Performance of an open machine learning model to classify sleep/wake from actigraphy across ∼24-hour intervals without knowledge of rest timing.

GOAL AND AIMS: Commonly used actigraphy algorithms are designed to operate within a known in-bed interval. However, in free-living scenarios this interval is often unknown. We trained and evaluated a sleep/wake classifier that operates on actigraphy over ∼24-hour intervals, without knowledge of in-bed timing. FOCUS TECHNOLOGY: Actigraphy counts from ActiWatch Spectrum devices. REFERENCE TECHNOLOGY: Sleep staging derived from polysomnography, supplemented by observation of wakefulness outside of the staged interval. Classifications from the Oakley actigraphy algorithm were additionally used as performance reference. SAMPLE: Adults, sleeping in either a home or laboratory environment. DESIGN: Machine learning was used to train and evaluate a sleep/wake classifier in a supervised learning paradigm. The classifier is a temporal convolutional network, a form of deep neural network. CORE ANALYTICS: Performance was evaluated across ∼24 hours, and additionally restricted to only in-bed intervals, both in terms of epoch-by-epoch performance, and the discrepancy of summary statistics within the intervals. ADDITIONAL ANALYTICS AND EXPLORATORY ANALYSES: Performance of the trained model applied to the Multi-Ethnic Study of Atherosclerosis dataset. CORE OUTCOMES: Over ∼24 hours, the temporal convolutional network classifier produced the same or better performance as the Oakley classifier on all measures tested. When restricting analysis to the in-bed interval, the temporal convolutional network remained favorable on several metrics. IMPORTANT SUPPLEMENTAL OUTCOMES: Performance decreased on the Multi-Ethnic Study of Atherosclerosis dataset, especially when restricting analysis to the in-bed interval. CORE CONCLUSION: A classifier using data labeled over ∼24-hour intervals allows for the continuous classification of sleep/wake without knowledge of in-bed intervals. Further development should focus on improving generalization performance.

A non-pharmacological multi-modal therapy to improve sleep and cognition and reduce mild cognitive impairment risk: Design and methodology of a randomized clinical trial.

Aging populations are at increased risk of sleep deficiencies (e.g., insomnia) that are associated with a variety of chronic health risks, including Alzheimer's disease and related dementias (ADRD). Insomnia medications carry additional risk, including increased drowsiness and falls, as well as polypharmacy risks. The recommended first-line treatment for insomnia is cognitive behavioral therapy for insomnia (CBTi), but access is limited. Telehealth is one way to increase access, particularly for older adults, but to date telehealth has been typically limited to simple videoconferencing portals. While these portals have been shown to be non-inferior to in-person treatment, it is plausible that telehealth could be significantly improved. This work describes a protocol designed to evaluate whether a clinician-patient dashboard inclusive of several user-friendly features (e.g., patterns of sleep data from ambulatory devices, guided relaxation resources, and reminders to complete in-home CBTi practice) could improve CBTi outcomes for middle- to older-aged adults (N = 100). Participants were randomly assigned to one of three telehealth interventions delivered through 6-weekly sessions: (1) CBTi augmented with a clinician-patient dashboard, smartphone application, and integrated smart devices; (2) standard CBTi (i.e., active comparator); or (3) sleep hygiene education (i.e., active control). All participants were assessed at screening, pre-study evaluation, baseline, throughout treatment, and at 1-week post-treatment. The primary outcome is the Insomnia Severity Index. Secondary and exploratory outcomes span sleep diary, actiwatch and Apple watch assessed sleep parameters (e.g., efficiency, duration, timing, variability), psychosocial correlates (e.g., fatigue, depression, stress), cognitive performance, treatment adherence, and neurodegenerative and systemic inflammatory biomarkers.

Recovery Sleep After Sleep Restriction Is Insufficient to Return Elevated Daytime Heart Rate and Systolic Blood Pressure to Baseline Levels.

