Does sleep fragmentation impact recuperation? A review and reanalysis.

Studies have shown that next-day performance and alertness are impaired by sleep fragmentation procedures even when total sleep time (TST) is unaffected. Based on these studies it has been hypothesized that both the duration and continuity of sleep determine its recuperative value. This review of the literature suggests that when sleep fragmentation procedures increase the relative amount of stage 1 sleep, next-day performance and alertness are impaired. Other studies suggest that stage 1 sleep has little or no recuperative value. Total sleep time, however, is typically defined as the sum of time spent in sleep stages 1, 2, 3, 4, and REM. In the present paper it is shown that when stage 1 sleep is excluded from TST, a stronger relationship between TST and subsequent alertness and performance emerges--and the need to invoke 'sleep continuity' as a variable that contributes independently to recuperative sleep processes is obviated. In the same way that partial or total sleep deprivation impairs alertness and performance, it is proposed that sleep disruption also impairs alertness and performance by reducing true recuperative sleep time.

Dissociated pattern of activity in visual cortices and their projections during human rapid eye movement sleep.

Positron emission tomography was used to measure cerebral activity and to evaluate regional interrelationships within visual cortices and their projections during rapid eye movement (REM) sleep in human subjects. REM sleep was associated with selective activation of extrastriate visual cortices, particularly within the ventral processing stream, and an unexpected attenuation of activity in the primary visual cortex; increases in regional cerebral blood flow in extrastriate areas were significantly correlated with decreases in the striate cortex. Extrastriate activity was also associated with concomitant activation of limbic and paralimbic regions, but with a marked reduction of activity in frontal association areas including lateral orbital and dorsolateral prefrontal cortices. This pattern suggests a model for brain mechanisms subserving REM sleep where visual association cortices and their paralimbic projections may operate as a closed system dissociated from the regions at either end of the visual hierarchy that mediate interactions with the external world.

Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study.

To assess dynamic changes in brain function throughout the sleep-wake cycle, CBF was measured with H2(15)O and PET in 37 normal male volunteers: (i) while awake prior to sleep onset; (ii) during Stage 3-4 sleep, i.e. slow wave sleep (SWS); (iii) during rapid eye movement (REM) sleep; and (iv) upon waking following recovery sleep. Subjects were monitored polysomnographically and PET images were acquired throughout the course of a single night. Stage-specific contrasts were performed using statistical parametric mapping. Data were analysed in repeated measures fashion, examining within-subject differences between stages [pre-sleep wakefulness-SWS (n = 20 subjects); SWS-post-sleep wakefulness (n = 14); SWS-REM sleep (n = 7); pre-sleep wakefulness-REM sleep (n = 8); REM sleep-post-sleep wakefulness (n = 7); pre-sleep wakefulness-post-sleep wakefulness (n = 20)]. State dependent changes in the activity of centrencephalic regions, including the brainstem, thalamus and basal forebrain (profound deactivations during SWS and reactivations during REM sleep) are consistent with the idea that these areas are constituents of brain systems which mediate arousal. Shifts in the level of activity of the striatum suggested that the basal ganglia might be more integrally involved in the orchestration of the sleep-wake cycle than previously thought. State-dependent changes in the activity of limbic and paralimbic areas, including the insula, cingulate and mesial temporal cortices, paralleled those observed in centrencephalic structures during both REM sleep and SWS. A functional dissociation between activity in higher order, heteromodal association cortices in the frontal and parietal lobes and unimodal sensory areas of the occipital and temporal lobes appeared to be characteristic of both SWS and REM sleep. SWS was associated with selective deactivation of the heteromodal association areas, while activity in primary and secondary sensory cortices was preserved. SWS may not, as previously thought, represent a generalized decrease in neuronal activity. On the other hand, REM sleep was characterized by selective activation of certain post-rolandic sensory cortices, while activity in the frontoparietal association cortices remained depressed. REM sleep may be characterized by activation of widespread areas of the brain, including the centrencephalic, paralimbic and unimodal sensory regions, with the specific exclusion of areas which normally participate in the highest order analysis and integration of neural information. Deactivation of the heteromodal association areas (the orbital, dorsolateral prefrontal and inferior parietal cortices) constitutes the single feature common to both non-REM and REM sleep states, and may be a defining characteristic of sleep itself. The stages of sleep could also be distinguished by characteristic differences in the relationships between the basal ganglia, thalamic nuclei and neocortical regions of interest.

