Baseline Night Research Articles

Improvement in self-reported, but not actigraphic, sleep measures with suvorexant in people with well-controlled Restless Legs Syndrome and persistent insomnia

BackgroundSleep disturbance remains common in people with Restless Legs Syndrome (RLS), even after RLS symptoms are sufficiently controlled with medication. We conducted a placebo-controlled crossover trial to examine the efficacy of suvorexant in improving sleep quality and quantity in people with well-controlled RLS and persistent insomnia. MethodsIn this double-blind, randomized, placebo-controlled crossover trial, 34 participants (70.6 % female, mean age = 62.7) with well-controlled RLS were randomized to placebo or suvorexant (10–20 mg) for 6 weeks, followed by a 2-week washout and then the opposite treatment. Study inclusion required an IRLS score <15, insomnia diagnosis per DSM-5, and a diary-reported combined Sleep Onset Latency (SOL) and Wake After Sleep Onset (WASO) > 45 min and a Total Sleep Time (TST) < 7 h on 7/14 baseline nights. The primary outcome was actigraphically-derived TST, and secondary outcomes were Insomnia Severity Index (ISI) score and actigraphically-derived WASO. Data for all sleep metrics were collected at baseline and for the last two weeks of each treatment period. ResultsThere were no significant improvements in actigraphically-derived TST (p = 0.58) or WASO (p = 0.99) while taking suvorexant compared to placebo. However, there were significant reductions in insomnia symptoms, measured by the ISI, as well as increases in diary-reported TST (p = 0.01) while taking suvorexant compared to placebo. The most commonly reported side effect of suvorexant was fatigue (29.4 %). ConclusionsWe observed no significant differences between treatments in actigraphically-derived sleep measures, but support for suvorexant's benefit for overall insomnia and self-reported quantity of sleep in people with well-controlled RLS who continue to suffer from insomnia. Clinical trials registration numberNCT04706091.

Acoustic Stimulation to Improve Slow-Wave Sleep in Alzheimer's Disease: A Multiple Night At-Home Intervention

ObjectivesTo investigate the efficacy of closed-loop acoustic stimulation (CLAS) during slow-wave sleep (SWS) to enhance slow-wave activity (SWA) and SWS in patients with Alzheimer's disease (AD) across multiple nights and to explore associations between stimulation, participant characteristics, and individuals’ SWS response. DesignA 2-week, open-label at-home intervention study utilizing the DREEM2 headband to record sleep data and administer CLAS during SWS. Setting and participantsFifteen older patients with AD (6 women, mean age: 76.27 [SD = 6.06], mean MOCA-score: 16.07 [SD = 6.94]), living at home with their partner, completed the trial. InterventionPatients first wore the device for two baseline nights, followed by 14 nights during which the device was programmed to randomly either deliver acoustic stimulations of 50 ms pink noise (± 40 dB) targeted to the slow-wave up-phase during SWS or only mark the wave (sham). ResultsOn a group level, stimulation significantly enhanced SWA and SWS with consistent SWS enhancement throughout the intervention. However, substantial variability existed in individual responses to stimulation. Individuals received more stimulations on nights with increased SWS compared to baseline than on nights with no change or a decrease. In individuals, having lower baseline SWS correlated with receiving fewer stimulations on average during the intervention. ConclusionCLAS during SWS is a promising nonpharmacological method to enhance SWA and SWS in AD. However, patients with lower baseline SWS received fewer stimulations during the intervention, possibly resulting in less SWS enhancement. Individual variability in response to stimulation underscores the need to address personalized stimulation parameters in future research and therapy development.

Multi-night acoustic stimulation is associated with better sleep, amyloid dynamics, and memory in older adults with cognitive impairment.

