"First-dose" response to mianserin: effects of age.
Swift, C.G., Swift, M.R., Tiplady, B..
Psychopharmacology (Berl). (1988) 96: 273-6
The effects of single 10 mg oral doses of the antidepressant mianserin on psychomotor performance, subjective sedation and supine and standing blood pressure were compared in ten young and nine elderly healthy volunteers. Immediate and residual sedation following this subtherapeutic dose was readily detected in both groups. In contrast to previous studies with benzodiazepines, the sedation effect was not accentuated in the older subjects. Subjective awareness of sedation was significant in the young but not, however, in the elderly. "First-dose" postural hypotension, presumably due to post-synaptic alpha-blockade also occurred in young subjects only. Caution may be needed on initial dosage of mianserin in young individuals who drive or undertake skilled tasks and in the elderly who may be unaware of psychomotor impairment. The reported alpha 2 receptor selectivity of mianserin might explain the lack of postural effects in the elderly, and might constitute a potentially useful characteristic in the development of new compounds

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A comparison of the CNS effects of enprofylline and theophylline in healthy subjects assessed by performance testing and subjective measures
Tiplady, B., Fagan, D., Lamont, M., Brockway, M., Scott, D.B.
British Journal of Clinical Pharmacology (1990) 30: 55-61
1 The effects of intravenous infusions of enprofylline, theophylline, and placebo on subjective ratings and on psychological test performance were studied in a double-blind crossover experiment in 12 healthy subjects who abstained from caffeine throughout the experimental procedures.

2 Mean plasma concentrations of enprofylline were: mean 2.9 mg l-1 (range 1.9-3.4). Those for theophylline were: mean 12.1 mg l-1 (range 9.0-14.4).

3 Performance on the auditory vigilance task showed a significant improvement with theophylline compared with both enprofylline and placebo. The correct detection rates (out of 90) were 50.3, 43.4 and 39.1 respectively. A similar effect was seen with finger tapping rates: 404, 394 and 390 taps min-1 respectively. Other measures showed no significant effects, although choice reaction time showed a trend towards faster responses with theophylline.

4 Subjective ratings showed that subjects were significantly more alert with theophylline than with enprofylline. Subjects reported themselves as significantly more dizzy and ill with both active drugs compared with placebo.

5 These results suggest that enprofylline largely lacks the CNS stimulant effects of theophylline, but that the incidence of other unwanted effects of the drugs may be similar.

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Effects of i.v. lignocaine on psychological performance and subjective state in healthy volunteers
Armstrong, P.J., Morrison, L.J., Noble, D., Sinclair, W.A., Tiplady, B., Wildsmith, J.A.W.
British Journal of Anaesthesia (1991) 67: 532-538
In order to assess the effects of different doses of lignocaine on performance, nine healthy volunteers aged 21-34 yr received i. v. infusions of saline, low and high dose lignocaine (mean plasma concentrations 0.92 and 1.78,µgml-l respectively) in a double-blind randomized order. The Digit-Symbol Substitution Test (DSST) and Visual Analogue Scales (VAS) were performed repeatedly and a battery of performance tests once. The median (lower, upper quartile) number of correct responses for the DSST during the infusion period was: placebo 69 (67, 77); low 74 (71, 80); high 66 (61, 75) (P < 0. 00 1, General Linear Models; all pairwise comparisons P < 0.05). None of the measures in the full battery showed any significant changes. VAS showed that subjects felt more interested (P < 0. 05), drowsy (P < 0. 0 1), dizzy, tense, abnormal, drunk and muzzy (P < 0.001) with lignocaine than with placebo. These results confirm that lignocaine can produce acute performance effects (both improvements and impairments). Subjects were clearly aware of the presence of lignocaine, suggesting that subjective reports may be a useful indicator of its CNS effects.
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Continuous attention: Rationale and discriminant validation of a test designed for use in psychopharmacology
Tiplady, B.
Behavior Research Methods, Instruments, & Computers (1992) 24: 16-21
The continuous attention task (CAT) is a test designed to assess changes in attention due to a variety of factors, for example, drugs. Subjects view a series of 3 x 3 patterns of squares on a monitor screen, each displayed for 100 msec at intervals of 1.5-2.5 sec, and respond whenever two successive patterns are identical For such a measure to be valid, factors other than attention should be investigated, and shown not to be a factor in performance. Nineteen subjects took part in a study in which information-processing rate and recall of CAT figures was measured. The results showed that a viewing time of 50-60 msec: was sufficient for 50% correct recognition of CAT figures, and that recognition with a masked presentation of 100 msec did not differ significantly from an unmasked presentation of 100 msec. Mean recall of CAT figures 2 sec after a 100 msec exposure was 98.2%. These results suggest that performance on the CAT is not limited by either information processing speed or memory capacity, but is a valid measure of the ability to sustain attention.
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Effects of Nitrous Oxide on Psychological Performance
Tiplady, B., Sinclair, W.A., Morrison, L.M.M.
Psychopharmacology Bulletin (1992) 28: 207-211
Thirty healthy volunteers took part in this doubleblind crossover study comparing 15 percent nitrous oxide in oxygen with 100 percent oxygen. They received each treatment for 45 minutes, in counterbalanced order, with no break between treatments. Central nervous system (CNS) effects of nitrous oxide were assessed by a battery of performance tests and by the Visual Analog Scales. The Digit Symbol Substitution Test showed significant slowing with nitrous oxide as did Symbol Digit Substitution and Sentence Verification. Subjects rated themselves as more drowsy, dizzy, abnormal, drunk, and muzzy on nitrous oxide than on oxygen. Significant carryover effects were seen only for the Alert-Drowsy scale at 2.5 minutes after the start of treatment, and not at any later time point. These results show that the onset and offset of the CNS effects of 15 percent nitrous oxide are sufficiently rapid to permit the study of two treatment periods within a single experimental session.
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A dose-response study of the effects of inhaled nitrous oxide on psychological performance and mood
Fagan, D., Paul, D.L., Tiplady, B., Scott, D.B.
Psychopharmacology (1994) 116: 333-338
In this five-period randomised double-blind crossover study, 12 healthy volunteers inhaled mixtures of nitrous oxide at concentrations of 0% (placebo); 5%, 10%; 20% and 40% in oxygen. Each concentration was inhaled for about 1 h, each period being on a separate day. The effects of nitrous oxide were measured using a comprehensive battery of performance tests including measures of attention, psychomotor function, memory and cognition. Mood was assessed with visual analogue scales. All tests except critical flicker fusion showed substantial effects at the highest does (40%). No measure showed evidence of change at the lowest concentration (5%). Several measures showed significant impairment at 10%, viz: digit-symbol substitution, choice reaction time (latency and total), tapping, and continuous attention. Subjects felt dizzy and muzzy on nitrous oxide, but no significant effect was seen on the Alert-Drowsy VAS. The dose-response profiles of the various tests showed substantial differences. Thus tapping was virtually linear, while choice reaction motor time and body sway showed steeply accelerating impairment with increasing dose. These results indicate that comparisons of profiles of drug-induced change must take into account the variable effects of dose before interpretations in terms of specific drug effects can be made.
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Effects of ethanol on psychomotor performance under steady-state conditions
Fagan, D., Tiplady, B., Scott, D.B.
Journal of Psychopharmacology (1994) 8; 75-80
Ethanol was administered to eight male volunteers using an oral loading dose followed by repeated small oral doses to achieve approximate steady-state drug concentrations in a double-blind placebo controlled crossover design. Ethanol or placebo were administered over a 5 h period in two sessions at least 7 days apart. The effects of ethanol were assessed using a short battery of psychomotor tests and visual analogue scales which was administered repeatedly during the steady-state period, and a long battery administered once before and once during the steady-state period. The concentrations of ethanol in plasma and breath were determined at 20 min intervals. Mean plasma concentrations of 94 mg/100 ml were obtained. Ethanol produced a clear impairment to psychomotor performance, with a 41% increase in body sway, a 61% increase in errors on a maze task, a 6.5% reduction in digit-symbol substitution and an 8% slowing in tapping. Subjective feelings of drunkenness and sedation were noted. No measure showed evidence for acute tolerance, as assessed by comparison of the slopes fitted to the performance measures in the short battery.
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Effects of chlormethiazole on psychological performance under conditions of constant plasma concentrations
Fagan, D., Scott, D.B., Tiplady, B.
Journal of Psychopharmacology (1994) 8: 164-167
Chlormethiazole was administered intravenously to six healthy volunteers (four male, two female, aged 20-33 years) using a loading dose followed by a maintenance infusion lasting ~ 90 min. Doses were individually calculated from previous pharmacokinetic investigations in these subjects to produce a target steady-state plasma concentration of 1.5 µg ml-1. Effects of chlormethiazole were determined using a short battery consisting of digit-symbol substitution, body sway and visual analogue scales, which was performed repeatedly before, during and after the active infusion. A more comprehensive battery of performance tests was performed once before and once during the active infusion. The mean plasma concentration of chlormethiazole obtained was 1.33 µg ml-1. This produced marked sedation, with subjects scoring themselves as much more drowsy on chlormethiazole than on placebo, and global impairment to performance. An analysis of the slopes of scores on the performance tests in the short battery showed no evidence of a diminution of the effects of chlormethiazole over the infusion period. The same was true of the majority of the visual analogue scales, but two scales, rating eye symptoms and nose symptoms, did decline over the period of the infusion. Recovery was rapid, subjects returning to approximately baseline levels of performance within 30 min of discontinuation of the infusion. These results suggest that acute tolerance to the CNS effects of chlormethiazole does not occur over this time scale, but is found for peripheral effects such as eye and nose symptoms.
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The use of personal digital assistants in performance testing in psychopharmacology
Tiplady, B.
Proceedings of the British Pharmacological Society, 5-7 January 1994 523P
The personal digital assistant (PDA) is a notebook-sized electronic device with a touch-sensitive screen that can display text or graphics and accept input using a stylus or by finger touch. The ability to program such devices means that they can be used to administer psychological performance measures, including both traditional computerised tests, and many of those normally given as pencil and paper tests. The latter are often difficult or impossible to program on conventional computer systems, at least without making significant modifications to the test. The small size of the device makes it suitable for use in those situations where the portability of pencil and paper tests is valuable, e.g. in testing patients on hospital wards. Data are automatically collected, avoiding the need for manual scoring of test sheets by the experimenter. A further advantage for many tests is that multiple test versions can be automatically generated, an important factor when some published tests have only one or two versions.

The use of the PDA will be demonstrated on an Apple Newton using a letter cancellation task. In such tasks, subjects are presented with a sheet on which are printed rows of letters. The subject crosses out each occurrence of a target letter, e.g. "e", working along the rows as quickly as possible. The total time is recorded using a stopwatch, and the number of correct cancellations scored. In the PDA  version, sets of letters are automatically generated and displayed on the screen. The subject uses the stylus to cancel each target letter. All scoring is automated, which is particularly beneficial for this task,  where manual scoring is time consuming.

Other types of test measure which may be programmed on PDAs include mazes, digit-symbol substitution (where the subject will be able to write the symbol, as in the original, rather than press a button, as is generally the case in automated versions), verbally administered tasks such as word-list learning, and visual analogue scales, as well as many of the tests found in current automated test systems.  The PDA is thus a very versatile device, which may prove extremely useful in administering a wide range of automated performance tests.

