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.

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.

The P300 component in sleep.

The present investigation utilized the P300 component of the auditory evoked potential as an index of information processing (discrimination) in sleep. Auditory evoked potentials were recorded to target and nontarget stimuli during sleep stages 3/4, 2 and REM under two probability conditions. Corresponding "nontone" waveforms were generated in each sleep stage, representing averaged EEG activity with no tones presented. Target P300 amplitude was higher than both corresponding "nontone" targets and tone nontargets. Probability did not affect the target-nontarget relationship. Latency of P300 increased and amplitude decreased from wakefulness through sleep; however, neither amplitude nor latency differed among sleep stages. Amplitude and latency of N200 increased during sleep. While N200 amplitude was highest in Stage 3-4, N200 latency did not differ among sleep stages. These findings suggest that the P300 recorded in sleep indexes similar cognitive processes as the P300 recorded in wakefulness. That P300 as well as N200 latency increased in sleep suggests that processes indexed by these components may slow during sleep.

Time of day, repeated testing, and interblock interval effects on P300 amplitude.

Time of day, repeated testing, and interblock interval effects on P300 amplitude were investigated. Subjects (N = 50) were tested using a standard oddball paradigm in either morning or afternoon sessions consisting of six test blocks per session. Amplitude of P300 was significantly higher in the morning than in the afternoon for all test blocks. In addition, amplitude of P300 habituated across test blocks from a mean of 9.59 microV on Block 1 to a mean of 4.98 microV on Block 6. Inserting a one-hour interval between Blocks 2 and 3 attenuated the rate of habituation. The results indicate that time of day, repeated testing, and interblock intervals affect P300 amplitude. Amplitude changes due to time of day may reflect circadian variations in cognitive resources indexed by the P300 component, while decrements due to repeated testing may reflect changes in allocation of resources across test sessions.

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.

Time of day and semantic category effects on late components of the visual ERP.

The N100, P200, N400 and P600 components of the visual event-related potential were recorded from 11 female subjects every 2 h from 09:00 to 21:00 hours using a semantic categorization task. All subjects scored as "Intermediate" or marginal "Evening" types on a Morningness-Eveningness questionnaire. Amplitude and latency of components, tympanic temperature, and performance measures for positive and negative category instances were assessed. Amplitude of P200 increased across the day. Amplitude of N400 was larger, and latency of P600 was longer, for negative category instances, but neither component varied with time of day. N100 was unaffected by time of day. The results suggest that previous reports of diurnal variations in visual N100-P200 were due to variations in P200 alone, and that diurnal variations in P200 may reflect diurnal variations in underlying arousal levels. In addition, overlap with P600 may have obscured time of day effects for N400.

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.

Effects of simulated high altitude exposure on long-latency event-related brain potentials and performance.

The N100, P200, N200 and P300 components of the auditory event-related potential were recorded from 10 male subjects at 0900, 1600, and 1830 hours at sea level and again following a rapid ascent to simulated 4300 m altitude. Amplitude and latency of components, ear oximetry, and concurrent performance measures (reaction time and counting errors) were assessed. Amplitude of P300 decreased, while P300 latency and reaction time increased, following ascent to altitude. However, the time course of altitude effects differed for amplitude versus latency. Components N100, P200, N200, and counting errors were unaffected by altitude. The results indicate that central measures of cognitive capacities are differentially sensitive to high altitude. The time course of altitude effects on P300 amplitude versus P300 latency suggests that the two measures reflect different aspects of a response to hypobaric hypoxia exposure.

Anchoring effects on judgement, estimation, and discrimination of numerosity.

Three experiments (N = 234) examined anchoring effects on judgement, estimation, and discrimination of numerosity. Subjects were anchored by preexposing them to random dot patterns with a mean quantity of 25, 50, or 75 dots. Subsequent testing with patterns having greater or less numerosity than the anchoring point resulted in predictable effects, including positive or negative contrast effects for numerosity judgements (Exp. 1), positive or negative contrast for the numerical estimation of quantity (Exp. 2), and a larger number of errors when subjects attempted simultaneous discrimination between two dot patterns (Exp. 3). The results extend previous findings for anchoring effects to the stimulus dimension of numerosity.

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.

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.