Thiamin, riboflavin, and vitamins B-6 and C: impact of combined restricted intake on functional performance in man.

A double-blind study of combined restriction of thiamin, riboflavin, and vitamins B-6 and C was carried out with 23 healthy males. During 8 wk of low vitamin intake, 12 deficient subjects consumed daily a diet of normal food products, providing maximally 32.5% of the Dutch Recommended Dietary Allowances (RDA) for thiamin, riboflavin, vitamins B-6 and C. Other vitamins were supplemented at twice the RDA. Eleven control subjects consumed the same diet but with a supplementation of twice the RDA of all vitamins. In deficient subjects blood vitamin levels, urinary vitamin excretion, and erythrocytic enzyme activities decreased; in vitro enzyme stimulation increased. Vitamin depletion had no ill effects on health, physical activity, and mental performance. A significant decrease was observed in aerobic power (VO2max) and onset of blood lactate accumulation (p less than 0.001) of 9.8 and 19.6%, respectively. A combined restricted intake of thiamin, riboflavin, and vitamins B-6 and C causes a decrease in physical performance within a few weeks.

Pharmacokinetics and pharmacodynamics of Ro 41-3696, a novel nonbenzodiazepine hypnotic.

This report describes the first evaluation in humans of Ro 41-3696. Based on its preclinical profile, Ro 41-3696, a nonbenzodiazepine partial agonist at the benzodiazepine receptor, offers promising perspectives as an innovative hypnotic drug in that it does not exhibit most of the disadvantages associated with full agonists. Single oral doses of 0.1, 0.3, 1.0, 3.0, 10, and 30 mg were administered sequentially to six groups of six healthy male volunteers in a placebo-controlled, double-blind design. Tolerability was assessed and pharmacokinetic and pharmacodynamic measurements were conducted during a period of 28 hours after drug intake. Ro 41-3696 was well tolerated at all doses, causing no clinically relevant changes in vital signs or laboratory parameters. At doses of 10 and 30 mg there were signs of unsteady gait, indicating a central nervous system depressant effect. Pharmacokinetic analyses revealed that Ro 41-3696 was absorbed and eliminated rapidly (tmax = approximately 1 hour; t1/2 = approximately 4 hours). At all times plasma levels of Ro 41-3290, the desethylated derivative of Ro 41-3696, were higher than those of the parent drug (tmax and t1/2 values = approximately 2 and 8 hours, respectively). Area under the curve (AUC) data indicated dose-proportional pharmacokinetics for both Ro 41-3696 and Ro 41-3290. Performance in both a tracking and a memory search test was significantly affected by doses of 10 and 30 mg, and long-term memory, as assessed by a word learning and recall test, was slightly impaired at these doses. The results of this study support the initiation of therapeutic efficacy studies with Ro 41-3696 in doses up to approximately 5 mg and further exploration of the characteristics of Ro 41-3290.

Some effects of an ACTH 4-9 analog (Org 2766) on human performance.

The effects (on human beings) of the ACTH analog Org 2766 were investigated for a range of performance tests: complicated serial reaction task, running memory span, verbal learning and non-verbal mental ability tests (closure flexibility and non-verbal abstraction). Subjective ratings on feelings were taken and heart rate was measured. Only the 30-min reaction task produced significant drug effects. In this task performance tends to deteriorate as a function of time on task. During the test period there is a gradual increase in the number of lapses in performance due to moments of inattention. This deterioration is counteracted by the ACTH 4-9 analog, a result also found in previous study using ACTH 4-10 (Org OI63). Thus ACTH fragments which are devoid of endocrine effects seem to have a beneficial effect on goal-directed motivation oriented on the requirements of the task.

Social loafing under fatigue.

In 2 experiments, 64 male students worked almost continuously for 20 hr without sleep under varying social conditions. In Experiment 1, participants worked either individually or as a group. As hypothesized, performance deteriorated over time, especially in the group condition, which allowed participants to loaf. In Experiment 2, all participants worked in groups. They were instructed that public feedback would be provided either on the group result only or on the individual results of all group members. As expected, when individual results were made public, performance deteriorated less. Overall, the data suggest that fatigue increases social loafing. However, both individualizing the task and providing public individual feedback seem to counteract these effects.

Problems and paradigms in ERP research.

The ERP technique may provide noninvasive measures that are associated with the processing of psychological information during the performance of a task. Some investigators even regard ERPs as direct manifestations of the psychological processes induced by the demands of the task. Before such a strong claim can be made several methodological problems must be resolved. The present paper discusses the definition and identification of the endogenous components in the ERP, the separation of endogenous components from exogenous components, and the different ways in which inferences can be made about psychological processes on the basis of ERP measures.

Effects of warning-signal modality on the contingent negative variation (CNV).

