Total Sleep Deprivation Increases Brain Age Prediction Reversibly in Multisite Samples of Young Healthy Adults.

Sleep loss pervasively affects the human brain at multiple levels. Age-related changes in several sleep characteristics indicate that reduced sleep quality is a frequent characteristic of aging. Conversely, sleep disruption may accelerate the aging process, yet it is not known what will happen to the age status of the brain if we can manipulate sleep conditions. To tackle this question, we used an approach of brain age to investigate whether sleep loss would cause age-related changes in the brain. We included MRI data of 134 healthy volunteers (mean chronological age of 25.3 between the age of 19 and 39 years, 42 females/92 males) from five datasets with different sleep conditions. Across three datasets with the condition of total sleep deprivation (>24 h of prolonged wakefulness), we consistently observed that total sleep deprivation increased brain age by 1-2 years regarding the group mean difference with the baseline. Interestingly, after one night of recovery sleep, brain age was not different from baseline. We also demonstrated the associations between the change in brain age after total sleep deprivation and the sleep variables measured during the recovery night. By contrast, brain age was not significantly changed by either acute (3 h time-in-bed for one night) or chronic partial sleep restriction (5 h time-in-bed for five continuous nights). Together, the convergent findings indicate that acute total sleep loss changes brain morphology in an aging-like direction in young participants and that these changes are reversible by recovery sleep.SIGNIFICANCE STATEMENT Sleep is fundamental for humans to maintain normal physical and psychological functions. Experimental sleep deprivation is a variable-controlling approach to engaging the brain among different sleep conditions for investigating the responses of the brain to sleep loss. Here, we quantified the response of the brain to sleep deprivation by using the change of brain age predictable with brain morphologic features. In three independent datasets, we consistently found increased brain age after total sleep deprivation, which was associated with the change in sleep variables. Moreover, no significant change in brain age was found after partial sleep deprivation in another two datasets. Our study provides new evidence to explain the brainwide effect of sleep loss in an aging-like direction.

Effects of moderate alcohol consumption and hypobaric hypoxia: implications for passengers' sleep, oxygen saturation and heart rate on long-haul flights.

BACKGROUND: Passengers on long-haul flights frequently consume alcohol. Inflight sleep exacerbates the fall in blood oxygen saturation (SpO2) caused by the decreased oxygen partial pressure in the cabin. We investigated the combined influence of alcohol and hypobaric hypoxia on sleep, SpO2 and heart rate. METHODS: Two groups of healthy individuals spent either two nights with a 4-hour sleep opportunity (00:00-04:00 hours) in the sleep laboratory (n=23; 53 m above sea level) or in the altitude chamber (n=17; 753 hPa corresponding to 2438 m above sea level, hypobaric condition). Participants consumed alcohol before one of the nights (mean±SE blood alcohol concentration 0.043±0.003%). The order of the nights was counterbalanced. Two 8-hour recovery nights (23:00-07:00 hours) were scheduled between conditions. Polysomnography, SpO2 and heart rate were recorded. RESULTS: The combined exposure to alcohol and hypobaric condition decreased SpO2 to a median (25th/75th percentile) of 85.32% (82.86/85.93) and increased heart rate to a median (25th/75th percentile) of 87.73 bpm (85.89/93.86) during sleep compared with 88.07% (86.50/88.49) and 72.90 bpm (70.90/78.17), respectively, in the non-alcohol hypobaric condition, 94.97% (94.59/95.33) and 76.97 bpm (65.17/79.52), respectively, in the alcohol condition and 95.88% (95.72/96.36) and 63.74 bpm (55.55/70.98), respectively, in the non-alcohol condition of the sleep laboratory group (all p<0.0001). Under the combined exposure SpO2 was 201.18 min (188.08/214.42) below the clinical hypoxia threshold of 90% SpO2 compared with 173.28 min (133.25/199.03) in the hypobaric condition and 0 min (0/0) in both sleep laboratory conditions. Deep sleep (N3) was reduced to 46.50 min (39.00/57.00) under the combined exposure compared with both sleep laboratory conditions (alcohol: 84.00 min (62.25/92.75); non-alcohol: 67.50 min (58.50/87.75); both p<0.003). CONCLUSIONS: The combination of alcohol and inflight hypobaric hypoxia reduced sleep quality, challenged the cardiovascular system and led to extended duration of hypoxaemia (SpO2 <90%).

