine-rich mini-proteins in human biology

Understanding the relationship between structure and function underpins both biochemistry and chemical biology, and has enabled the discovery of numerous agricultural and therapeutic agents. Small cysteine-rich proteins, which form a unique set of protein frameworks and folds, are found in all living organisms and often play crucial roles as hormones, growth factors, ion channel modulators and enzyme inhibitors in various biological pathways. Here we review secreted human cysteine-rich mini-proteins, classify them into broad families and briefly describe their structure and function. To systematically investigate this protein sub-class we designed a step-wise high throughput algorithm that is able to isolate the mature and active forms of human secreted cysteine-rich proteins (up to 200 amino acids in length) and extract their cysteine scaffolds. We limited our search to frameworks that contain an even number of cysteine residues ( < 20), all of which are engaged in intra-molecular disulfide bonds. We found 53 different cysteine-rich frameworks spread over 378 secreted cysteine-rich mini-proteins. Restricting our search to those that contain > 5% cysteine residues led to the identification of 22 cysteine-rich frameworks representing 21 protein families. Analysis of their molecular targets showed that these mini-proteins are frequently ligands for G protein- and enzyme-coupled receptors, transporters, extracellular enzyme inhibitors, and antimicrobial peptides. It is clear that these human secreted mini-proteins possess a wide diversity of frameworks and folds, some of which are conserved across the phylogenetic spectrum. Further study of these proteins will undoubtedly lead to insights into unresolved questions of basic biology, and the development of system-specific human therapeutics.     

The effects of caffeine and automaticity on a visual information processing task

The present study examined caffeine's effect on mental performance in contrast to a recent study (Loke and Goh, 1992) which examined the effects of caffeine user-effect on mental performance. Taken together, the studies would provide a detailed understanding of the effects of caffeine and automaticity on the visual search/detection domain of information processing. Analyses of the baseline measures of the visual search/detection task showed significant differences between low and high levels of automaticity and levels of task difficulty. Performance on the low difficulty level was higher than the high difficulty level, and performance on automatic task was higher than on non-automatic task. Caffeine, however, did not interact with automaticity and task difficulty. Therefore, given that the present study used unpractised (novice) subjects with similar levels of caffeine consumptions and personality characteristics, the visual search/detection domain of information processing is shown to be insensitive to the effects of caffeine. This supports the general view that caffeine does not affect cognition, learning, and memory performance. Also, the non-significant three-way interaction of drug, automaticity, and task difficulty would therefore suggest that caffeine does not affect resource capacity. Of note is that knowledge of drug administration assessments (drug guessing) was sensitive to the effects of caffeine in the automatic condition and not in the non-automatic condition, suggesting that the effects of caffeine are task-dependent. In contrast, the expected sensitivity of mood assessments to caffeine's effects was not shown. Since caffeine is shown to be a ‘weak’ stimulant, given its commonly known non-significant effects on mental performance, caffeine-administered subjects may lack sufficient external cues to allow them to perceive and report correctly that they were given caffeine.     

High-throughput electronic biology: mining information for drug discovery

The vast range of in silico resources that are available in life sciences research hold much promise towards aiding the drug discovery process. To fully realize this opportunity, computational scientists must consider the practical issues of data integration and identify how best to apply these resources scientifically. In this article we describe in silico approaches that are driven towards the identification of testable laboratory hypotheses; we also address common challenges in the field. We focus on flexible, high-throughput techniques, which may be initiated independently of 'wet-lab' experimentation, and which may be applied to multiple disease areas. The utility of these approaches in drug discovery highlights the contribution that in silico techniques can make and emphasizes the need for collaboration between the areas of disease research and computational science.