Raymond W. Matthews

Sleep, Wake and Phase Dependent Changes in Neurobehavioral Function under Forced Desynchrony

STUDY OBJECTIVES The homeostatic-circadian regulation of neurobehavioral functioning is not well understood in that the role of sleep dose in relation to prior wake and circadian phase remains largely unexplored. The aim of the present study was to examine the neurobehavioral impact of sleep dose at different combinations of prior wake and circadian phase. DESIGN A between-participant design involving 2 forced desynchrony protocols varying in sleep dose. Both protocols comprised 7 repetitions of a 28-h sleep/wake cycle. The sleep dose in a standard protocol was 9.33 h per 28-h day and 4.67 h in a sleep-restricted protocol. SETTING A time-isolation laboratory at the Centre for Sleep Research, the University of South Australia. PARTICIPANTS A total of 27 young healthy males participated in the study with 13 in the standard protocol (age 22.5 ± 2.2 y) and 14 in the sleep-restricted protocol (age 21.8 ± 3.8 y). INTERVENTIONS Wake periods during both protocols were approximately 4 h delayed each 28-h day relative to the circadian system, allowing performance testing at different combinations of prior wake and circadian phase. The manipulation in sleep dose between the 2 protocols, therefore, allowed the impact of sleep dose on neurobehavioral performance to be examined at various combinations of prior wake and circadian phase. MEASUREMENTS AND RESULTS Neurobehavioral function was assessed using the psychomotor vigilance task (PVT). There was a sleep dose × circadian phase interaction effect on PVT performance such that sleep restriction resulted in slower and more variable response times, predominantly during the biological night. This interaction was not altered by prior wakefulness, as indicated by a nonsignificant sleep dose × circadian phase × prior wake interaction. CONCLUSIONS The performance consequence of sleep restriction in our study was prominent during the biological night, even when the prior wake duration was short, and this performance consequence was in forms of waking state instability. This result is likely due to acute homeostatic sleep pressure remaining high despite the sleep episode.

Mismatch between subjective alertness and objective performance under sleep restriction is greatest during the biological night

Subjective alertness may provide some insight into reduced performance capacity under conditions suboptimal to neurobehavioural functioning, yet the accuracy of this insight remains unclear. We therefore investigated whether subjective alertness reflects the full extent of neurobehavioural impairment during the biological night when sleep is restricted. Twenty‐seven young healthy males were assigned to a standard forced desynchrony (FD) protocol (n = 13; 9.33 h in bed/28 h day) or a sleep‐restricted FD protocol (n = 14; 4.67 h in bed/28 h day). For both protocols, subjective alertness and neurobehavioural performance were measured using a visual analogue scale (VAS) and the psychomotor vigilance task (PVT), respectively; both measures were given at various combinations of prior wake and circadian phase (biological night versus biological day). Scores on both measures were standardized within individuals against their respective baseline average and standard deviation. We found that PVT performance and VAS rating deviated from their respective baseline to a similar extent during the standard protocol, yet a greater deviation was observed for PVT performance than VAS rating during the sleep‐restricted protocol. The discrepancy between the two measures during the sleep‐restricted protocol was particularly prominent during the biological night compared with the biological day. Thus, subjective alertness did not reflect the full extent of performance impairment when sleep was restricted, particularly during the biological night. Given that subjective alertness is often the only available information upon which performance capacity is assessed, our results suggest that sleep‐restricted individuals are likely to under‐estimate neurobehavioural impairment, particularly during the biological night.

