Sally A. Ferguson

Thermoregulation as a sleep signalling system

Temperature and sleep are interrelated processes. Under normal environmental conditions, the rhythms of core body temperature Tc and sleep propensity vary inversely across the day and night in healthy young adults. Although this relationship has drawn considerable interest, particularly in recent years, it is still not known whether this relationship is causative or merely coincidental. As somnogenic brain areas contain thermosensitive cells, it is possible that the sleep/wake cycle may be directly affected by thermoregulatory changes themselves. That is, that changes in temperature may trigger, either directly or indirectly, somnogenic brain areas to initiate sleep. There is now an emerging body of evidence from both physiological and neuroanatomical studies to indicate that this may indeed be the case. This paper will examine the literature relating to this relationship and propose a model where thermoregulatory changes provide an additional signal to the brain regions that regulate sleep and wakefulness. The model attempts to explain how temperature changes before and after sleep onset act in a positive feedback loop to maintain a consolidated sleep bout.

The dynamics of neurobehavioural recovery following sleep loss.

Rate of recovery of daytime performance and sleepiness following moderate and severe sleep deprivation (SD) was examined when recovery opportunity was either augmented or restricted. Thirty healthy non‐smokers, aged 18–33 years, participated in one of three conditions: moderate SD with augmented (9‐h) recovery opportunities, moderate SD with restricted (6‐h) recovery opportunities, or severe SD with augmented recovery opportunities. Each participant attended the laboratory for 8–9 consecutive nights: an adaptation and baseline night (23:00–08:00 hours), one or two night(s) of wakefulness, and five consecutive recovery sleep opportunities (23:00–08:00 hours or 02:00–08:00 hours). On each experimental day, psychomotor vigilance performance (PVT) and subjective sleepiness (SSS) were assessed at two‐hourly intervals, and MSLTs were performed at 1000h. PSG data was collected for each sleep period. For all groups, PVT performance significantly deteriorated during the period of wakefulness, and sleepiness significantly increased. Significant differences were observed between the groups during the recovery phase. Following moderate SD, response speed, lapses and SSS returned to baseline after one 9‐h sleep opportunity, while sleep latencies required two 9‐h opportunities. When the recovery opportunity was restricted to six hours, neither PVT performance nor sleepiness recovered, but stabilised at below‐baseline levels. Following severe SD, sleepiness recovered after one (SSS) or two (physiological) 9‐h sleep opportunities, however PVT performance remained significantly below baseline for the entire recovery period. These results suggest that the mechanisms underlying the recovery process may be more complicated than previously thought, and that we may have underestimated the impact of sleep loss and/or the restorative value of subsequent sleep.

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.

The sensitivity of a palm-based psychomotor vigilance task to severe sleep loss

In this study, we evaluated the sensitivity of a 5-min personal digital assistant—psychomotor vigilance test (PDA-PVT) to severe sleep loss. Twenty-one participants completed a 10-min PVT-192 and a 5-min PDA—PVT at two hourly intervals during 62 h of sustained wakefulness. For both tasks, response speed and number of lapses (RTs > 500) per minute significantly increased with increasing hours of wakefulness. Overall, standardized response speed scores on the 5-min PDA—PVT closely tracked those of the PVT-192; however, the PDA—PVT was generally associated with more lapses/minute. Closer inspection of the data indicated that when the level of sleep loss and fatigue became more severe (i.e., Day 3), the 5-min PDA—PVT was not quite as sensitive as the 10-min PVT-192 when 2- to 10-sec foreperiods were used for both. It is likely, however, that the observed differences between the two devices was due to differences in task length. Thus, the findings provide further evidence of the validity of the 5-min PDA—PVT as a substitute for the 10-min PVT-192, particularly in circumstances in which a shorter test is required and/or the PVT-192 is not as practical.

Melatonin agonists and insomnia.

The ability of melatonin to shift biological rhythms is well known. As a result, melatonin has been used in the treatment of various circadian rhythm sleep disorders, such as advanced and delayed sleep phase disorders, jet lag and shiftwork disorder. The current evidence for melatonin being efficacious in the treatment of primary insomnia is less compelling. The development of agents that are selective for melatonin receptors provides opportunity to further elucidate the actions of melatonin and its receptors and to develop novel treatments for specific types of sleep disorders. The agonists reviewed here – ramelteon, tasimelteon and agomelatine – all appear to be efficacious in the treatment of circadian rhythm sleep disorders and some types of insomnia. However, further studies are required to understand the mechanisms of action, particularly for insomnia. Clinical application of the agonists requires a good understanding of their phase-dependent properties. Long-term effects of melatonin should be evaluated in large-scale, independent randomized controlled trials.