Sleep is a potential early, modifiable risk factor for cognitive decline and dementia. Impaired slow wave sleep (SWS) is pronounced in individuals with cognitive impairment (CI). Cognitive decline and impairments of SWS are bi-directionally linked in a vicious cycle. SWS can be enhanced non-invasively using phase-locked acoustic stimulation (PLAS), potentially breaking this vicious cycle. Eighteen healthy older adults (HC, agemean±sd, 68.3 ± 5.1) and 16 older adults (agemean±sd, 71.9 ± 3.9) with CI (Montreal Cognitive Assessment ≤ 25) underwent one baseline (sham-PLAS) night and three consecutive stimulation nights (real-PLAS). EEG responses and blood-plasma amyloid beta Aβ42/Aβ40 ratio were measured pre- and post-intervention, as was episodic memory. The latter was again evaluated 1week and 3months after the intervention. In both groups, PLAS induced a significant electrophysiological response in both voltage- and time-frequency analyses, and memory performance improved in association with the magnitude of this response. In the CI group, both electrophysiological and associated memory effects were delayed compared to the healthy group. After 3 intervention nights, electrophysiological response to PLAS was no longer different between CI and HC groups. Only in the CI sample, stronger electrophysiological responses were significantly associated with improving post-intervention Aβ42/Aβ40 ratios. PLAS seems to improve SWS electrophysiology, memory, and amyloid dynamics in older adults with CI. However, effects on memory require more time to unfold compared to healthy older adults. This indicates that PLAS may become a potential tool to ameliorate cognitive decline, but longer interventions are necessary to compensate for declining brain integrity. This study was pre-registered (clinicaltrials.gov: NCT04277104).

Individualised prediction of resilience and vulnerability to sleep loss using EEG features.

It is well established that individuals differ in their response to sleep loss. However, existing methods to predict an individual's sleep-loss phenotype are not scalable or involve effort-dependent neurobehavioural tests. To overcome these limitations, we sought to predict an individual's level of resilience or vulnerability to sleep loss using electroencephalographic (EEG) features obtained from routine night sleep. To this end, we retrospectively analysed five studies in which 96 healthy young adults (41 women) completed a laboratory baseline-sleep phase followed by a sleep-loss challenge. After classifying subjects into sleep-loss phenotypic groups, we extracted two EEG features from the first sleep cycle (median duration: 1.6 h), slow-wave activity (SWA) power and SWA rise rate, from four channels during the baseline nights. Using these data, we developed two sets of logistic regression classifiers (resilient versus not-resilient and vulnerable versus not-vulnerable) to predict the probability of sleep-loss resilience or vulnerability, respectively, and evaluated model performance using test datasets not used in model development. Consistently, the most predictive features came from the left cerebral hemisphere. For the resilient versus not-resilient classifiers, we obtained an average testing performance of 0.68 for the area under the receiver operating characteristic curve, 0.72 for accuracy, 0.50 for sensitivity, 0.84 for specificity, 0.61 for positive predictive value, and 3.59 for likelihood ratio. We obtained similar performance for the vulnerable versus not-vulnerable classifiers. These results indicate that logistic regression classifiers based on SWA power and SWA rise rate from routine night sleep can largely predict an individual's sleep-loss phenotype.

Sleep and Thermoregulation in Birds: Cold Exposure Reduces Brain Temperature but Has Little Influence on Sleep Time and Sleep Architecture in Jackdaws (Coloeus monedula).

Birds have an electrophysiological sleep state that resembles mammalian rapid-eye-movement (REM) sleep. However, whether its regulation and function are similar is unclear. In the current experiment, we studied REM sleep regulation in jackdaws (Coloeus monedula) by exposing the birds to low ambient temperature, a procedure that selectively suppresses REM sleep in mammals. Eight jackdaws were equipped with electrodes to record brain activity and neck muscle activity and a thermistor to record cortical brain temperature. Recordings covered a three-day period starting with a 24 h baseline day at an ambient temperature of 21 °C, followed by a 12 h cold night at 4 °C, after which the ambient temperature was restored to 21 °C for the remaining recovery period. Cold exposure at night caused a significant drop in brain temperature of 1.4 °C compared to the baseline night. However, throughout the cold night, jackdaws expressed NREM sleep and REM sleep levels that were not significantly different from the baseline. Also, EEG spectral power during NREM sleep was unaffected by cold exposure. Thus, while cold exposure had a clear effect on brain temperature in jackdaws, it did not have the same REM sleep suppressing effect reported for mammals. These findings suggest that the REM-sleep-like state in birds, unlike REM sleep in mammals, is protected against the influence of low temperature.

Nocturnal Smartphone Use Affects Sleep Quality and Cognitive and Physical Performance in Tunisian School-Age Children.

