Order matters: sleep spindles contribute to memory consolidation only when followed by rapid-eye-movement sleep

Sleep is known to benefit memory consolidation, but little is known about the contribution of sleep stages within the sleep cycle. The sequential hypothesis proposes that memories are first replayed during non-rapid-eye-movement (NREM or N) sleep and then integrated into existing networks during rapid-eye-movement (REM or R) sleep, two successive critical steps for memory consolidation. However, it lacks experimental evidence as N always precedes R sleep in physiological conditions. We tested this sequential hypothesis in patients with central hypersomnolence disorder, including patients with narcolepsy who present the unique, anti-physiological peculiarity of frequently falling asleep in R sleep before entering N sleep. Patients performed a visual perceptual learning task before and after daytime naps stopped after one sleep cycle, starting in N or R sleep and followed by the other stage (i.e. N-R vs. R-N sleep sequence). We compared over-nap changes in performance, reflecting memory consolidation, depending on the sleep sequence during the nap. Thirty-six patients who slept for a total of 67 naps were included in the analysis. Results show that sleep spindles are associated with memory consolidation only when N is followed by R sleep, that is in physiologically ordered N-R naps, thus providing support to the sequential hypothesis in humans. In addition, we found a negative effect of rapid-eye-movements in R sleep on perceptual consolidation, highlighting the complex role of sleep stages in the balance to remember and to forget.

Dyscoordination of Non-Rapid Eye Movement Sleep Oscillations in Autism Spectrum Disorder

Study Objectives Converging evidence from neuroimaging, sleep, and genetic studies suggests that dysregulation of thalamocortical interactions mediated by the thalamic reticular nucleus (TRN) contribute to autism spectrum disorder (ASD). Sleep spindles assay TRN function, and their coordination with cortical slow oscillations (SOs) indexes thalamocortical communication. These oscillations mediate memory consolidation during sleep. In the present study, we comprehensively characterized spindles and their coordination with SOs in relation to memory and age in children with ASD. Methods Nineteen children and adolescents with ASD, without intellectual disability, and 18 typically developing (TD) peers, aged 9-17, completed a home polysomnography study with testing on a spatial memory task before and after sleep. Spindles, SOs, and their coordination were characterized during stages 2 (N2) and 3 (N3) non-rapid eye movement sleep. Results ASD participants showed disrupted SO-spindle coordination during N2 sleep. Spindles peaked later in SO upstates and their timing was less consistent. They also showed a spindle density (#/min) deficit during N3 sleep. Both groups showed significant sleep-dependent memory consolidation, but its relations with spindle density differed. While TD participants showed the expected positive correlations, ASD participants showed the opposite. Conclusions The disrupted SO-spindle coordination and spindle deficit provide further evidence of abnormal thalamocortical interactions and TRN dysfunction in ASD. The inverse relations of spindle density with memory suggest a different function for spindles in ASD than TD. We propose that abnormal sleep oscillations reflect genetically mediated disruptions of TRN-dependent thalamocortical circuit development that contribute to the manifestations of ASD and are potentially treatable.

Characteristics of Obstructive Sleep Apnea Patients With Hypertension and Factors Associated With Autotitration Acceptance

In order to explore the characteristics and treatment status of obstructive sleep apnea (OSA) patients with hypertension, a retrospective study was conducted on 306 patients admitted from October 2018 to December 2019. According to the apnea hypopnea index (AHI), OSA patients with hypertension were divided into three groups. 69 cases were mild OSA (5 ≤ AHI < 15), 86 cases were moderate (15 ≤ AHI < 30), and 151 cases were severe (AHI ≥ 30). Compared with patients in the mild and moderate groups, the severe group had more male patients, with higher body mass index (BMI) and non-rapid eye movement stage 1 accounted for total sleep time (N1%), and lower non-rapid eye movement stage 2 accounted for total sleep time (N2%), average and minimum blood oxygen. Among all the patients, those who underwent the titration test accounted for 20.6% (63/306). Multivariate analysis showed that sleep efficiency (p < 0.001) and AHI (p < 0.001) were independent factors for patients to accept titration test. OSA patients with hypertension had a low acceptance of titration therapy. These people with higher sleep efficiency and AHI were more likely to receive autotitration.

