It has long been thought that links between affect and sleep are bidirectional. However, few studies have directly assessed the relationships between (1) pre-sleep affect and sleep EEG activity, and (2) sleep EEG activity and post-sleep affect. This study aims to systematically explore the correlations between pre-/post-sleep affect and EEG activity during sleep. In a community sample of adults (n=51), we measured participants’ positive and negative affect in the evening before sleep and in the next morning after sleep. Participants slept at their residence for one night of EEG recording. Using Fourier transforms, the EEG power at each channel was estimated during rapid eye movement (REM) sleep and non-REM (NREM) sleep for the full range of sleep EEG frequencies. We first present heatmaps of the raw correlations between pre-/post-sleep affect and EEG power during REM and NREM sleep. We then thresholded the raw correlations with a medium effect size |r| ≥ 0.3. Using a cluster-based permutation test, we identified a significant cluster indicating a negative correlation between pre-sleep positive affect and EEG power in the alpha frequency range during REM sleep. This result suggests that more positive affect during the daytime may be associated with less fragmented REM sleep that night. Overall, our exploratory results lay the foundation for confirmatory research on the relationship between daytime affect and sleep EEG activity.

Pre-sleep affect is thought to influence sleep, but associations with both sleep architecture and the electroencephalographic (EEG) power spectrum are mixed. In this pre-registered study, we assessed negative valence and arousal 1 h pre-sleep in 52 adults drawn from the community, then recorded one night of polysomnography (PSG) in participants’ own homes. Pre-sleep affect was not associated with nonrapid eye movement (NREM) or rapid eye movement (REM) sleep architecture parameters, but we did observe inverted U-shaped relationships between both negative valence and arousal and REM frontal theta power, such that theta power was highest at moderate negative valence and arousal, and lowest at either affective extreme. When entered into a model together, both valence and arousal accounted for independent variance. Secondary analyses revealed a similar quadratic association with pre-sleep positive valence, suggesting a nonspecific effect of pre-sleep valence on REM frontal theta. Robustness checks confirmed that effects were not explained by homeostatic sleep pressure or sleep timing. Our results suggest that mixed findings in the literature may reflect different ends of a quadratic function, underscoring the importance of assessing how different components of pre-sleep affect relate to sleep.

Cognitive-behavioral therapy for insomnia (CBT-I) is an effective multi-component treatment known to improve subjective and objective sleep markers in those with insomnia, including slow-wave activity (SWA, 0.5-4.75Hz). However, it remains unknown whether treatment-related increases in SWA are associated with improvements in memory performance or how individual components of CBT-I treatment contribute to these improvements.

ObjectivePoor sleep is associated with hypertension, a major risk factor for cardiovascular disease. However, the mechanism(s) through which sleep loss affects cardiovascular health remains largely unknown, including the brain and body systems that regulate vascular function.MethodsSixty-six healthy adults participated in a repeated-measures, crossover, experimental study involving assessments of cardiovascular function and brain connectivity after a night of sleep and a night of sleep deprivation.ResultsFirst, sleep deprivation significantly increased blood pressure-both systolic and diastolic. Interestingly, this change was independent of any increase in heart rate, inferring a vasculature-specific rather than direct cardiac pathway. Second, sleep loss compromised functional brain connectivity within the vascular control network, specifically the insula, anterior cingulate, amygdala, and ventral and medial prefrontal cortices. Third, sleep loss-related changes in brain connectivity and vascular tone were not independent, but significantly interdependent, with changes within the vascular control brain network predicting the sleep-loss shift toward hypertension.ConclusionsThese findings establish an embodied framework in which sleep loss confers increased risk of cardiovascular disease through an impact upon central brain control of vascular tone, rather than a direct impact on accelerated heart rate itself.