Nocturnal smartphone use emits blue light, which can adversely affect sleep, leading to a variety of negative effects, particularly in children. Therefore, the present study aimed to determine the effect of acute (AC) (one night) and repeated (RC) (five nights) nocturnal smartphone exposure on sleep, cortisol, and next-day performance in Tunisian children. Thirteen participants (seven girls and six boys, age 9 ± 0.6, height 1.32 ± 0.06, weight 34.47 ± 4.41) attended six experimental nights. The experiment started with a baseline night (BL) with no smartphone exposure, followed by repeated sessions of nocturnal smartphone exposure lasting 90 minutes (08:00 pm-09:30 pm). Actigraphy; salivary cortisol; the Stroop test (selective attention); choice reaction time (CRT); N-back (working memory); counter-movement jump (CMJ), composed of flight time (time spent in the CMJ flight phase) and jump height; and a 30 m sprint were assessed the morning after each condition. Both AC and RC shortened total sleep time (TST) (p < 0.01), with a greater decrease with RC (-46.7 min, ∆% = -9.46) than AC (-28.8 min, ∆% = -5.8) compared to BL. AC and RC significantly increased waking after sleep onset (3.5 min, ∆% = 15.05, to 9.9 min, ∆% = 43.11%) and number of errors made on the Stroop test (1.8 error, ∆% = 74.23, to 3.07 error, ∆% = 97.56%). Children made 0.15 and 0.8 more errors (∆% = 6.2 to 57.61%) and spent 46.9 s and 71.6 s more time on CRT tasks (∆% = 7.22 to 11.11%) with AC and RC, respectively, compared to BL. The high-interference index of the Stroop task, CMJ performance, and 30 m sprint speed were only altered (p < 0.01) following RC (0.36, Δ% = 41.52%; -34 s, Δ% = -9.29%, for flight time and -1.23 m, -8.72%, for jump height; 0.49 s, Δ% = 6.48, respectively) when compared to BL. In conclusion, one- or five-night exposure to smartphones disturbed the children's sleep quality and their performance, with more pronounced effects following RC.

The effect of slow wave sleep deprivation on mood in adolescents with depressive symptoms: A pilot study

BackgroundThere is an urgent need for safe, rapid-acting treatment strategies for adolescent depression. In depressed adults, slow wave sleep deprivation (SWSD) improved next-day mood without disrupting sleep duration, but SWSD has not been tested in adolescents. In a pilot study, the aim was to assess the effect of SWSD on sleep physiology and mood outcomes (depression, rumination, anhedonia) among adolescents with depressive symptoms. MethodsSixteen adolescents (17.44 ± 1.46 yr, 12 female) completed three nights of polysomnographic sleep recording: Baseline, SWSD, and Recovery nights. Acoustic stimulation (tones of random pitch, duration, and volume) suppressed slow wave sleep (SWS) in real-time during SWSD. After each night, depression, rumination, and anhedonia severity were assessed. ResultsSWSD successfully suppressed SWS, increased N2, and had minimal impact on Rapid Eye Movement (REM), nocturnal awakenings, and total sleep time. While SWSD did not improve depression or anhedonia severity overall, lower baseline non-REM alpha activity and greater SWS rebound during recovery sleep correlated with SWSD-related reduction in clinician-rated depression severity. Next-day rumination severity decreased after SWSD, with sustained improvements following recovery sleep. However, rumination improvement was not associated with SWS suppression, but rather reduction in total sleep time and REM in exploratory correlation models. LimitationsSmall sample size and large proportion of females. ConclusionSWSD did not improve depression in adolescents overall but a subset with low non-REM alpha activity and intact homeostatic sleep regulation may benefit from this approach. Findings from this pilot study also suggest that partial sleep deprivation may be a beneficial therapeutic strategy for rumination in adolescents.

Short-term and long-term phenotypic stability of actigraphic sleep metrics involving repeated sleep loss and recovery.