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Effects of nitrous oxide on psychological performance. A dose-response study using inhalation of concentrations up to 15%
Armstrong. P.J., Morton, C., Sinclair, W., Tiplady, B.
Psychopharmacology (1995) 117: 486-490
In this six-period randomised double-blind study, 12 healthy volunteers inhaled mixtures of nitrous oxide at concentrations of 0% (placebo), 3%, 5%. ,7%,  10%, and 15% in oxygen. Each concentration was inhaled for 55 min, each period being on a separate day. The order of treatments was randomised using a Latin-Square design. The effects of nitrous oxide were assessed using a battery of performance tests which included measures of attention, psychomotor function. memory and cognition. Mood was assessed using visual analogue scales. Measures of attention and psychomotor performance showed impairment at 15 % nitrous oxide. and subjective measures showed sedation at this dose. The Buschke Selective Reminding Task showed impairment to long-term recall at all doses of nitrous oxide compared to placebo. while short-term recall was impaired only at 15%. These results suggest that consolidation of memory may be particularly sensitive to disruption as a result of CNS depression.
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Electronic quality of life questionnaires: a comparison of pen-based electronic questionnaires with conventional paper in a gastrointestinal study
Drummond, H.E., Ghosh, S., Ferguson, A., Brackenridge, D., Tiplady, B.
Quality of Life Research (1995)  4: 21- 26
The use of pen-based electronic questionnaires and conventional paper questionnaires was compared in a randomized crossover study. Forty-six patients, aged 17-81 years, suffering from gastrointestinal disorders, initially filled in a paper quality of life questionnaire for familiarization purposes, then on two subsequent visits completed electronic and paper questionnaires in randomized order. At the last visit they completed a preference survey. The results showed a high degree of acceptability of the electronic questionnaire, with 57% of patient preferring electronic and 13% preferring paper, while the remaining 30% expressed no preference. Neither age, gender nor familiarity with technology showed any marked association with patients' preferences. All patients found both paper and electronic questionnaires easy to use. Data were more complete on the electronic questionnaire (100%) than on the paper (99.1%). Data handling procedures were greatly simplified. These results show that major benefits in completeness of data, speed of data flow, and data handling workload can be obtained from the use of pen-based electronic questionnaires.
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The effects of inhaled nitrous oxide on some measures of attention
Fried, M., Garrioch, M., Tiplady, B., Wildsmith, J.A.W.
Journal of Psychopharmacology (1995) 9: 123-126
This study compared the sensitivity of various measures of attention to the effects of CNS depression, using a randomised single-blind two-period cross-over study. Nineteen healthy volunteers, 10 males and nine females, aged 20-49 took part in a single session in which they inhaled 15% nitrous oxide in oxygen or 100% oxygen (placebo) through a face-mask for 45 min, followed by a 10 min interval after which they received the other treatment in counterbalanced order. They performed a battery of five attention tasks and completed visual analogue scales starting 10 min after the beginning of each inhalation period. The most sensitive measures of the effects of this dose of nitrous oxide were letter cancellation, which had three target letters to cancel, and an auditory attention task with different stimuli to the two ears. Measures of concentrated attention without distractors (continuous attention task and continuous performance task) were less sensitive, though clear effects were seen at these doses. Tests of differing complexities may involve distinct functions which could be differentially affected by different classes of drug. Thus both simple and more complex tasks should be represented in studies assessing attentional function in detail.
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Ethanol-Induced CNS Depression and Divided Attention
Millar S.A., Duncan, L., Tiplady, B.
Human Psychopharmacology (1995) 10: 327-331 
Subject performed a divided attention task in which they detected occurrences of a target letter in a stimulus figure which was a large letter made up of an array of small letters. Subjects pressed one button if the large letter was the target, another if the small letters were the target.

Performance on this task was compared to other attention and psychomotor tasks in a three-way randomized crossover study comparing two doses of alcohol with placebo in 12 healthy volunteers (six male, six female, aged 19-41). The higher dose of alcohol produced blood concentrations of 43 mg/100 ml, the lower dose 16 mg/100 ml.

Subjects reported themselves significantly more drunk on both doses of alcohol than on placebo, showed poorer long-term recall on the Buschke selective reminding task than on placebo, and made more errors on a letter cancellation task. They performed letter cancellation faster, however. No significant effects were seen on the divided attention or continuous attention tasks, though continuous attention showed a trend towards impairment.

These results suggest that the greater sensitivity showed by some multiple task combinations to low doses of drugs such as alcohol is not due to divided attention as such, but results from some aspect of task combination. The coupling of increased errors but increased speed on letter cancellation has obvious implications for the interpretation of the effects of alcohol on complex real-life tasks such as driving.

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The effects of remoxipride and chlorpromazine on eye movements and psychomotor performance in healthy volunteers
King, D.J., Best, P., Lynch, G., Mannion, M.F., Montgomery, R.C., Tiplady, B., Yisak, W.
Journal of Psychopharmacology (1995) 9: 143-149
Fifteen healthy male volunteers received single doses of 100 mg immediate release remoxipride (IR), 150 mg controlled release remoxipride (CR), 50 mg chlorpromazine (CPZ), 2 mg lorazepam (LZ), and placebo in a randomised, five-period cross-over study. Both saccadic (SEM) and smooth pursuit eye movements (SPEM) as well as a battery of psychomotor performance tests were assessed at 1.5 h intervals over 9 h following drug administration. The areas under the response-time curves and the maximum effect during the study period were analysed by analysis of variance. The most consistent impairments were produced by LZ. The neuroleptics caused impairments to SEM, and tended to impair critical flicker fusion, continuous attention and both paced and unpaced versions of the digit=symbol substitution test as well as subjective measures of sedation. Only LZ impaired SPEM. Neither paced nor unpaced psychomotor tests distinguished between neuroleptics and benzodiazepines. The low therapeutic doses of IR and CR produced similar impairments to a sub-therapeutic dose of CPZ. Selectivity of pharmacological action does not appear to predict selectivity of effect on psychomotor function.
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Ethanol and Negative Priming
Cameron, C-A., Hopper, E.S., Tiplady, B.
Human Psychopharmacology (1996) 11: 131-136 
In order to investigate the effect of ethanol on negative priming, 18 subjects aged 18-24 took part in a three-period crossover study in which they received placebo (PL), and two doses of ethanol in random order. The higher dose (E2) produced peak breath alcohol concentrations equivalent to 62.7 mg/100 ml blood, the lower dose (E1) 36.4 mg/ 100 ml. Subjects performed a negative priming task in which they detected the larger of two circles which could appear in any of four positions on a monitor. A prime trial was rapidly followed by a probe trial in which either both circles were in previously unoccupied positions (C), or the non-target was in a previously unoccupied position and the target in the same location and the same size as the previous non-target (IR). Negative priming (IR-C) was increased by alcohol, the effect being significant for the lower dose (PL: 13.1 ms; E1: 25.2 ms; E2: 21.6 ms). Other performance tasks showed an impairment to divided attention at the higher dose. Subjective drunkenness was significantly increased for both ethanol doses. These results indicate that negative priming is sensitive to the effects of ethanol in doses that do not produce major disruption to performance. These results are in the same direction as those previously noted for drugs acting upon catecholamine systems, and suggest that the specificity of the previous findings may need to be re-evaluated.
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Effects of Ethanol on Control of Attention
Newman, D., Speake, D.J., Armstrong, P.J., Tiplady, B.
Human Psychopharmacology (1997) 12: 235-241
In order to investigate the effect of ethanol on visual attention, 18 subjects aged 20-50 years took part in a three period crossover study in which they received placebo (PL) and two doses of ethanol in random order. The higher dose (E2: 0.88 g/kg, maximum 66 g for males, 55 g for females) was calculated to produce blood ethanol concentrations of 60-80 mg/100 ml. The lower dose (E1) was 75 per cent of E2. Subjects showed highly significant subjective drunkenness at both doses (p < 0.01) and on the higher dose were slowed by 6-11 per cent on most speeded measures, in agreement with previous results. In a Four-Choice Reaction Time Task, subjects responded for part of the time to a fixed, repetitive sequence, and at other times to a random sequence of stimuli. At the transition from repetitive to random sequences, subjects on ethanol showed a disproportionate slowing (60 per cent on the higher dose). This slowing may be of particular relevance to driving, as the time taken to engage control processing after a period of relatively automatic activity may be important in dealing with unexpected events on the road.
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The use of electronic diaries in respiratory studies
Tiplady, B., Crompton, G.K., Dewar,M.H., Bollert, F.G.E., Matuslewicz, S.P., Campbell,L.M., Brackenridge, D.
Drug Information Journal, (1997) 31: 759-764,
Background-Electronic diary cards have advantages over paper diaries for daily collection of data on lung function and symptoms in patients with respiratory disorders. The suitability of a pen-based electronic daily (Apple MessagePad) for this purpose was assessed in a clinical trial setting.

Methods-Two studies were carried out in patients with chronic obstructive airways disease: 1. An open randomized two-period crossover study comparing electronic and paper diaries in 22 clinic outpatients aged 18-70. Data were collected for four weeks on each type of diary, and 2. An open study in 37 patients in general practice aged 13-80. Data were collected for four weeks on electronic diaries only.

Results-In Study 1, 59% of patients preferred the electronic diary and 18% preferred paper. Both paper and electronic diaries were found to be easy to use. There were fewer problematic data from the electronic diaries (0.24% of data points) compared with paper (5.6%), resulting in improved data reliability. There were more missing data, however, with electronic diaries (8.9% vs 0.2%; p = 0.0001) which probably relates to the fact that the electronic diary did not permit retrospective entry.  Data handling procedures were greatly simplified for the electronic diaries. Problems occurred with battery life and power management. Study 2 confirmed the acceptability of electronic diaries in this patient group, and showed no battery problems using a later model of the hardware (MP 110).

Conclusions-Pen-based electronic diaries are acceptable to patients, and offer major benefits in terms of data reliability and simplification of data handling.

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Psychomotor performance: investigating the dose-response relationship for caffeine and theophylline in elderly volunteers
Bryant, C. A., Farmer, A., Tiplady, B., Keating, J., Sherwood, R., Swift, C. G., & Jackson, S. H.
Eur.J.Clin.Pharmacol. (1998) 54, 309-313 
Objective: The aim of this study was to investigate the dose-response relationship for psychomotor performance, caffeine and theophylline in healthy elderly volunteers. Methods: In a randomized, double-blind, placebo-controlled, six-period cross-over study we compared the effect of three doses of theophylline (predicted peak concentrations of 3, 6 mg · l-1 and 12 mg · l-1), two doses of caffeine (predicted peak concentrations of 4.5 mg · l-1 and 9 mg · l-1) and placebo on ten healthy elderly volunteers. Psychomotor performance was measured using a continuous attention task, symbol digit substitution test and choice reaction time. Subjective effects were assessed using visual analogue scales. Following drug administration, subjects received the test battery at 30-min intervals, up to 150 min. Maximum and mean effects from baseline on each variable were included in the analysis. Results: Significant improvement on the continuous attention task was seen at the lowest concentration of caffeine and theophylline used, while at higher concentrations there was a non-significant trend towards placebo scores. There was little effect of either drug on the subjective effects measured by visual analogue scales. Conclusion: Caffeine and theophylline increase psychomotor performance measures of attention at low plasma concentrations in healthy elderly volunteers. This effect is not increased by higher drug concentrations and there is trend towards a return to placebo scores. The lack of effect of both caffeine and theophylline on subjective measures is consistent with previous studies of caffeine in the elderly. 
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Effects of Ethanol and Temazepam on Performance in Memory and Psychomotor Tasks: a Dose-Response Comparison
Tiplady, B., Faineteau, H., Loganathan, A., Spiegelberg, M.,  Taylor, Z., Wright, P.
Human Psychopharmacology (1998) 13: 285-291 
In order to compare the effects of ethanol and a benzodiazepine on psychomotor performance and memory, 15 subjects (nine male, six female) aged 20-27 years took part in a five-period crossover study in which they received by mouth in randomised order: (1) ethanol 0.88 g/kg, maximum 66 g for males, 55 g for females; (2) ethanol, 0.75 of condition 1; (3) temazepam 20 mg; (4) temazepam 15 mg; (5) placebo. Both drugs led to significant subjective drunkenness and drowsiness; drunkenness was more marked for ethanol, drowsiness for temazepam. Psychomotor slowing in Digit/Symbol substitution tasks was similar for the two drugs. In the Four-Choice Reaction-Time Task, subjects on ethanol tended to respond faster during the sections of the task where a repetitive sequence of stimuli was given, while those on temazepam slowed down. In the sections with random stimulus sequences, both drugs led to slowing. Ethanol, but not temazepam, led to increased errors in this task. The effect of ethanol on long-term memory in the Buschke selective reminding task was very marked. The trend for temazepam was in the same direction, but not statistically significant. All performance effects were dose-dependent, except the speeding on the Four-Choice task, where the two doses of ethanol had similar effects. These results show that dissociations occur between ethanol and temazepam, ethanol producing more errors at a similar degree of slowing of performance. The effects of ethanol on memory are particularly marked relative to its sedative effect.
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Validity and sensitivity of visual analogue scales in young and older healthy subjects
Tiplady, B., Jackson, S.H.D., Maskrey, V.M., Swift, C.G.
Age ond Ageing (1998) 27: 63-66
Background: previous findings from studies on the acute effects of drugs indicate that older subjects report less change on visual analogue scales than do younger subjects, when the observed drug effects on objective performance measures are as great or greater.

