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Eating and its relationships with subjective alertness and sleep in narcoleptic subjects living without temporal cues.

The sleep and meal patterns of normal subjects appear to be governed by a common timing mechanism. To investigate whether the postulated mechanism may be disordered in narcolepsy, a disorder of sleep timing, we analyzed the sleep, eating, and subjective alertness of six narcoleptic subjects and seven normal controls while they lived in a temporal isolation laboratory. When subjects were free to eat and sleep whenever they chose ("free-running"), the meal patterns and nutrient intakes of the free-running narcoleptic subjects and controls were similar; no evidence of an eating disorder intrinsic to narcolepsy was found. When meals were offered on a 24-h schedule, narcoleptic subjects ate more frequently than did the controls. In two of three narcoleptic subjects whose free-running biological days markedly lengthened, intermeal intervals lengthened proportionately. This was evidence that the timing of sleep (bed-dark) periods and meals was indeed governed by a common mechanism. Meal onsets of narcoleptic subjects were preceded by a 90-min period of decreased napping and, when meals were scheduled, by increased subjective alertness. They were followed by a 150-min period of increased napping and decreased subjective alertness. Postprandial deactivation was not found in controls. The deactivation could not be explained by a post-absorptive effect of food, since the contents of meals that were followed by naps did not differ from those that were not followed by naps. While a preabsorptive effect of meals has not been ruled out, we suggest that postmeal deactivation may be evidence that the mechanism that times sleep periods and meals also modulates the temporal pattern of narcoleptic naps.

Adult

Effect of caffeine on physiological sleep tendency and ability to sustain wakefulness at night.

Marked sleepiness occurs during typical night shift work hours and this reduced alertness is associated with marked performance deficits. The effect of caffeine (versus placebo) upon sleepiness at night was studied using objective measures of physiological sleep tendency and ability to sustain wakefulness. Both measures show caffeine to reduce sleepiness at a single dose roughly the equivalent of two to four cups of coffee. Despite impressive objective differences in alertness with caffeine, subjects did not consistently differentiate between drug conditions on subjective alertness assessments. The use of CNS stimulants to promote alertness during night shift hours should be considered, particularly for occupations for which alertness is critical.

Adult

Twenty-four-hour patterns in human performance, subjective and physiological variables and differences between morning and evening active subjects.

A study was undertaken to investigate differences between habitually morning active and evening active subjects as regards 24-hr patterns in physiological and subjective arousal and performance efficiency under conditions of 72 hr of sleep deprivation. The results were that very consistent 24-hr rhythmic were present in some of the performance variables, subjective alertness, oral temperature and urinary adrenaline excretion. No significant differences in 24-hr patterns could be detected between a group of habitually morning active and a group of evening active subjects. Significant correlations were obtained between oral temperature and some of the performance measures, while adrenaline excretion was not significantly correlated with performance. There were rather high correlations between subjective alertness ratings and some of the performances.

Adult

Psychophysiological effects of early morning bright light exposure in young adults.

The effects of bright light on circadian rhythms in man are well documented. Nevertheless the theoretical basis and the rules for the practical utilization of light exposure as therapy need still to be better defined. The present study determined to what extent a 2-hr bright light exposure (0500-0700 h) improved the adjustment to an early rising in normal adults. Phase changes were assessed in subjective alertness, performance in several search tasks, time estimation, and a visual discrimination task, as well as in body motility, plasma cortisol concentrations, and body temperature. In comparison with a dim light exposure, the bright light resulted in increased motor activity during waking, in earlier peak of subjective alertness, and an improvement in performance speed in three out of five tasks in the morning. Cortisol and body temperature also were phase-advanced. In summary, light applied to a portion of the circadian cycle sensitive to phase advance shifts influenced rhythms with strong endogenous components (temperature and cortisol), while other rhythms with strong exogenous components were more sensitive to sleep deprivation caused by the early rising time.

Adult

Computerized analysis of pupillograms in studies of alertness.