A genetic variation in the adenosine A2A receptor gene contributes to variability in oscillatory alpha power in wake and sleep EEG and A1 adenosine receptor availability in the human brain.

The EEG alpha rhythm (∼ 8-13 Hz) is one of the most salient human brain activity rhythms, modulated by the level of attention and vigilance and related to cerebral energy metabolism. Spectral power in the alpha range in wakefulness and sleep strongly varies among individuals based on genetic predisposition. Knowledge about the underlying genes is scarce, yet small studies indicated that the variant rs5751876 of the gene encoding A2A adenosine receptors (ADORA2A) may contribute to the inter-individual variation. The neuromodulator adenosine is directly linked to energy metabolism as product of adenosine tri-phosphate breakdown and acts as a sleep promoting molecule by activating A1 and A2A adenosine receptors. We performed sleep and positron emission tomography studies in 59 healthy carriers of different rs5751876 alleles, and quantified EEG oscillatory alpha power in wakefulness and sleep, as well as A1 adenosine receptor availability with 18F-CPFPX. Oscillatory alpha power was higher in homozygous C-allele carriers (n = 27, 11 females) compared to heterozygous and homozygous carriers of the T-allele (n(C/T) = 23, n(T/T) = 5, 13 females) (F(18,37) = 2.35, p = 0.014, Wilk's Λ = 0.487). Furthermore, a modulatory effect of ADORA2A genotype on A1 adenosine receptor binding potential was found across all considered brain regions (F(18,40) = 2.62, p = 0.006, Wilk's Λ = 0.459), which remained significant for circumscribed occipital region of calcarine fissures after correction for multiple comparisons. In female participants, a correlation between individual differences in oscillatory alpha power and A1 receptor availability was observed. In conclusion, we confirmed that a genetic variant of ADORA2A affects individual alpha power, while a direct modulatory effect via A1 adenosine receptors in females is suggested.

Cerebral A1 adenosine receptor availability in female and male participants and its relationship to sleep.

The neuromodulator adenosine and its receptors are mediators of sleep-wake regulation which is known to differ between sexes. We, therefore, investigated sex differences in A1 adenosine receptor (A1AR) availability in healthy human subjects under well-rested conditions using [18F]CPFPX and positron emission tomography (PET). [18F]CPFPX PET scans were acquired in 50 healthy human participants (20 females; mean age ± SD 28.0 ± 5.3 years). Mean binding potential (BPND; Logan's reference tissue model with cerebellum as reference region) and volume of distribution (VT) values were calculated in 12 and 15 grey matter brain regions, respectively. [18F]CPFPX BPND was higher in females compared to males in all investigated brain regions (p < 0.025). The largest differences were found in the pallidum and anterior cingulate cortex, where mean BPND values were higher by 29% in females than in males. In females, sleep efficiency correlated positively and sleep latency negatively with BPND in most brain regions. VT values did not differ between sexes. Sleep efficiency correlated positively with VT in most brain regions in female participants. In conclusion, our analysis gives a first indication for potential sex differences in A1AR availability even under well-rested conditions. A1AR availability as measured by [18F]CPFPX BPND is higher in females compared to males. Considering the involvement of adenosine in sleep-wake control, this finding might partially explain the known sex differences in sleep efficiency and sleep latency.

Adverse interaction effects of chronic and acute sleep deficits on spatial working memory but not on verbal working memory or declarative memory.

