The human thalamus orchestrates neocortical oscillations during NREM sleep.

A hallmark of non-rapid eye movement (NREM) sleep is the coordinated interplay of slow oscillations (SOs) and sleep spindles. Traditionally, a cortico-thalamo-cortical loop is suggested to coordinate these rhythms: neocortically-generated SOs trigger spindles in the thalamus that are projected back to neocortex. Here, we used direct intrathalamic recordings from human epilepsy patients to test this canonical interplay. We show that SOs in the anterior thalamus precede neocortical SOs, whereas concurrently-recorded SOs in the mediodorsal thalamus are led by neocortical SOs. Furthermore, sleep spindles, detected in both thalamic nuclei, preceded their neocortical counterparts and were initiated during early phases of thalamic SOs. Our findings indicate an active role of the anterior thalamus in organizing the cardinal sleep rhythms in the neocortex and highlight the functional diversity of specific thalamic nuclei in humans. The concurrent coordination of sleep oscillations by the thalamus could have broad implications for the mechanisms underlying memory consolidation.

Abnormal sleep physiology in children with 15q11.2-13.1 duplication (Dup15q) syndrome

Background Sleep disturbances in autism spectrum disorder (ASD) represent a common and vexing comorbidity. Clinical heterogeneity amongst these warrants studies of the mechanisms associated with specific genetic etiologies. Duplications of 15q11.2-13.1 (Dup15q syndrome) are highly penetrant for neurodevelopmental disorders (NDDs) such as intellectual disability and ASD, as well as sleep disturbances. Genes in the 15q region, particularly UBE3A and a cluster of GABAA receptor genes, are critical for neural development, synaptic protein synthesis and degradation, and inhibitory neurotransmission. During awake electroencephalography (EEG), children with Dup15q syndrome demonstrate increased beta band oscillations (12–30 Hz) that likely reflect aberrant GABAergic neurotransmission. Healthy sleep rhythms, necessary for robust cognitive development, are also highly dependent on GABAergic neurotransmission. We therefore hypothesized that sleep physiology would be abnormal in children with Dup15q syndrome. Methods To test the hypothesis that elevated beta oscillations persist in sleep in Dup15q syndrome and that NREM sleep rhythms would be disrupted, we computed: (1) beta power, (2) spindle density, and (3) percentage of slow-wave sleep (SWS) in overnight sleep EEG recordings from a cohort of children with Dup15q syndrome (n = 15) and compared them to age-matched neurotypical children (n = 12). Results Children with Dup15q syndrome showed abnormal sleep physiology with elevated beta power, reduced spindle density, and reduced or absent SWS compared to age-matched neurotypical controls. Limitations This study relied on clinical EEG where sleep staging was not available. However, considering that clinical polysomnograms are challenging to collect in this population, the ability to quantify these biomarkers on clinical EEG—routinely ordered for epilepsy monitoring—opens the door for larger-scale studies. While comparable to other human studies in rare genetic disorders, a larger sample would allow for examination of the role of seizure severity, medications, and developmental age that may impact sleep physiology. Conclusions We have identified three quantitative EEG biomarkers of sleep disruption in Dup15q syndrome, a genetic condition highly penetrant for ASD. Insights from this study not only promote a greater mechanistic understanding of the pathophysiology defining Dup15q syndrome, but also lay the foundation for studies that investigate the association between sleep and cognition. Abnormal sleep physiology may undermine healthy cognitive development and may serve as a quantifiable and modifiable target for behavioral and pharmacological interventions.

Senses and Sensors of Sleep

This chapter analyzes sleep technology products designed to mediate and modulate patterns of sleep. Products analyzed include sleep-tracking applications and wearable devices for customizing personal phases of sleep architecture, and “smart” bedroom systems that use sensors and Internet connectivity to monitor and automate sensory environments to optimize the architectural spaces of sleep. Drawing on theories of digital disconnection, this chapter highlights how historical and theoretical notions of sleep as a site of subjective, social, and technological disconnection are reworked by contemporary media technologies. The now ubiquitous use of smartphones in bed reflects ongoing demands for digital participation and productivity. Yet such arrangements are unevenly distributed, with disconnective sleep technologies operating as a form of privilege and distinction for those who have the resources to reshape the architectures of personal sleep rhythms and spaces.

Waveform detection by deep learning reveals multi-area spindles that are selectively modulated by memory load

Sleep is generally considered to be a state of large-scale synchrony across thalamus and neocortex; however, recent work has challenged this idea by reporting isolated sleep rhythms such as slow-oscillations and spindles. What is the spatial scale of sleep rhythms? To answer this question, we adapted deep learning algorithms initially developed for detecting earthquakes and gravitational waves in high-noise settings for analysis of neural recordings in sleep. We then studied sleep spindles in non-human primate ECoG, human EEG, and clinical intracranial recordings (iEEG) in the human. We find a widespread extent of spindles, which has direct implications for the spatiotemporal dynamics we have previously studied in spindle oscillations (Muller et al., 2016) and the distribution of memory engrams in the primate.

048 Increased Cognitive Load Under Stress Modulates Sleep Spindles and Slow Oscillations in a Sleep-Stage Dependent Manner

Introduction The effect of increased cognitive load especially under duress has been known to affect brain rhythms in humans. However, this effect has been shown primarily in the awake brain; the effect of stressful cognitive load on sleep rhythms is yet unclear. We leveraged a unique opportunity to understand the effect of cognitive load under laboratory stress on sleep spindles and slow oscillations that are hallmark rhythms of NREM sleep. Methods Cortical 6-channel EEG nap data were collected from 45 subjects over two separate days: after a control session without laboratory stressors and after an experimental session in which they underwent fear condiitoning and negative-emotional-image viewing sessions. We detected sleep spindles (11-13Hz over frontal regions and 13-16Hz over centroposterior regions) and slow oscillations (0.16–1.25Hz oscillations) as discrete events at each of the six electrodes, and staged them by the sleep hypnogram. We evaluated the spindle rate in N2 sleep and the proportion of slow oscillations nested with a spindle in N3 sleep. Results Over all 6 EEG electrodes, N2 spindle rates increased on average by 14% in the experimental session compared to the control session (mixed-effect models p<0.001). In addition, over all 6 electrodes, the proportion of slow oscillations in N3 nested with a spindle increased by 2.3% in the experimental session compared to the control session (mixed effect model, p=0.005). Conclusion We show for the first time how increased cognitive load under stressful laboratory conditions affects sleep rhythms. Such an increased response in sleep might correspond to a continued emotional response due to the cognitive load under duress. Ongoing work seeks to tie these findings to possible emotional memory consolidation. Support (if any) VA Career Development Award to Dr. Richards (5IK2CX000871-05)

Circadian Rhythms, Sleep, and Aging

Circadian mechanisms and the sleep-wakefulness rhythms guarantee survival, adaptation, efficient action in everyday life or in emergencies and well-being. Disordered circadian processes at central and/or cellular levels, sleep disorders, and unhealthy wakefulness/sleep rhythms can impair the physiological circadian organization and result in subjective, professional, or behavioral changes ranging from functional inadequacy to higher risks at work or on the road to medical relevance. Circadian rhythms and the sleep organization change ontogenetically; major changes result from normal aging and from the multiple diseases that are often associated. There are circular functional interactions involving sleep/sleep disorders, the autonomic and immune systems, and the functional changes in the circadian system due to aging that deserve attention but have been overlooked thus far.