Aim: to validate the use of visual analogue scales independently of internal perceptions.

Subjects and methods: 50 younger and 50 older subjects rated attributes of four animals -tortoise, crow, tiger and wasp-on a series of 10cm lines. The attributes rated included physical qualities (size, noise) and psychological aspects (danger).

Results: ratings were generally similar for the two groups, although older subjects tended to rate slightly greater differences between animals, but the variability was also slightly greater. Thus the mean difference between tiger and wasp for size was 60.1 (SD 15.6) in the younger group and 68.8 (SD 18.4) in the older group.

Conclusions: these results support the validity of the use of visual analogue scales in both groups. Explanations for the previously observed discrepancy may need to be sought in terms of an effect of age on the perception of internal changes rather than on any difference in the use of the scales.

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Computer anxiety: A comparison of pen-based personal digital assistants, conventional computer and paper assessment of mood and performance
Tseng, H-M., Tiplady, B., Macleod, H.A., Wright, P.
British Journal of Psychology (1998) 89: 599-610 
The recent growth of pen-based devices, such as the Personal Digital Assistant (PDA), offer mobility and a more natural interface than that of a conventional computer. The feasibility and application of the PDA for mood and cognitive assessment were investigated by examining possible interactions of individual characteristics and administration medium. Previous studies have provided evidence that individual characteristics of ‘computer anxiety’ and ‘private self-consciousness’ divergently covaried with mood scores measured by computer and paper methods. To investigate the relationship between individual characteristics and medium effects, 136 paid participants were allocated to and completed mood assessment tasks and a short battery of cognitive tasks by either the computer, PDA or the paper method. Self-ratings of mood measured by these three modalities covaried divergently with measures of computer anxiety and private self-consciousness. In addition, computer anxiety covaried with reaction time on the visual search task obtained on computers, but there was no such relationship when measured by a PDA. These results show that computer anxiety can affect the results of assessments of cognitive function as well as of mood ratings, and suggest that pen-based systems may have advantages over conventional computers in this respect.
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Single dose pharmacodynamics of thioridazine and remoxipride in healthy younger and older volunteers
Swlft, C.G., Lee, D.R., Maskrey, V.L., Yisak, W., Jackson, S.H.D., Tiplady, B.
Journal of Psychophannacology (1999) 13: 159-165
Phenothiazines are widely used in older patients, but little experimental work has been carried out in this age group. Two groups of healthy volunteers, a younger group (Y. six males and six females, aged 20-42 years) and an older group (O six males and eight females, aged 65-77 years) took part in a randomized double-blind three period crossover study in which they received by mouth single doses of thioridazine (Y. 50 mg; 0: 25 mg) remoxipride (Y.. 100 mg; 0: 50 mg) or placebo. Measures of central nervous system (CNS) and haemodynamic function were carried out before drug administration and at 1.5 h intervals up to 9 h post-dose, and blood samples were collected over a 24 h period. No significant differences in dose-corrected pharmacokinetic variables were found between the two groups. There was evidence of marked CNS depressant effects of thioridazine from both objective and subjective measures. The effects for remoxipride were similar, though generally less marked. After allowance was made for dose, there was little indication of any difference in degree of CNS depression between the two age groups. Haemodynamic measures showed orthostatic reductions in blood pressure with thioridazine which were particularly marked in the older group, who also showed lower compensatory increases in pulse rate. These results indicate potential problems with orthostatic hypotension with thioridazine in older patients. CNS depression may also be a problem, especially in patients with compromised cholinergic function.
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Effects of Ethanol and Temazepam on Episodic and Semantic Memory: A Dose-Response Comparison
Tiplady, B., Harding, C., Mclean, D., Ortner, C., Porter K., Wright, P. 
Human psychopharmacology (1999) 14: 263-269 
Drug-induced memory impairment is most apparent for long-term memory, but it is unclear whether this effect is restricted to episodic memory with no effect on semantic memory. Here we compare how the formation of new, semantic and episodic memories are affected by ethanol and temazepam. Eighteen subjects (12 male, 6 female- age 19-43 years; weight 52-104 kg) took part in five sessions in which they received by mouth, in random order: (E2) ethanol, 0.8 g/kg, maximum 60 g males, 50 g females; (E1) ethanol, 75 per cent of the dose for E1; (T2) temazepam 20 mg; (T1) temazepam 15 mg; (P) placebo. They carried out a series of tests including learning of invented 'facts’, a measure of the acquisition of new semantic memory; the Buschke test, a measure of short- and long-term learning of words; Digit-Symbol substitution, a measure of psychomotor speed; and Visual Analogue Scales. Both acquisition of new semantic memory and the long-term measure from the Buschke were impaired by both drugs. The effects of ethanol were more marked than those of temazepam for the memory tests at the doses used here, particularly for the Buschke. Psychomotor impairment as assessed by Digit-Symbol substitution speed was equally affected by both drugs. Subjects rated themselves more drunk on ethanol than on temazepam, but drowsiness was similar for the two drugs. These results show that both drugs impair the acquisition of new semantic memory as well as new episodic memory, and suggest that it is new long-term memory formation that is impaired by these drugs and not the formation of a specific type of memory, such as episodic memory.
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Trail making without Trails: The use of a Pen Computer Task for Assessing Effects of Brain Injury
Fryer, S., Sutton, E., Tiplady, B., Wright, P.
Clinical NeuropsycbologicalAssessment (2000) 2: 151-165
A version of the trail making task (TMT) has been set up on a pen computer. Subjects tap on a sequence of screen targets instead of drawing a line connecting targets on paper.

Two studies, were carried out. The first was a between group comparison of paper and computer versions of TMT in healthy volunteers (24 males, 36 females, aged 18-38 years). The second study compared patients with brain injury (24 male, 8 female, aged 14-74) with a control group (15 males, 6 females, aged 18-68), who were administered both forms of TMT and a Sentence Verification task (SEVT) in randomised order

The first study confirmed previous findings that factors such as trail length and stimulus interference as well as sequence type (A: numeric; B: number/letter alternation) have important effects on performance. Results were similar between paper and computer versions of the task. The second study showed that TMT A, TMT B as well as SEVT all showed good discrimination between patients and controls, comparable to that reported previously; that discrimination was very similar for paper and computer versions of the tasks; and that the computer version of the task was acceptable to users, and was preferred to paper by a majority of patients.

The computer version of TMT offers advantages over paper in that (1) presentation is standardised; (2) errors are handled in a more systematic way than is possible with paper; and (3) multiple equivalent versions are straightforward to generate.

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Use of pen-based electronic diaries in an international clinical trial of asthma
Tiplady, B., Jamieson, A.H., Crompton, G.K.
Drug Information Journal ( 2000) 34: 129-136
The use of pen-based electronic diaries was evaluated in an international clinical trial
of asthma. The study compared bambuterol with salmeterol in nocturnal asthma, and was carried our in Italy, Norway, and the United Kingdom. Two hundred and sixty-five patients were enrolled, of whom 135 were randomized and 118 completed the eight-week study period. Patients completed the electronic diary at home each morning and evening
throughout the eight-week study period. Data could be entered into the diary only within specified time "windows". No retrospective entry was permitted.

Data collection was very satisfactory. Ninety-four percent of patients enrolled completed their diaries during the run-in period to the required standard for inclusion in the study (at least five out of the last seven days of the run-in complete). After randomization, entries were completed on 86% of scheduled occasions.

At the randomization stage, a review facility was provided for the investigator which gave a summary of the run-in data to indicate whether the patient met the inclusion criteria. This saved work for the investigators, and helped to reduce the rate of incorrect randomization compared to a previous similar study.

Data handling was substantially faster than in similar paper-based studies, contributing to locking the database well within schedule. Thus, the potential gains seen with this method in earlier evaluation studies have been realized in a full-scale clinical trial.