The accumulation of chronic sleep deficits combined with acute sleep loss is common in shift workers and increases the risk of errors and accidents. We investigated single and combined effects of chronic and acute sleep loss and recovery sleep on working memory performance (N-back task) and on overnight declarative memory recall (paired-associate lists) in 36 healthy participants. After baseline measurements, the chronic sleep restriction group (n = 21; mean [SD] age 26 [4] years) underwent 5 nights of sleep restriction (5-hr time in bed [TIB]), whereas the control group (n = 15; mean [SD] age 28 [6] years) had 8-hr TIB during those nights. Afterwards, both groups spent 1 night with 8-hr TIB prior to acute sleep deprivation for 38 hr, and a final recovery night (10-hr TIB). Chronic sleep restriction decreased spatial N-back performance compared to baseline (omissions: p = .001; sensitivity: p = .012), but not letter N-back performance or word-pair recall. Acute sleep deprivation impaired spatial N-back performance more in the chronic sleep restriction group than in the control group (interaction between group and time awake: p ≤ .02). No group differences during acute sleep loss appeared in letter N-back performance or word recall. It is concluded that chronic sleep loss, even when followed by a night of recovery sleep, increases the vulnerability to impairments in spatial working memory during subsequent acute sleep loss. Verbal working memory and declarative memory were not affected by restricted sleep.

Cognitive impairments by alcohol and sleep deprivation indicate trait characteristics and a potential role for adenosine A1 receptors.

Trait-like differences in cognitive performance after sleep loss put some individuals more at risk than others, the basis of such disparities remaining largely unknown. Similarly, interindividual differences in impairment in response to alcohol intake have been observed. We tested whether performance impairments due to either acute or chronic sleep loss can be predicted by an individual's vulnerability to acute alcohol intake. Also, we used positron emission tomography (PET) to test whether acute alcohol infusion results in an up-regulation of cerebral A1 adenosine receptors (A1ARs), similar to the changes previously observed following sleep deprivation. Sustained attention in the psychomotor vigilance task (PVT) was tested in 49 healthy volunteers (26 ± 5 SD years; 15 females) (i) under baseline conditions: (ii) after ethanol intake, and after either (iii) total sleep deprivation (TSD; 35 hours awake; n = 35) or (iv) partial sleep deprivation (PSD; four nights with 5 hours scheduled sleep; n = 14). Ethanol- versus placebo-induced changes in cerebral A1AR availability were measured in 10 healthy male volunteers (31 ± 9 years) with [18F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (CPFPX) PET. Highly significant correlations between the performance impairments induced by ethanol and sleep deprivation were found for various PVT parameters, including mean speed (TSD, r = 0.62; PSD, r = 0.84). A1AR availability increased up to 26% in several brain regions with ethanol infusion. Our studies revealed individual trait characteristics for being either vulnerable or resilient to both alcohol and to sleep deprivation. Both interventions induce gradual increases in cerebral A1AR availability, pointing to a potential common molecular response mechanism.

Impact of acute sleep deprivation on dynamic functional connectivity states.

Sleep deprivation (SD) could amplify the temporal fluctuation of spontaneous brain activities that reflect different arousal levels using a dynamic functional connectivity (dFC) approach. Therefore, we intended to evaluate the test-retest reliability of dFC characteristics during rested wakefulness (RW), and to explore how the properties of these dynamic connectivity states were affected by extended durations of acute sleep loss (28/52 hr). We acquired resting-state fMRI and neuropsychological datasets in two independent studies: (a) twice during RW and once after 28 hr of SD (n = 15) and (b) after 52 hr of SD and after 14 hr of recovery sleep (RS; n = 14). Sliding-window correlations approach was applied to estimate their covariance matrices and corresponding three connectivity states were generated. The test-retest reliability of dFC properties demonstrated mean dwell time and fraction of connectivity states were reliable. After SD, the mean dwell time of a specific state, featured by strong subcortical-cortical anticorrelations, was significantly increased. Conversely, another globally hypoconnected state was significantly decreased. Subjective sleepiness and objective performances were separately positive and negative correlated with the increased and decreased state. Two brain connectivity states and their alterations might be sufficiently sensitive to reflect changes in the dynamics of brain mental activities after sleep loss.

Recovery sleep after extended wakefulness restores elevated A1 adenosine receptor availability in the human brain.