For the first time, we determined whether actigraphic-assessed sleep measures show inter-individual differences and intra-individual stability during baseline (BL) and recovery (REC) phases surrounding repeated total sleep deprivation (TSD). We conducted a 5-day experiment at Months 2 and 4 in two separate studies (N = 11). During each experiment, sleep measures were collected via wrist actigraphy during two BL 8 h time-in-bed (TIB) nights (B1, B2) and during two REC 8-10 h TIB nights (R1, R2). Intraclass correlation coefficients (ICCs) assessed actigraphic measure long-term stability between 2 and 4 months for (1) the pre-experimental phase before BL; and (2) the BL (B1 + B2), REC (R1 + R2), and BL and REC average (BL + REC) phases; and short-term stability at Month 2 and at Month 4; and (3) between B1 versus B2 and R1 versus R2 in each 5-day experiment. Nearly all ICCs during the pre-experimental, BL, REC, and BL + REC phases were moderate to almost perfect (0.446-0.970) between Months 2 and 4. B1 versus B2 ICCs were more stable (0.440-0.899) than almost all R1 versus R2 ICCs (-0.696 to 0.588) at Month 2 and 4. Actigraphic sleep measures show phenotypic long-term stability during BL and REC surrounding repeated TSD between 2 and 4 months. Furthermore, within each 5-day experiment at Month 2 and 4, the two BL nights before TSD were more stable than the two REC nights following TSD, likely due to increased R1 homeostatic pressure. Given the consistency of actigraphic measures across the short-term and long-term, they can serve as biomarkers to predict physiological and neurobehavioral responses to sleep loss.

Acoustic stimulation during sleep predicts long-lasting increases in memory performance and beneficial amyloid response in older adults.

Sleep and neurodegeneration are assumed to be locked in a bi-directional vicious cycle. Improving sleep could break this cycle and help to prevent neurodegeneration. We tested multi-night phase-locked acoustic stimulation (PLAS) during slow wave sleep (SWS) as a non-invasive method to improve SWS, memory performance and plasma amyloid levels. 32 healthy older adults (agemean: 68.9) completed a between-subject sham-controlled three-night intervention, preceded by a sham-PLAS baseline night. PLAS induced increases in sleep-associated spectral-power bands as well as a 24% increase in slow wave-coupled spindles, known to support memory consolidation. There was no significant group-difference in memory performance or amyloid-beta between the intervention and control group. However, the magnitude of PLAS-induced physiological responses were associated with memory performance up to 3 months post intervention and beneficial changes in plasma amyloid. Results were exclusive to the intervention group. Multi-night PLAS is associated with long-lasting benefits in memory and metabolite clearance in older adults, rendering PLAS a promising tool to build upon and develop long-term protocols for the prevention of cognitive decline.

Electroencephalographic markers from routine sleep discriminate individuals who are vulnerable or resilient to sleep loss.

Sleep loss impairs cognition; however, individuals differ in their response to sleep loss. Current methods to identify an individual's vulnerability to sleep loss involve time-consuming sleep-loss challenges and neurobehavioural tests. Here, we sought to identify electroencephalographic markers of sleep-loss vulnerability obtained from routine night sleep. We retrospectively analysed four studies in which 50 healthy young adults (21 women) completed a laboratory baseline-sleep phase followed by a sleep-loss challenge. After classifying subjects as resilient or vulnerable to sleep loss, we extracted three electroencephalographic features from four channels during the baseline nights, evaluated the discriminatory power of these features using the first two studies (discovery), and assessed reproducibility of the results using the remaining two studies (reproducibility). In the discovery analysis, we found that, compared to resilient subjects, vulnerable subjects exhibited: (1) higher slow-wave activity power in channel O1 (p < 0.0042, corrected for multiple comparisons) and in channels O2 and C3 (p < 0.05, uncorrected); (2) higher slow-wave activity rise rate in channels O1 and O2 (p < 0.05, uncorrected); and (3) lower sleep spindle frequency in channels C3 and C4 (p < 0.05, uncorrected). Our reproducibility analysis confirmed the discovery results on slow-wave activity power and slow-wave activity rise rate, and for these two electroencephalographic features we observed consistent group-difference trends across all four channels in both analyses. The higher slow-wave activity power and slow-wave activity rise rate in vulnerable individuals suggest that they have a persistently higher sleep pressure under normal rested conditions.

The impacts of intra-individual daily sleep variability on daytime functioning and sleep architecture in healthy young adults: An experimental study.