Abstract Introduction As individuals age, the circadian-driven timing of their sleep shifts to an earlier hour. Whether such a shift moderates the effectiveness of insomnia treatment on sleep disturbances and mood in older adults is unknown. Methods We tested the hypothesis that circadian preference moderates improvements in mood and insomnia symptoms following a non-pharmacological insomnia treatment. Older adults (N=111, age=69±6.4 years, female=65%) with insomnia (Insomnia Severity Index (ISI) score >10) received a 6-session treatment regimen. Circadian preference was measured at baseline with the Composite Scale of Morningness (CSM mean score=41.2±7.3, median=42). Chronotypes were classified based on a median split of CSM scores. Depression, (Geriatric Depression Scale, GDS), insomnia severity (ISI), cognitive arousal (Glasgow Content of Thoughts Inventory, GCTI), and time in bed (TIB), total sleep time (TST), and sleep efficiency (TST /TIB=SE) from sleep diaries were collected pre- and post-treatment. Tests of proportion were used to characterize differences in demographic variables between chronotypes. Ranked correlation tests were used to test associations between circadian preference and variables of interest at pre- and post-treatment. T-tests with unequal variance were used to examine whether treatment outcomes differed between chronotypes. Results In this study, 58% of females and 38% of males were later chronotypes (p=0.04). Later chronotype was associated with greater pre-treatment TIB (p=0.01), and earlier chronotype was associated with higher post-treatment cognitive arousal (p=0.04). Later chronotypes had greater reduction in depression symptoms (Cohen’s d=0.43, p=0.04), cognitive arousal (d=0.39, p=0.05), and a trend for greater reduction in TIB (d=0.37, p=0.07). Earlier chronotypes had a greater increase in TST (d=0.42, p=0.04). However, both chronotypes saw equivalent changes in SE (d=0.12, p=0.58). Conclusion Later chronotypes had a greater reduction in TIB, while earlier chronotypes demonstrated a significant increase in TST due to insomnia treatment, and both chronotypes had improved SE. These patterns suggest that treatment equivalently improves the consolidation of sleep, but the mechanism of this treatment effect differs by chronotype. That is, a moderating effect of circadian preference on the mechanism of improved sleep consolidation by insomnia treatment in older adults. These results suggest greater attention to age-related changes in chronotype in insomnia treatment. Support (If Any) NIMHR01MH101468-01; MIRECC at the VAPAHCS

Abstract Introduction In general, higher physical activity is related to lower symptoms of insomnia, depression, and anxiety. The COVID-19-pandemic and its related restrictions unfavorably impacted both physical activity and sleep patterns. However, it remains unknown how better sleep and physical activity prior to the pandemic confer resilience to psychological and health-related disturbances during the pandemic. We investigated whether people with higher physical activity and lower insomnia scores before the COVID-19-pandemic also reported higher physical activity, lower insomnia scores, and lower symptoms of depression and anxiety during COVID-19-pandemic-related restrictions. Methods A total of 826 adults (mean age: 34.58±12.37 years) completed self-rating questionnaires covering physical activity, and symptoms of insomnia, depression, and anxiety during the COVID-19-pandemic. Further, participants retrospectively rated their physical activity and insomnia before the COVID-19-pandemic. Hypotheses were tested using Pearson’s correlations and paired t-tests with significance at p < 0.05. Results Retrospectively assessed higher physical activity levels before the COVID-19-pandemic were associated with lower symptoms of depression (r = 0.84, p = 0.041), but neither insomnia (r = 0.02, p = 0.67) nor anxiety scores during the COVID-19-pandemic (r = 0.05, p = 0.20). Retrospectively assessed lower insomnia scores before the COVID-19-pandemic were associated with lower symptoms of insomnia (r = 0.57, p < 0.001), depression (r = 0.30, p < 0.001) and anxiety (r = 0.31, p < 0.001) during the COVID-19-pandemic. Consistent with other studies both insomnia and physical activity worsened; insomnia scores increased (p < 0.001, d = 0.66) and physical activity decreased (p < 0.001, d = 0.19) from before to during the COVID-19 pandemic. Conclusion These results suggest that those with lower levels of insomnia prior to the pandemic may be resilient to the psychological and health-related consequences of the COVID-19-pandemic and its related restrictions in everyday life, while those with higher physical activity prior to the pandemic were more resilient specifically to depression during the pandemic). Support (If Any)