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Validity and sensitivity of a pen computer battery of performance tests
Cameron, E., Sinclair, W., Tiplady, B.
Journal of Psychopharmacology (2001) 15: 105-110
This study compared administration of performance tests and visual analogue scales (VAS) using a newly developed pen computer (PenC) battery with established tests using either paper and pencil (PP) or conventional computer (BBC). The performance of 47 subjects (23 male, age 18-45 years, weight 51-112 kg) was compared on the two systems after a dose of ethanol (0.8 g/kg up to a maximum of 60 g for males, 50 g for females) or placebo in a double-blind two-period randomised crossover study.      Mean (standard deviation) blood ethanol concentrations (breathalyser) were 94.5 mg/100ml (21.9) at the start of the test battery (30 minutes post-drink) and 80.2 (13.0) at the end of the battery (75 minutes post-drink). Ethanol effects were found in all tests, with most outcome measures showing significant slowing or loss of accuracy. Results from the Rapid Visual Information Processing, Sentence Verification and Continuous Attention tasks show that the ethanol-placebo difference and the statistical significance of this difference are in close correspondence for the two modes of administration. The pen computer versions of these tasks may therefore be used as direct replacements for the previous versions. Digit-Symbol and Maze tasks did not correspond so closely both showing differences in the speed-accuracy  trade-off between the two modes. These tests however are sensitive to the effects of ethanol, and may be useful in their own right.      Principal component analysis suggested that VAS may be grouped into two factors, “I: functional integrity”, including measures of alertness and perceived proficiency, and “II: mood”, including happiness and sociability. Factor I showed substantial effects of ethanol, while Factor II was unchanged. There was close agreement between the results from PP and PenC for both factors as well as for the Sober—Drunk scale, which showed the expected effects of ethanol. Thus pen computer VAS perform in a similar way to the paper and pencil versions.
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Ethanol, Errors, and the Speed-Accuracy Trade-Off.
Tiplady, B., Drummond, G.B., Cameron, E., Gray, E., Hendry, J., Sinclair, W., Wright, P.
Pharmacology, Biochemistry and Behavior (2001)  69: 635-641
Ethanol has been shown to have a relatively greater effect on error rates in speeded tasks than temazepam, and this may be due to a differential effect on the Speed-Accuracy Trade-Off (SATO). This study used different instruction sets to influence the SATO. Forty-nine healthy volunteers (24 males, aged 18-41 years) were allocated at random to one of three instruction conditions – emphasising accuracy; neutral; and emphasising speed. After familiarisation, they took part in two sessions spaced at least four days apart in which they received either ethanol (0.8 g/kg, max 60 g males, 50 g females) or placebo in randomised order. Tests were administered starting at 30 and 75 minutes post-drug. Instructions significantly affected performance. In two maze tasks, one on paper , the other on a pen computer, the pattern of instruction effects was as expected. A significant increase in errors with ethanol was seen for both maze tasks, and there was a tendency to speed up with ethanol (significant only for the pen computer task). Responses to fixed stimulus sequences on the Four-Choice Reaction Test also showed a tendency to speed up and an increase in errors with ethanol, while all other tests showed both slowing and increases in errors with ethanol compared to placebo. Error scores are consistently increased by ethanol in all test situations, while the effects of ethanol on speed are variable across tests.
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Effects of temazepam on memory and psychomotor performance: A dose response study.
Begg, A., Drummond, G., Tiplady, B
Human Psychopharmacology  (2001) 16: 475-480
We tested psychomotor performance and memory and assessed mood for 3 hr after single doses of placebo (PL), 20 mg temazepam (T20) or 30 mg of temazepam (T30) given to 6 healthy females aged 21-23, in a randomised three-period crossover study. A composite measure of psychomotor speed showed a dose-dependent slowing (Page’s L trend test: p<0.001; sign test PL vs T20 and T30 vs T20: p<0.05). Errors were increased, significantly for some measures. Explicit memory (Buschke selective reminding) showed significant impairment of long-term but not short term memory (Page’s L trend test: p<0.05). The form of the dose response curve was positively accelerating, with the difference between performance on T30 and T20 at least as great as that between T20 and placebo. Visual analogue scales showed a decrease in a factor representing functional integrity (Page’s L trend test: p<0.05; sign test PL vs T20: p<0.05), but no changes in mood. These results show that T30 is a useful extension of the dose range of temazepam, being well tolerated, and producing a substantially greater impairment of performance than T20.
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Interactions between alcohol and caffeine in relation to psychomotor speed and accuracy
Mackay, M., Tiplady, B., & Scholey, A. 
Human Psychopharmacology (2002:) 17: 151-156.
Unlike other CNS depressants, alcohol intoxication is associated with increased error rates, coupled with unaffected (or speeded) response rates during psychomotor and cognitive processing. The present study examined whether concurrent consumption of caffeine may differentially affect these aspects of alcohol and performance.
A randomised, double-blind, placebo-controlled design was utilised where sixty-four healthy young volunteers received either 0.66g/kg alcohol, caffeine (110 - 120 mg), both or neither. Performance was assessed using a Four Choice Reaction Time task (FCRT) with elements of repetitive (predictable) and random stimuli sequences and the Digit Symbol Substitution Task (DSST).
Individuals on alcohol made significantly more errors during both fixed and random FCRT sequences, and there was evidence of weak antagonism of these effects by caffeine on the latter measure. On the DSST test of psychomotor speed, alcohol was associated with a significant slowing, the caffeine group were significantly faster and there was clear antagonism of the effects of alcohol by caffeine. These findings confirm that alcohol consumption is associated a greater number of errors and provide some evidence for task-specific antagonism of alcohol's cognitive effects by caffeine..
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Effect of Ethanol on psychomotor performance and on risk taking behaviour
Farquhar K, Lambert K, Drummond GB, Tiplady B, Wright P. 
Journal of Psychopharmacology (2002) 16: 379-384
Ethanol may increase the willingness to take risks, but this issue remains controversial. We used a risk-taking paradigm in which volunteers answered a series of general knowledge questions with numerical answers and were asked to judge the length of a line that would just fit into a given gap. A maximum score was given for an exactly correct answer. For answers that were less than the correct value, the score was reduced gradually to zero, while answers even slightly over the correct value were penalised considerably. Total points were rewarded by cash payments, so volunteers were taking real risks when making their responses. Performance was assessed in a two-period double-blind crossover study, comparing ethanol (0.7g/kg) with placebo in 20 female volunteers aged 19-20. Tests were carried out before and at 45 minutes after dosing. Mean ethanol blood alcohol concentrations were 65 mg/100ml (SD 10.5). Ethanol impaired the skill/ability measure of the length estimation test (standard deviation of difference between length of line and gap), which increased from 5.9 to 6.6 (p<0.05), indicating reduced accuracy of estimation. The risk measures in both tasks were not significantly affected. The skill/ability measure in the general knowledge task was not significantly affected. Other performance tests showed that ethanol produced the expected impairment of both speed and accuracy. These results suggest that risk-taking is not increased by ethanol at doses approaching the UK legal limit for driving. .
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Assessment of postsurgical recovery after discharge using a pen computer diary
Begg, A., Drummond, G., & Tiplady, B.
Anaesthesia (2003)  58: 1101-1105
We assessed patients after their return home following gynaecological surgery, using a daily electronic diary. Thirty-two females aged 27-77 years took part. After a hospital stay of 1-6 days (mean 2.3), they were given a pen-based electronic diary and asked to record symptoms and other data over one month. They also completed a questionnaire at the end of the study. Substantial effects on quality and duration of sleep, pain during both the night and day, interference with daily activities, energy, and ability to concentrate were recorded, mostly during the first week of treatment. Symptoms reported in the final questionnaire correlated significantly with diary data. Most patients found the electronic diary easy to use, and none found it difficult. Daily electronic diaries are an acceptable method of obtaining better information on the extent and duration of symptoms and other difficulties after discharge following surgery.
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A comparison of target-controlled therapy with patient-controlled administration of propofol combined with midazolam for sedation during dental surgery.
Burns, R., McCrae, A. F., & Tiplady, B.
Anaesthesia (2003) 58, 170-176
Forty anxious day case patients undergoing extraction of third molar teeth under local anaesthesia with sedation, were studied in a randomised double-blind controlled trial. A target-controlled infusion of propofol was compared with patient-controlled propofol for sedation, combined with a small dose of midazolam to improve amnesia. The objectives of the study were to measure the total dose of propofol used by the two groups and assess recovery and patient satisfaction. The mean dose of propofol used in the patient-controlled sedation group was significantly less than the target-controlled group (p < 0.00007). Five patients became over-sedated in the target-controlled group compared with none in the patient-controlled group. Only one of the three tests of performance showed that the target-controlled patients were more sedated. Patient satisfaction was high in both groups despite a greater recollection of events in the patient-controlled group.
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Errors in performance testing: A comparison of ethanol and temazepam.
Tiplady, B., Hiroz, J., Holmes L., Drummond, G.
Journal of Psychopharmacology (2003) 17: 41-49
Rationale: Both ethanol and benzodiazepines impair psychomotor function. Previous work has suggested that ethanol may have a greater effect on errors while benzodiazepines may cause greater slowing, but this has not been tested in a direct comparison. 
Objectives: To assess the effects of ethanol, at blood concentrations of approximately 80-100 mg/100 ml, compared to two doses of temazepam (20 mg and 30 mg) on psychomotor speed and accuracy and on long term memory.
Methods: Sixteen healthy volunteers (8 male, aged 20-25 years) in a four period placebo controlled crossover study. Performance was evaluated using ANOCOVA (critical significance level p=0.05) comparing the areas under the response-time curves. 
Results: Performance on a psychomotor maze showed an almost complete dissociation, with ethanol leading to a substantial and significant increase in errors with little effect on speed, while temazepam slowed performance with no significant change in accuracy. Other tasks showed a similar pattern, but the dissociation was less complete. Handwriting size was substantially increased by ethanol, but not by temazepam. Information processing capacity and long-term memory formation were reduced by a similar amount both for ethanol and 30 mg temazepam. 
Conclusions: The faster, more error-prone, behaviour on ethanol than a with similarly-impairing dose of temazepam has clear implications for the relative potential of the two drugs to contribute to accidents. The results are also important in understanding the differential effects of drugs with different mechanisms of action on human performance.
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Use of a digital pen to administer a psychomotor test
Tiplady B, Baird R, Lütcke H, Drummond G, Wright P
Journal of Psychopharmacology (2003) 17 (Suppl 3): A71
Psychomotor and cognitive tasks are increasingly administered by computer, and the use of a computer with pen input has many advantages (Tseng et al., 1998, British Journal of Psychology 89: 599-610). However the screens on such computers are too small for some types of test, and the feel of the pen on the screen is not the same as that of paper, raising questions of equivalence with speeded tests. Recently a new digital pen and paper system (Anoto) has been introduced which records pen strokes as they are made by scanning an irregular pattern of small dots on the paper. The dots are not visible in normal use, the paper simply appearing slightly off-white. In order to assess the suitability of this system for psychomotor testing, we studied seven volunteers, 3 male, 4 female, aged 20-22 who were taking part in a larger study on ethanol and motor control. They were asked to draw ten 1cm squares as quickly as possible on a sheet of paper without being able to see what they were drawing. They did this before and 45 minutes after consuming a dose of ethanol producing blood alcohol concentrations of 60-85 mg/100 ml (mean 73). The pen used was the Logitech io, which provided xy coordinates of the position of the pen as well as pressure information at a fixed sampling rate of 100 Hz. Data were transferred to an XML file on a PC. This was then analysed using SAS. The sizes of the sides of the squares drawn were increased by 6.8% in the ethanol condition (p<0.05, Wilcoxon signed ranks test), showing an increase in size similar to the findings from other measures in the study. The mean time to write the squares decreased by 5.2%, but this difference was not significant. These results show that the digital pen is a practicable method of administering a psychomotor test. It allows automation of data collection but also obtains information on stroke speed that cannot be obtained using a normal pen.
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Effects of ethanol on kinaesthetic sensation
Tiplady B, Baird R, Lütcke H, Drummond G, Wright P
Journal of Psychopharmacology (2003) 17 (Suppl 3): A72
Both ethanol and nitrous oxide increase the size of handwritten words, while temazepam does not have this effect (Legge et al., 1964,Percept Motor Skills18: 549-558; Tiplady et al., 2003, J Psychopharmacol 17: 41-49). We studied the suggestion of Legge et al. that this is due to an effect on kinaesthetic feedback. 30 healthy volunteers, 15 male, aged 18-29 years (mean 21) weighing 55-92 kg (mean 69.3) received oral ethanol producing peak blood alcohol concentrations of 65-110 mg/100 ml (mean 86). Testing was carried out before the drink (BL) and at 45 and 90 minutes post-drink. Ethanol increased handwriting size for simple words, and also increased the size of copied patterns and of signatures. Errors were increased on maze tasks, but speed was unchanged, indicating that the pattern of ethanol effects was as expected. Volunteers were asked to move a pen from a starting position a distance of 10 cm either horizontally (H) or vertically (V), with a reference line in view (IV) or with no reference line (NV). The movements were out of the volunteer's sight. The estimated lengths were increased after ethanol in all conditions, as shown in the Table Volunteers also visually  estimated a distance of 10 cm  moved by the experimenter (E). This estimate was much less affected.

Task

BL

45 minutes

90 minutes

H-IV

11.1

12.2 (10%) **

12.1   (9%) **

H-NV

11.2

12.4 (11%) ***

12.4 (11%) **

V-IV

13.6

14.5   (7%) ***

14.5   (7%) **

V-NV

13.7

14.7   (7%) ***

14.3   (4%) n.s.