Sleep variability is commonly seen in the young populations. This study aimed to examine the impacts of experimentally induced sleep variability on sleepiness, mood, cognitive performance and sleep architectures among young adults. Thirty-six healthy individuals (aged 18-22 years) were randomly assigned to either variable sleep schedule (n = 20) or control (n = 16) groups. The protocol involved 1 week of regular sleep (time in bed = 7.5 hr) in the home setting, followed by one adaptation night (time in bed = 7.5 hr), one baseline night (time in bed = 7.5 hr), and 6 nights of sleep manipulation in the laboratory monitored by polysomnography (three cycles of variable sleep schedule by changing daily time in bed alternating between 6 hr and 9 hr for variable sleep schedule group versus fixed sleep schedule with daily time in bed for 7.5 hr for control group). Sleepiness, mood, sustained attention, processing speed, response inhibition and working memory were measured every morning and evening. The variable sleep schedule group reported a higher level of sleepiness, especially in the mornings, and increased negative mood in the evenings. There were no significant differences in positive mood, cognitive performance and sleep macro- and micro-structures. Our results showed the negative effects of sleep variability on daytime functioning especially sleepiness and negative mood, suggesting the need to address variable sleep schedules through sleep intervention.

Phenotypic Interindividual Differences in the Dynamic Structure of Sleep in Healthy Young Adults.

Evaluating the dynamic structure of sleep may yield new insights into the mechanisms underlying human sleep physiology. We analyzed data from a 12-day, 11-night, strictly controlled laboratory study with an adaptation night, 3 iterations of a baseline night followed by a recovery night after 36 h of total sleep deprivation, and a final recovery night. All sleep opportunities were 12 h in duration (22:00-10:00) and recorded with polysomnography (PSG). The PSG records were scored for the sleep stages: rapid eye movement (REM) sleep; non-REM (NREM) stage 1 sleep (S1), stage 2 sleep (S2), and slow wave sleep (SWS); and wake (W). Phenotypic interindividual differences were assessed using indices of dynamic sleep structure - specifically sleep stage transitions and sleep cycle characteristics - and intraclass correlation coefficients across nights. NREM/REM sleep cycles and sleep stage transitions exhibited substantial and stable interindividual differences that were robust across baseline and recovery nights, suggesting that mechanisms underlying the dynamic structure of sleep are phenotypic. In addition, the dynamics of sleep stage transitions were found to be associated with sleep cycle characteristics, with a significant relationship between the length of sleep cycles and the degree to which S2-to-W/S1 and S2-to-SWS transitions were in equilibrium. Our findings are consistent with a model for the underlying mechanisms that involves three subsystems - characterized by S2-to-W/S1, S2-to-SWS, and S2-to-REM transitions - with S2 playing a hub-like role. Furthermore, the balance between the two subsystems within NREM sleep (S2-to-W/S1 and S2-to-SWS) may serve as a basis for the dynamic regulation of sleep structure and may represent a novel target for interventions aiming to improve sleep.

0199 Effects of acute sleep deprivation on cognitive performance in depressed individuals

Abstract Introduction Acute sleep deprivation (SD) is an effective, rapid antidepressant treatment. However, SD has adverse effects on cognitive performance. The effects of SD on cognitive performance in depression remain underexplored. This study investigated relationships between depression and performance on Cognition – a neurocognitive battery of 10 tests that cover a range of cognitive domains – during acute SD. Methods Thirty-six individuals with current depression (69.4% female; 33±9.5 yrs) and 10 euthymic controls (40% female; 35±9.5 yrs) underwent a baseline night of sleep followed by 36 hours SD in the laboratory. Participants completed the Cognition battery twice after each protocol night. Each of the 10 Cognition tests has two separate metrics of performance: speed and accuracy. Multivariable linear regressions were used to assess effects of depression status, age, and gender on each performance metric at baseline. Mixed effects models were used to assess effects of depression status, sleep deprivation, and their interaction on performance metrics. All models included a random effect over participants and were adjusted for age, gender, and time of day. Results At baseline, depressed individuals were significantly faster than controls on three tests of working memory (β=-72.6; p=0.03), spatial orientation (β=-2944.7; p=0.01), and emotion recognition (β=-537.5; p=0.005) respectively, although these effects did not survive correction for multiple comparisons. Mixed effects model results revealed a significant effect of depression status on the speed metric from the spatial orientation test, whereby depressed individuals were faster across the protocol (β=-2579.6; p=0.04) and a significant interaction effect between depression status and study day on the speed metric from a risk-taking behavior test, whereby depressed individuals were slower after SD (β=480.9, p=0.01); neither effect survived correction for multiple comparisons. However, sleep deprivation was significantly associated with reductions in performance in models for 10 out of 20 metrics (all adjusted ps &amp;lt; 0.05). Conclusion These results suggest that currently depressed individuals exhibit the same decrements in cognitive performance after acute SD as non-depressed individuals. Future analyses will examine whether baseline depression severity predicts cognitive performance and whether differences in performance exist between SD responders versus non-responders. Support (if any) This work was supported by the National Institute of Mental Health (R01MH107571).