CNVs were recorded during the S1-S2 interval of a prolonged simple reaction task. In the task, a warning stimulus S1 is followed by an imperative stimulus S2, to which the subject makes a motor response. The differential effects of a visual and an auditory S1 were investigated under two interstimulus interval (ISI) durations (1 and 3 sec). Under the 3 sec ISI condition, the form of the slow negative wave demonstrated clearly a biphasic character: an orientation wave (O wave) following S1 with a peak latency at about 650 msec and an expectancy wave (E wave), which reaches its largest amplitude towards the end of the ISI. Under the 1 sec ISI condition the two components of the CNV are confounded. The O wave had a fronto-central distribution, while the E wave was located precentrally. The O wave was enhanced after an auditory S1, as compared to a visual S1.

Mismatch negativity in a phonetic discrimination task.

The hypothesis was tested that in a discrimination task the number of phonetic features available determines the latencies and amplitudes of the components of the evoked potentials. Six conditions varying in the number and type of discriminatory cues were compared. The condition containing a three phonetic feature discrimination produced shorter latency evoked potentials as compared with the conditions containing one or two such features or an acoustic difference only. The N2 component, the so-called mismatch negativity, was particularly sensitive to the number of phonetic features.

The terminal CNV and stimulus discriminability in motor and sensory tasks.

Slow EEG potentials were recorded during the foreperiod of a signal detection task which involved different levels of discrimination difficulty. The subject was required to react to S2 as quickly as possible or to delay his response by 1 s. It was found that the contingent negative variation (CNV) was attenuated when no speeded response was required and that larger amplitudes preceded the easy rather than the difficult discrimination. In addition, no differences were found between correct and incorrect detections. On these grounds it is concluded that the CNV is not positively correlated with perceptual sensitivity.

Some baseline effects on the CNV.

A method is described to investigate how the contingent negative variation (CNV), developing in the S1-S2 interval of a reaction task, is influenced by slow potential shifts (SPSs) occurring before S1. Enhanced CNV amplitudes were found when the SPSs before S1 were positive, whereas with negative SPSs attenuated amplitudes were obtained.

Event-related potentials (ERPs) in a learning and memory test.

The present study outlines a new paradigm to investigate the effects of learning and memory on event-related potentials (ERPs). In the learning phase, subjects had to learn a sequence of 12 auditory consonant-vowel syllables. In the test phase, subjects had to detect and report a change in the learned sequence. Auditory ERPs were recorded from the frontal, vertex, and parietal midline positions. In the learning phase, an early negative effect (EN) and a P3 with a slow wave (SW) occurred for the learned syllables, whereas a pre-stimulus negativity (PSN) occurred prior to the syllables not yet learned. In the test phase, the PSN preceded both the replaced syllables and those presented in their old positions. The EN and an N2-P3 complex were elicited by the replaced syllables, the EN by the syllables presented in their old positions. It was concluded that the ERPs can display specific effects related to cognitive processes underlying learning and memory. The PSN was suggested to reflect the expectation of the stimuli, the EN the activation of a template and the rehearsal of the stimuli. The SW was suggested to be related to a template match process with the learned syllables. The N2, elicited by the replaced stimuli, could imply a cognitive template mismatch and the P3 with the SW the updating of working memory.

Physiological indices of workload in a simulated flight task.

The sensitivity of physiological measures to evaluate workload was investigated in a simulated flight task. Heart rate, blood pressure (from beat to beat), respiration and eye blinks were recorded in 14 subjects while they performed a complex task in a flight simulator. Workload was manipulated by introducing an additional task and by varying the task difficulty of segments of the flight scenarios. Heart rate and blood pressure were both affected by the different levels of task difficulty. Heart-rate variability was found to be confounded by respiration. Slow respiratory activity contributed considerably to heart rate variability, especially after periods of high workload (for example, after landing). The gain between blood-pressure and heart-rate variability (modulus) was sensitive to mental effort and was not influences by respiration. Eye blinks, in particular the duration, were specifically affected by the visual demands of the task and not by the workload in general. When subjects had to process visual information, the number and duration of blinks decreased.

Attention effects on auditory EPs as a function of inter-stimulus interval.

The present study focuses on the effect of the duration of the inter-stimulus interval (ISI) on the 'processing negativity', the endogeneous negative brain potential elicited by attended stimuli in various selective-attention paradigms. Three constant ISIs are used, 250 msec. 800 msec, and 2000 msec, in a selective dichotic-listening situation in which the subject's task is to detect occasional slight pitch changes in the input to a designated ear. Frontal (Fz), vertex (Cz), and parietal (Pz) evoked potentials (EP) are recorded. The processing negativity is observed in each condition, even in that involving the 2 sec ISI, which is in contrast with the commonly held view that this attention effect is only obtained with very short ISIs. The processing negativity was observed to have two components: (1) an early, central component of small amplitude which appears to be independent of the ISI: (2) a later, frontal component of large amplitude and long duration which is certainly elicited with long ISIs such as the 800 msec and 2000 msec ISIs used here, but also appears to be present even in the short-ISI condition overlapping the central component. This suggests that it is the frontal component which is sensitive to the ISI.