When alert subjects sit in a quiet, darkened room for 10-15 min, their pupils remain dilated. If the subjects become sleepy or fatigued, their pupils become miotic and oscillate. Pupillometry, the recording of pupil diameter, has been used to study alertness. Pupillograms are typically graded by subjective assessment on the basis of oscillations of pupil diameter (hippus) and miosis. In this study, numeric parameters were calculated from pupillograms and were compared to subjective ratings by clinicians. Pupil diameters were recorded for 15 min at five samples per second with a custom built video pupillometer. Subjects sat in the dark and fixated a small red light. Digital filtering techniques and Fourier analysis were used to calculate several parameters designed to report hippus and miosis. The same set of pupillograms was graded by three physicians familiar with pupillometry. Grades were assigned on a scale of 1 to 4, 1 being most alert and 4 least alert. A linear combination of three of the numeric parameters had the highest correlation with the average subjective grade (r = 0.92). These techniques provide a quantitative way to evaluate pupillograms that will be used in the assessment of alertness.

Adolescent

Classical conditioning of autonomic responses in alert and drowsy subjects.

The primary purpose of this experiment was to study classically conditioned autonomic responses of alert versus drowsy subjects. Sixty-nine subjects in conditioning and pseudo-conditioning groups were subdivided into alert and drowsy groups on the basis of EEG recordings during conditioning trials, giving a total of four groups: conditioning-alert, conditioning-drowsy, pseudoconditioning-alert and pseudoconditioning-drowsy. Using the latency criterion to define responses, significant conditioning occurred only in the conditioning-alert group for the following measures: skin resistance anticipatory and UCS-omission responses, and finger plethysmograph anticipatory response. Both conditioning groups showed evidence of conditioned UCS-omission plethysmograph responses. Discussion centered primarily on (1) the implications of the results on the question of the feasibility of learning during sleep; and (2) the importance of including EEG recordings in studies of classically conditioned autonomic responses. The relationship between the various responses was also evaluated.

Acoustic Stimulation

P300 and time of day: circadian rhythms, food intake, and body temperature.

The P300 or P3 component of the event-related brain potential (ERP) was obtained from five groups of 24 young adult subjects, with each group measured at a different time of day (8 a.m., 11 a.m., 2 p.m., 5 p.m., 8 p.m.). An activity-preference questionnaire was used to ensure that an equitable number of morning- and evening-preferring subjects were obtained for each testing time. P3 measures, physiological (body temperature, heart rate, subjective alertness), and cognitive performance (digit span, prose memory, digit symbol) variables were assessed. P3 amplitude and latency were not affected directly by the time of day. However, P3 amplitude was smaller in subjects who had not eaten within 6 hours of testing relative to subjects who had a recent meal, and P3 latency was correlated negatively with body temperature. The findings suggest that although the P3 ERP is not influenced by circadian rhythms, it is related to recency of food intake and physiological factors which change with time of day.

Adolescent

Central effects of the angiotensin-converting enzyme inhibitor, captopril. I. Performance and subjective assessments of mood.

1. Central effects of single doses of captopril (12.5, 25 and 50 mg) were studied in fourteen healthy male subjects. Two placebos and an active control drug, oxazepam (15 mg), were included, together with a single dose of atenolol (100 mg). The drugs were administered double-blind at 11.00 h, and performance and subjective feelings were assessed before and from 1.5-2.5 h and 3.5-4.5 h after ingestion. 2. Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, together with critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. 3. Captopril did not impair performance on any of the tests, but improved short-term memory (P less than 0.05) and increased the number of letters cancelled (P less than 0.05). Oxazepam reduced the number of substitutions completed in the digit symbol test (P less than 0.01), accuracy on continuous attention (P less than 0.05), number of letters cancelled (P less than 0.05), and rate of finger tapping (P less than 0.05), and increased choice reaction time (P less than 0.001). Atenolol reduced the rate of finger tapping (P less than 0.05), but increased the number of letters cancelled (P less than 0.05). 4. No effects on mood or on subjective feelings were evident with captopril. Oxazepam reduced subjective alertness (P less than 0.05), and atenolol increased feelings of sleepiness (P less than 0.05). 5. Although these observations suggest that central effects may exist with captopril, no adverse consequences have been established on performance or on subjective assessment of mood. Captopril may, therefore, be an appropriate drug for hypertensive patients engaged in skilled activity.

Adult

The effect of betel nut on human performance.