CONTRIBUTION OF CORE BODY TEMPERATURE, PRIOR WAKE TIME, AND SLEEP STAGES TO COGNITIVE THROUGHPUT PERFORMANCE DURING FORCED DESYNCHRONY

Shiftworkers are often required to sleep at inappropriate phases of their circadian timekeeping system, with implications for the dynamics of ultradian sleep stages. The independent effects of these changes on cognitive throughput performance are not well understood. This is because the effects of sleep on performance are usually confounded with circadian factors that cannot be controlled under normal day/night conditions. The aim of this study was to assess the contribution of prior wake, core body temperature, and sleep stages to cognitive throughput performance under conditions of forced desynchrony (FD). A total of 11 healthy young adult males resided in a sleep laboratory in which day/night zeitgebers were eliminated and ambient room temperature, lighting levels, and behavior were controlled. The protocol included 2 training days, a baseline day, and 7 × 28-h FD periods. Each FD period consisted of an 18.7-h wake period followed by a 9.3-h rest period. Sleep was assessed using standard polysomnography. Core body temperature and physical activity were assessed continuously in 1-min epochs. Cognitive throughput was measured by a 5-min serial addition and subtraction (SAS) task and a 90-s digit symbol substitution (DSS) task. These were administered in test sessions scheduled every 2.5 h across the wake periods of each FD period. On average, sleep periods had a mean (± standard deviation) duration of 8.5 (±1.2) h in which participants obtained 7.6 (±1.4) h of total sleep time. This included 4.2 (±1.2) h of stage 1 and stage 2 sleep (S1–S2 sleep), 1.6 (±0.6) h of slow-wave sleep (SWS), and 1.8 (±0.6) h of rapid eye movement (REM) sleep. A mixed-model analysis with five covariates indicated significant fixed effects on cognitive throughput for circadian phase, prior wake time, and amount of REM sleep. Significant effects for S1–S2 sleep and SWS were not found. The results demonstrate that variations in core body temperature, time awake, and amount of REM sleep are associated with changes in cognitive throughput performance. The absence of significant effect for SWS may be attributable to the truncated range of sleep period durations sampled in this study. However, because the mean and variance for SWS were similar to REM sleep, these results suggest that cognitive throughput may be more sensitive to variations in REM sleep than SWS. (Author correspondence: david.darwent@unisa.edu.au)

Simulated driving under the influence of extended wake, time of day and sleep restriction.

Around a fifth of all road accidents can be attributed to fatigued drivers. Previous studies indicate that driving performance is influenced by time of day and decreases with sustained wakefulness. However, these influences occur naturally in unison, confounding their effects. Typically, when people drive at a poor time of day and with extended wake, their sleep is also restricted. Hence, the aim of the current study was to determine the independent effects of prior wake and time of day on driving performance under conditions of sleep restriction. The driving performance of fourteen male participants (21.8 ± 3.8 years, mean ± SD) was assessed during a 10 min simulated driving task with speed/lane mean, variability and violations (speeding and crashes) measured. Participants were tested at 2.5h intervals after waking, across 7 × 28 h days with a sleep:wake ratio of 1:5. By forced desynchrony each driving session occurred at 9 doses of prior wake and within 6 divisions of the circadian cycle based on core body temperature. A mixed models ANOVA revealed significant main effects of circadian phase, prior wake and sleep debt on lane violations. In addition, three significant two-way interactions (circadian phase × prior wake, prior wake × sleep debt, sleep debt × circadian phase) and one three-way interaction (circadian × prior wake × sleep debt) were identified. The presence of the large interaction effects shows that the influence of each factor is largely dependent on the magnitude of the other factors. For example, the presence of the time of day influence on driving performance is dependent on the length of prior wake or the presence of sleep debt. The findings suggest that people are able to undertake a low-difficulty simulated drive safely, at least for a short period, during their circadian nadir provided that they have had sufficient sleep and have not been awake too long.