OBJECTIVE: Sleep restriction alters daytime cardiac activity, including elevating heart rate (HR) and blood pressure (BP). There is minimal research on the cumulative effects of sleep loss and the response after subsequent recovery sleep on HR and BP. This study examined patterns of HR and BP across baseline, sleep restriction, and recovery conditions using multiple daytime cardiac measurements. METHODS: Participants (15 healthy men, mean [standard deviation] = 22.3 [2.8] years) completed an 11-day inpatient protocol with three nights of 10 hours/night baseline sleep opportunity, five sleep restriction nights (5-hour/night sleep opportunity), and two recovery nights (10-hour/night sleep opportunity). Resting HR and BP were measured every 2 hours during wake. Multilevel models with random effects for individuals examined daytime HR and BP across study conditions and days into the study. RESULTS: Mean daytime HR was 1.2 (0.5) beats/min lower during sleep restriction compared with baseline ( p < .001). During recovery, HR was 5.5 (1.0) beats/min higher ( p < .001), and systolic BP (SBP) was 2.9 (1.1) mm Hg higher ( p = .009). When accounting for days into the study (irrespective of condition) and measurement timing across the day, HR increased by 7.6 beats/min and SBP increased by 3.4 mm Hg across the study period ( p < .001). CONCLUSIONS: Our findings suggest that daytime HR and SBP increase after successive nights of sleep restriction, even after accounting for measurement time of day. HR and SBP did not recover to baseline levels after two recovery nights of sleep, suggesting that longer recovery sleep may be necessary to recover from multiple, consecutive nights of moderate sleep restriction.

Six multidimensional sleep health facets in older adults identified with factor analysis of actigraphy: Results from the Einstein Aging Study.

OBJECTIVES: The concept of multi-dimensional sleep health, originally based on self-report, was recently extended to actigraphy in older adults, yielding five components, but without a hypothesized rhythmicity factor. The current study extends prior work using a sample of older adults with a longer period of actigraphy follow-up, which may facilitate observation of the rhythmicity factor. METHODS: Wrist actigraphy measures of participants (N = 289, Mage = 77.2 years, 67% females; 47% White, 40% Black, 13% Hispanic/Others) over 2 weeks were used in exploratory factor analysis to determine factor structures, followed by confirmatory factor analysis on a different subsample. The utility of this approach was demonstrated by associations with global cognitive performance (Montreal Cognitive Assessment). RESULTS: Exploratory factor analysis identified six factors: Regularity: standard deviations of four sleep measures: midpoint, sleep onset time, night total sleep time (TST), and 24-hour TST; Alertness/Sleepiness (daytime): amplitude, napping (mins and #/day); Timing: sleep onset, midpoint, wake-time (of nighttime sleep); up-mesor, acrophase, down-mesor; Efficiency: sleep maintenance efficiency, wake after sleep onset; Duration: night rest interval(s), night TST, 24-hour rest interval(s), 24-hour TST; Rhythmicity (pattern across days): mesor, alpha, and minimum. Greater sleep efficiency was associated with better Montreal Cognitive Assessment performance (ß [95% confidence interval] = 0.63 [0.19, 1.08]). CONCLUSIONS: Actigraphic records over 2 weeks revealed that Rhythmicity may be an independent factor in sleep health. Facets of sleep health can facilitate dimension reduction, be considered predictors of health outcomes, and be potential targets for sleep interventions.

Discrimination and Education Quality Moderate the Association of Sleep With Cognitive Function in Older Black Adults: Results From the Einstein Aging Study.

OBJECTIVES: Heterogeneity among Black adults' experiences of discrimination and education quality independently influence cognitive function and sleep, and may also influence the extent to which sleep is related to cognitive function. We investigated the effect of discrimination on the relationship between objective sleep characteristics and cognitive function in older Black adults with varying education quality. METHOD: Cross-sectional analyses include Black participants in the Einstein Aging Study (N = 104, mean age = 77.2 years, 21% males). Sleep measures were calculated from wrist actigraphy (15.4 ± 1.3 days). Mean ambulatory cognitive function (i.e., spatial working memory, processing speed/visual attention, and short-term memory binding) was assessed with validated smartphone-based cognitive tests (6 daily). A modified Williams Everyday Discrimination Scale measured discriminatory experiences. Linear regression, stratified by reading literacy (an indicator of education quality), was conducted to investigate whether discrimination moderated associations between sleep and ambulatory cognitive function for individuals with varying reading literacy levels. Models controlled for age, income, sleep-disordered breathing, and sex assigned at birth. RESULTS: Higher reading literacy was associated with better cognitive performance. For participants with both lower reading literacy and more discriminatory experiences, longer mean sleep time was associated with slower processing speed, and lower sleep quality was associated with worse working memory. Later sleep midpoint and longer nighttime sleep were associated with worse spatial working memory for participants with low reading literacy, independent of their discriminatory experiences. DISCUSSION: Sociocultural factors (i.e., discrimination and education quality) can further explain the association between sleep and cognitive functioning and cognitive impairment risk among older Black adults.