Abstract Introduction Cognitive-behavioral therapy for insomnia (CBT-I) is an effective multi-component treatment known to improve sleep in older adults with insomnia, including increasing NREM slow-wave activity (SWA) EEG power (0.5 – 4.75Hz) and sleep depth. However, the relative contributions of distinct components of CBT-I to changes in SWA remain unknown. Methods We examined the relative impact of specific components of CBT-I: behavioral therapy (sleep restriction + stimulus control) (BT), cognitive therapy (CT), and combined BT and CT (CBT) on SWA in 111 older adults (75 female; mean age: 69±6.1 years) with insomnia (Insomnia Severity Index >10). Participants underwent polysomnography (PSG) at baseline prior to being randomized to a 6-session treatment regimen of BT, CT, or CBT. PSG was reassessed immediately following treatment and at 6-months follow-up. We computed SWA and time-accumulated slow-wave energy (SWE) at each time point. Mixed-effects models compared treatment efficacy on SWA and SWE outcomes. Results We identified significant time-by-treatment interactions for both SWA (B=0.69, t=2.14, p=0.034) and SWE (B=0.93, t=1.98, p=0.049). Post-hoc tests revealed that SWA/SWE increased from baseline to the end of treatment for CT group (SWA: d=0.42, SWE: d=0.54), while there were limited changes in the BT (SWA: d=0.27, SWE: d=0.29) and in the CBT groups (SWA: d=0.18, SWE: d=0.06). These changes were absent at 6-month follow up. Conclusion Our preliminary results indicated that different components of CBT-I have distinct effects on SWA/SWE with CT alone indicating improved NREM sleep quality. Given previous findings of lower SWA for sleep misperceptors underestimating their sleep depth, compared with good-sleepers, this result may suggest that reducing misperception of sleep with CT increases SWA/SWE. Further study is needed to dissociate the effect of BT from CT in combined CBT-I. Support (If Any)

Abstract Introduction Sleep Reactivity (SR), a trait-like tendency for stressful events to trigger sleep disturbances, is an established diathesis for insomnia and depression. However, no studies to date have examined SR in the context of the COVID-19 pandemic and it’s related restrictions. Thus, the goal of this analysis is to test whether SR confers a vulnerability for greater sleep and mood symptoms due to the stress of COVID-19 and it’s related restrictions. We hypothesized that (1) The onset of the pandemic will trigger greater increases in insomnia symptoms in highly sleep reactive individuals. 2) Sleep-reactive individuals would experience reduced recovery of insomnia, anxiety, and depression symptoms over the course of the pandemic. Methods SR, insomnia, anxiety, and depressive symptoms were assessed by the Ford Insomnia Response to Stress Test (FIRST), Insomnia Severity Index (ISI), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI II), respectively, at two time points (early-pandemic, 6-month follow-up). Additionally, participants retrospectively reported ISI prior to the pandemic. N = 253 adults from Stanford’s COVID-19 Pandemic Sleep Study (April-November 2020) provided baseline insomnia measures, and were excluded if they reported pre-pandemic clinical insomnia (ISI >10). Ranked-correlation tests were used to test the current hypotheses. Paired t-tests were used to evaluate changes in mean insomnia, depression, and anxiety scores. Covariates included essential worker status, sex, and age. Results ISI after COVID-19 was significantly higher than retrospective, pre-pandemic ISI (t = 8.2, d = 0.55, p < 0.0001). However, SR was not significantly correlated with the pandemic-related increase in ISI (ρ = 0.07, p = 0.34). Depression significantly increased after 6-months (t = 2.0, d = 0.27, p = 0.047), whereas anxiety did not (t = 1.7, d = 0.26, p = 0.10). Neither changes in depression nor anxiety were predicted by SR (Depression: ρ = 0.15, p = 0.32; Anxiety: ρ = -0.13, p = 0.40). Conclusion Insomnia and depression, but not anxiety, increased with the onset of the pandemic. However, trait SR was not a predisposing factor for pandemic-related sleep and mood changes. This is the first analysis examining SR as a risk factor for insomnia and mood symptoms in the pandemic. Support (If Any)