Serotonin agonists mimic the phase shifting effects of light on the melatonin rhythm in rats

The effect of serotonin agonists on the rhythmic excretion of the melatonin metabolite 6-sulphatoxymelatonin was examined in rats. The animals were maintained in 12L:12D and administered saline, quipazine (10 mg/kg), (+/-)-2-propylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT, 5 mg/kg) or buspirone (10 mg/kg), 4 h after dark (ZT16). All three drugs caused an acute, transient suppression of 6-sulphatoxymelatonin excretion and a significant delay (P < 0.01) in the onset of the nocturnal rise on the following night of 2.1 +/- 0.6, 1.4 +/- 0.7 and 1.5 +/- 0.3 h respectively while saline administration had no effect (0.4 +/- 0.2 h delay, P > 0.01). To examine the effects of the time of day of agonist administration, groups of rats were treated with quipazine (10 mg/kg) or 8-OH-DPAT (5 mg/kg) 18, 24 or 30 h after the initiation of continuous darkness (CT6, CT12 or CT18) and monitored for a further two nights. Quipazine but not 8-OH-DPAT injection at CT6 resulted in a small but significant delay in the onset of 6-sulphatoxymelatonin excretion on the following night (1.0 +/- 0.2 h and 0.3 +/- 0.2 h) while treatment with both agonists at CT12 failed to affect the onset of excretion (0.8 +/- 0.2 and 0.1 +/- 0.2 h). When quipazine (10 mg/kg) was administered at CT18, 6-sulphatoxymelatonin excretion was acutely suppressed for the rest of the night and there was a large significant delay in the onset of 6-sulphatoxymelatonin excretion (1.2 +/- 0.2 h) while a smaller delay was observed following 8-OH-DPAT administration (0.8 +/- 0.2 h). The acute suppression of 6-sulphatoxymelatonin excretion and subsequent phase delay following quipazine treatment at CT18 was also evident at doses of 1 mg/kg (1.6 +/- 0.4 h) and 3 mg/kg (1.5 +/- 0.6 h). These results show that peripheral administration of serotonin agonists active at 5HT1a/5HT7 receptors mimic the dual effects of light on melatonin production in the rat and raise the possibility that serotonin pathways are more important in mediating the effects of retinally perceived light in the rat than previously believed.

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)

The impact of short, irregular sleep opportunities at sea on the alertness of marine pilots working extended hours

The aim of this study was to examine the impact of brief, unscheduled naps during work periods on alertness and vigilance in coastal pilots along the Great Barrier Reef. On certain routes, the duration of the work period can extend well beyond 24 h. Seventeen coastal pilots volunteered for the study, representing almost one‐third of the population. Participants collected sleep/wake and performance data for 28 days using a sleep and work diary and the palm PVT task. The average length of sleep on board was 1.4±1.0 h. Naps were taken regularly such that the average length of time awake between sleep periods on board a ship was 5.3±4.3 h. There was no change in mean reaction time across either the length of a pilotage or across the 24 h day. The results indicate that even though the naps were taken opportunistically, they tended to cluster at the high sleep propensity times. Further, frequent, opportunistic naps appeared to provide adequate recovery such that PVT performance remained stable. Pilots did report increases in subjective fatigue ratings at certain times of the 24 h day and at the end of a work period; however, these did not reach the high range. The fatigue‐risk minimization strategies employed by the Australian Maritime Safety Authority and the coastal pilots appear to be effective in maintaining alertness and vigilance while at work aboard ships.

The effect of sleep restriction on snacking behaviour during a week of simulated shiftwork

Due to irregular working hours shiftworkers experience circadian disruption and sleep restriction. There is some evidence to indicate that these factors adversely affect health through changes in snacking behaviour. The aim of this study was to investigate the impact of sleep restriction, prior wake and circadian phase on snacking behaviour during a week of simulated shiftwork. Twenty-four healthy males (age: 22.0 ± 3.6 years, mean ± SD) lived in a sleep laboratory for 12 consecutive days. Participants were assigned to one of two schedules: a moderate sleep restriction condition (n=10) equivalent to a 6-h sleep opportunity per 24h or a severe sleep restriction condition (n=14) equivalent to a 4-h sleep opportunity per 24h. In both conditions, sleep/wake episodes occurred 4h later each day to simulate a rotating shiftwork pattern. While living in the laboratory, participants were served three meals and were provided with either five (moderate sleep restriction condition) or six (severe sleep restriction condition) snack opportunities daily. Snack choice was recorded at each opportunity and assigned to a category (sweet, savoury or healthy) based on the content of the snack. Data were analysed using a Generalised Estimating Equations approach. Analyses show a significant effect of sleep restriction condition on overall and sweet snack consumption. The odds of consuming a snack were significantly greater in the severe sleep restriction condition (P<0.05) compared to the moderate sleep restriction condition. In particular, the odds of choosing a sweet snack were significantly increased in the severe sleep restriction condition (P<0.05). Shiftworkers who are severely sleep restricted may be at risk of obesity and related health disorders due to elevated snack consumption and unhealthy snack choice. To further understand the impact of sleep restriction on snacking behaviour, future studies should examine physiological, psychological and environmental motivators.