Sleep Spindle Density Research Articles

Sleep Spindles Preferentially Consolidate Weakly Encoded Memories.

Sleep has been shown to be critical for memory consolidation, with some research suggesting that certain memories are prioritized for consolidation. Initial strength of a memory appears to be an important boundary condition in determining which memories are consolidated during sleep. However, the role of consolidation-mediating oscillations, such as sleep spindles and slow oscillations, in this preferential consolidation has not been explored. Here, 54 human participants (76% female) studied pairs of words to three distinct encoding strengths, with recall being tested immediately following learning and again 6 h later. Thirty-six had a 2 h nap opportunity following learning, while the remaining 18 remained awake throughout. Results showed that, across 6 h awake, weakly encoded memories deteriorated the fastest. In the nap group, however, this effect was attenuated, with forgetting rates equivalent across encoding strengths. Within the nap group, consolidation of weakly encoded items was associated with fast sleep spindle density during non-rapid eye movement sleep. Moreover, sleep spindles that were coupled to slow oscillations predicted the consolidation of weak memories independently of uncoupled sleep spindles. These relationships were unique to weakly encoded items, with spindles not correlating with memory for intermediate or strong items. This suggests that sleep spindles facilitate memory consolidation, guided in part by memory strength.SIGNIFICANCE STATEMENT Given the countless pieces of information we encode each day, how does the brain select which memories to commit to long-term storage? Sleep is known to aid in memory consolidation, and it appears that certain memories are prioritized to receive this benefit. Here, we found that, compared with staying awake, sleep was associated with better memory for weakly encoded information. This suggests that sleep helps attenuate the forgetting of weak memory traces. Fast sleep spindles, a hallmark oscillation of non-rapid eye movement sleep, mediate consolidation processes. We extend this to show that fast spindles were uniquely associated with the consolidation of weakly encoded memories. This provides new evidence for preferential sleep-based consolidation and elucidates a physiological correlate of this benefit.

Sleep Spindle Characteristics in Obstructive Sleep Apnea Syndrome (OSAS).

Background: We compared the density and duration of sleep spindles topographically in stage 2 and 3 of non-rapid eye movement sleep (N2 and N3) among adults diagnosed with Obstructive Sleep Apnea Syndrome (OSAS) and healthy controls.Materials and Methods: Thirty-one individuals with OSAS (mean age: 48.50 years) and 23 healthy controls took part in the study. All participants underwent a whole night polysomnography. Additionally, those with OSAS were divided into mild, moderate and severe cases of OSAS.Results: For N2, sleep spindle density did not significantly differ between participants with and without OSAS, or among those with mild, moderate and severe OSAS. For N3, post-hoc analyses revealed significantly higher spindle densities in healthy controls and individuals with mild OSAS than in those with moderate or severe OSAS. Last, in N2 a higher AHI was associated with a shorter sleep spindle duration.Conclusion: OSAS is associated with a significantly lower spindle density in N3 and a shorter spindle duration in N2. Our results also revealed that, in contrast to moderate and severe OSAS, the sleep spindle characteristics of individuals with mild OSAS were very similar to those of healthy controls.

Consolidation and generalisation across sleep depend on individual EEG factors and sleep spindle density

Sleep is involved in both the consolidation of discrete episodes, as well as the generalisation of acquired memories into schemata. Here, we have isolated early versus late periods of sleep in order to replicate previous behavioural findings and to demonstrate: i) that distinct sleep and sleep electroencephalography (EEG) factors influence the generalisation of learned information, and; ii) that the consolidation and generalisation of memory across sleep depends on individual alpha frequency (IAF) and strength of initial encoding. Subjects underwent a night-half protocol with polysomnography (PSG), and completed a Chinese character-English paired associates learning task. Recognition accuracy of learned word-pairs, the extent to which the subject was able to generalise this knowledge, and the extent of explicit transfer of knowledge were measured. Results demonstrate that quality of initial learning determined the relationship between sleep neurophysiology and outcome, with IAF modulating this effect. We also note an effect of IAF in modulating the effect of sleep spindles in determining generalisation of learned materials. Finally, we note a complex relationship between initial learning, IAF and sleep spindle density in determining when information will reach explicit awareness across sleep. Together, these data implicate encoding factors in subsequent offline processing, demonstrate a potential role for individual differences in the EEG and subsequently add to our understanding of the the conditions in which sleep may benefit both memory and learning.

Impact of menstrual cycle phase and oral contraceptives on sleep and overnight memory consolidation.

