Ivy Y. Chen

How sleep medications affect brain physiology over time remains largely unknown. Prior pharmacodynamic work has established distinct spectral signatures of GABA-A receptor modulators vs. DORAs in younger or mixed adult samples. Here, we report how sleep EEG effects evolve from acute (days 1–2) to chronic (days 29–30) exposure in older adults with insomnia meeting DSM-5 criteria, and how within-person changes relate to Insomnia Severity Index (ISI). This analysis used data from a randomized, double-blind, placebo-controlled, active-comparator phase III trial (May 2016–January 2018). A subset of 249 participants was analyzed for EEG outcomes. Participants received 5 mg or 10 mg LEM (LEM5, LEM10), 6.25 mg extended-release zolpidem (ZOL), or placebo nightly for 30 days. Polysomnography was collected at baseline, after acute exposure, and after chronic exposure. Acute ZOL exposure produced significant increases in non-rapid eye movement (NREM) slow oscillation (SO), sigma, beta, and gamma power, with decreases in delta and theta compared to all treatment groups. These effects persisted with chronic exposure, alongside an alpha increase from acute to chronic exposure. LEM10 showed minimal acute effects but, with continued use, increased SO and decreased alpha power. The degree of SO power increase from acute to chronic exposure predicted improvements in ISI scores, driven by the LEM10 group. ZOL showed similar REM effects, whereas LEM5, but not LEM10, reduced REM sigma and beta power. These findings demonstrate that ZOL and LEM differentially modulate sleep EEG, with sustained SO enhancement under LEM10 linked to symptom improvement.

Study Objectives: Memory consolidation during non-rapid eye movement slow wave sleep (NREM SWS) involves reactivation of a hippocampal index which integrates distributed cortical representations of an experience. This study examined whether individual differences in brain network properties that align with this theoretical organization were associated with interindividual variability in memory consolidation during sleep. Methods: Thirty-six older adults (μage = 72.9 ± 5.6) completed overnight polysomnography with pre- and post-sleep emotional memory testing. Slow oscillation (SO) power and SO-sleep spindle (SO-SP) coupling were computed. Participants also completed 3T structural and resting-state functional magnetic resonance imaging (rsfMRI). Resting-state fMRI network modularity (Q), hippocampal and amygdala eigenvector centrality (EC), and betweenness centrality (BC) were calculated. Results: Greater Q was associated with reduced emotional memory retention and greater SWS. Hippocampal and amygdala EC were associated with better emotional memory retention. Hippocampal BC was associated with immediate test performance, whereas amygdala BC was associated with delayed test and memory retention. Hippocampal centrality measures were associated with SO power and SO-SP coupling. Random forest classification revealed distinct network measure combinations predict different stages of memory processing. Conclusions: Network integration supports overnight emotional memory retention. Individuals with more influential medial temporal lobe nodes exhibited better memory consolidation, suggesting functional network architecture contributes to memory processing. These measures were associated with sleep oscillations implicated in consolidation. Individual differences in functional network organization may predict the capacity of older adults to consolidate memories.

In healthy adolescents, better cardiorespiratory fitness, as assessed by the gold standard measure [laboratory-based assessment of peak oxygen consumption (V̇o₂)], was associated with earlier circadian timing of sleep/wake patterns, rest-activity rhythms and chronotype, and less social jetlag. These findings highlight the close interrelationships between fitness and rhythms and raise the possibility that maintaining higher cardiorespiratory fitness levels alongside earlier sleep/wake schedule and activity rhythms may be important behavioral intervention targets to promote health in adolescents.

Wrist actigraphy has been used to assess sleep in older adult populations for nearly half a century. Over the years, the continuous raw activity data derived from actigraphy has been used for the characterization of factors beyond sleep/wake such as physical activity patterns and circadian rhythms. Behavioral activity rhythms (BAR) are useful to describe individual daily behavioral patterns beyond sleep and wake, which represent important and meaningful clinical outcomes. This paper reviews common rhythmometric approaches and summarizes the available data from the use of these different approaches in older adult populations. We further consider a new approach developed in our laboratory designed to provide graphical characterization of BAR for the observed behavioral phenomenon of activity patterns across time. We illustrate the application of this new approach using actigraphy data collected from a well-characterized sample of older adults (age 60+) with osteoarthritis (OA) pain and insomnia. Generalized additive models (GAM) were implemented to fit smoothed nonlinear curves to log-transformed aggregated actigraphy-derived activity measurements. This approach demonstrated an overall strong model fit (R² = 0.82, SD = 0.09) and was able to provide meaningful outcome measures allowing for graphical and parameterized characterization of the observed activity patterns within this sample.

Hyperarousal is a 24-h state of elevated cognitive and physiological activation, and is a core feature of insomnia. The extent to which sleep quality is affected by stressful events—so-called sleep reactivity—is a vulnerability factor for developing insomnia. Given the increasing prevalence of insomnia with age, we aimed to investigate how hyperarousal and sleep reactivity were related to insomnia severity in different adult age groups. Data were derived from a large cohort study investigating the natural history of insomnia in a population-based sample (n = 1693). Baseline data of the Arousal Predisposition Scale (APS) and Ford Insomnia Response to Stress Test (FIRST) were examined across age and sleep/insomnia subgroups: 25–35 (n = 448), 35–45 (n = 528), and 45–55 year olds (n = 717); good sleepers (n = 931), individuals with insomnia symptoms (n = 450), and individuals with an insomnia syndrome (n = 312). Results from factorial analyses of variance (ANOVA) showed that APS scores decreased with increasing age, but increased with more severe sleep problems. FIRST scores were not significantly different across age groups, but showed the same strong increase as a function of sleep problem severity. The findings indicate that though arousal predisposition and sleep reactivity increase with more severe sleep problems, only arousal decreases with age. How arousing events affect an individual during daytime thus decreases with age, but how this arousal disrupts sleep is equivalent across different adult age groups. The main implication of these findings is that treatment of insomnia could be adapted for different age groups and take into consideration vulnerability factors such as hyperarousal and stress reactivity.