E

  9.8

10.2   (3%) **

10.1   (2%) *

Mean estimated lengths in cm. In brackets, % change from baseline.
*** p<0.001; ** p<0.01; * p<0.05; n.s. not significant (Wilcoxon signed ranks test, compared to baseline)

These results support the suggestion that ethanol increases handwriting size by an effect on kinaesthetic perception. A similar mechanism could be involved in the effects of ethanol on other psychomotor measures including tracking, and standing steadiness. Further studies are needed to determine the relationship between this
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Effects of clonidine on psychomotor performance and memory
Tiplady, B., Goodall, H., van Rossum, B., Drummond, G.
Journal of Psychopharmacology (2003) 17 (Suppl 3): A73

Clonidine is a centrally acting anti-hypertensive drug which also has sedative effects, and is used both to reduce blood pressure and  for pre-medication before surgical procedures. It has been suggested that clonidine may have a relatively greater effect on subjective sedation that on objective performance (Frith et al., 1985, Psychopharmacology 87: 490-493). It is important to use dose-ranging studies to assess such profiles. The present study was designed to obtain information on the tolerability of various doses of clonidine as well as investigating relative effects on objective and subjective measures. Eleven healthy volunteers, 10 male, aged 20-23 years, weighing 60-97 kg (mean 73.8) took part in a within-subjects study in which they were to receive increasing doses of clonidine (150, 300 450 µg) or placebo on four separate days. The position of the placebo arm was randomised. Measurements of blood pressure (body position 0, 40 or 80 using a tilt table) subjective feeling and performance were made over the next 3 h. All volunteers showed a decrease in mean arterial pressure >= 30% at a single assessment or >= 20% at more than one post-dose assessment during the 300 µg session. This met the pre-determined stopping rule, and no volunteer therefore progressed to the 450 µg dose. The table shows that both speed and accuracy on Memory Scanning were impaired at 300µg and that drowsiness was increased by both doses. Psychomotor performance (Maze Task) and attention (Number Pair Matching) were not significantly affected.

Test Measure

Placebo

150 µg

300 µg

S.E

Memory Scanning  

 

 

 

 

RT Correct (ms)

784

813

942 *

51.1

N incorrect

4.30

3.85

5.74 *

0.71

Visual Analogue Scale

 

 

 

 

Alert—Drowsy (mm)

31.6

46.1 *

66.4 *

5.55

Figures are mean values of the normalised areas under the response-time curve.
* significant difference from placebo, p<0.05 (Analysis of Variance)

These results suggest that 300 µg is close to the maximum dose of clonidine that is suitable for use in volunteer studies in psychopharmacology, and demonstrate marked effects of this drug on working memory function.
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Effect of ethanol on judgments of performance
Tiplady, B., Franklin, N., & Scholey, A.
British Journal of Psychology (2004)  95: 105-118.
Ethanol impairs cognitive and psychomotor performance, although the precise reasons for this remain unclear.We investigated the effect of ethanol on individuals' judgment of their performance. Eighteen healthy volunteers (19-22 years) received a high dose of ethanol (0.8 g/kg for males and 0.7 g/kg, for females), a medium dose (75% of the high dose) and a placebo in counterbalanced order on three study days. A general knowledge (GK) test was administered on a pen computer 75 min after the drink. An adaptive algorithm adjusted the difficulty of questions so that scores were similar on all three study days. Volunteers then rated how well they believed they had performed the GK task using a visual analogue scale. A battery of other performance tests and mood ratings was also completed both before and after the GK test. These showed the expected effects of ethanol. There were no significant differences in scores on the GK test between treatment sessions. There was a highly significant dose-dependent increase with ethanol on volunteers' ratings of their performance on this test. These findings suggest that ethanol leads to an overoptimistic assessment of ability which may contribute to ethanol's impairment of performance
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Electronic diaries and questionnaires:
Designing user interfaces that are easy for all patients to use
Mikael Palmblad, Brian Tiplady
Quality of Life Research (2004) 13:1199-207
We propose a set of requirements for designing handheld computer systems for electronic collection of patient diary and questionnaire data in clinical trials: (1) The system should be suitable for use by all types of patient to be included in the clinical trial programme; (2) Patients must be capable of using the system and be comfortable with it after a short period of training; (3) Responses should always result from an action by the user – defaults should not be taken as data; (4) All information necessary to a given question should be simultaneously available on the screen. This applies to both the questions and the response options.
We present guidelines as to how these requirements may be met in practice, so that bias may be avoided both in patient selection and in the responses made; so that electronic data collection may be as effective as possible, and so that study procedures are convenient and unobtrusive for the patients.
 
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Development of tests of psychological performance using a digital pen
Brian Tiplady
Proceedings of the British Psychological Society (2004) 12:72
Purpose: To automate the administration of paper and pencil tests, thus standardising administration, simplifying the experimenter's task, and allowing the collection of more detailed information about task performance. Background: Performance tests are increasingly being automated using computers or dedicated equipment, but this approach is problematic for many paper-based tests. In some cases, such as mazes, automation is possible using pen-based computers, but there are limitations with screen size. It is also possible that the different "feel" of a stylus on a screen might be a factor. Recently a digital pen/paper system (Anoto®) has become available which allows automatic recording of the position of a conventional ink pen on paper. Methods: Test material is printed on special paper which has an irregular pattern of dots. These dots are small enough to be invisible in normal use. The digital pen has a camera which records the dot pattern, and from this calculates the position of the pen on the sheet. The accuracy of this position is about 0.3 mm, and the position is recorded 100 times per second, allowing details of both position and speed of each written stroke to be recorded in considerable detail. This approach is suitable for a variety of test types, including maze/tracking tasks, figure drawing or copying, trails, handwriting analysis, and visual analogue scales. Conclusion: The digital pen may be a valuable addition to the methods available for automated test administration.
 
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Selective effects of clonidine and temazepam on attention and memory
Tiplady, B., Bowness, E., Stien, L., & Drummond, G. B
Proceedings of the British Psychological Society (2004) 12:72
Objectives: To compare the effects of temazepam (a GABAA receptor antagonist) and clonidine (an alpha-2 adrenoceptor agonist) on tests of psychomotor function, attention, memory, logical reasoning, and mood..Design: Five-period crossover comparing placebo (PL); clonidine 150 µg (C1);  clonidine 300 µg (C2); temazepam 15 mg (T1) and temazepam 30 mg (T2) in separate sessions at least four days apart. Methods: Fifteen healthy volunteers, 7 male 8 female, aged 18-25 years (mean 21) and weighing 51-127 kg (mean 69) took part in a familiarisation session and then in five experimental sessions each lasting about 4 hours. A baseline test battery was administered after which volunteers received one of the five treatments by mouth according to a Williams square allocation. Testing was again carried out at 45, 90 and 135 minutes post-dose. Results: Analysis of Variance was used to test for overall treatment effect, followed by pair-wise comparisons. The sedative and impairing effects of both drugs were clearly demonstrated, particularly in the larger doses. In general the impairments to performance due to T2 were greater than those due to C2. Exceptions were the Arrow Flanker Task, where the effect of C2 was substantially greater than T2, and Selective Reminding, where long term memory formation was very substantially impaired by T2 but where no significant effect of clonidine was observed. Conclusions: Clonidine differs from temazepam in causing a relatively greater impairment on a measure of attention in the presence of distractors, while having little effect on formation of new memories
 
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The use of a mobile phone to administer a cognitive task
Tiplady, B.
Poster presented at the Psychobiology Section of the British Psychologiacl Society, Lake District, September 2004
Background: Portable handheld devices are increasingly being used to administer cognitive and psychomotor tests outside the laboratory, for example in a hospital ward, at home, in clubs or music festivals, or for driver assessment at the roadside. The use of a mobile phone would increase portability and also allow tests to be run on a volunteer's own phone.
Methods: The Arrow Flanker Test was evaluated. Five symbols appeared on the screen. The central symbol (target) was a left or right arrow. The other four (non-targets) were all the same, and could be congruent (arrows in same directions as the target); incongruent (opposite direction); neutral (squares); or nogo (crosses). The task was to press the left or right button corresponding to the target direction as quickly as possible unless the non-targets were crosses, in which case no response should be made. The Java test program was run on a Nokia 6610 (27 X 27 mm screen). The test lasted about 3 minutes. Eleven volunteers aged 18-24 years practised the task twice, and then carried out the test four times.
Results: No volunteer reported difficulty with the tests.  Mean response times were: congruent (easiest condition) 627 ms; neutral 643 ms; incongruent (most difficult condition) 720 ms (Page's L test; p < 0.001).
Conclusions: The highly significant increase in response times with increasing difficulty is in agreement with previous results and indicates that the test is functioning as expected. Mobile phones are a practical platform for performance test administration
 
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Zig-zag tracking: A test of psychomotor speed and accuracy designed for repeated administration
Tiplady, B.
Journal of Psychopharmacology (2004):  18, A48
Introduction. Speed and accuracy of tracking performance may be assessed in a number of ways, including the use of "maze" tasks where a track is followed with a pen. A new format for presenting such a task has been developed to allow the generation of multiple equivalent versions.
Methods. The task consists of a regular grey zig-zag track 9 mm wide running from top to bottom of a sheet of A4 paper, on which are superimposed a series of circular obstacles about 4 mm in diameter. The task is to follow the track with a pen as fast as possible while avoiding the obstacles. The total time and an error score based on hitting either obstacles or the side of the track are recorded. The test was evaluated in a study in which 30 female and 27 male volunteers aged 18-25 were randomized to receive a single dose of either ethanol or placebo. Performance on zig-zag tracking (ZZTR) and other tests including the Gibson Spiral Maze (GSM) was assessed before ethanol and at 30, 75 and 105 minutes post dose. Tests were practiced twice before baseline assessment.
Results. Maximum blood alcohol concentration were obtained at 30 minutes post-drink (mean 77.1 mg/100ml, S.D. 24.0). Both ZZTR and GSM showed increased error scores with ethanol at all time points, with no significant effect on speed. Maximum effects were seen at 30 minutes. Error score for ZZTR at 30 min  increased from 16.5 to 25.6 (t=2.41, p<0.05), that for GSM increased from 6.2 to 11.7 (t=2.39, p<0.05). GSM but not ZZTR showed a marked practice effect, with error score decreasing from 8.4 baseline) to 5.1 (105 minutes) in the placebo group.
Conclusions. These data confirm results from previous studies showing that ethanol impairs accuracy but not speed of performance in this type of tracking task (Tiplady et al., J. Psychopharmacol 17: 41-49, 2003). Error scores on both tracking tasks showed similar sensitivity to the effects of ethanol, but the lack of a practice effect with ZZTR indicates potential advantages for this test. The regular structure of the ZZTR allows the standardized generation of multiple versions of equivalent difficulty, particularly important in psychopharmacology, where a test may be performed many times by a particular volunteer.
 
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Zig-zag tracking: Evaluation of a test of psychomotor speed and accuracy designed for repeated administration
Tiplady, B.
Poster presented at the Psychobiology Section of the British Psychological Society, Lake District, September 2004
Background. Tracking performance may be assessed in a number of ways, including the use of "maze" tasks where a track is followed with a pen. A new format for presenting such a task has been developed which is suitable for use with a digital pen.
Methods. The zig-zag tracking task (ZZTR) consists of a regular grey zig-zag track with circular obstacles on an A4 sheet of paper. The task is to follow the track with a pen as fast as possible while avoiding the obstacles. The total time and an error score based on hitting either obstacles or the side of the track are recorded. Seven female and four male volunteers aged 18-25 took part. Performance on ZZTR and the Gibson Spiral Maze (GSM) were compared between ethanol and placebo conditions of a larger study.
Results. Maximum blood alcohol concentrations in the ethanol condition were: mean 77.1 mg/100ml, S.D. 21.7. The error score for ZZTR was 12.2 on placebo and 20.1 on ethanol, an increase of 65% (t=5.25, p<0.0001). For GSM the error score was 4.7 on placebo and 7.8 on ethanol, an increase of 66% (t=3.16, p=0.0040).  Neither task showed any marked effect on speed.
Conclusions. These data confirm results from previous studies showing that ethanol impairs accuracy but not speed of performance in this type of task. The ability to generate multiple equivalent versions may be particularly useful in experimental situations where a test has to be repeated many times by an individual volunteer.
 