Sleep spindles benefit declarative memory consolidation and are considered to be a biological marker for general cognitive abilities. However, the impact of sexual hormones and hormonal oral contraceptives (OCs) on these relationships are less clear. Thus, we here investigated the influence of endogenous progesterone levels of naturally cycling women and women using OCs on nocturnal sleep and overnight memory consolidation. Nineteen healthy women using OCs (MAge = 21.4, SD = 2.1 years) were compared to 43 healthy women with a natural menstrual cycle (follicular phase: n = 16, MAge = 21.4, SD = 3.1 years; luteal phase: n = 27, MAge = 22.5, SD = 3.6 years). Sleep spindle density and salivary progesterone were measured during an adaptation and an experimental night. A word pair association task preceding the experimental night followed by two recalls (pre‐sleep and post‐sleep) was performed to test declarative memory performance. We found that memory performance improved overnight in all women. Interestingly, women using OCs (characterized by a low endogenous progesterone level but with very potent synthetic progestins) and naturally cycling women during the luteal phase (characterized by a high endogenous progesterone level) had a higher fast sleep spindle density compared to naturally cycling women during the follicular phase (characterized by a low endogenous progesterone level). Furthermore, we observed a positive correlation between endogenous progesterone level and fast spindle density in women during the luteal phase. Results suggest that the use of OCs and the menstrual cycle phase affects sleep spindles and therefore should be considered in further studies investigating sleep spindles and cognitive performance.

Averaging sleep spindle occurrence in dogs predicts learning performance better than single measures

Although a positive link between sleep spindle occurrence and measures of post-sleep recall (learning success) is often reported for humans and replicated across species, the test–retest reliability of the effect is sometimes questioned. The largest to date study could not confirm the association, however methods for automatic spindle detection diverge in their estimates and vary between studies. Here we report that in dogs using the same detection method across different learning tasks is associated with observing a positive association between sleep spindle density (spindles/minute) and learning success. Our results suggest that reducing measurement error by averaging across measurements of density and learning can increase the visibility of this effect, implying that trait density (estimated through averaged occurrence) is a more reliable predictor of cognitive performance than estimates based on single measures.

Protocol for the Prognosticating Delirium Recovery Outcomes Using Wakefulness and Sleep Electroencephalography (P-DROWS-E) study: a prospective observational study of delirium in elderly cardiac surgical patients

IntroductionDelirium is a potentially preventable disorder characterised by acute disturbances in attention and cognition with fluctuating severity. Postoperative delirium is associated with prolonged intensive care unit and hospital stay, cognitive...

Post-exposure environment modulates long-term developmental ethanol effects on behavior, neuroanatomy, and cortical oscillations

Developmental exposure to ethanol has a wide range of anatomical, cellular, physiological and behavioral impacts that can last throughout life. In humans, this cluster of effects is termed fetal alcohol spectrum disorder and is highly prevalent in western cultures. The ultimate expression of the effects of developmental ethanol exposure however can be influenced by post-exposure experience. Here we examined the effects of developmental binge exposure to ethanol (postnatal day 7) in C57BL/6By mice on a specific cohort of inter-related long-term outcomes including contextual memory, hippocampal parvalbumin-expressing neuron density, frontal cortex oscillations related to sleep-wake cycling including delta oscillation amplitude and sleep spindle density, and home-cage behavioral activity. When assessed in adults that were raised in standard housing, all of these factors were altered by early ethanol exposure compared to saline controls except home-cage activity. However, exposure to an enriched environment and exercise from weaning to postnatal day 90 reversed most of these ethanol-induced impairments including memory, CA1 but not dentate gyrus PV+ cell density, delta oscillations and sleep spindles, and enhanced home-cage behavioral activity in Saline- but not EtOH-treated mice. The results are discussed in terms of the inter-dependence of diverse developmental ethanol outcomes and potential mechanisms of post-exposure experiences to regulate those outcomes.

Sleep, sleep spindles, and cognitive functions in drug-naive patients with first-episode psychosis.