Evoked heart rate and blood pressure in an S1-S2 paradigm.

Phasic changes in heart rate (HR) and blood pressure (BP) in an S1-S2 paradigm were studied in three experiments. In each experiment, a memory search task was performed at S1. The outcome of this task indicated whether a fast or a delayed response had to be given after S2. Besides this response instruction, there were two other task manipulations: in one experiment the memory load at S1 was varied, whereas in each experiment a different kind of performance feedback was given. Both HR and BP showed a triphasic pattern, consisting of an initial decrease, followed by an increase and another decrease. The BP patterns were quite consistent, and delayed a few seconds relative to the HR pattern. The memory load manipulation at S1 showed that the changes early in the S1-S2 interval (initial decrease and subsequent increase) reflect the processing of S1. The effects of response instruction showed that the second HR deceleration, and the subsequent BP decrease, reflect the preparation of the motor response. In Experiment 2 the level of the evoked HR and BP pattern was shifted as a function of the type of reward (a bonus or noise).

Influence of drive and timing mechanisms on breathing pattern and ventilation during mental task performance.

Assessment of multiple respiratory measures may provide insight into how behavioral demands affect the breathing pattern. This is illustrated by data from a study among 44 subjects, in which tidal volume, respiration rate, minute ventilation and indices of central drive and timing mechanisms were assessed via inductive plethysmography, in addition to end-tidal PCO2. After a baseline, three conditions of a memory comparison task were presented. The first two conditions differed only with regard to the presence or absence of feedback of performance (NFB and FB). In the third 'all-or-nothing' (AON) condition, subjects only received a monetary bonus, if their performance exceeded that of the previous two conditions. Minute ventilation increased from baseline to all task conditions, and from NFB and FB to AON. Respiration rate increased in all task conditions, but there were no differences between task conditions. Tidal volume decreased during NFB, but was equal to baseline during FB and AON. Of the respiratory control indices, inspiratory flow rate covaried much more closely with minute ventilation than duty cycle. The task performance induced a minor degree of hyperventilation. The discussion focusses on how behavioral demands affect respiratory control processes to produce alterations in breathing pattern and ventilation.

EP components, visual processing stages, and the effect of a barbiturate.

In a 2 x 2 x 2 factorial experiment, ten subjects carried out a visual choice reaction task. In addition to RT measurement, evoked potentials (EPs) were recorded from the central (Cz) and occipital (Oz) derivations. Independent variables were drug treatment (barbiturate versus placebo), visual stimulus intensity and visual stimulus degradation. The reaction time data showed that visual intensity and degradation had additive effects, which indicates that these variables affect independent stages, i.e. stimulus preprocessing and stimulus encoding. The effect of barbiturate on RT was additive with intensity but appeared to interact with degradation. This suggests a selective effect of that drug on the encoding state. EP components also showed selective effects of intensity, degradation and drug treatment. It was suggested that these components may be related to stages in the reaction process.

The influence of mental fatigue on facial EMG activity during a simulated workday.

The present study investigated whether facial EMG measures are sensitive to the effects of fatigue. EMG activity of the corrugator and frontalis muscles was recorded during and after a simulated workday. Fatigue was evaluated in four ways: (a) the building up of fatigue effects during the workday, (b) the building up of fatigue during a test period, (c) examination of after-effects of the workday in two test sessions in the evening, and (d) comparison of subjects with a high-and low-score on an Emotional Exhaustion questionnaire. EMG activity decreased during the workday and increased again in the evening. EMG activity also increased during a test period, reflecting increased mobilization to maintain performance. High-score subjects showed a lower level of EMG activity throughout the entire workday. They reported a higher need for recovery, experienced the workday as more fatiguing, and were less well rested when getting up. EMG measures seem to reflect that high-score subjects have problems with investing sufficient energy to maintain performance during a workday.

The relation between event-related brain potential, heart rate, and blood pressure responses in an S1-S2 paradigm.

Event-related brain potential (ERP), heart rate (HR), and blood pressure (BP) responses were examined during the 6 s foreperiod of a choice-reaction task. Low and high trait-anxious males were required to make same/different judgements based on the similarity of two successively presented visual patterns. The pitch of a warning tone, presented at the beginning of the foreperiod, indicated whether speed or accuracy was to be emphasized on that trial. In different conditions, subjects received either a monetary reward or aversive noise, depending on their performance. Two clusters of parallel variations were observed in the foreperiod: (1) speed/accuracy instructions affected the amplitude of the CNV and, in interaction with anxiety group, the initial decreases in HR and diastolic BP; (2) type of reward, in interaction with speed/accuracy instructions, affected the amplitude of the P300 and PSW, the mid-interval HR acceleration, and subsequent increases in diastolic and systolic BP. A correlational analysis showed a close relationship between changes in HR and BP, whereas no relationship was evident between changes in ERPs and changes in HR and BP.