Age-associated sleep spindle characteristics in Duchenne muscular dystrophy.

Brain oscillations of non-rapid eye movement sleep, including slow oscillations (SO, 0.5-1.5 Hz) and spindles (10-16 Hz), mirror underlying brain maturation across development and are associated with cognition. Hence, age-associated emergence and changes in the electrophysiological properties of these rhythms can lend insight into cortical development, specifically in comparisons between pediatric populations and typically developing peers. We previously evaluated age-associated changes in SOs in male patients with Duchenne muscular dystrophy (DMD), finding a significant age-related decline between 4 and 18 years. While primarily a muscle disorder, male patients with DMD can also have sleep, cognitive, and cortical abnormalities, thought to be driven by altered dystrophin expression in the brain. In this follow-up study, we characterized the age-associated changes in sleep spindles. We found that age-dependent spindle characteristics in patients with DMD, including density, frequency, amplitude, and duration, were consistent with age-associated trends reported in the literature for typically developing controls. Combined with our prior finding of age-associated decline in SOs, our results suggest that SOs, but not spindles, are a candidate intervention target to enhance sleep in patients with DMD.

Good sleep is a mood buffer for young women during menses.

STUDY OBJECTIVES: We sought to elucidate the interaction between sleep and mood considering menstrual cycle phase (menses and non-menses portions of the cycle) in 72 healthy young women (18-33 years) with natural, regular menstrual cycles and without menstrual-associated disorders. This work fills a gap in literature of examining mood in context of sleep and menstrual cycle jointly, rather than individually. METHODS: Daily subjective measures of sleep and mood, and date of menses were remotely, digitally collected over a 2-month period. Each morning, participants rated their sleep on the previous night, and each evening participants rated the extent of positive and negative mood for that day. Objective sleep was tracked with a wearable (OURA ring) during month 2 of the study. Time-lag cross-correlation and mixed linear models were used to analyze the significance and directionality of the sleep-mood relationship, and how the interaction between menstrual cycle status and sleep impacted mood levels. RESULTS: We found that menstrual status alone did not impact mood. However, subjective sleep quality and menstrual status interacted to impact positive mood (p < .05). After a night of perceived poor sleep quality, participants reported lower positive mood during menses compared to non-menses portions of the cycle, while after a night of perceived good sleep quality participants reported equivalent levels of positive mood across the cycle. CONCLUSIONS: We suggest that the perception of good sleep quality acts as a mood equalizer, with good sleep providing a protective buffer to positive mood across the menstrual cycle.

The functions of sleep: A cognitive neuroscience perspective.

This Special Feature explores the various purposes served by sleep, describing current attempts to understand how the many functions of sleep are instantiated in neural circuits and cognitive structures. Our feature reflects current experts' opinions about, and insights into, the dynamic processes of sleep. In the last few decades, technological advances have supported the updated view that sleep plays an active role in both cognition and health. However, these roles are far from understood. This collection of articles evaluates the dynamic nature of sleep, how it evolves across the lifespan, becomes a competitive arena for memory systems through the influence of the autonomic system, supports the consolidation and integration of new memories, and how lucid dreams might originate. This set of papers highlights new approaches and insights that will lay the groundwork to eventually understand the full range of functions supported by sleep.

Sleep facilitates spatial memory but not navigation using the Minecraft Memory and Navigation task.

Sleep facilitates hippocampal-dependent memories, supporting the acquisition and maintenance of internal representation of spatial relations within an environment. In humans, however, findings have been mixed regarding sleep's contribution to spatial memory and navigation, which may be due to task designs or outcome measurements. We developed the Minecraft Memory and Navigation (MMN) task for the purpose of disentangling how spatial memory accuracy and navigation change over time, and to study sleep's independent contributions to each. In the MMN task, participants learned the locations of objects through free exploration of an open field computerized environment. At test, they were teleported to random positions around the environment and required to navigate to the remembered location of each object. In study 1, we developed and validated four unique MMN environments with the goal of equating baseline learning and immediate test performance. A total of 86 participants were administered the training phases and immediate test. Participants' baseline performance was equivalent across all four environments, supporting the use of the MMN task. In study 2, 29 participants were trained, tested immediately, and again 12 h later after a period of sleep or wake. We found that the metric accuracy of object locations, i.e., spatial memory, was maintained over a night of sleep, while after wake, metric accuracy declined. In contrast, spatial navigation improved over both sleep and wake delays. Our findings support the role of sleep in retaining the precise spatial relationships within a cognitive map; however, they do not support a specific role of sleep in navigation.

Zolpidem Maintains Memories for Negative Emotions Across a Night of Sleep.