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Effects of ethanol on awareness of errors and judgements of performance
Acons, K., Chan, L. S., Drummond, G. B., Tiplady, B.
Paper presented at the Psychobiology Section of the British Psychological Society, Lake District, September 2004
Background: Ethanol produces a distinctive pattern of performance impairments characterised by an increase in error rates with relatively little change in speed. A dynamic model suggests that feedback from errors is monitored, and leads to continuous adjustment of the speed-accuracy trade-off. Ethanol might impair this feedback, leading to faster, more error-prone performance than with other impairing drugs.
Methods: Seven female and four male volunteers aged 18-24 received placebo, ethanol, promethazine 20mg and promethazine 30 mg on separate days. Error processing was evaluated using a computerised four choice reaction test (FCRT) in which volunteers verbalised to indicate errors. A microphone monitored these reported errors, which were compared to actual errors recorded by the computer. A breathalyser was used to measure blood alcohol concentration (BAC) over the three hour period.
Results: Maximum BAC was obtained at 30 minutes (mean 77.1 mg/100ml, S.D. 21.7). Ethanol greatly increased the number of FCRT errors (Placebo: 1.8; Ethanol 5.2; p<0.001 - ANOVA followed by t-test). The proportion of errors detected was slightly, but not significantly reduced by ethanol. Ethanol impaired performance in most other tests employed. Promethazine had little effect except on subjective sedation.
Conclusions: The effect of ethanol on error detection was small, and not statistically significant. Volunteers clearly knew that they were making many more errors with ethanol, and this was confirmed by a post-test rating of performance. The distinctive pattern of ethanol impairment seems not to be due to impaired awareness of errors during performance.
 
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Effects of ethanol on sensitivity to future consequences of action and on response suppression
Barton, C., Dudman, A., Drummond, G. B., Tiplady, B.,Wright, P.
Poster presented at the Psychobiology Section of the British Psychological Society, Lake District, September 2004
Background: Acute ethanol consumption has effects that resemble frontal lesions in some respects, for example executive dysfunction and disinhibition. We have examined the effects of ethanol on two tasks that assess distinct aspects of frontal lobe/executive function, the Bechara Gambling Task (BGT), which assesses sensitivity to future consequences of actions, and the Hayling Task (HT) which measures response initiation and suppression.
Methods: We randomised thirty female and 27 male volunteers aged 18-25 to receive a single dose of ethanol or placebo. BGT and HT were assessed starting at 45 minutes post-dose.  A battery of other tests of attention, psychomotor function and mood was carried out starting at 30, 75 and 105 minutes post-dose. Blood alcohol concentrations (BAC) were measured using a breathalyser.
Results: BAC was greatest at 30 minutes (mean 77.1 mg/100ml, S.D. 24.0). We found the expected performance impairments - the number of correct substitutions in the Digit-Symbol task at 30 minutes was 72.6 for placebo and 60.8 for ethanol (Wilcoxon z = 3.55, p<0.001). We did not find differences in performance on the BGT.  The HT showed a trend for slowing in the response suppression part of the task (Placebo 17.0 s; Ethanol 29.1 s; Wilcoxon  z = 1.57. p = 0.116).
Conclusions: In this unpaired study we were unable to show that acute ethanol consumption impairs the ability to judge future consequences of actions. Ethanol may impair the process of response suppression. Further work could usefully address the issue of response suppression in a within-subjects design.
 
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Selective effects of clonidine and temazepam on attention and memory
Tiplady, B., Bowness, E., Stien, L., Drummond, G.
Journal of Psychopharmacology (2005) 19 (3) 259-265

The present study compared the effects of clonidine and temazepam on performance on a range of tasks aiming to assess the role of central noradrenergic mechanisms in cognitive function. Fifteen healthy volunteers (seven male, eight female), aged 18-25 years, took part in a five-period crossover study in which they received placebo, temazepam (15 and 30 mg) and clonidine (150 and 300 microg) by mouth incounterbalanced order in sessions at least 4 days apart. A test battery was administered before treatment and at 45, 90 and 135 min after the dose. Performance on most tests was significantly impaired in a dose-related fashion, and subjective sedation was recorded for both drugs. The greatest impairments with clonidine were on attention in thepresence of distractors. Clonidine did not affect the formation of new long-term memories, in contrast to temazepam, but did impair measures of working memory. Subjective effects, especially feelings of drunkenness and abnormality, were particularly marked with clonidine. These results support the suggestion that central noradrenergic function may be involved in preventing distraction, but do not confirm other reports suggesting that some aspects of performance are improved with clonidine.

 
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Effects of ethanol on kinaesthetic perception
Tiplady, B., Baird, R., Lutcke, H., Drummond, G., & Wright, P.
Journal of Psychopharmacology (2005) 19: 627-632

In normal subjects, alcohol increases handwriting size, but the mechanism is not understood. Here we show that the alcohol effect on handwriting can be explained by a selective impairment of kinaesthetic perception. Thirty volunteers (15 male, aged 18-29 years) took part in an open study. They were tested before and after a drink containing vodka intended to produce a blood alcohol concentration of about 80 mg/100 ml. Tests included kinaesthetic distance estimation, in which volunteers worked with preferred hand and arm behind a screen which hid their movements; visual distance estimation; and measures of handwriting and drawing. Blood alcohol concentration at 55 min, based on breathalyser measurements, was 76.7 mg/100 ml (S.D. 9.8). When asked to move the hand and mark a distance of 10 cm from a starting point, distances estimates increased by 7-10% (p<0.01). Similar increases were seen for writing words and drawing characters. Signatures were increased in height but not in length. Distances estimated visually were increased much less, by 3-4% (p<0.05). Tests of psychomotor performance indicated the expected effects of ethanol. These results suggest that ethanol affects writing size by  reducing kinaesthetically perceived distances . 

 
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Assessment of driver impairment: Evaluation of a two-choice tester using ethanol
Tiplady, B., Degia, A., & Dixon, P...
Transportation Research Part F: Traffic Psychology and Behaviour (2005) 8: 299-310.

Fifteen healthy volunteers aged 18–35 years took part in this three period crossover study evaluating a portable performance tester designed for roadside use. They received by mouth placebo and two doses of ethanol on separate days. Doses were calculated to produce blood alcohol levels of 50 and 80 mg/100 ml. Testing was carried out before the drink and starting at 40 min after the drink. Breathalyser readings showed peak blood alcohol levels of 54.4 mg/100 ml (S.D 11.1) for the smaller dose and 83.0 mg/100 ml (S.D. 8.4) at the larger dose. Significant impairment was seen with the larger dose of ethanol. Response time was increased for the arrow flankers test (attention in the presence of distractors), and errors were increased for paired associates (visuospatial working memory) and for length estimation (judgement). A composite measure showed a clear dose-related pattern of impairment. These results indicate that a short test battery taking about ten minutes to complete can reliably show the effects of ethanol under controlled laboratory conditions. Further work is needed in the field, and with a more varied population to assess the use of such a device to assess impairment due to alcohol and drugs at the roadside

 
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A pilot field study on the effects of alcohol on human performance
Scholey, A. B., Mayes, R., & Tiplady, B.
Behavioural Pharmacology (2005) 16: S30.

Given the widespread use of alcohol, and concerns regarding its social impact, there are surprising few studies into its effects on performance in real-life settings. The current pilot study aimed to assess the effects of drinking in a natural setting on aspects of performance. Thirty individuals were tested individually in a bar on the university campus. Each was breathalysed at the start and end of a computerized test battery. They provided details regarding alcoholic drinks consumed and length of time since their first drink. They were also invited to record information regarding other recreational drug use. A short test battery was administered on a hand-held Newton computer (www.penscreen.com). The battery consisted of a series of psychomotor and cognitive tests previously shown to be sensitive to ethanol intoxication in the laboratory. This included a maze, hand-writing, Serial Sevens and a test of `self-calibration' (the General Knowledge Adaptive test). Visual analogue scales (VAS) were also presented. There were highly significant inter-correlations between measured blood alcohol concentrations, estimated units of alcohol consumed and scores on a `sober-drunk' VAS (P<0.001 in all cases). The effects of alcohol intoxication followed similar patterns to those found in laboratory studies, leading to a characteristic shift in the speed/accuracy trade-off which was reflected as production of significantly more errors with little effect on speed across several measures (including maze performance and Serial Sevens). Individuals who were more intoxicated were also significantly less alert. Such findings emphasize the ramifications for alcohol consumption in real-life settings. The data suggest that controlled laboratory tests into the effects of alcohol intoxication may have ecological validity. Further work is needed to extend the range of tasks similarly affected by alcohol, including direct comparison of these effects in field and the laboratory studies within the same cohort.

 
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Mobile phones as a means of assessing mood and cognitive performance: a pilot field study assessing effects of eating behaviour
Tiplady, B., Paterson, H., & Scholey, A. B.
Behavioural Pharmacology (2005) 16: S30-S31

Recent technological advances and the ubiquity of mobile phone use amongst young adults affords an ideal opportunity to combine cognitive testing in real-life settings with levels of control more typical of the laboratory. This pilot study used mobile phones to examine the effects of feeding behaviour on mood and performance. Fourteen healthy young women (mean age 21.1 years, range 18-32) participated. Initial screening included familiarization with the testing system and completion of the Dutch Eating Behaviour Questionnaire (DEBQ, which provides measures of retrained, emotional and externally cued eating. Additional questions assessed disordered eating. The mobile phone battery contained visual analogue scales assessing `alert', `tense', `tired', `hungry' and `full', and cognitive tests assessing aspects of attention and spatial working memory. Over 14 days each participant was sent a daily text message asking them to complete the mobile phone test battery. The times of these messages varied systematically so that each volunteer received messages twice at each of seven time-points ranging from 08.00 to 20.00 hours. No dietary restrictions were placed on the participants. There was a significant time-of-day effect on `hunger' with lower ratings at later times. Individuals with higher DEBQ restraint scores were significantly more hungry through the day. There were significant interactions on Serial Sevens response times between time-of-day and both restraint and externally cued eating scores, in both cases individuals with higher DEBQ scores (indicating less feeding control) were slower, especially at the 11.00 to 14.00 hours time-point. There was a significant interaction between fullness and disordered eating scores, with individuals with higher scores having lower ratings at earlier times and lower scores at later times. These data suggest that the mobile phone testing system is sensitive to the effects of feeding behaviour in humans. This finding offers exciting possibilities for cognitive testing in the field with larger samples.