Effects of daytime administration of zolpidem and triazolam on performance.

UNLABELLED: BACKGROUND AND HYPOTHESES: The performance-impairing effects of the short-acting imidazopyridine zolpidem (Ambien) were compared to those of triazolam (Halcion) following daytime administration. METHODS: There were 70 male subjects who received oral zolpidem (5, 10 or 15 mg), triazolam (0.125, 0.25 or 0.5 mg), or placebo at 1000 hours. Performance on Logical Reasoning, Column Addition, and Repeated Acquisition (computerized tasks of the Walter Reed Performance Assessment Battery) was assessed prior to drug administration, then at 1.5 h (estimated time of peak drug effects) and 6 h post-administration. RESULTS: Number of trials completed (TC) and response time (RT) for correct answers on the Logical Reasoning (LR) and Column Addition (CA) tasks (expressed as percentage of pre-drug performance) were impaired by triazolam 0.5 mg (TC = 76.6 and 67.4% for LR and CA; RT = 182.1 and 127.0% for LR, CA) and zolpidem 15 mg (TC = 87.0 and 75.8% for LR, CA; RT = 198.7 and 161.8% for LR, CA) at 1.5 h post-administration. By 6 h post-administration, drug effects on performance had dissipated. Other doses of triazolam and zolpidem failed to impair performance significantly. CONCLUSIONS: These results indicate substantial performance impairment at estimated peak plasma concentrations of both triazolam and zolpidem, at or near doses coinciding with somnogenic efficacy. Thus, the present results suggest no advantage of benzodiazepine receptor-subtype-specific drugs (e.g., zolpidem). Rather, these results suggest that the performance-impairing effects of both drugs are dose-dependent and functionally coupled to their sleep-inducing properties.

Reversal of triazolam- and zolpidem-induced memory impairment by flumazenil.

The effects of flumazenil, a benzodiazepine receptor antagonist, on triazolam- and zolpidem-induced memory impairment were investigated. Sixty subjects received oral triazolam 0.5 mg, zolpidem 20.0 mg, or placebo at 10 a.m. (n = 20 per drug). Ninety minutes later, half of the subjects (n = 10) in each oral drug group were administered flumazenil 1.0 mg, while the remaining half received placebo (normal saline), through indwelling venous catheters. Learning/memory tests (including Simulated Escape, Restricted Reminding, Paired-Associates, and Repeated Acquisition) were administered at that time, and at 1.5-h intervals over the next 6 h. Triazolam/placebo and zolpidem/placebo drug combinations impaired memory on all tests (all Ps < 0.05). However, the triazolam/flumazenil and zolpidem/flumazenil groups showed no evidence of impairment during any test session. These results demonstrate that flumazenil 1.0 mg rapidly and lastingly reverses memory impairment caused by agonists of the benzodiazepine receptor. Furthermore, nonsignificant trends suggested that performance of the placebo/flumazenil group was consistently better than that of the placebo/placebo group, denoting a possible role of endogenous benzodiazepine agonists in natural sleep/wake processes.

Visual performance with the Aviator Night Vision Imaging System (ANVIS) at a simulated altitude of 4300 meters.