Zolpidem, a common medication for sleep complaints, also shows secondary, unexpected memory benefits. We previously found that zolpidem prior to a nap enhanced negative, highly arousing picture memory. As zolpidem is typically administered at night, how it affects overnight emotional memory processing is relevant. We used a double-blind, placebo-controlled, within-subject, cross-over design to investigate if zolpidem boosted negative compared to neutral picture memory. Subjects learned both pictures sets in the morning. That evening, subjects were administered zolpidem or placebo and slept in the lab. Recognition was tested that evening and the following morning. We found that zolpidem maintained negative picture memory compared to forgetting in the placebo condition. Furthermore, zolpidem increased slow-wave sleep time, decreased rapid eye movement sleep time, and increased the fast spindle range in NREM. Our results suggest that zolpidem may enhance negative memory longevity and salience. These findings raise concerns for zolpidem administration to certain clinical populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-021-00079-1.

Autonomic central coupling during daytime sleep differs between older and younger people.

Decreased functioning in the elderly is mirrored by independent changes in central and autonomic nervous systems. Additionally, recent work suggests that the coupling of these systems may also serve an important role. In young adults, Autonomic and Central Events (ACEs), measured in the temporal coincidence of heart rate bursts (HRBs) and increased slow-wave-activity (SWA, 0.5-1 Hz) and sigma activity (12-15 Hz), followed by parasympathetic surge (RRHF) during non-rapid eye movement (NREM) sleep, predicted cognitive improvements. However, ACEs have not been examined in the elderly. Thus, the current study compared ACEs during wake and daytime sleep in older and younger adults and examined associations with working memory improvement before and after a nap. Compared to youngers, older adults showed lower amplitude of ACEs during NREM sleep, but not during wake. Furthermore, while younger adults demonstrated a parasympathetic surge after HRBs, older adults showed an earlier rise and longer maintenance of the RRHF. Taken together, our results demonstrate that autonomic-central coupling declines with age. Pathological aging implicates independent roles for decreased autonomic and central nervous system functioning, the current findings suggest that the coupling of these systems may also deserve attention.

Tracking Sleep, Temperature, Heart Rate, and Daily Symptoms Across the Menstrual Cycle with the Oura Ring in Healthy Women.

Background and Objective: The ovulatory menstrual cycle is characterized by hormonal fluctuations that influence physiological systems and functioning. Multi-sensor wearable devices can be sensitive tools capturing cycle-related physiological features pertinent to women's health research. This study used the Oura ring to track changes in sleep and related physiological features, and also tracked self-reported daily functioning and symptoms across the regular, healthy menstrual cycle. Methods: Twenty-six healthy women (age, mean (SD): 24.4 (1.1 years)) with regular, ovulatory cycles (length, mean (SD): 28.57 (3.8 days)) were monitored across a complete menstrual cycle. Four menstrual cycle phases, reflecting different hormone milieus, were selected for analysis: menses, ovulation, mid-luteal, and late-luteal. Objective measures of sleep, sleep distal skin temperature, heart rate (HR) and vagal-mediated heart rate variability (HRV, rMSSD), derived from the Oura ring, and subjective daily diary measures (eg sleep quality, readiness) were compared across phases. Results: Wearable-based measures of sleep continuity and sleep stages did not vary across the menstrual cycle. Women reported no menstrual cycle-related changes in perceived sleep quality or readiness and only marginally poorer mood in the midluteal phase. However, they reported moderately more physical symptoms during menses (p < 0.001). Distal skin temperature and HR, measured during sleep, showed a biphasic pattern across the menstrual cycle, with increased HR (p < 0.03) and body temperature (p < 0.001) in the mid- and late-luteal phases relative to menses and ovulation. Correspondingly, rMSSD HRV tended to be lower in the luteal phase. Further, distal skin temperature was lower during ovulation relative to menses (p = 0.05). Conclusion: The menstrual cycle was not accompanied by significant fluctuations in objective and perceived measures of sleep or in mood, in healthy women with regular, ovulatory menstrual cycles. However, other physiological changes in skin temperature and HR were evident and may be longitudinally tracked with the Oura ring in women over multiple cycles in a natural setting.

Progressive muscle relaxation increases slow-wave sleep during a daytime nap.

Sleep is critical for health, cognition, and restorative processes, and yet, many experience chronic sleep restriction. Sleep interventions have been designed to enhance overnight sleep quality and physiology. Components of these interventions, like relaxation-based progressive muscle relaxation (PMR), have been studied in isolation and have shown direct effects on sleep architecture, including increasing time in restorative, slow-wave sleep (SWS). These relaxation methods have been understudied in naps, which are effective fatigue countermeasures that reduce deleterious effects of chronic sleep restriction. We hypothesised that PMR should boost SWS in a nap, as compared to an active control. We used a between-subject design in which healthy young adults underwent PMR training or listened to Mozart music (control) prior to a 90-min nap opportunity. We assessed changes in the amount and lateralisation of SWS, as evidence suggests left hemispheric lateralisation may be a proxy for recuperative sleep needs, and changes to state-dependent anxiety and fatigue before and after the nap to assess intervention success. We found PMR participants spent ~10 min more in SWS, equivalent to 125% more time, than the control group, and concomitantly, significantly less time in rapid eye movement sleep. PMR participants also had greater right lateralised slow-wave activity and delta activity compared to the control suggesting a more well-rested brain profile during sleep. Further, pre-sleep anxiety levels predicted nap architecture in the intervention group, suggesting benefits may be impacted by anxiety. The feasibility and accessibility of PMR prior to a nap make this an interesting research avenue to pursue with strong translational application.