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Effects of ethanol on reconsolidation of human memory
Tiplady, B.
Behavioural Pharmacology (2005) 16: S24

Activation of previously-consolidated memory may return it to a labile state, sensitive to disruption by agents which prevent consolidation (electroconvulsive shock, inhibition of protein synthesis, NMDA receptor inhibition). Ethanol impairs memory consolidation, and its effects include NMDA antagonism. We investigated the effect of ethanol on re-consolidation of memory in 40 healthy volunteers (19 male), aged 23 (19-50) years weighing 70 (54-89) kg (mean, min, max). On Day 1 they learnt a set of 90 "facts" of which 60 were false, target items. They learned four lists of words in a selective reminding format, and practised and performed a battery of performance tests. On Day 2, they received ethanol or placebo. Peak blood alcohol concentrations (mean 83.3 mg/100ml, S.D. 23.0) were reached at 35 minutes, and remained approximately constant for the next hour. Starting at 45 minutes they were asked to recall half the facts and two of the lists. Recall sets were randomised and balanced between conditions. They performed the test battery before and after recall. On Day 3, recall of all material was tested. For both facts and words, and for both ethanol and placebo groups, items tested on Day 2 were recalled better on Day 3 than items not tested on Day 2. Fact recall (ethanol, placebo) was 55.8 and 50.1% for facts tested on Day 2 and 42.0 and 40.6% for facts not tested on Day 2. Effect of day 2 presentation was significant, paired t: 4.80 (p=0.0002), 3.70 (p=0.0018). We found the expected impairments with ethanol on a choice reaction task and a maze task. Although previous studies have shown ethanol to impair consolidation in the memory tasks we used, we found no evidence for disruption of re-consolidation. Our results do not support the concept that re-consolidation is essentially a repetition of initial consolidation.

 

 

Effects of ethanol and promethazine on awareness of errors and judgements of performance
Acons, K., Chan, L-S., Drummond, G., Tiplady, B. 
Journal of Psychopharmacology (2005) 20: 661-669

Ethanol may affect detection and processing of errors in performance tasks, and thus influence the speed accuracy trade-off. In this double-blind study, eleven volunteers, (7 female, 4 male) took part in four sessions in which they received ethanol (Eth; mean blood alcohol concentration at 60 minutes : 87.3, S.D.: 18.4); placebo (Pla); promethazine 20 mg (P20) and 30 mg (P30) in randomised order. A computerised four choice reaction time test (FCRT), other performance measures, and visual analogue scales (VAS) were administered before dosing and at intervals up to 2.5 h after. During the FCRT volunteers reported errors verbally. These reports were recorded together with error signals from the computer. The overall pattern of effects was as expected for Eth, with increases in errors for most tasks, and subjective drowsiness. P30 affected only the FCRT, and both P30 and P20 caused drowsiness. The number of errors in the FCRT was significantly increased for both Eth (N = 5.20, p<0.01) and P30 (N = 3.81, p<0.01) compared to Pla (1.84) with no significant change in response speed. The proportion of errors detected was slightly but not significantly reduced. The number of errors reported was increased by a factor of 2.1 for ethanol (p<0.01). These results show that error processing is not significantly impaired by ethanol, and a reduction in awareness of errors cannot account for the increased errors which occur when performance is impaired by ethanol.

 

 

Studying the effects of alcohol in the field
Tiplady, B. 
Paper presented at the Psychobiology Section of the British Psychological Society, Lake District, September 2006.

Background: Many studies in the laboratory have demonstrated the impairment caused by alcohol to human cognitive and psychomotor performance, and epidemiological work has repeatedly shown the increased risk of accidents associated with alcohol use in driving and other everyday life situations. However little field research has been carried out to document the effects of ethanol on human performance in an everyday setting. 

Methods: In a series of studies, cognitive performance and subjective state were assessed in social settings associated with alcohol use such as pubs and music festivals. Cognitive and mood assessments were set up on portable devices (handheld computers and/or mobile phones). Tests were selected to assess a variety of aspects of performance known to be affected by alcohol in laboratory studies. Blood alcohol concentrations (BAC) were obtained using a breathalyser. 

Results: A wide range of BACs was observed, with a substantial proportion of zero readings and values up to more than twice the UK legal limit for driving (80 mg/100 ml). Higher BACs were clearly associated with performance decrements and with subjective reports, particularly of drunkenness. There was also a strong correlation between BAC and reported alcohol consumption. The pattern and magnitude of the changes was consistent with previous placebo-controlled lab-based studies. 

Conclusions: These results suggest that similar effects of alcohol on performance and subjective state are found whether evaluated in the field or in the lab. Future work will attempt to provide more direct evidence by recruiting volunteers for lab projects from the field studies and comparing results from the two settings in the same group of volunteers.

 

 

Cognitive functioning in polycystic ovary syndrome
Barnard, L., Balen, A. H., Ferriday, D., Tiplady, B., & Dye, L
Psychoneuroendocrinology (2007) 32: 906-914
To date there have been no published studies of cognitive functioning in polycystic ovary syndrome (PCOS). This large internet-based study compared neuropsychological functioning in right-handed women with (minimum n=135) and without PCOS (minimum n=322), stratified according to use of anti-androgen medication and level of depression. Women with PCOS are thought to have hyperandrogenism and hyperestrogenism which was hypothesized to differentially influence cognitive function across cognitive domains. Performance did not differ according to diagnosis on mental rotation and spatial location tasks. Hence, no evidence to support the view that women with PCOS display a more masculine cognitive profile due to hyperandrogenism. Despite presumed hyperestrogenism, women with PCOS demonstrated impaired performance in terms of speed and accuracy, on reaction time and word recognition tasks. These findings are intriguing given the well-documented roles of estrogen and testosterone in cognitive function. Overall, these findings suggest that PCOS is not associated with masculinized cognitive functioning, and, although associated with impaired performance on tasks considered to demonstrate female-advantage, such impairments are subtle and are unlikely to affect daily functioning

 

 

Comparison of the sedative, cognitive, and analgesic effects of nitrous oxide, sevoflurane, and ethanol
Duarte,R.; McNeill,A.; Drummond,G.; Tiplady,B.
British Journal of Anaesthesia (2008) 100: 203-210
Background Anaesthetics which work by different mechanisms may have different patterns of effect. Measurement of these patterns thus may elucidate their mechanisms of action and allow therapeutic choices between the agents. Methods We compared the effects of ethanol ([~]80 mg per 100 ml), and different end-tidal concentrations of nitrous oxide (15% and 25%) and sevoflurane (0.3% and 0.5%) in volunteers. We measured speed and accuracy in psychomotor tests, reaction time and memory, touch and pain sensitivity to von Frey filaments, and subjective mood for a range of descriptors. Results All treatments caused the same degree of overall abnormal feelings, but sevoflurane caused more obtunding (subjective drowsiness, slow reaction times, and loss of memory function) and nitrous oxide was more analgesic. Ethanol caused a marked feeling of drunkenness, but little drowsiness or analgesia. Conclusions In the same volunteer subjects, direct comparison of sub-anaesthetic doses of these agents showed a clear and characteristic pattern of effects. These support the possible mechanisms for these disparate agents and may help choose appropriate agents for specific desired anaesthetic outcomes such as sedation or analgesia

 

 

Cognitive and mood effects in healthy children during 12 weeks' supplementation with multi-vitamin/minerals
Haskell, C. F., Scholey, A. B., Jackson, P. A., Elliott, J. M., Defeyter, M. A., Greer, J., Robertson, B. C., Buchanan, T., Tiplady, B., & Kennedy, D. O.
British Journal of Nutrition (2008) 100: 1086-1096
Adequate levels of vitamins and minerals are essential for optimal neural functioning. A high proportion of individuals, including children, suffer from deficiencies in one or more vitamins or minerals. This study investigated whether daily supplementation with vitamins/minerals could modulate cognitive performance and mood in healthy children. In this randomised, double-blind, placebo-controlled, parallel groups investigation, eighty-one healthy children aged from 8 to 14 years underwent laboratory assessments of their cognitive performance and mood pre-dose and at 1 and 3 h post-dose on the first and last days of 12 weeks' supplementation with a commercially available vitamins/mineral product (Pharmaton Kidditrade mark). Interim assessments were also completed at home after 4 and 8 weeks at 3 h post-dose. Each assessment comprised completion of a cognitive battery, delivered over the Internet, which included tasks assessing mood and the speed and accuracy of attention and aspects of memory (secondary, semantic and spatial working memory). The vitamin/mineral group performed more accurately on two attention tasks: 'Arrows' choice reaction time task at 4 and 8 weeks; 'Arrow Flankers' choice reaction time task at 4, 8 and 12 weeks. A single task outcome (Picture Recognition errors) evinced significant decrements at 12 weeks. Mood was not modulated in any interpretable manner. Whilst it is possible that the significant improvements following treatment were due to non-significant numerical differences in performance at baseline, these results would seem to suggest that vitamin/mineral supplementation has the potential to improve brain function in healthy children. This proposition requires further investigation

 

 

Evaluation of a new method of assessing depth of sedation using two-choice visual reaction time testing on a mobile phone
Thomson, A.J., Nimmo, A.F., Tiplady, B., Glen, J.B.
Anaesthesia (2009) 64(1):32-8.
The utility of two-choice visual reaction time testing using a specially programmed mobile telephone as a measure of sedation level was investigated in 20 healthy patients sedated with target controlled infusions of propofol. At gradually increasing target concentrations visual reaction time was compared with patient-assessed visual analogue scale sedation scores and an observer-rated scale. Propofol sedation caused dose-dependent increases in visual reaction time and visual analogue scale scores that were statistically significant when the calculated effect-site concentration reached 0.9 microg.ml(-1) (p < 0.05) and 0.5 microg.ml(-1) (p < 0.01) respectively. While visual analogue scale scores were more sensitive at lower levels of sedation than visual reaction time, the latter demonstrated marked increase in values at higher levels of sedation. Visual reaction time may be useful for identifying impending over-sedation.

 

 

Cognitive and mood effects of 8 weeks' supplementation with 400 mg or 1000 mg of the omega-3 essential fatty acid docosahexaenoic acid (DHA) in healthy children aged 10-12 years
Kennedy, D.O., Jackson, P.A., Elliott, J.M., Scholey, A.B., Robertson, B.C., Greer, J., Tiplady, B., Buchanan, T., Haskell, C.F.
Nutr Neurosci. 2009 12(2):48-56.
INTRODUCTION: Despite media and public expectation of efficacy, no study to date has investigated the cognitive and mood effects of omega 3 supplementation in healthy children. SUBJECTS AND METHODS: This randomised, double-blind, placebo-controlled, parallel groups pilot study assessed the cognitive and mood effects of either 400 mg or 1000 mg of docosahexaenoic acid (DHA) in 90 healthy children aged 10-12 years. Cognitive performance and mood was assessed prior to, and 8 weeks following, commencement of treatment. RESULTS: There was a significant treatment effect on one cognitive measure (speed of word recognition), with the lower dose speeding, and the higher dose slowing, performance. Overall, the pattern of results strongly suggests that this effect was due to chance fluctuations in performance and that the treatments had no consistent or interpretable effect on performance. CONCLUSIONS: The results here do not suggest that supplementation with these doses of DHA for 8 weeks has any beneficial effect on brain function in cognitively intact children.

 

 

Evaluation of a roadside impairment test device using alcohol
Dixon, P.R., Clark, T., Tiplady, B.
Accid Anal Prev. 2009 41(3):412-8.
The main objective of this study was to compare the performance of a portable impairment test device known as roadside impairment testing apparatus (RITA) with the field impairment tests (FIT) that are used at the roadside by UK police. One hundred and twenty two healthy volunteers aged 18-70 years took part in this two-period crossover evaluation. The volunteers received a dose of alcohol and placebo, in the form of a drink, on separate days. Doses were calculated to produce blood alcohol concentrations of 90 mg/100ml and RITA and FIT testing was carried out between 30 and 75 min post-drink. FIT was found to have a diagnostic accuracy of 62.7%. However, there was a substantial age effect for FIT scores, with volunteers aged over 40 showing failure rates on placebo similar to the failure rates on alcohol of younger volunteers. The accuracy of RITA was between 66 and 70%, not significantly higher than that of FIT. However, RITA did not show a marked age effect. Advantageously, this could result in fewer false positives being recorded if RITA were deployed at the roadside. Horizontal gaze nystagmus (HGN) was also investigated and posted an accuracy of 74%. The inclusion of HGN as one component of a UK roadside impairment test battery warrants further exploration with other drugs.