This study determined if visual performance with Aviator Night Vision Imaging System (ANVIS) was degraded by the degree of hypoxia experienced at the maximum flight altitude currently authorized (U.S. Army regulations) without supplemental oxygen. Visual acuity and contrast sensitivity with ANVIS were tested under simulated starlight and full moonlight illumination in a hypobaric chamber: at ground level (93 m), 5 min and 30 min after ascent to 4300 m, and 10 min after return to ground level. Visual acuity was significantly (p < 0.05) degraded by a small amount (0.05 log minimal angle resolvable) after 30 min at 4300 m. Contrast sensitivity was not significantly degraded at any time. No significant difference between males (n = 11) and females (n = 6) on any measure of visual performance was detected. Females did have a significantly lower percent oxygen saturation of hemoglobin compared with males at altitude (72% versus 80% after 30 min). The results suggests that visual acuity ANVIS is degraded slightly after 30 min of exposure to 4300 m, although less than what would be expected with unaided night vision under these conditions.

Effects of daytime administration of zolpidem versus triazolam on memory.

To determine whether zolpidem (an imidazopyridine hypnotic) produces amnestic effects which are similar to those produced by triazolam (a benzodiazepine hypnotic), 70 subjects were administered either triazolam (0.125, 0.25, or 0.5 mg), zolpidem (5, 10, or 15 mg) or placebo, then tested on Simulated Escape, Restricted Reminding, and Paired-Associates memory tests at 1.5 hours post-dosing (i.e., near the time of estimated peak blood concentration for both drugs) and again at 6 hours post-dosing. Triazolam 0.5 mg produced the greatest memory impairment at both test times, and also produced the greatest degree of sedation during intervening daytime naps in a non-sleep-conducive environment. Other doses of triazolam and zolpidem produced less memory impairment, but also failed to significantly enhance sleep. The results are consistent with the view that the amnestic and hypnotic effects of these sleep-inducing medications are functionally coupled.

Altitude and time of day effects on EEG spectral parameters.

Electroencephalographic (EEG) recordings were obtained from nine male subjects at sea level and again following rapid ascent to high altitude (4300 meters) at 0900, 1600, and 1830 h. Electroencephalographic data were subjected to Fast Fourier Transformation and analyzed for beta, spindle, alpha, theta, delta, and total amplitudes. Total amplitude increased from baseline to altitude while relative theta (absolute theta/total amplitude) decreased from baseline to altitude. Amplitude for absolute and relative spindle and total amplitude increased across the day. The results indicate that altitude exerts an effect on the waking electroencephalogram which can be quantified via spectral analysis.

Plasma glucose levels and leverpress avoidance versus escape behaviors in rats.

The relationship between performance in an avoidance conditioning paradigm and the plasma glucose levels of Sprague-Dawley rats was examined in two experiments. In Experiment 1 we investigated whether glucose levels varied with the animal's relative success at acquiring the avoidance task. Results indicated that animals classified as avoiders (60% avoidance and above) had lower glucose levels than animals classified as escapers (30% avoidance and below). In Experiment 2 we looked at whether glucose levels showed within-subject changes with avoidance acquisition. Results demonstrated that glucose levels showed reductions if an animal learned the avoidance response. Subjects that did not learn the response showed no such reduction. Such results suggest that the physiological response to stress is attenuated by acquisition of successful coping behaviors that exercise control over the onset of aversive events.

Comparison of the daytime sleep and performance effects of zolpidem versus triazolam.

Fifty healthy male subjects were administered zolpidem (5, 10, or 20 mg), triazolam (0.5 mg) or placebo, then attempted to sleep in a non-sleep-conducive environment. Subjects were awakened at 90 min post-drug (near peak blood concentration for both drugs) and tested on several cognitive tasks, including Two Column Addition, Logical Reasoning, and a Simulated Escape Task. This was followed by a second, 3.5-h sleep period. Hypnotic efficacy of the 20 mg zolpidem (Z-20) dose was similar to that of the 0.5 mg triazolam (TRIAZ) dose, as indicated by comparably shortened sleep latencies and lengthened total sleep times. Though accuracy on most performance measures was not affected by either drug, a reduction in speed of responding on logical reasoning and addition tasks was evident for the TRIAZ group at 90 min post-drug (Ps less than 0.05). On the simulated escape task, only triazolam significantly increased the mean number of errors, and interfered with subsequent memory of the task. Thus, zolpidem had milder effects on performance than triazolam. However, 60% of the Z-20 subjects experienced mild, adverse physical reactions. Performance differences between somnogenically comparable doses of zolpidem and triazolam may be due to their differential affinities for the BZ1 and BZ2 receptor subtypes.