Various lines of clinical findings have suggested abnormalities in macro- or microstructural parameters of sleep in patients with schizophrenia. Meanwhile findings are inconclusive due to some confounding factors, such as the heterogeneity of the disorder, drug regimen, and duration of the illness. There are a few studies in the literature that have been conducted on drug-free patients with first-episode psychosis (FEP). Based on this knowledge, we aimed to explore sleep characteristics, sleep spindles, and neuropsychological profiles of the drug-naive patients with FEP. The study sample consisted of 21 drug-naive patients with FEP and 21 healthy participants. Polysomnography recordings were conducted for 2 subsequent nights. A neuropsychological test battery was administered for assessing cognitive functions. The Positive and Negative Syndrome Scale was applied to measure symptom severity of the patients. Spindle detection was performed visually. According to the results of the study, the patient group's percentage of stage N2 sleep and sleep efficiency index was lower than in the control group. Among sleep spindle parameters, spindle density was found to be reduced in the patient group. The results of neuropsychological tests measuring executive functions, learning, and memory support the idea that there is a global cognitive deterioration from the early course of the disorder. In the psychotic group, negative symptoms were negatively correlated with verbal memory, learning, verbal fluency, and semantic organization. We found that the percentage of stage N3 sleep decreased while negative symptom severity increased. In addition, the percentage of stage N1 sleep increased as negative symptom severity increased. Reduction in stage N3 sleep was associated with an impairment in learning, verbal fluency, and response inhibition. The sleep spindle density and cognitive functions did not show any associations. Taken together, these findings suggest that patients with FEP show global cognitive impairment (except for attention and processing speed), which is associated with changes in sleep architecture and higher score in a scale assessing negative symptoms. We conclude that cognitive function and spindle parameters differ nonlinearly among patients with FEP.

0093 Topographical Analysis of Sleep Spindles and Their Coordination with Slow Oscillations

Abstract Introduction Brain oscillations found during sleep are hypothesized to mediate sleep-dependent memory consolidation, by coordinating cortical-subcortical activity and enabling synaptic plasticity. In particular, sleep spindles (10-16Hz) density and coordination with slow oscillations (SOs, 0.5–1.5 Hz) have been shown to correlate with memory performance post-sleep. In this study, we characterize how spindles are organized on the electrode manifold, and their relation to SO topography. Methods We conducted a sleep-memory study where subjects learned word-pair associations in the morning and were tested in the evening and the next morning. Polysomnography was collected during the night. We detected sleep spindles at each electrode independently and study their basic biophysical properties (density, amplitude, frequency, duration) in light sleep (stage 2, S2) and deep sleep (slow wave sleep, SWS) separately, including their co-occurrence with SOs. We categorize spindles that are co-detected across electrodes within a short time window and study how properties change across groups. Results We find a gradual increase in average spindle frequency in the frontal-occipital axis, but no bimodality in frequency distribution. Furthermore, spindles paired to SOs (a minority in both stages) are shorter than non-paired spindles. We find that coordination between spindles and SO troughs is frequency but not amplitude selective; and differs between the two sleep stages. In S2, slow spindles precede SOs in frontal electrodes and fast spindles follow SOs in centro-posterior electrodes. Our clusters of spindle topography include a Frontal and a Posterior cluster. These clusters mirror the commonly considered slow-frontal and fast-posterior spindles, but contain less than half of all S2 spindles. Clustering identifies sub-types of spindle-SO complexes whose density is linked to memory performance. Conclusion Our study shows that specific sub-types of sleep oscillations, defined by their topography, support the coordination between spindles and SOs which could mediate cortical-subcortical dialogue during sleep. Support This work was supported by NIH grant (R01 AG046646) to Sara C. Mednick

Multimodal assessment shows misalignment of structural and functional thalamocortical connectivity in children and adolescents born very preterm

Thalamocortical connections are altered following very preterm birth but it is unknown whether structural and functional alterations are linked and how they contribute to neurodevelopmental deficits. We used a multimodal approach in 27 very preterm and 35 term-born children and adolescents aged 10–16 years: Structural thalamocortical connectivity was quantified with two measures derived from probabilistic tractography of diffusion tensor data, namely the volume of thalamic segments with cortical connections and mean fractional anisotropy (FA) within the respective segments. High-density sleep EEG was recorded and sleep spindles were identified at each electrode. Sleep spindle density and integrated spindle activity (ISA) were calculated to quantify functional thalamocortical connectivity. In term-born participants, the volume of the global thalamic segment with cortical connections was strongly related to sleep spindles across the entire head (mean r ​= ​.53 ​± .10; range ​= ​0.35 to 0.78). Regionally, the volume of the thalamic segment connecting to frontal brain regions correlated with sleep spindle density in two clusters of electrodes over fronto-temporal brain regions (.42 ​± .06; 0.35 to 0.51 and 0.43 ​± .08; 0.35 to 0.62) and the volume of the thalamic segment connecting to parietal brain regions correlated with sleep spindle density over parietal brain regions (mean r ​= ​.43 ​± .07; 0.35 to 0.61). In very preterm participants, the volume of the thalamic segments was not associated with sleep spindles. In the very preterm group, mean FA within the global thalamic segment was negatively correlated with ISA over a cluster of frontal and temporo-occipital brain regions (mean r ​= ​−.53 ​± .07; −.41 to −.72). No association between mean FA and ISA was found in the term-born group. With this multimodal study protocol, we identified a potential misalignment between structural and functional thalamocortical connectivity in children and adolescents born very preterm. Eventually, this may shed further light on the neuronal mechanisms underlying neurodevelopmental sequelae of preterm birth.

