David M. Warburton

Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease.

This single-blind, placebo controlled study reports on the effects of administering three acute doses of nicotine (0.4, 0.6 and 0.8 mg) subcutaneously to a group of Alzheimers disease (DAT) patients (n=22), young adult controls (n=24), and normal aged controls (n=24). The study extends our previous findings obtained using smaller groups of subjects. Drug effects were examined on three computerised tests: the first measuring rapid visual information processing, sustained visual attention and reaction time (RVIP task); a delayed response matching to location-order task measuring sustained visual attention and visual short-term memory (DRMLO task); and a finger tapping test measuring simple reaction time (FT task). The critical flicker fusion test (CFF) was used as a measure of perception and the WAIS digit span forwards (DS), of auditory short-term memory. Tests were graded in difficulty, titrated to avoid floor and ceiling effects so that meaningful, direct comparisons between groups could be made. Nicotine significantly improved sustained visual attention (in both RVIP and DRMLO tasks), reaction time (in both FT and RVIP tasks), and perception (CFF task — both ascending and descending thresholds). Nicotine administration did not improve auditory and visual short-term memory. There were no consistent, overall patterns of difference in performance between smokers and non-smokers in the control groups, or between males and females in any group. Despite the absence of change in memory functioning, these results demonstrate that DAT patients have significant perceptual and visual attention deficits which are improved by nicotine administration. The importance of measuring multiple abilities in future drug studies is emphasized and results are discussed in terms of nicotines actions on attention, information processing and short-term memory.

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 Smoking on Rapid Information Processing Performance

In this paper two experiments are reported which were designed to investigate the effects of smoking on the performance of a rapid information processing task. The task involves the detection of sequences of three consecutive digits of the same parity from a series of digits presented visually at the rate of 100/min. In the first experiment smoking improved both the speed and accuracy of performance above rested baseline levels, the greatest improvement occurring with the highest nicotine and tar delivery cigarette. In the second experiment smoking again improved the speed and accuracy of performance above baseline levels, while performance deteriorated over time after not smoking as well as after smoking a nicotine-free cigarette. These findings demonstrate that smoking produces absolute improvements in performance and are explained in terms of the action of nicotine on central cholinergic pathways.

Effects of Scopolamine on Stimulus Sensitivity and Response Bias in a Visual Vigilance Task

Signal detection analysis was used to examine the effects of scopolamine on a visual vigilance task. A group of non-smokers performed the 60-min task on three separate occasions, receiving a different dose of scopolamine each time. Scopolamine significantly lowered stimulus sensitivity and prevented the rise in response bias which occurred over time in the placebo condition. In a second study methscopolamine was found to have no effect on either stimulus sensitivity or response bias, showing that peripheral cholinergic blockade was not involved in the effects of scopolamine on these measures. It is concluded (1) that in this study central cholinergic blockade disrupted vigilance performance by lowering stimulus sensitivity, and (2) that this finding provides further evidence that central cholinergic pathways are involved in the control of human information processing.

NICOTINE AS A COGNITIVE ENHANCER

1. Nicotine improves attention in a wide variety of tasks in healthy volunteers. 2. Nicotine improves immediate and longer term memory in healthy volunteers. 3. Nicotine improves attention in patients with probable Alzheimers Disease. 4. While some of the memory effects of nicotine may be due to enhanced attention, others seem to be the result of improved consolidation as shown by post-trial dosing.

Effects of caffeine on cognition and mood without caffeine abstinence

The objective of this study was to evaluate the effects of low doses (75 mg and 150 mg) of caffeine on mood and cognition in healthy people, with minimal abstinence of 1 hr from caffeine. Improvements were obtained in cognition for attention, problem solving and delayed recall, but not immediate recall or working memory, but performance in the placebo condition was close to the maximum, giving little margin for improvement. For mood, there were statistically significant increase in clearheadedness, happiness and calmness and decreases in tenseness. These mood and performance-enhancing effects of caffeine cannot be seen as representing an alleviation of deficits induced by caffeine abstinence, because there was only minimal deprivation from caffeine.

Evidence of more rapid stimulus evaluation following cigarette smoking

Experienced male smokers (greater than 15 cigarettes daily) performed a rapid visual information processing (RVIP) task requiring the detection of sequences of three consecutive odd or even digits in a series presented singly on a TV screen, at a rate of 100 digits/minute. Approximately 80 targets occurred every 10 minutes. All subjects took part in three test sessions: (a) Baseline of 10 minutes on the RVIP task, (2) treatment phase of 10 minutes smoking one cigarette (0.9mg or 1.5mg standard machine delivery of nicotine) or not smoking (NS), (3) posttreatment phase of 20 minutes on the task. Before these morning sessions subjects abstained from smoking for at least 12 hours. Smoking increased the number of correct detections and decreased response time compared with pre-smoking baseline and NS sessions. Analysis of vertex Event-Related Potentials to correct detections revealed a significant reduction in P300 latency following smoking compared to NS sessions. It is suggested that smoking has speeded up stimulus evaluation processes in these individuals. These data are consistent with the common self-report by smokers that smoking aids concentration.

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.

Selective effects of nicotine on attentional processes

Abstract  Rationale: It is now well established from electrophysiological and behavioural evidence that nicotine has effects on information processing. The results are usually explained either by a primary effect of nicotine or by a reversal effect of a nicotine-induced, abstinence deficit. In addition, there is dispute about the cognitive processes underlying the changes in performance. Methods: This study has approached the first question by using the nicotine patch, in order to administer nicotine chronically. In addition, we examined the effects of nicotine on attention with a selection of tests which assessed the intensity and selectivity features of attention, using the Random Letter Generation test, the Flexibility of Attention test and the Stroop test. Results: Nicotine enhanced the speed of number generation and the speed of processing in both the control and interference conditions of the Stroop test. There were no effects on attentional switching of the Flexibility of Attention test. Conclusion: The results are consistent with the hypothesis that nicotine mainly improves the intensity feature of attention, rather than the selectivity feature.

The effects of scopolamine on working memory in healthy young volunteers

Twenty healthy young adults completed a series of nonverbal and problem solving tasks in a repeated measures design involving placebo and 0.6 mg scopolamine, administered by subcutaneous injection. Subjects completed the test battery under standard presentation conditions and with concurrent articulation, which precludes verbal recoding of test material. Under standard presentation conditions, scopolamine significantly impaired performance on the problem solving task and on tasks of visuo-spatial and spatial memory; memory for abstract shapes was not impaired. Concurrent articulation impaired performance on the shape recognition and interacted with drug treatment on the problem solving task. The results suggest that scopolamine impairs working memory, and that the decrement is at the level of the central executive mechanism rather than the subsystems which it controls.