An orderly sequence of autonomic and neural events at transient arousal changes.

Resting-state functional magnetic resonance imaging (rsfMRI) allows the study of functional brain connectivity based on spatially structured variations in neuronal activity. Proper evaluation of connectivity requires removal of non-neural contributions to the fMRI signal, in particular hemodynamic changes associated with autonomic variability. Regression analysis based on autonomic indicator signals has been used for this purpose, but may be inadequate if neuronal and autonomic activities covary. To investigate this potential co-variation, we performed rsfMRI experiments while concurrently acquiring electroencephalography (EEG) and autonomic indicator signals, including heart rate, respiratory depth, and peripheral vascular tone. We identified a recurrent and systematic spatiotemporal pattern of fMRI (named as fMRI cascade), which features brief signal reductions in salience and default-mode networks and the thalamus, followed by a biphasic global change with a sensory-motor dominance. This fMRI cascade, which was mostly observed during eyes-closed condition, was accompanied by large EEG and autonomic changes indicative of arousal modulations. Importantly, the removal of the fMRI cascade dynamics from rsfMRI diminished its correlations with various signals. These results suggest that the rsfMRI correlations with various physiological and neural signals are not independent but arise, at least partly, from the fMRI cascades and associated neural and physiological changes at arousal modulations.

A longitudinal study of the impact of university student return to campus on the SARS-CoV-2 seroprevalence among the community members.

Returning university students represent large-scale, transient demographic shifts and a potential source of transmission to adjacent communities during the COVID-19 pandemic. In this prospective longitudinal cohort study, we tested for IgG antibodies against SARS-CoV-2 in a non-random cohort of residents living in Centre County prior to the Fall 2020 term at the Pennsylvania State University and following the conclusion of the Fall 2020 term. We also report the seroprevalence in a non-random cohort of students collected at the end of the Fall 2020 term. Of 1313 community participants, 42 (3.2%) were positive for SARS-CoV-2 IgG antibodies at their first visit between 07 August and 02 October 2020. Of 684 student participants who returned to campus for fall instruction, 208 (30.4%) were positive for SARS-CoV-2 antibodies between 26 October and 21 December. 96 (7.3%) community participants returned a positive IgG antibody result by 19 February. Only contact with known SARS-CoV-2-positive individuals and attendance at small gatherings (20-50 individuals) were significant predictors of detecting IgG antibodies among returning students (aOR, 95% CI 3.1, 2.07-4.64; 1.52, 1.03-2.24; respectively). Despite high seroprevalence observed within the student population, seroprevalence in a longitudinal cohort of community residents was low and stable from before student arrival for the Fall 2020 term to after student departure. The study implies that heterogeneity in SARS-CoV-2 transmission can occur in geographically coincident populations.

Interindividual differences in attentional vulnerability moderate cognitive performance during sleep restriction and subsequent recovery in healthy young men.

We investigated whether interindividual attentional vulnerability moderates performance on domain-specific cognitive tasks during sleep restriction (SR) and subsequent recovery sleep. Fifteen healthy men (M ± SD, 22.3 ± 2.8 years) were exposed to three nights of baseline, five nights of 5-h time in bed SR, and two nights of recovery sleep. Participants completed tasks assessing working memory, visuospatial processing, and processing speed approximately every two hours during wake. Analyses examined performance across SR and recovery (linear predictor day or quadratic predictor day2) moderated by attentional vulnerability per participant (difference between mean psychomotor vigilance task lapses after the fifth SR night versus the last baseline night). For significant interactions between day/day2 and vulnerability, we investigated the effect of day/day2 at 1 SD below (less vulnerable level) and above (more vulnerable level) the mean of attentional vulnerability (N = 15 in all analyses). Working memory accuracy and speed on the Fractal 2-Back and visuospatial processing speed and efficiency on the Line Orientation Task improved across the entire study at the less vulnerable level (mean - 1SD) but not the more vulnerable level (mean + 1SD). Therefore, vulnerability to attentional lapses after SR is a marker of susceptibility to working memory and visuospatial processing impairment during SR and subsequent recovery.