Adenosine and functional A1 adenosine receptor (A1AR) availability are supposed to mediate sleep-wake regulation and cognitive performance. We hypothesized that cerebral A1AR availability after an extended wake period decreases to a well-rested state after recovery sleep. [18F]CPFPX positron emission tomography was used to quantify A1AR availability in 15 healthy male adults after 52 h of sleep deprivation and following 14 h of recovery sleep. Data were additionally compared with A1AR values after 8 h of baseline sleep from an earlier dataset. Polysomnography, cognitive performance, and sleepiness were monitored. Recovery from sleep deprivation was associated with a decrease in A1AR availability in several brain regions, ranging from 11% (insula) to 14% (striatum). A1AR availabilities after recovery did not differ from baseline sleep in the control group. The degree of performance impairment, sleepiness, and homeostatic sleep-pressure response to sleep deprivation correlated negatively with the decrease in A1AR availability. Sleep deprivation resulted in a higher A1AR availability in the human brain. The increase that was observed after 52 h of wakefulness was restored to control levels during a 14-h recovery sleep episode. Individuals with a large increase in A1AR availability were more resilient to sleep-loss effects than those with a subtle increase. This pattern implies that differences in endogenous adenosine and A1AR availability might be causal for individual responses to sleep loss.

Reestablishment of individual sleep structure during a single 14-h recovery sleep episode after 58 h of wakefulness.

Sleep structure is highly stable within individuals but different between individuals. The present study investigated robustness of the individual sleep structure to extended total sleep deprivation. Seventeen healthy men spent a baseline night (23:00-07:00 hours), 58 h of sleep deprivation and a 14-h recovery night (17:00-07:00 hours) in the laboratory. Intraclass correlation coefficients showed that the agreement between baseline and recovery with respect to the proportion of the different sleep stages increased as a function of recovery sleep duration. High values were reached for most of the sleep stages at the end of 14 h of recovery sleep (intraclass correlation coefficients between 0.38 and 0.76). If sleep duration of the recovery night is extended to 14 h, sleep stage distribution resembles that of a baseline night underlining the robustness of the individual sleep structure.

Circadian variation of metabotropic glutamate receptor 5 availability in the rat brain.

The metabotrophic subtype 5 glutamate receptor (mGluR5) plays a critical role in synaptic plasticity besides its involvement in numerous neurological disorders, such as depression. As mGluR5 availability in humans is altered in sleep deprivation, we hypothesized that mGluR5 availability underlies a circadian variation. To investigate whether mGluR5 underlies potential circadian changes we measured its density in a randomized fashion at six different daytimes in 11 adult Sprague-Dawley rats. mGluR5 density was quantified by positron emission tomography (PET) using the radioactive ligand [11 C]ABP688. [11 C]ABP688 uptake was quantified in nine regions of interest with a reference tissue model. Significant differences in the binding potential (BPND ) and therefore mGluR5 availability between the different circadian times were found in cortex, cingulate cortex, amygdala, caudate putamen and nucleus accumbens. Further post-hoc statistical analysis (Tukey-Kramer test) of the different time-points revealed significant changes in BPND between 07:00 hours (start of light-on phase) and 15:00 hours (last time-point of the light-on phase) in the caudate putamen. This study shows that mGluR5 availability is increased during the light-on, or sleep phase, of rodents by approximately 10%. Given that altered mGluR5 densities play a role in psychiatric disorders, further investigation is warranted to evaluate their circadian involvement in mood changes in humans.

Significance of time awake for predicting pilots' fatigue on short-haul flights: implications for flight duty time regulations.

European regulations restrict the duration of the maximum daily flight duty period for pilots as a function of the duty start time and the number of scheduled flights. However, late duty end times that may include long times awake are not specifically regulated. In this study, fatigue levels in pilots finishing their duty late at night (00:00-01:59 hour) were analysed and compared with pilots starting their duty early (05:00-06:59 hour). Fatigue levels of 40 commercial short-haul pilots were studied during a total of 188 flight duty periods, of which 87 started early and 22 finished late. Pilots used a small handheld computer to maintain a duty and sleep log, and to indicate fatigue levels immediately after each flight. Sleep logs were checked with actigraphy. Pilots on late-finishing flight duty periods were more fatigued at the end of their duty than pilots on early-starting flight duty periods, despite the fact that preceding sleep duration was longer by 1.1 h. Linear mixed-model regression identified time awake as a preeminent factor predicting fatigue. Workload had a minor effect. Pilots on late-finishing flight duty periods were awake longer by an average of 5.5 h (6.6 versus 1.1 h) before commencing their duty than pilots who started early in the morning. Late-finishing flights were associated with long times awake at a time when the circadian system stops promoting alertness, and an increased, previously underestimated fatigue risk. Based on these findings, flight duty limitations should consider not only duty start time, but also the time of the final landing.