Slow oscillation-spindle cross-frequency coupling predicts overnight declarative memory consolidation in older adults.

Cross-frequency coupling (CFC) between brain oscillations during non-rapid-eye-movement (NREM) sleep (e.g. slow oscillations [SO] and spindles) may be a neural mechanism of overnight memory consolidation. Declines in CFC across the lifespan might accompany coinciding memory problems with ageing. However, there are few reports of CFC changes during sleep after learning in older adults, controlling for baseline effects. Our objective was to examine NREM CFC in healthy older adults, with an emphasis on spindle activity and SOs from frontal electroencephalogram (EEG), during a learning night after a declarative learning task, as compared to a baseline night without learning. Twenty-five older adults (M [SD] age = 69.12 [5.53]years; 64% female) completed a two-night study, with a pre- and post-sleep word-pair associates task completed on the second night. SO-spindle coupling strength and a measure of coupling phase distance from the SO up-state were both examined for between-night differences and associations with memory consolidation. Coupling strength and phase distance from the up-state peak were both stable between nights. Change in coupling strength between nights was not associated with memory consolidation, but a shift in coupling phase towards (vs. away from) the up-state peak after learning predicted better memory consolidation. Also, an exploratory interaction model suggested that associations between coupling phase closer to the up-state peak and memory consolidation may be moderated by higher (vs. lower) coupling strength. This study supports a role for NREM CFC in sleep-related memory consolidation in older adults.

0218 Changes in sleep architecture and topography of sleep EEG slow wave activity following acute wake extension in early adolescence

Abstract Introduction A progression of peak sleep EEG slow wave activity (SWA; EEG power 0.5-4Hz) from posterior to anterior expression reflects brain development. Further, increased EEG SWA after extended wakefulness is a marker of sleep pressure. However, it is unclear whether recovery sleep SWA in later youth is expressed in a similar scalp topography as typical sleep. Using experimental wake-extension, we investigated homeostatic changes in sleep architecture and SWA topography in early adolescence. Methods Twenty-two young adolescents (M±SD: 12.03±1.14y, 12F) participated in two consecutive laboratory stays after at least a week of at-home actigraphy-monitored stabilization (9.5h in bed). A baseline night (BSL; 9.5h 21:00-06:30) was followed by wake-extension (WE) to 02:30 and a 4h recovery sleep opportunity (RS; 02:30-06:30), each monitored by polysomnography including a 25-channel EEG array. The current analyses examined R&amp;K sleep architecture at BSL and RS. SWA in RS was compared to the first 4h of BSL in two ways: (1) absolute NREM power (µV2); (2) an index (TI) of the topographical distribution of midline SWA (FPz-AFz-Fz-FCz-Cz-CPz-Pz-POz-Oz) providing a score of 1 to 9 indicating frontal to occipital peak distribution. Results WE significantly altered RS sleep architecture, including an increase in slow-wave sleep (%TST) versus BSL (M±SD BSL: 26.76±5.69%, RS: 51.65±7.83%, t(21)=-17.09, p&amp;lt;.001, d=-3.65). SWA was also significantly greater in RS (channel-averaged SWA BSL: 11883.50±5142.17 µV2, RS: 18955.82±7451.20 µV2, t(21)=-8.67, p&amp;lt;.001) with 22/25 individual electrodes meeting Bonferroni-corrected significance (ps&amp;lt;.001). Finally, we observed a small frontal shift (t(21)=2.39, p=.027, d=.51) of maximal SWA in RS (TI: 4.46±2.58; i.e., FCz/Cz) compared to BSL (5.32±2.78, i.e., Cz/CPz). Conclusion These data indicate robust sleep homeostasis in young adolescents after wake extension, expressed as increased SWA across the scalp. The findings also add to existing literature by indicating that SWA topography may also be sensitive to homeostatic challenge. Specifically, a baseline centroparietal locus of maximal SWA typical to this age became more frontocentral in recovery sleep. This anterior shift may reflect a homeostatic need over developmentally sensitive prefrontal cortex. Next steps will assess how individual responses may reflect a child’s neurodevelopment (e.g., inattention symptoms) or manifested behavior after wake extension and recovery sleep. Support (if any) K01MH109854, P20GM139743, R01HD103655