 

 

Alcohol and cognitive function: assessment in everyday life and laboratory settings using mobile phones
Tiplady, B., Oshinowo, B., Thomson, J., Drummond, G.B.
Alcohol Clin Exp Res. 2009 Dec;33(12):2094-102. 
BACKGROUND: Mobile phone (cellphone) technology makes it practicable to assess cognitive function in a natural setting. We assessed this method and compared impairment of performance due to alcohol in everyday life with measurements made in the laboratory. METHODS: Thirty-eight volunteers (20 male, aged 18-54 years) took part in the everyday study, completing assessments twice a day for 14 days following requests sent by text messages to the mobile phone. Twenty-six of them (12 male, aged 19-54) took part in a subsequent two-period crossover lab study comparing alcohol with no alcohol (placebo). RESULTS: Everyday entries with 5 or more units of alcohol consumed in the past 6 hours (inferred mean blood alcohol concentration 95 ml/100 ml) showed higher scores for errors in tests of attention and working memory compared with entries with no alcohol consumed that day. Response times were impaired for only 1 test, sustained attention to response. The laboratory comparison of alcohol (mean blood alcohol concentration 124 mg/100 ml) with placebo showed impairment to both reaction time and error scores for all tests. A similar degree of subjective drunkenness was reported in both settings. CONCLUSIONS: We found that mobile phones allowed practical research on cognitive performance in an everyday life setting. Alcohol impaired function in both laboratory and everyday life settings at relevant doses of alcohol.

 

 

Cognitive effects of creatine ethyl ester supplementation
Ling, J., Kritikos, M., Tiplady, B.
Behav Pharmacol. 2009 20:673-679
Supplementation with creatine-based substances as a means of enhancing athletic performance has become widespread. Until recently, however, the effects of creatine supplementation on cognitive performance has been given little attention. This study used a new form of creatine - creatine ethyl ester - to investigate whether supplementation would improve performance in five cognitive tasks, using a double-blind, placebo-controlled study. Creatine dosing led to an improvement over the placebo condition on several measures. Although creatine seems to facilitate cognition on some tasks, these results require replication using objective measures of compliance. The improvement is discussed in the context of research examining the influence of brain energy capacity on cognitive performance..

 

 

Patient Reported Outcomes in Rheumatoid Arthritis: Assessing the equivalence of electronic and paper data collection
Tiplady, B., Goodman, K., Cummings, G., Lyle, D., Carrington, R., Battersby, C., & Ralston, S.
The Patient 2010, 3: 133-143
Background The questionnaires used in clinical research have often been developed and validated using paper, and in such cases it is necessary to show that the electronic versions are equivalent to the originals.

Objective To determine if electronic versions of questionnaires assessing severity and impact of rheumatoid arthritis (RA) are equivalent to the original paper versions.Methods Patients (n = 43; 31 female) aged 32-83 years (25 aged <60 years) took part in a single session during which they completed paper and electronic assessments in randomized order, with an interval of 45 minutes between the two modes. Electronic assessments were set up on a Palm® TX handheld device. Assessments included measures of pain, fatigue, disability, and health status.

Results Scores were similar between the two modes. All effect sizes for electronic-paper differences were <0.2, and there was no overall tendency for one mode to show higher scores than the other. Intraclass correlation coefficients (ICCs) ranged from 0.72 to 0.96, and were generally similar to reported retest reliabilities of the scales in their paper versions. The Disability Index of the Health Assessment Questionnaire (HAQ-DI) showed an ICC of 0.96. ICCs for the EQ-5D health status scale were utility: 0.79; profile: 0.91; visual analog scale: 0.75. Most patients reported that both modes were easy to use. In general, patients preferred the electronic version over the paper, and this was true for the older as well as the younger patients.

Conclusions Electronic versions of questionnaires assessing severity and impact of RA provide data that correspond closely to those of paper originals, are easy to use, and are acceptable to patients. using paper, and in such cases it is necessary to show that the electronic versions are equivalent to the originals.

 

 

 

Vitamins and psychological functioning: a mobile phone assessment of the effects of a B vitamin complex, vitamin C and minerals on cognitive performance and subjective mood and energy
Kennedy, D. O., Veasey, R. C., Watson, A. W., Dodd, F. L., Jones, E. K., Tiplady, B., & Haskell, C. F.
Human Psychopharmacology: Clinical and Experimental, 2011, 26: 338-347
Objectives Despite being widely consumed, the effects of multi-vitamin supplements on psychological functioning have received little research attention. 

Methods Using a mobile phone testing paradigm, 198 males (30-55 years) in full-time employment took part in this randomised, placebo-controlled, double-blind, parallel-groups trial assessing the effects of a multi-vitamin/mineral on cognitive performance and psychological state/mood. Participants completed two cognitive tasks and a number of visual analogue scales (VAS) before and after a full day's work, on the day before, and 7, 14, 21 and 28 days after, commencing their treatment. 

Results Participants in the vitamin/mineral group rated themselves as having greater physical stamina across assessments and weeks. They also rated themselves as having had greater concentration and mental stamina during the working day at the assessment carried out after a day's work, but not at the time of the assessment completed prior to work. Participants in this group also reported greater subjective alertness on Bond and Lader mood scales during the post-work assessment on day 14 and both the pre and post-work assessments on day 28. 

Conclusions These findings complement the results from the laboratory-based, randomised-controlled trial in the same cohort and suggest that healthy members of the general population may benefit from augmented levels of vitamins/minerals via direct dietary supplementation.

 

 

 

Neurocognitive and mood effects of alcohol in a naturalistic setting
Scholey, A. B., Benson, S., Neale, C., Owen, L., & Tiplady, B
Journal of Psychopharmacology (2012) , 27: 514-516
Objective: The current pilot study aimed to assess the effects of drinking alcohol in a naturalistic setting on aspects of performance. 

Methods: Thirty individuals were approached and tested individually in a university campus bar. They provided details regarding alcoholic drinks consumption. Each was breathalysed before and after completion of a computerised test battery administered on a handheld device. The battery consisted of Visual analogue mood scales a series of alcohol-sensitive psychomotor and cognitive tests.

Results: There were highly significant correlations between measured blood alcohol concentrations, estimated units of alcohol consumed and scores on a 'sober-drunk' VAS (p < 0.001 in all cases). For performance there was a characteristic alcohol-associated shift in the speed/accuracy trade-off (SATO) which was reflected as significantly more errors with less effect on speed across several measures (including maze performance and Serial Sevens). Individuals who were more intoxicated were also significantly less alert. 

Conclusions: The data suggest that controlled laboratory tests into the effects of alcohol intoxication may have ecological validity, with SATO shifts amongst the characteristic impairments seen in both controlled and naturalistic settings.

 

 

 

The effects of multivitamin supplementation on mood and general well-being in healthy young adults. A laboratory and at-home mobile phone assessment
Pipingas, A., Camfield, D. A., Stough, C., Cox, K. H. M., Fogg, E., Tiplady, B., Sarris, J., White, D. J., Sali, A., Wetherell, M. A., & Scholey, A. B.
Appetite (2013), 69: 123-136
Previous research has suggested that multivitamin (MV) supplementation may be associated with beneficial effects for mood and general well-being, although treatment durations have typically been less than 90 days, samples have often been restricted to males only and acute effects have not been adequately differentiated from chronic effects. In the current study a MV supplement containing high levels of B-vitamins was administered daily to 138 healthy young adult participants between the ages of 20 and 50 years over a 16-week period. Chronic mood measures (GHQ-28, POMS, Chalder fatigue, PILL, Bond-Lader and custom visual analogue scales) were administered pre-dose at baseline, 8- and 16-weeks. Changes in Bond-Lader and VAS in response to a multi-tasking framework (MTF) were also assessed at 8- and 16-weeks. For a subset of participants, at-home mobile-phone assessments of mood were assessed on a weekly basis using Bond-Lader and VAS. No significant treatment effects were found for any chronic laboratory mood measures. In response to the MTF, a significant treatment x time interaction was found for STAI-S, with a trend towards a greater increase in stress ratings for male participants in the MV group at 16 weeks. However, this finding may have been attributable to a larger proportion of students in the male MV group. In contrast, at-home mobile-phone assessments, where assessments were conducted post-dose, revealed significantly reduced stress, physical fatigue and anxiety in the MV group in comparison to placebo across a number of time points. Further research using both acute and chronic dosing regimens are required in order to properly differentiate these effects

 

 

 

Does breakfast size affect cognition, mood and appetite following morning exercise in active females?
Veasey, R. C., Haskell, C. F., Kennedy, D. O., Tiplady, B., & Stevenson, E. J.
Appetite (2014), 83: 357
Breakfast consumption and sub-maximal exercise can both improve mood and some facets of cognitive performance acutely. Beneficial pre-exercise nutritional practices for those who exercise for mood and cognitive benefits have not been well established. This study aimed to assess the effect of breakfast prior to exercise on cognitive performance, mood and appetite later in the day in this population. Active females (N = 24, aged 20.9 ± 2.3 y) completed3 trials in a randomised, cross-over design. Participants completed baseline tasks (FCRT, Stroop, NBack and RVIP) and mood and appetite VAS at 0815 h and were then administered a cereal breakfast providing 118 or 236 kcal) or no breakfast. After 45 min, they completed a 30 min treadmill run at approx. 65% HRR. Cognition, mood and appetite were re-assessed immediately after exercise, then hourly until lunch and immediately post-lunch. Participants were then free to leave the lab but completed tasks (Arrow RT, NBack and RVIP) and mood and appetite VAS via a mobile phone at 1500 and 1900 h. Breakfast improved mental fatigue and overall mood until at least 5 h post-exercise, though a larger breakfast led to poorer NBack and RVIP performance mid-afternoon. Breakfast was beneficial for subjective appetite at every time point up until post lunch.These data suggest that a small breakfast eaten prior to exercise can benefit post-exercise mood and appetite control and avoid the cognitive decline associated with consuming a larger breakfast.

 

 

 

The Effect of Breakfast Prior to Morning Exercise on Cognitive Performance, Mood and Appetite Later in the Day in Habitually Active Women
Veasey, R. C., Haskell-Ramsay, C. F., Kennedy, D. O., Tiplady, B., & Stevenson, E. J.
Nutrients (2015), 7: 5712-5732
Pre-exercise nutritional practices for active females exercising for mood, cognitive and appetite benefits are not well established. Results from an initial field pilot study showed that higher energy intake at breakfast was associated with lower fatigue and higher overall mood and alertness post-exercise (all p < 0.05). In a follow-up, randomised, controlled trial, 24 active women completed three trials in a balanced, cross-over design. At 0815 h participants completed baseline cognitive tasks, mood and appetite visual analogue scales (VAS) and were administered a cereal breakfast (providing 118 or 236 kcal) or no breakfast. After 45 min, they completed a 30 min run at 65% heart rate reserve (HRR). Parameters were re-assessed immediately after exercise, then hourly until lunch (~1240 h), immediately post-lunch and at 1500 and 1900 h via a mobile phone. Breakfast enhanced feelings of relaxation before lunch (p < 0.05, d > 0.40), though breakfast was detrimental for working memory mid-afternoon (p = 0.019, d = 0.37) and mental fatigue and tension later in the day (all p < 0.05, d > 0.038). Breakfast was also beneficial for appetite control before lunch irrespective of size (all p < 0.05, d > 0.43). These data provide information on pre-exercise nutritional practices for active females and suggest that a small breakfast eaten prior to exercise can benefit post-exercise mood and subjective appetite ratings.

 

 

 

 

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