A preliminary study of the effects of nighttime administration of the serotonin agonist, m-CPP, on sleep architecture and behavior in healthy volunteers.

The effects of m-chlorophenylpiperazine (m-CPP) (0.5 mg/kg) on sleep architecture and behavior were examined in six healthy volunteers following a single oral dose of the drug in a randomized, double-blind, placebo-controlled study. m-CPP reduced total sleep time (TST) and sleep efficiency in all subjects. Slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep were decreased and stage 1 sleep was prolonged in a majority of subjects. Prominent behavioral and psychological effects were reported in five out of six subjects following m-CPP (but not following placebo) that interfered with sleep. The sleep disruption and behavioral activation following nighttime administration of m-CPP contrasts with the sedative properties of its parent compound, trazodone, suggesting that the hypnotic effect of trazodone is not related to the agonist profile of its metabolite, m-CPP.

Administration of triazolam prior to recovery sleep: effects on sleep architecture, subsequent alertness and performance.

The effects of triazolam (0.125, 0.25, and 0.5 mg) versus placebo on recovery sleep staging, subsequent alertness and psychomotor performance were evaluated in humans. Forty-five healthy male subjects were deprived of sleep for 24 h, then administered a single dose of triazolam or placebo using a double-blind procedure. Subjects then attempted to obtain recovery sleep under non-sleep-conducive conditions (sitting upright in a well-lit, crowded chamber) for the next 6 h, followed by 18 more hours of sleep deprivation. During all sleep deprivation periods subjects were tested bihourly on a performance assessment battery which included symbol digit modalities tests (SDMT), four-letter search (FLS), logical reasoning (LR), time estimation (TE), visual vigilance (VV), and short term memory (STM) tasks. Sleepiness levels were measured objectively with multiple sleep latency tests (MSLT) and subjectively with the Stanford Sleepiness Scale (SSS). Compared to placebo, all doses of triazolam resulted in increased amounts of stage 3-4 sleep, and the 0.5 mg dose significantly reduced awakenings (Ps less than 0.05). Although subjects receiving triazolam averaged 21-42 min more total sleep time (TST) than subjects receiving placebo, differences in TST were not statistically significant. Apparent triazolam-mediated benefits to sleep quality resulted in no obvious improvements in performance or alertness levels during subsequent sleep deprivation. It was concluded that the increases in stage 3-4 sleep amounts were most likely due to triazolam-mediated increases arousal thresholds, and the triazolam mediated changes in sleep parameters obtained in the present study were not indicative of substantial changes in the recuperative value of sleep.

Relationship between sleep inertia and sleepiness: cumulative effects of four nights of sleep disruption/restriction on performance following abrupt nocturnal awakenings.

Performance deficits are usually evident following both extended wakefulness (sleep deprivation effects) and immediately upon awakening from sleep (sleep inertia effects). In order to determine whether sleep inertia effects are qualitatively different from sleep deprivation effects, performance on addition tests, Stanford Sleepiness Scale (SSS) ratings, and return-to-sleep latencies (RSLs) were assessed during four nights of sleep disruption/restriction. Eight subjects were polygraphically monitored in the sleep laboratory for five consecutive nights, from 2400 to 0700. On the last four nights (after an adaptation night) subjects were awakened at 0040, 0140, 0240, 0340, 0440, and 0540 for a 20-min test session. Sleepiness ratings and performance on 5-min addition tests were measured at 1.5, 7.5, and 13.5 min post-awakening, and RSL was measured at the end of each test session. Analysis of addition test performance across nights revealed that both speed and accuracy of calculations were adversely affected by the sleep disruption/restriction procedure, indicating that increasing sleepiness exacerbates sleep performance deficits upon awakening. Although divergence of SSS ratings and addition test performance across nights was suggestive, there was no conclusive evidence that sleep inertia is qualitatively different from "typical" sleepiness.