Effects of sleep fragmentation and partial sleep restriction on heart rate variability during night

We developed a cross-over study design with two interventions in randomized order to compare the effects of sleep fragmentation and partial sleep restriction on cardiac autonomic tone. Twenty male subjects (40.6 ± 7.5 years old) underwent overnight polysomnography during 2 weeks, each week containing one undisturbed baseline night, one intervention night (either sleep restriction with 5 h of sleep or sleep fragmentation with awakening every hour) and two undisturbed recovery nights. Parameters of heart rate variability (HRV) were used to assess cardiac autonomic modulation during the nights. Sleep restriction showed significant higher heart rate (p = 0.018) and lower HRV-pNN50 (p = 0.012) during sleep stage N1 and lower HRV-SDNN (p = 0.009) during wakefulness compared to the respective baseline. For HR and SDNN there were recovery effects. There was no significant difference comparing fragmentation night and its baseline. Comparing both intervention nights, sleep restriction had lower HRV high frequency (HF) components in stage N1 (p = 0.018) and stage N2 (p = 0.012), lower HRV low frequency (LF) (p = 0.007) regarding the entire night and lower SDNN (p = 0.033) during WASO during sleep. Sleep restriction increases sympathetic tone and decreases vagal tone during night causing increased autonomic stress, while fragmented sleep does not affect cardiac autonomic parameters in our sample.

Effort during prolonged wakefulness is associated with performance to attentional and executive tasks but not with cortical excitability in late-middle-aged healthy individuals.

Sleep loss negatively affects brain function with repercussion not only on objective measures of performance but also on many subjective dimensions, including effort perceived for the completion of cognitive processes. This may be particularly important in aging, which is accompanied by important changes in sleep and wakefulness regulation. We aimed to determine whether subjectively perceived effort covaried with cognitive performance in healthy late-middle-aged individuals. We assessed effort and performance to cognitive tasks in 99 healthy adults (66 women; 50-70 years) during a 20-hr wake extension protocol, following 7 days of regular sleep and wake times and a baseline night of sleep in the laboratory. We further explored links with cortical excitability using transcranial magnetic stimulation coupled to electroencephalography. Perceived effort increased during wake extension and was highly correlated to subjective metrics of sleepiness, fatigue, and motivation, but not to variations in cortical excitability. Moreover, effort increase was associated with decreased performance to some cognitive tasks (psychomotor vigilance and two-back working memory task). Importantly, effort variations during wakefulness extension decreased from age 50 to 70 years, while more effort is associated with worse performance in older individuals. In healthy late-middle-aged individuals, more effort is perceived to perform cognitive tasks, but it is not sufficient to overcome the performance decline brought by lack of sleep. Entry in the seventh decade may stand as a turning point in the daily variations of perceived effort and its link with cognition. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Comparison of polysomnography in people with Alzheimer's disease and insomnia versus non-demented elderly people with insomnia