Nocturnal air, road, and rail traffic noise and daytime cognitive performance and annoyance.

Various studies indicate that at the same noise level and during the daytime, annoyance increases in the order of rail, road, and aircraft noise. The present study investigates if the same ranking can be found for annoyance to nocturnal exposure and next day cognitive performance. Annoyance ratings and performance change during combined noise exposure were also tested. In the laboratory 72 participants were exposed to air, road, or rail traffic noise and all combinations. The number of noise events and LAS,eq were kept constant. Each morning noise annoyance questionnaires and performance tasks were administered. Aircraft noise annoyance ranked first followed by railway and road noise. A possible explanation is the longer duration of aircraft noise events used in this study compared to road and railway noise events. In contrast to road and rail traffic, aircraft noise annoyance was higher after nights with combined exposure. Pooled noise exposure data showed small but significant impairments in reaction times (6 ms) compared to nights without noise. The noise sources did not have a differential impact on performance. Combined exposure to multiple traffic noise sources did not induce stronger impairments than a single noise source. This was reflected also in low workload ratings.

Repeated caffeine intake suppresses cerebral grey matter responses to chronic sleep restriction in an A1 adenosine receptor-dependent manner: a double-blind randomized controlled study with PET-MRI.

Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired performance caused by insufficient sleep. It is unclear (1) whether daily use of caffeine could prevent or exacerbate the GM alterations induced by 5-day sleep restriction (i.e. chronic sleep restriction, CSR), and (2) whether the potential impact on GM plasticity depends on individual differences in the availability of adenosine receptors, which are involved in mediating effects of caffeine on sleep and waking function. Thirty-six healthy adults participated in this double-blind, randomized, controlled study (age = 28.9 ± 5.2 y/; F:M = 15:21; habitual level of caffeine intake < 450 mg; 29 homozygous C/C allele carriers of rs5751876 of ADORA2A, an A2A adenosine receptor gene variant). Each participant underwent a 9-day laboratory visit consisting of one adaptation day, 2 baseline days (BL), 5-day sleep restriction (5 h time-in-bed), and a recovery day (REC) after an 8-h sleep opportunity. Nineteen participants received 300 mg caffeine in coffee through the 5 days of CSR (CAFF group), while 17 matched participants received decaffeinated coffee (DECAF group). We examined GM changes on the 2nd BL Day, 5th CSR Day, and REC Day using magnetic resonance imaging and voxel-based morphometry. Moreover, we used positron emission tomography with [18F]-CPFPX to quantify the baseline availability of A1 adenosine receptors (A1R) and its relation to the GM plasticity. The results from the voxel-wise multimodal whole-brain analysis on the Jacobian-modulated T1-weighted images controlled for variances of cerebral blood flow indicated a significant interaction effect between caffeine and CSR in four brain regions: (a) right temporal-occipital region, (b) right dorsomedial prefrontal cortex (DmPFC), (c) left dorsolateral prefrontal cortex (DLPFC), and (d) right thalamus. The post-hoc analyses on the signal intensity of these GM clusters indicated that, compared to BL, GM on the CSR day was increased in the DECAF group in all clusters  but decreased in the thalamus, DmPFC, and DLPFC in the CAFF group. Furthermore, lower baseline subcortical A1R availability predicted a larger GM reduction in the CAFF group after CSR of all brain regions except for the thalamus. In conclusion, our data suggest an adaptive GM upregulation after 5-day CSR, while concomitant use of caffeine instead leads to a GM reduction. The lack of consistent association with individual A1R availability may suggest that CSR and caffeine affect thalamic GM plasticity predominantly by a different mechanism. Future studies on the role of adenosine A2A receptors in CSR-induced GM plasticity are warranted.