Gentle rocking movements during sleep in the elderly.

Vestibular stimulation in the form of rocking movements could be a promising non‐pharmacological intervention for populations with reduced sleep quality, such as the elderly. We hypothesized that rocking movements influence sleep by promoting comfort. We assessed whether gentle rocking movements can facilitate the transition from wake to sleep, increase sleep spindle density and promote deep sleep in elderly people. We assessed self‐reported comfort using a pilot protocol including translational movements and movements along a pendulum trajectory with peak linear accelerations between 0.10 and 0.20 m/s2. We provided whole‐night stimulation using the settings rated most comfortable during the pilot study (movements along a pendulum trajectory with peak linear acceleration of 0.15 m/s2). Sleep measures (polysomnography) of two baseline and two movement nights were compared. In our sample (n = 19; eight female; mean age: 66.7 years, standard deviation: 3 years), vestibular stimulation using preferred stimulation settings did not improve sleep. A reduction of delta power was observed, suggesting reduced sleep depth during rocking movements. Sleep fragmentation was similar in both conditions. We did not observe a sleep‐promoting effect using settings optimized to be comfortable. This finding could imply that comfort is not the underlying mechanism. At frequencies below 0.3 Hz, the otoliths cannot distinguish tilt from translation. Translational movement trajectories, such as used in previous studies reporting positive effects of rocking, could have caused sensory confusion due to a mismatch between vestibular and other sensory information. We propose that this sensory confusion might be essential to the sleep‐promoting effect of rocking movements described in other studies.

Different Patterns of Sleep-Dependent Procedural Memory Consolidation in Vipassana Meditation Practitioners and Non-meditating Controls.

AimRapid eye movement (REM) sleep, non-rapid eye movement (NREM) sleep, and sleep spindles are all implicated in the consolidation of procedural memories. Relative contributions of sleep stages and sleep spindles were previously shown to depend on individual differences in task processing. However, no studies to our knowledge have focused on individual differences in experience with Vipassana meditation as related to sleep. Vipassana meditation is a form of mental training that enhances proprioceptive and somatic awareness and alters attentional style. The goal of this study was to examine a potential role for Vipassana meditation experience in sleep-dependent procedural memory consolidation.MethodsGroups of Vipassana meditation practitioners (N = 22) and matched meditation-naïve controls (N = 20) slept for a daytime nap in the laboratory. Before and after the nap they completed a procedural task on the Wii Fit balance platform.ResultsMeditators performed slightly better on the task before the nap, but the two groups improved similarly after sleep. The groups showed different patterns of sleep-dependent procedural memory consolidation: in meditators, task learning was positively correlated with density of slow occipital spindles, while in controls task improvement was positively associated with time in REM sleep. Sleep efficiency and sleep architecture did not differ between groups. Meditation practitioners, however, had a lower density of occipital slow sleep spindles than controls.ConclusionResults suggest that neuroplastic changes associated with meditation practice may alter overall sleep microarchitecture and reorganize sleep-dependent patterns of memory consolidation. The lower density of occipital spindles in meditators may mean that meditation practice compensates for some of the memory functions of sleep.

Effect of Rocking Movements on Afternoon Sleep.