Changes in Subjective Motivation and Effort During Sleep Restriction Moderate Interindividual Differences in Attentional Performance in Healthy Young Men.

PURPOSE: The effects of sleep restriction on subjective alertness, motivation, and effort vary among individuals and may explain interindividual differences in attention during sleep restriction. We investigated whether individuals with a greater decrease in subjective alertness or motivation, or a greater increase in subjective effort (versus other participants), demonstrated poorer attention when sleep restricted. PARTICIPANTS AND METHODS: Fifteen healthy men (M±SD, 22.3±2.8 years) completed a study with three nights of 10-hour time in bed (baseline), five nights of 5-hour time in bed (sleep restriction), and two nights of 10-hour time in bed (recovery). Participants completed a 10-minute psychomotor vigilance task (PVT) of sustained attention and rated alertness, motivation, and effort every two hours during wake (range: 3-9 administrations on a given day). Analyses examined performance across the study (first two days excluded) moderated by per-participant change in subjective alertness, motivation, or effort from baseline to sleep restriction. For significant interactions, we investigated the effect of study day2 (day*day) on the outcome at low (mean-1 SD) and high (mean+1 SD) levels of the moderator (N = 15, all analyses). RESULTS: False starts increased across sleep restriction in participants who reported lower (mean-1 SD) but not preserved (mean+1 SD) motivation during sleep restriction. Lapses increased across sleep restriction regardless of change in subjective motivation, with a more pronounced increase in participants who reported lower versus preserved motivation. Lapses increased across sleep restriction in participants who reported higher (mean+1 SD) but not preserved (mean-1 SD) effort during sleep restriction. Change in subjective alertness did not moderate the effects of sleep restriction on attention. CONCLUSION: Vigilance declines during sleep restriction regardless of change in subjective alertness or motivation, but individuals with reduced motivation exhibit poorer inhibition. Individuals with preserved subjective alertness still perform poorly during sleep restriction, while those reporting additional effort demonstrate impaired vigilance.

SARS-CoV-2 Seroprevalence in a University Community: A Longitudinal Study of the Impact of Student Return to Campus on Infection Risk Among Community Members.

BACKGROUND: Returning university students represent large-scale, transient demographic shifts and a potential source of transmission to adjacent communities during the COVID-19 pandemic. METHODS: In this prospective longitudinal cohort study, we tested for IgG antibodies against SARS-CoV-2 in a non-random cohort of residents living in Centre County prior to the Fall 2020 term at the Pennsylvania State University and following the conclusion of the Fall 2020 term. We also report the seroprevalence in a non-random cohort of students collected at the end of the Fall 2020 term. RESULTS: Of 1313 community participants, 42 (3.2%) were positive for SARS-CoV-2 IgG antibodies at their first visit between 07 August and 02 October 2020. Of 684 student participants who returned to campus for fall instruction, 208 (30.4%) were positive for SARS-CoV-2 antibodies between 26 October and 21 December. 96 (7.3%) community participants returned a positive IgG antibody result by 19 February. Only contact with known SARS-CoV-2-positive individuals and attendance at small gatherings (20-50 individuals) were significant predictors of detecting IgG antibodies among returning students (aOR, 95% CI: 3.1, 2.07-4.64; 1.52, 1.03-2.24; respectively). CONCLUSIONS: Despite high seroprevalence observed within the student population, seroprevalence in a longitudinal cohort of community residents was low and stable from before student arrival for the Fall 2020 term to after student departure. The study implies that heterogeneity in SARS-CoV-2 transmission can occur in geographically coincident populations.

Enhancing Slow Oscillations and Increasing N3 Sleep Proportion with Supervised, Non-Phase-Locked Pink Noise and Other Non-Standard Auditory Stimulation During NREM Sleep.