Slow oscillation density and amplitude decrease across development in pediatric Duchenne and Becker muscular dystrophy.

STUDY OBJECTIVES: From childhood through adolescence, brain rhythms during non-rapid eye movement (NREM) sleep show dramatic development that mirror underlying brain maturation. For example, the function and characteristics of slow oscillations (SOs, <1 Hz) in healthy children are linked to brain development, motor skill, and cognition. However, little is known of possible changes in pediatric populations with neurologic abnormalities. METHODS: We measured slow oscillations in 28 Duchenne and Becker muscular dystrophy male patients from age 4 to 20 years old during overnight in-lab clinical sleep studies. We compared our pediatric patients by age to evaluate the developmental changes of SOs from childhood to early and late adolescence. RESULTS: Consistent with the current neuro- and physically typical literature, we found greater slow oscillation density (count of SOs per minute of each sleep stage) in NREM N3 than N2, and significantly greater slow oscillation density in frontal compared to central and occipital regions. However, separating patients into age-defined groups (child, early adolescent, and late adolescent) revealed a significant age effect, with a specific decline in the rate and amplitude of SOs. CONCLUSIONS: We found that with age, pediatric patients with Duchenne muscular dystrophy show a significant decline in slow oscillation density. Given the role that slow oscillations play in memory formation and retention, it is critical to developmentally characterize these brain rhythms in medically complex populations. Our work converges with previous pediatric sleep literature that promotes the use of sleep electroencephalographic markers as prognostic tools and identifies potential targets to promote our patients' quality of life.

Parameters of Memory Reconsolidation: Learning Mode Influences Likelihood of Memory Modification.

When previously consolidated hippocampally dependent memory traces are reactivated they enter a vulnerable state in which they can be altered with new information, after which they must be re-consolidated in order to restabilize the trace. The existing body of literature on episodic reconsolidation largely focuses on the when and how of successful memory reactivation. What remains poorly understood is how the nature of newly presented information affects the likelihood of a vulnerable episodic memory being altered. We used our episodic memory reconsolidation paradigm to investigate if the intention to encode impacts what subsequently becomes attributed to an older, reactivated memory. Participants learned two lists of objects separated by 48 h. We integrated a modified item-list directed-forgetting paradigm into the encoding of the second object list by cueing participants to learn some of the objects intentionally (intentional learning), while other objects were presented without a cue (incidental learning). Under conditions of memory reactivation, subjects showed equal rates of memory modification for intentionally- and incidentally-learned objects. However, in the absence of reactivation we observed high misattribution rates of incidentally-learned objects. We consider two interpretations of these data, with contrasting implications for understanding the conditions that influence memory malleability, and suggest further work that should help decide between them.

Losing memories during sleep after targeted memory reactivation.

Targeting memories during sleep opens powerful and innovative ways to influence the mind. We used targeted memory reactivation (TMR), which to date has been shown to strengthen learned episodes, to instead induce forgetting (TMR-Forget). Participants were first trained to associate the act of forgetting with an auditory forget tone. In a second, separate, task they learned object-sound-location pairings. Shortly thereafter, some of the object sounds were played during slow wave sleep, paired with the forget tone to induce forgetting. One week later, participants demonstrated lower recall of reactivated versus non-reactivated objects and impaired recognition memory and lowered confidence for the spatial location of the reactivated objects they failed to spontaneously recall. The ability to target specific episodic memories for forgetting during sleep has implications for developing novel therapeutic techniques for psychological disorders such as PTSD and phobias.

Brain correlates of memory reconsolidation: A role for the TPJ.

In this paper, we investigate the process by which new experiences reactivate and potentially update old memories. Such memory reconsolidation appears dependent on the extent to which current experience deviates from what is predicted by the reactivated memory (i.e. prediction error). If prediction error is low, the reactivated memory is likely to be updated with new information. If it is high, however, a new, separate, memory is more likely to be formed. The temporal parietal junction TPJ has been shown across a broad range of content areas (attention, social cognition, decision making and episodic memory) to be sensitive to the degree to which current information violates the observer's expectations - in other words, prediction error. In the current paper, we investigate whether the level of TPJ activation during encoding predicts if the encoded information will be used to form a new memory or update a previous memory. We find that high TPJ activation predicts new memory formation. In a secondary analysis, we examine whether reactivation strength - which we assume leads to a strong memory-based prediction - mediates the likelihood that a given individual will use new information to form a new memory rather than update a previous memory. Individuals who strongly reactivate previous memories are less likely to update them than individuals who weakly reactivate them. We interpret this outcome as indicating that strong predictions lead to high prediction error, which favors new memory formation rather than updating of a previous memory.