The effects of low doses of betel nut on early-stage visual information processing were examined, using a cross-over experimental design. Three assessment measures were used, critical flicker fusion (an index of the efficiency of the visual processing system), heart rate, and analogue scales of subjective alertness. Only heart rate was shown to be significantly elevated, immediately following betel nut administration. From these results, it was concluded that there is no evidence to suggest that betel nut usage facilitates visual information processing at low-dose levels in habituated subjects, but there is some evidence that peripheral stimulation occurs.

Adolescent

Tests of memory in narcoleptics.

This study attempted to evaluate the validity of self-reports of memory deficits in narcoleptics by comparing the scores of these patients with the scores of matched control subjects on standardized tests of memory function. After completing a short interview designed to elicit qualitative information about memory difficulties, 30 narcoleptic subjects and 30 control subjects completed the Wechsler Memory Scale (WMS), Rey-Auditory Verbal Learning Test, the Rey Complex Figure Test, Strub and Black's List of Letters, and the Symbol Digits Modalities Test (SDMT). In addition, the Profile of Mood States (POMS) was used to detect variation in performance due to anxiety or fatigue. Continuous polygraphic recordings were obtained during the testing to detect any changes in alertness. Subjects with narcolepsy experienced more difficulty in maintaining attention than control subjects, as evidenced by significantly more perseveration errors (p less than or equal to 0.01) on Strub and Black's List of Letters. Despite differences in their ability to sustain attention, there were no significant differences between narcoleptic and control subjects on measures of concentration (Digit Span from the WMS, and the SDMT). Furthermore, there was no objective evidence of memory impairment when the scores of narcoleptic and control subjects were compared on standardized tests of immediate and delayed recall, as well as on tests of verbal and visual memory.

Adolescent

A preliminary study of the effects of flosequinan on psychomotor function in healthy volunteers.

The central nervous system effects of flosequinan (100 mg), a chemically novel quinolone vasodilator, were assessed by a double-blind crossover comparison with placebo and diazepam (10 mg) in 12 healthy volunteers. After five practice sessions on a battery of automated psychomotor tests, assessments of psychomotor function and mood ratings were made on each volunteer at baseline and 1, 3, 6 and 24 h after dosing. Compared with placebo, diazepam (10 mg), the verum control, significantly (p less than 0.05) reduced subjective alertness, impaired critical flicker fusion threshold at 1 and 3 h, digit symbol substitution at 6 h, overall total choice reaction time and overall rate on two of five finger tapping tests. Flosequinan (100 mg), however, was indistinguishable from placebo in all tests with two contrasting exceptions: improved alternate right and left finger tapping (mean 5.1/s) compared to either diazepam (4.7/s) or placebo (4.8/s) (p less than 0.05), and impaired digit symbol substitution at 6 h (45.7/min) in comparison with placebo (50.7/min) (p less than 0.01). Ten volunteers reported 12 adverse effects after flosequinan treatment (10 of which were headaches), two reported drowsiness after diazepam and one reported headache after placebo. It was concluded that flosequinan has no central nervous system depressant effects despite the occurrence of headache in 10 volunteers.

Administration, Oral

Sleep manipulation prior to airborne exercises.

Airborne operations may demand an intense level of activity prior to parachuting. In addition the movement of troops to the theatre of operations may well involve the crossing of several time zones. These factors may well deprive the troops of sleep. Furthermore, a parachute assault may well be at night leading to a long period without rest. Scheduled sleep may help ameliorate this sleep deprivation. Studies have shown that daytime sleep prior to overnight activity can improve performance. A study was undertaken to see whether temazepam would improve daytime sleep during a scheduled rest period compared to placebo. The results showed a significant increase in the average sleep period in the group taking 20mg and 10mg of temazepan compared to placebo. The quality of sleep was also improved yet there was no difference in subjective alertness between the groups six hours post ingestion.

Aerospace Medicine

Stereoencephalotomy and control of skeletal muscle tone.

Stereotactic interventions at the thalamic or subtalamic level for treatment of pathological hyperkinesias provide a good model for investigation of the systems controlling tonic innervation in the alert subject. It is suggested that the poststereotactic muscular hypotonia observed contralaterally to the lesion is due to changes in the tonic innervation pattern caused by interruption of a proprioceptive feedback loop.