Associations between resting state brain activity and A1 adenosine receptor availability in the healthy brain: Effects of acute sleep deprivation.

Introduction: Previous resting-state fMRI (Rs-fMRI) and positron emission tomography (PET) studies have shown that sleep deprivation (SD) affects both spontaneous brain activity and A1 adenosine receptor (A1AR) availability. Nevertheless, the hypothesis that the neuromodulatory adenosinergic system acts as regulator of the individual neuronal activity remains unexplored. Methods: Therefore, fourteen young men underwent Rs-fMRI, A1AR PET scans, and neuropsychological tests after 52 h of SD and after 14 h of recovery sleep. Results: Our findings suggested higher oscillations or regional homogeneity in multiple temporal and visual cortices, whereas decreased oscillations in cerebellum after sleep loss. At the same time, we found that connectivity strengths increased in sensorimotor areas and decreased in subcortical areas and cerebellum. Discussion: Moreover, negative correlations between A1AR availability and rs-fMRI metrics of BOLD activity in the left superior/middle temporal gyrus and left postcentral gyrus of the human brain provide new insights into the molecular basis of neuronal responses induced by high homeostatic sleep pressure.

Annoyance and self-reported sleep disturbance due to night-time railway noise examined in the field.

Railway noise interferes with daytime activities and disturbs sleep leading to annoyance of exposed residents. The main objective of this paper was to establish exposure-response relationships between nocturnal railway noise exposure and annoyance and to examine self-reported sleep disturbances as short-term reactions to noise. In a field study 33 residents living close to railway tracks in the Cologne/Bonn area (Germany) were investigated. Railway noise was measured indoors during nine consecutive nights at each site. Questionnaires referring to annoyance and non-acoustical factors were performed. Annoyance ratings increased significantly with the total number of trains and freight trains per night, and non-significantly with rising number of passenger trains and energy equivalent sound pressure level (L(Aeq)), when adjusting the model for non-acoustical variables. The total number of trains and the number of freight trains also significantly affected self-reported awakening frequency, but no other aspects of subjective sleep disturbances. The responses of this subject sample referring to railway noise in the previous night point to rather low impairments of exposed residents.

Critical appraisal of methods for the assessment of noise effects on sleep.

Various sleep measurement techniques have been applied in past studies on the effects of environmental noise on sleep, complicating comparisons between studies and the derivation of pooled exposure-response relationships that could inform policy and legislation. To date, a consensus on a standard measurement technique for the assessment of environmental noise effects on sleep is missing. This would be desirable to increase comparability of future studies. This manuscript provides a detailed description of the sleep process, typical indicators of disturbed sleep, and how noise interferes with sleep. It also describes and discusses merits and drawbacks of five established methods commonly used for the assessment of noise effects on sleep (i.e., polysomnography, actigraphy, electrocardiography, behaviorally confirmed awakenings, and questionnaires). Arguments supporting the joint use of actigraphy and a single channel electrocardiogram as meaningful, robust, and inexpensive methods that would allow for the investigation of large representative subject samples are presented. These could be used as a starting point for the generation of an expert consensus.

Sleep-Induced Hypoxia under Flight Conditions: Implications and Countermeasures for Long-Haul Flight Crews and Passengers.

PURPOSE: Recuperation during sleep on board of commercial long-haul flights is a safety issue of utmost importance for flight crews working extended duty periods. We intended to explore how sleep and blood oxygenation (in wake versus sleep) are affected by the conditions in an airliner at cruising altitude. METHODS: Healthy participants' sleep was compared between 4-h sleep opportunities in the sleep laboratory (n = 23; sleep lab, ie, 53 m above sea level) and in an altitude chamber (n = 20; flight level, ie, 753 hPa, corresponding to 2438 m above sea level). A subgroup of 12 participants underwent three additional conditions in the altitude chamber: 1) 4-h sleep at ground level, 2) 4-h sleep at flight level with oxygen partial pressure equivalent to ground level, 3) 4-h monitored wakefulness at flight level. Sleep structure and blood oxygenation were analysed with mixed ANOVAs. RESULTS: Total sleep time at flight level compared to in the sleep laboratory was shorter (Δ mean ± standard error -11.1 ± 4.2 min) and included less N3 sleep (Δ -17.6 ± 5.4 min), while blood oxygenation was decreased. Participants spent 69.7% (± 8.3%) of the sleep period time but only 13.2% (± 3.0%) of monitored wakefulness in a hypoxic state (<90% oxygen saturation). Oxygen enrichment of the chamber prevented oxygen desaturation. CONCLUSION: Sleep - but not wakefulness - under flight conditions induces hypobaric hypoxia which may contribute to impaired sleep. The results caution against the assumption of equivalent crew recovery in-flight and on the ground but hold promise for oxygen enrichment as a countermeasure. The present results have implications for flight safety and possible long-term consequences for health in crews.