Time-of-day mediates the influences of extended wake and sleep restriction on simulated driving

Although a nonlinear time-of-day and prior wake interaction on performance has been well documented, two recent studies have aimed to incorporate the influences of sleep restriction into this paradigm. Through the use of sleep-restricted forced desynchrony protocols, both studies reported a time-of-day × sleep restriction interaction, as well as a time-of-day × prior wake × sleep dose three-way interaction. The current study aimed to investigate these interactions on simulated driving performance, a more complex task with ecological validity for the problem of fatigued driving. The driving performance of 41 male participants (mean ± SD: 22.8 ±2.2 yrs) was assessed on a 10-min simulated driving task with the standard deviation of lateral position (SDLAT) measured. Using a between-group design, participants were subjected to either a control condition of 9.33 h of sleep/18.66 h of wake, a moderate sleep-restriction (SR) condition of 7 h of sleep/21 h of wake, or a severe SR condition of 4.66 h of sleep/23.33 h of wake. In each condition, participants were tested at 2.5-h intervals after waking across 7 × 28-h d of forced desynchrony. Driving sessions occurred at nine doses of prior wake, within six divisions of the circadian cycle based on core body temperature (CBT). Mixed-models analyses of variance (ANOVAs) revealed significant main effects of time-of-day, prior wake, sleep debt, and sleep dose on SDLAT. Additionally, significant two-way interactions of time-of-day × prior wake and time-of-day × sleep debt, as well as significant three-way interactions of time-of-day × prior wake × sleep debt and time-of-day × sleep debt × sleep dose were observed. Although limitations such as the presence of practice effects and large standard errors are noted, the study concludes with three findings. The main effects demonstrate that extending wake, reducing sleep, and driving at poor times of day all significantly impair driving performance at an individual level. In addition to this, combining either extended wake or a sleep debt with the early morning hours greatly decreases driving performance. Finally, operating under the influence of a reduced sleep dose can greatly decrease performance at all times of the day. (Author correspondence: raymond.matthews@unisa.edu.au)

INTERINDIVIDUAL DIFFERENCES IN NEUROBEHAVIORAL PERFORMANCE IN RESPONSE TO INCREASING HOMEOSTATIC SLEEP PRESSURE

Neurobehavioral function deteriorates with increasing homeostatic sleep pressure during wakefulness. It has been claimed that some individuals exhibit a quicker rate of such deterioration than others, thus being more vulnerable than others to the detrimental impact of increasing homeostatic sleep pressure. Evidence supporting the claim, however, has been limited by methodological issues. To overcome these limitations, the current study used a 12-calendar-day, 28-h forced desynchrony (FD) protocol (sleep:wake period = 1:2) to study individual differences in the rate of change in neurobehavioral performance with increasing homeostatic sleep pressure. Neurobehavioral performance was assessed with a psychomotor vigilance task and a serial addition subtraction task. A significant performance decline on both tasks was revealed within as short as 17 h of wakefulness. The rates of decline of individual performance trajectories were, however, not different from the group average rate. This suggests that individuals are not differentially vulnerable to the detrimental impact of increasing homeostatic sleep pressure. (Author correspondence: xuan.zhou@unisa.edu.au)

The efficacy of objective and subjective predictors of driving performance during sleep restriction and circadian misalignment.

Fatigue is a significant contributor to motor-vehicle accidents and fatalities. Shift workers are particularly susceptible to fatigue-related risks as they are often sleep-restricted and required to commute around the clock. Simple assays of performance could provide useful indications of risk in fatigue management, but their effectiveness may be influenced by changes in their sensitivity to sleep loss across the day. The aim of this study was to evaluate the sensitivity of several neurobehavioral and subjective tasks to sleep restriction (SR) at different circadian phases and their efficacy as predictors of performance during a simulated driving task. Thirty-two volunteers (M±SD; 22.8±2.9 years) were time-isolated for 13-days and participated in one of two 14-h forced desynchrony protocols with sleep opportunities equivalent to 8h/24h (control) or 4h/24h (SR). At regular intervals during wake periods, participants completed a simulated driving task, several neurobehavioral tasks, including the psychomotor vigilance task (PVT), and subjective ratings, including a self-assessment measure of ability to perform. Scores transformed into standardized units relative to baseline were folded into circadian phase bins based on core body temperature. Sleep dose and circadian phase effect sizes were derived via mixed models analyses. Predictors of driving were identified with regressions. Performance was most sensitive to sleep restriction around the circadian nadir. The effects of sleep restriction around the circadian nadir were larger for simulated driving and neurobehavioral tasks than for subjective ratings. Tasks did not significantly predict driving performance during the control condition or around the acrophase during the SR condition. The PVT and self-assessed ability were the best predictors of simulated driving across circadian phases during SR. These results show that simple performance measures and self-monitoring explain a large proportion of the variance in driving when fatigue-risk is high.