PURPOSE: In non-rapid eye movement (NREM) stage 3 sleep (N3), phase-locked pink noise auditory stimulation can amplify slow oscillatory activity (0.5-1 Hz). Open-loop pink noise auditory stimulation can amplify slow oscillatory and delta frequency activity (0.5-4 Hz). We assessed the ability of pink noise and other sounds to elicit delta power, slow oscillatory power, and N3 sleep. PARTICIPANTS AND METHODS: Participants (n = 8) underwent four consecutive inpatient nights in a within-participants design, starting with a habituation night. A registered polysomnographic technologist live-scored sleep stage and administered stimuli on randomized counterbalanced Enhancing and Disruptive nights, with a preceding Habituation night (night 1) and an intervening Sham night (night 3). A variety of non-phase-locked pink noise stimuli were used on Enhancing night during NREM; on Disruptive night, environmental sounds were used throughout sleep to induce frequent auditory-evoked arousals. RESULTS: Total sleep time did not differ between conditions. Percentage of N3 was higher in the Enhancing condition, and lower in the Disruptive condition, versus Sham. Standard 0.8 Hz pink noise elicited low-frequency power more effectively than other pink noise, but was not the most effective stimulus. Both pink noise on the "Enhancing" night and sounds intended to Disrupt sleep administered on the "Disruptive" night increased momentary delta and slow-wave activity (ie, during stimulation versus the immediate pre-stimulation period). Disruptive auditory stimulation degraded sleep with frequent arousals and increased next-day vigilance lapses versus Sham despite preserved sleep duration and momentary increases in delta and slow-wave activity. CONCLUSION: These findings emphasize sound features of interest in ecologically valid, translational auditory intervention to increase restorative sleep. Preserving sleep continuity should be a primary consideration if auditory stimulation is used to enhance slow-wave activity.

Detecting sleep using heart rate and motion data from multisensor consumer-grade wearables, relative to wrist actigraphy and polysomnography.

STUDY OBJECTIVES: Multisensor wearable consumer devices allowing the collection of multiple data sources, such as heart rate and motion, for the evaluation of sleep in the home environment, are increasingly ubiquitous. However, the validity of such devices for sleep assessment has not been directly compared to alternatives such as wrist actigraphy or polysomnography (PSG). METHODS: Eight participants each completed four nights in a sleep laboratory, equipped with PSG and several wearable devices. Registered polysomnographic technologist-scored PSG served as ground truth for sleep-wake state. Wearable devices providing sleep-wake classification data were compared to PSG at both an epoch-by-epoch and night level. Data from multisensor wearables (Apple Watch and Oura Ring) were compared to data available from electrocardiography and a triaxial wrist actigraph to evaluate the quality and utility of heart rate and motion data. Machine learning methods were used to train and test sleep-wake classifiers, using data from consumer wearables. The quality of classifications derived from devices was compared. RESULTS: For epoch-by-epoch sleep-wake performance, research devices ranged in d' between 1.771 and 1.874, with sensitivity between 0.912 and 0.982, and specificity between 0.366 and 0.647. Data from multisensor wearables were strongly correlated at an epoch-by-epoch level with reference data sources. Classifiers developed from the multisensor wearable data ranged in d' between 1.827 and 2.347, with sensitivity between 0.883 and 0.977, and specificity between 0.407 and 0.821. CONCLUSIONS: Data from multisensor consumer wearables are strongly correlated with reference devices at the epoch level and can be used to develop epoch-by-epoch models of sleep-wake rivaling existing research devices.

Four nights of sleep restriction suppress the postprandial lipemic response and decrease satiety.

Chronic sleep restriction, or inadequate sleep, is associated with increased risk of cardiometabolic disease. Laboratory studies demonstrate that sleep restriction causes impaired whole-body insulin sensitivity and glucose disposal. Evidence suggests that inadequate sleep also impairs adipose tissue insulin sensitivity and the NEFA rebound during intravenous glucose tolerance tests, yet no studies have examined the effects of sleep restriction on high-fat meal lipemia. We assessed the effect of 5 h time in bed (TIB) per night for four consecutive nights on postprandial lipemia following a standardized high-fat dinner (HFD). Furthermore, we assessed whether one night of recovery sleep (10 h TIB) was sufficient to restore postprandial metabolism to baseline. We found that postprandial triglyceride (TG) area under the curve was suppressed by sleep restriction (P = 0.01), but returned to baseline values following one night of recovery. Sleep restriction decreased NEFAs throughout the HFD (P = 0.02) and NEFAs remained suppressed in the recovery condition (P = 0.04). Sleep restriction also decreased participant-reported fullness or satiety (P = 0.03), and decreased postprandial interleukin-6 (P < 0.01). Our findings indicate that four nights of 5 h TIB per night impair postprandial lipemia and that one night of recovery sleep may be adequate for recovery of TG metabolism, but not for markers of adipocyte function.