Traffic noise-induced changes in wake-propensity measured with the Odds-Ratio Product (ORP).

Nocturnal traffic noise can disrupt sleep and impair physical and mental restoration, but classical sleep scoring techniques may not fully capture subtle yet clinically relevant alterations of sleep induced by noise. We used a validated continuous measure of sleep depth and quality based on automatic analysis of physiologic sleep data, termed Wake Propensity (WP), to investigate temporal changes of sleep in response to nocturnal noise events in 3-s epochs. Seventy-two healthy participants (mean age 40.3 years, range 18-71 years, 40 females, 32 males) slept for 11 nights in a laboratory, during which we measured sleep with polysomnography. In 8 nights, participants were exposed to 40, 80 or 120 road, rail and/or aircraft noise events with maximum noise levels of 45-65 dB LAS,max during 8-h sleep opportunities. We analyzed sleep macrostructure and event-related change of WP during noise exposure with linear mixed models. Nocturnal traffic noise led to event-related shifts towards wakefulness and less deep, more unstable sleep (increase in WP relative to pre-noise baseline ranging from +29.5% at 45 dB to +38.3% at 65 dB; type III effect p < 0.0001). Sleep depth decreased dynamically with increasing noise level, peaking when LAS,max was highest. This change in WP was stronger and occurred more quickly for events where the noise onset was more rapid (road and rail) compared to more gradually time-varying noise (aircraft). Sleep depth did not immediately recover to pre-noise WP, leading to decreased sleep stability across the night compared to quiet nights, which was greater with an increasing number of noise events (standardized ß = 0.053, p = 0.003). Further, WP was more sensitive to noise than classical arousals. Results demonstrate the usefulness of WP as a measure of the effects of external stimuli on sleep, and show WP is a more sensitive measure of noise-induced sleep disruption than traditional methods of sleep analysis.

Road traffic noise impacts sleep continuity in suburban residents: Exposure-response quantification of noise-induced awakenings from vehicle pass-bys at night.

Nocturnal traffic noise has been associated with adverse health outcomes in exposed residents. Precise quantification of traffic noise effects on sleep is thus of great importance. Here we establish an exposure-response relationship for the awakening probability due to intermittent road traffic noise in suburban residents. We conducted a field study in residential areas where road traffic was the dominant noise source, and noise events were attributable to separate vehicle pass-bys. Forty healthy participants underwent polysomnography for five consecutive nights at their homes. A total of 11,003 road traffic noises derived from simultaneous acoustic measurements at the sleepers' ears were included in an event-related analysis of awakenings. Logistic regression analysis revealed that the awakening probability due to road traffic noise increased with the maximum sound pressure level (SPL) and the maximum slope of the increasing SPL of a vehicle pass-by, as well as the age of the exposed individual. Compared to sleep stage 2, the awakening probability was higher in rapid eye movement sleep (REMS) and lower in slow wave sleep (SWS). The protective effect of both stage 2 and SWS against awakenings decreased with age, whereas no age-dependent change was observed for REMS. When adjusting for other contributing factors, the probability of a noise-induced awakening ranged from 0% at a maximum SPL of 27.1 dB(A) to 2.0% at 70 dB(A). Road traffic noise at night - even in suburban areas with moderate traffic density - negatively impacts residents' sleep continuity. Exposure-response quantification for traffic noise-induced awakenings may serve as a basis for noise protection efforts by regulators and policy makers.