Daily Rhythms of Hunger and Satiety in Healthy Men during One Week of Sleep Restriction and Circadian Misalignment.

The impact of sleep restriction on the endogenous circadian rhythms of hunger and satiety were examined in 28 healthy young men. Participants were scheduled to 2 × 24-h days of baseline followed by 8 × 28-h days of forced desynchrony during which sleep was either moderately restricted (equivalent to 6 h in bed/24 h; n = 14) or severely restricted (equivalent to 4 h in bed/24 h; n = 14). Self-reported hunger and satisfaction were assessed every 2.5 h during wake periods using visual analogue scales. Participants were served standardised meals and snacks at regular intervals and were not permitted to eat ad libitum. Core body temperature was continuously recorded with rectal thermistors to determine circadian phase. Both hunger and satiety exhibited a marked endogenous circadian rhythm. Hunger was highest, and satiety was lowest, in the biological evening (i.e., ~17:00–21:00 h) whereas hunger was lowest, and satiety was highest in the biological night (i.e., 01:00–05:00 h). The results are consistent with expectations based on previous reports and may explain in some part the decrease in appetite that is commonly reported by individuals who are required to work at night. Interestingly, the endogenous rhythms of hunger and satiety do not appear to be altered by severe—as compared to moderate—sleep restriction.

Using interstimulus interval to maximise sensitivity of the Psychomotor Vigilance Test to fatigue.

There is some evidence that short interstimulus intervals (ISIs) on the Psychomotor Vigilance Test (PVT) are associated with longer and more varied reaction times (RTs). Preparation processes may impede RT following short ISIs, resulting in additional unexplained variance. The aims of this study were to investigate whether there is an effect of ISI on RT and errors within the PVT, and whether such an effect changes with three elements of fatigue: time of day, prior wake and time on task. Twelve male participants completed 49 PVTs across 7× 28h periods of forced desynchrony. For analysis, RTs, reciprocal reaction times (1/RT), false starts and lapse responses within each 10min session were assigned to a 1-s ISI group, a 2-min time of task group, a 2.5-h PW level and a 60° phase of the circadian rhythm of core body temperature (as a measure of time of day). Responses following short ISIs (2-5s) were significantly slower and more varied than responses following longer ISIs (5-10s). The likelihood of a lapse was also higher for short ISIs, while the probability of a false start increased as a function of ISI. These effects were independent of the influences of time of day, prior wake and time on task. Hence, mixed model ANOVAs comprising only long ISIs (5-10s) contained stronger effect sizes for fatigue than a model of all ISIs (2-10s). Including an ISI variable in a model improved the model fit and explained more variance associated with fatigue. Short ISIs resulted in long RTs both in the presence and absence of fatigue, possibly due to preparation processes or ISI conditioning. Hence, omitting short ISI trials from RT means or including an ISI variable in analysis can reduce unwanted variance in PVT data, improving the sensitivity of the PVT to fatigue.

Driving when distracted and sleepy: The effect of phone and passenger conversations on driving performance

ABSTRACT This study investigates the effect of passenger and phone conversations on sleep-restricted driving. Six volunteers (50% male, mean age 24.8 ± 4.3 years) had their sleep restricted to 4 h in bed followed by a 20-min simulated drive on three separate occasions. Each drive included either a passenger conversation, a mobile phone conversation or a quiet passenger. The effect size of a phone conversation on lane deviation was large while passenger conversation was small. The main effect of conversation on lane deviation was non-significant (F(2,10) = 2.57, p = 0.126). Combining sleep-restricted driving with conversations warrants further investigation.