Automatic analysis of muscular activity in the flexor digitorum superficialis muscles: A fast screening method for rapid eye movement sleep without atonia

Study objectives To identify a fast and reliable method for rapid eye movement (REM) sleep without atonia (RWA) quantification. Methods We analyzed 36 video-polysomnographies (v-PSGs) of isolated REM sleep behavior disorder (iRBD) patients and 35 controls’ v-PSGs. Patients diagnosed with RBD had: i) RWA, quantified with a reference method, i.e. automatic and artifact-corrected 3-s Sleep Innsbruck Barcelona (SINBAR) index in REM sleep periods (RSPs, i.e. manually selected portions of REM sleep); and ii) v-PSG-documented RBD behaviors. We quantified RWA with other (semi)-automated methods requiring less human intervention than the reference one: the indices proposed by the SINBAR group (the 3-s and 30-s phasic flexor digitorum superficialis (FDS), phasic/”any”/tonic mentalis), and the REM atonia, short and long muscle activity indices (in mentalis/submentalis/FDS muscles). They were calculated in whole REM sleep (i.e. REM sleep scored following international guidelines), in RSPs, with and without manual artifact correction. Area under curves (AUC) discriminating iRBD from controls were computed. Using published cut-offs, the indices’ sensitivity and specificity for iRBD identification were calculated. Apnea-hypopnea index in REM sleep (AHIREM) was considered in the analyses. Results RWA indices from FDS muscles alone had the highest AUCs and all of them had 100% sensitivity. Without manual RSP selection and artifact correction, the “30-s phasic FDS” and the “FDS long muscle activity” had the highest specificity (85%) with AHIREM<15/h. RWA indices were less reliable when AHIREM≥15/h. Conclusions If AHIREM<15/h, FDS muscular activity in whole REM sleep and without artifact correction is fast and reliable to rule out RWA.

The Basolateral Amygdala Mediates the Role of Rapid Eye Movement Sleep in Integrating Fear Memory Responses

The basolateral amygdala (BLA) mediates the effects of stress and fear on rapid eye movement sleep (REM) and on REM-related theta (θ) oscillatory activity in the electroencephalograph (EEG), which is implicated in fear memory consolidation. We used optogenetics to assess the potential role of BLA glutamate neurons (BLAGlu) in regulating behavioral, stress and sleep indices of fear memory, and their relationship to altered θ. An excitatory optogenetic construct targeting glutamatergic cells (AAV-CaMKIIα-hChR2-eYFP) was injected into the BLA of mice. Telemetry was used for real-time monitoring of EEG, activity, and body temperature to determine sleep states and stress-induced hyperthermia (SIH). For 3 h following shock training (ST: 20 footshocks, 0.5 mA, 0.5 s, 1 min interval), BLA was optogenetically stimulated only during REM (REM + L) or NREM (NREM + L). Mice were then re-exposed to the fear context at 24 h, 48 h, and 1 week after ST and assessed for behavior, SIH, sleep and θ activity. Control mice were infected with a construct without ChR2 (eYFP) and studied under the same conditions. REM + L significantly reduced freezing and facilitated immediate recovery of REM tested at 24 h and 48 h post-ST during contextual re-exposures, whereas NREM + L had no significant effect. REM + L significantly reduced post-ST REM-θ, but attenuated REM-θ reductions at 24 h compared to those found in NREM + L and control mice. Fear-conditioned SIH persisted regardless of treatment. The results demonstrate that BLAGlu activity during post-ST REM mediates the integration of behavioral and sleep indices of fear memory by processes that are associated with θ oscillations within the amygdalo-hippocampal pathway. They also demonstrate that fear memories can remain stressful (as indicated by SIH) even when fear conditioned behavior (freezing) and changes in sleep are attenuated.

The Regulation of Sleep

The words “regulation” and “control” have different meanings. A rich literature exists on the control mechanisms of sleep—the genomic, molecular, cellular, and circuit processes responsible for arousal state changes and characteristics. The regulation of sleep refers to functions and homeostatic maintenance of those functions. Much less is known about sleep regulation than sleep control, largely because functions of sleep are still unknown. Regulation requires information about the regulated variable that can be used as feedback information to achieve optimal levels. The circadian timing of sleep is regulated, and the feedback information is entraining stimuli such as the light–dark cycle. Sleep itself is homeostatically regulated, as evidenced by sleep deprivation experiments. Eletroenceophalography (EEG) slow-wave activity (SWA) is regulated, and it appears that adenosine is the major source of feedback information, and that fact indicates an energetic function for sleep. The last aspect of sleep regulation discussed in this short article is the non-rapid eye movement (NREM) and rapid eye movement (REM) sleep cycling. Evidence is discussed that supports the argument that NREM sleep is in a homeostatic relationship with wake, and REM sleep is in a homeostatic relationship with NREM sleep.