Dominance, Cerebral

The vestibulo-ocular response during transient arousal shifts in man.

Horizontal vestibulo-ocular response (VOR) evoked by continuous sinusoidal rotation (0.1 Hz, +/- 90 degrees) was recorded in 20 young and healthy volunteers by DC oculography (EOG). Arousal was assessed by EEG and by reaction time measurement. While alert subject showed the characteristic VOR with vestibular nystagmus, the quick repositioning flicks disappeared during light sleep and changed to largely compensatory smooth eye deviations. This state of reduced arousal was also characterized by EEG attenuation and slow reaction times. Furthermore, we observed brief states with complete extinction of the vestibular response but without significant EEG change. The results demonstrate the high variability of VOR with shifting arousal. The polysynaptic system in the reticular formation which generates the fast phase of the nystagmus beat is far more modifiable than the three-neuronal reflex arc of the slow nystagmus component.

Acceleration

[The relationship between the parameters of the early and late oscillations of human cortical evoked potentials and the rhythm of acoustic stimulation].

The amplitudes of all deflections of the slow auditory evoked potential (AEP) regularly decrease in alert subjects with the increase of stimulation rate. As compared with the late deflections (P2N2), the decrease of the amplitude of comparatively early deflections (N1P2) is more pronounced. It is a rather logarithmic, than a linear function of the interstimulus interval. The degree of amplitude diminution of slow AEPs due to a greater stimulation rate depends on the intensity of acoustic stimul: at greater sound intensities the decrease is more pronounced. The higher rates of stimulation produce, along with a decreased amplitude, a shorter peak latencies of all slow AEP deflections (except the peak of deflection P1). In narcotic (chloralhydrate) sleep higher rates of stimulation are not attended with any regular changes in the amplitude and peak latencies of the slow AEP.

Acoustic Stimulation

Circadian rhythmicity and sleep of aircrew during polar schedules.

Sleep and circadian rhythms of aircrew were studied during a 7-d polar schedule operated between London and Tokyo. Sleep, rectal temperature, and subjective alertness were recorded for 2 d before departure during the schedule, and for 10 d after the return. Changes in sleep during the early part of the trip were due to sleep loss on the outward journey, but later these changes were related to the displacement of the circadian rhythm. The acrophases of the circadian rhythms of temperature were delayed by the outward journey, and amplitudes were reduced throughout the trip. During the return, aircrew reported high levels of tiredness which persisted until the second recovery night. Though the amounts of sleep obtained during the schedule were satisfactory for the aircrew as a group, some crewmembers experienced difficulties. Realignment of circadian rhythms was attained by an advance of the circadian phase in eight aircrew and by a delay in three, and resynchronization was achieved in all cases within 6 d.

Adult

Nystagmus, turning sensations, and illusory movement in motion sickness susceptibility.

The relationships of motion sickness susceptibility to nystagmic eye movements, sensations of turning, and duration of the spiral aftereffect were determined with 48 subjects separated into groups on the basis of sex and extremes of motion sickness susceptibility. When subjective alertness levels were controlled, there was no enhancement of elicited nystagmus nor turning sensations in susceptible individuals. However, spiral aftereffect durations were significantly longer in susceptible individuals than in nonsusceptible individuals. The results are interpreted as favoring Graybiel's model of the structural elements in motion sickness.

Adolescent

Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam.

The Observer's Assessment of Alertness/Sedation (OAA/S) Scale was developed to measure the level of alertness in subjects who are sedated. This scale was tested in 18 subjects in a three-period crossover study to assess its reliability and its criterion, behavioral, and construct validity. After receiving either placebo or a titrated dose of midazolam to produce light or heavy sedation, each subject was administered two sedation scales (OAA/S Scale and a Visual Analogue Scale) and two performances tests (Digit Symbol Substitution Test and Serial Sevens Subtraction). Two raters individually evaluated the subject's level of alertness on each of the two sedation scales. The results obtained on the OAA/S Scale were reliable and valid as measured by high correlations between the two raters and high correlations between the OAA/S Scale and two of the three standard tests used in this study. The OAA/S Scale was sensitive to the level of midazolam administered; all pairwise comparisons were significant (p less than 0.05) for all three treatment levels at both test periods.

Adult