BackgroundWe used baseline polysomnography (PSG) data obtained during the clinical program development for suvorexant to compare the PSG profiles of people with Alzheimer's disease and insomnia (ADI) versus age-matched elderly individuals with insomnia (EI). MethodsSleep laboratory baseline PSG data from participants age 55–80 years from 2 trials in people with insomnia and a trial in people with ADI were included. ADI participants had dementia of mild-to-moderate severity. Diagnostic criteria for insomnia, exclusion for other sleep problems, PSG recording procedures, and endpoint derivations were similar across the trials. All participants underwent a night of in-laboratory PSG prior to the baseline night to allow for screening/adaptation. Participants in the EI and ADI groups were compared with regard to sleep architecture, sleep micro-structure, and quantitative EEG power spectral endpoints. The analysis was performed on a post hoc basis using propensity score matching to compare sleep parameters separately in women and men while accounting for age group and total sleep time. ResultsA total of 837 EI and 239 ADI participants were included, with the majority in each population (∼65%) being women. Compared to EI, those with ADI had a lower percentage of time spent in slow wave sleep (and a corresponding higher percentage of time spent in the lighter N1 sleep), a lower number of spindles per minute of N2 sleep, and lower absolute EEG power during NREM sleep, particularly in the lower-frequency bands. Trends for lower REM sleep percentage in ADI did not reach statistical significance. ConclusionsOur findings in this large data set, in which the influence of sleep problems was effectively subtracted out (since both groups had insomnia), provide strong confirmatory support of results from previous smaller studies in indicating that AD of mild-to-moderate severity is associated with less slow wave sleep, spindles, and lower-frequency EEG power. Trial registrationClinicalTrials.gov, numbers NCT01097616, NCT01097629, NCT02750306

Mild to Moderate Sleep Restriction Does Not Affect the Cortisol Awakening Response in Healthy Adult Males.

The cortisol awakening response (CAR) is a distinct rise in cortisol that occurs upon awakening that is thought to contribute to arousal, energy boosting, and anticipation. There is some evidence to suggest that inadequate sleep may alter the CAR, but the relationship between sleep duration and CAR has not been systematically examined. Healthy males (n = 111; age: 23.0 ± 3.6 yrs) spent 10 consecutive days/nights in a sleep laboratory. After a baseline night (9 h time in bed), participants spent either 5 h (n = 19), 6 h (n = 23), 7 h (n = 16), 8 h (n = 27), or 9 h (n = 26) in bed for seven nights, followed by a 9 h recovery sleep. The saliva samples for cortisol assay were collected at 08:00 h, 08:30 h and 08:45 h at baseline, on experimental days 2 and 5 and on the recovery day. The primary dependent variables were the cortisol concentration at awakening (08:00 h) and the cortisol area under the curve (AUC). There was no effect of time in bed on either the cortisol concentration at awakening or cortisol AUC. In all the time in bed conditions, the cortisol AUC tended to be higher at baseline and lower on experimental day 5. Five consecutive nights of mild to moderate sleep restriction does not appear to affect the CAR in healthy male adults.

Treatment with the novel TAAR1 agonist ulotaront is associated with reductions in quantitative polysomnographic REM sleep without atonia in healthy human subjects: Results of a post-hoc analysis

BackgroundIsolated REM sleep behavior disorder (RBD) is a potentially injurious parasomnia lacking an established treatment. Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist with 5-HT1A receptor agonist activity that has demonstrated efficacy in patients with schizophrenia. In a single dose challenge study in humans, ulotaront 50 mg demonstrated significant REM suppressant effects. We now report post-hoc exploratory analyses designed to evaluate the effect of ulotaront on quantitative REM sleep without atonia (RSWA). MethodsYoung healthy adult men (ages 19–35) were randomized to double-blind, cross-over treatment (after 7-day wash-out) with single doses of ulotaront (50 mg or 10 mg) versus placebo followed by polysomnography (PSG) on each of the nights following treatment. Quantitative RSWA was analyzed in a blinded fashion using established visual and automated methods. ResultsSubjects received 50 mg (n = 11) or 10 mg (n = 9) of ulotaront. Treatment with ulotaront 50 mg was associated with lower RSWA (p < 0.05), with greatest RSWA reduction (vs. placebo) observed in subjects with RSWA levels above the mean on the baseline night. RSWA levels were similar between treatment with ulotaront 10 mg and placebo. ConclusionTreatment with ulotaront 50 mg (but not 10 mg) was associated with reductions in RSWA levels in healthy subjects, especially in subjects with higher baseline RSWA levels, providing proof-of-concept for ulotaront efficacy in reducing RSWA levels. However, whether ulotaront might have efficacy as a treatment for human RBD awaits double-blind trials with ulotaront in clinical RBD populations.