Sleep Validity of a Non-Contact Bedside Movement and Respiration-Sensing Device.

STUDY OBJECTIVES: To assess the sleep detection and staging validity of a non-contact, commercially available bedside bio-motion sensing device (S+, ResMed) and evaluate the impact of algorithm updates. METHODS: Polysomnography data from 27 healthy adult participants was compared epoch-by-epoch to synchronized data that were recorded and staged by actigraphy and S+. An update to the S+ algorithm (common in the rapidly evolving commercial sleep tracker industry) permitted comparison of the original (S+V1) and updated (S+V2) versions. RESULTS: Sleep detection accuracy by S+V1 (93.3%), S+V2 (93.8%), and actigraphy (96.0%) was high; wake detection accuracy by each (69.6%, 73.1%, and 47.9%, respectively) was low. Higher overall S+ specificity, compared to actigraphy, was driven by higher accuracy in detecting wake before sleep onset (WBSO), which differed between S+V2 (90.4%) and actigraphy (46.5%). Stage detection accuracy by the S+ did not exceed 67.6% (for stage N2 sleep, by S+V2) for any stage. Performance is compared to previously established variance in polysomnography scored by humans: a performance standard which commercial devices should ideally strive to reach. CONCLUSIONS: Similar limitations in detecting wake after sleep onset (WASO) were found for the S+ as have been previously reported for actigraphy and other commercial sleep tracking devices. S+ WBSO detection was higher than actigraphy, and S+V2 algorithm further improved WASO accuracy. Researchers and clinicians should remain aware of the potential for algorithm updates to impact validity. COMMENTARY: A commentary on this article appears in this issue on page 935.

Breastfeeding Duration Is Associated with Regional, but Not Global, Differences in White Matter Tracts.

Extended breastfeeding through infancy confers benefits on neurocognitive performance and intelligence tests, though few have examined the biological basis of these effects. To investigate correlations with breastfeeding, we examined the major white matter tracts in 4-8 year-old children using diffusion tensor imaging and volumetric measurements of the corpus callosum. We found a significant correlation between the duration of infant breastfeeding and fractional anisotropy scores in left-lateralized white matter tracts, including the left superior longitudinal fasciculus and left angular bundle, which is indicative of greater intrahemispheric connectivity. However, in contrast to expectations from earlier studies, no correlations were observed with corpus callosum size, and thus no correlations were observed when using such measures of global interhemispheric white matter connectivity development. These findings suggest a complex but significant positive association between breastfeeding duration and white matter connectivity, including in pathways known to be functionally relevant for reading and language development.

Longitudinal relationship between sleep deficiency and pain symptoms among community-dwelling older adults in Japan and Singapore.

The association of sleep with pain is well documented among adult populations. Even though both sleep problems and pain are prevalent in older adults, the longitudinal and bidirectional relationship between sleep deficiency (i.e. insufficient and poor sleep) and pain is less well established. This study investigated the association between sleep deficiency and pain among community-dwelling adults aged 65 years and older across a 2- to 3-year period. We analyzed cross-country data from the Nihon University Japanese Longitudinal Study of Aging (N = 2888) and the Panel on Health and Aging of Singaporean Elderly (N = 2111). Sleep deficiency was operationalized as self-reported short sleep duration (<6 hours), frequent restlessness during the night, and/or non-restorative sleep. Pain was characterized in terms of any pain, multiple pain locations, and pain-related disability. Demographics, smoking, nap duration, depressive symptoms, chronic conditions, and body mass index were included as covariates. Baseline sleep deficiency was associated with any pain, multiple pain locations, and pain-related disability among older adults at follow-up, although differences by country of residence were observed. In Singaporeans, sleep deficiency predicted the new onset of any pain, and any pain also predicted the new emergence of sleep deficiency. Improving sleep of older adults may improve pain-related symptoms and help intervene on the vicious cycle of pain and sleep deficiency.