Abstract Introduction Pain worsens insomnia symptoms and increases hyperarousal during sleep. The effectiveness of treatments for improving insomnia symptoms may therefore be affected by co-occurring pain, though this currently remains unknown. Methods We tested the hypotheses that (1) higher levels of pain will lead to smaller improvements in subjective and objective markers of insomnia following a non-pharmacological insomnia treatment and (2) insomnia treatment will moderate the relationship between pain and markers of insomnia. 114 adults >60 years (age=69.7, SD=6.3, 66% female) with insomnia (Insomnia Severity Index [ISI] score >10, Mean=16.1, SD=4.5) underwent polysomnographic (PSG) recordings before and after completing a 6-session non-pharmacological insomnia treatment regimen. Pain severity (Brief Pain Inventory), insomnia symptoms (ISI), and hyperarousal derived from the PSG (relative α-band power [7.5-12.0Hz] across all sleep stages) were acquired at each time-point. Two-tailed paired t-tests were used to determine the main effects of treatment on insomnia and alpha power. Ranked-correlation tests were used to assess the impact of baseline pain on treatment outcomes, and mixed-effects models were employed to assess whether the relationship between pain and markers of insomnia differed pre- and post-treatment. Results Non-pharmacological insomnia treatment reduced insomnia symptom severity (t=19.4, p<0.001) but not α-power (t=0.97, p=0.33). Baseline pain severity was not associated with insomnia symptom improvement (ρ=-0.09, p=0.49) nor with changes in α-power (ρ=-0.19, p=0.23). There was no significant pain-by-time interaction in determining insomnia symptom improvement (β=-0.05, t=-0.18, p=0.86), and a trending pain-by-time interaction in determining changes in α-power (β=-0.007, t=-1.8, p = 0.07). Conclusion These findings suggest that pain is not likely to alter the effectiveness of non-pharmacological treatment for subjective insomnia symptoms, but pain may reduce change in the markers of hyperarousal in older adults with co-occurring pain and insomnia. Support (If Any) National Institute of Mental Health grant 1R01MH101468-01

Sleep loss increases the experience of pain. However, the brain mechanisms underlying altered pain processing following sleep deprivation are unknown. Moreover, it remains unclear whether ecologically modest night-to-night changes in sleep, within an individual, confer consequential day-to-day changes in experienced pain. Here, we demonstrate that acute sleep deprivation amplifies pain reactivity within human (male and female) primary somatosensory cortex yet blunts pain reactivity in higher-order valuation and decision-making regions of the striatum and insula cortex. Consistent with this altered neural signature, we further show that sleep deprivation expands the temperature range for classifying a stimulus as painful, specifically through a lowering of pain thresholds. Moreover, the degree of amplified reactivity within somatosensory cortex following sleep deprivation significantly predicts this expansion of experienced pain across individuals. Finally, outside of the laboratory setting, we similarly show that even modest nightly changes in sleep quality (increases and decreases) within an individual determine consequential day-to-day changes in experienced pain (decreases and increases, respectively). Together, these data provide a novel framework underlying the impact of sleep loss on pain and, furthermore, establish that the association between sleep and pain is expressed in a night-to-day, bidirectional relationship within a sample of the general population. More broadly, our findings highlight sleep as a novel therapeutic target for pain management within and outside the clinic, including circumstances where sleep is frequently short yet pain is abundant (e.g., the hospital setting).SIGNIFICANCE STATEMENT Are you experiencing pain? Did you have a bad night of sleep? This study provides underlying brain and behavioral mechanisms explaining this common co-occurrence. We show that sleep deprivation enhances pain responsivity within the primary sensing regions of the brain's cortex yet blunts activity in other regions that modulate pain processing, the striatum and insula. We further establish that even subtle night-to-night changes in sleep in a sample of the general population predict consequential day-to-day changes in pain (bidirectionally). Considering the societal rise in chronic pain conditions in lock-step with the decline in sleep time through the industrial world, our data support the hypothesis that these two trends may not simply be co-occurring but are significantly interrelated.

Key Points Sleep deprivation triggers a set of bidirectional changes in brain activity and connectivity, depending on the specific cognitive or affective behaviours engaged. Changes in brain activity are observed when averaged across a session of task performance and during on-task performance, wherein marked brain network instability seems to be a neural hallmark of sleep deprivation. Not all changes in brain function that are associated with sleep loss are maladaptive and thus represent deficiencies, as some predict resilience in behavioural ability and are therefore compensatory. These basic scientific findings offer causal mechanistic insights into select neurological and psychiatric disorders in which abnormalities in sleep and cognition or emotion are highly comorbid, indicating that sleep intervention is an underappreciated and novel target for disease treatment and/or prevention. The robust neural and behavioural phenotypes characterized by this Review can inform debates regarding sleep recommendations for both public and professional health policies, especially in light of the escalating sleep-loss epidemic prevalent throughout industrialized nations.