Study ObjectivesGentle rocking movements provided by a moving bed have been proposed as a promising non-pharmacological way to promote sleep. In rodents the sleep promoting effect of rocking movements depended on the peak acceleration (named “stimulation intensity”) perceived by the vestibular system. We set out to verify previous reports on the sleep promoting effect of rocking movements and to investigate the importance of stimulation intensity in this process.MethodsSide-to-side rocking movements along a pendulum trajectory with different peak accelerations (control: 0 m/s2, low intensity: 0.15 m/s2, medium intensity: 0.25 m/s2, high intensity: 0.35 m/s2) were provided for 45 min during an afternoon nap opportunity. Participants were assigned to a low intensity group (n = 10) experiencing control, low and medium intensity stimulation or a high intensity group (n = 12) experiencing control, medium and high intensity stimulation. Sleep and sleep-related memory performance were assessed using polysomnography and a word-pair memory task, respectively.ResultsParticipants transitioned faster into deep sleep under the influence of medium intensity rocking as was evident by a faster buildup of delta power compared to the control condition (n = 22). The faster buildup did not affect sleep architecture, since e.g., the proportion of the nap spent in deep sleep or latencies did not change. Previously reported effects like a shorter latency to stage N2 and a higher density of sleep spindles were not observed. Sleep quality during control naps of the low intensity group was worse than in the high intensity group. In the low intensity group, we also observed a significant increase in delta power throughout the nap, as well as a higher density of slow oscillations both under the influence of low and medium intensity vestibular stimulation. No such effects were observed in the high intensity group.ConclusionRocking movements may promote nap sleep in young adults. Due to a difference in sleep quality during control naps between the low and high intensity group no conclusion regarding the influence of stimulation intensity were possible. Thus, optimal stimulation settings in humans need further investigation.

Reduced sleep spindle density in adolescent patients with early-onset schizophrenia compared to major depressive disorder and healthy controls

ObjectivesDuring adolescence schizophrenia and major depressive disorder (MDD) increasingly emerge. Overlapping symptomatology during first presentation challenges the diagnostic process. Reduced sleep spindle density (SSD) was suggested as a biomarker in adults, discerning patients with schizophrenia from patients with depression or healthy controls (HC). We aimed to compare SSD in early-onset schizophrenia (EOS), with MDD, and HC, and to analyse associations of SSD with symptomatology and neurocognitive measures. MethodsAutomatic sleep spindle detection was performed on all-night high-density EEG (128 electrodes) data of 12 EOS, 19 MDD, and 57 HC (age range 9.8–19), allowing an age- and sex-matching of 1:2 (patients vs. HC). Severity of current symptoms and neurocognitive variables were assessed in all patients. ResultsSSD was defined between 13.75 and 14.50 Hz as within this frequency range SSD differed between EOS vs. HC in bin by bin analyses (12–15 Hz). In EOS, SSD was lower over 27 centro-temporal electrodes compared to HC and over 9 central electrodes compared to MDD. Reduced SSD in EOS compared to MDD and HC was accompanied by a high variability of SSD in all adolescents. SSD did not differ between MDD and HC. In the pooled sample of patients, lower SSD was associated with more severe Positive and Negative Symptoms Scale total score, more impaired memory consolidation and processing speed. ConclusionA high variability of SSD in all adolescents may reflect the evolving character of SSD. The association of reduced SSD with the symptom dimension of impaired cognition cuts across diagnostical entities.

Sleep spindles as a diagnostic and therapeutic target for chronic pain.

Pain is known to disrupt sleep patterns, and disturbances in sleep can further worsen pain symptoms. Sleep spindles occur during slow wave sleep and have established effects on sensory and affective processing in mammals. A number of chronic neuropsychiatric conditions, meanwhile, are known to alter sleep spindle density. The effect of persistent pain on sleep spindle waves, however, remains unknown, and studies of sleep spindles are challenging due to long period of monitoring and data analysis. Utilizing automated sleep spindle detection algorithms built on deep learning, we can monitor the effect of pain states on sleep spindle activity. In this study, we show that in a chronic pain model in rodents, there is a significant decrease in sleep spindle activity compared to controls. Meanwhile, methods to restore sleep spindles are associated with decreased pain symptoms. These results suggest that sleep spindle density correlates with chronic pain and may be both a potential biomarker for chronic pain and a target for neuromodulation therapy.

Naps reliably estimate nocturnal sleep spindle density in health and schizophrenia.

Sleep spindles, defining oscillations of non-rapid eye movement stage 2 sleep (N2), mediate memory consolidation. Spindle density (spindles/minute) is a stable, heritable feature of the sleep electroencephalogram. In schizophrenia, reduced spindle density correlates with impaired sleep-dependent memory consolidation and is a promising treatment target. Measuring sleep spindles is also important for basic studies of memory. However, overnight sleep studies are expensive, time consuming and require considerable infrastructure. Here we investigated whether afternoon naps can reliably and accurately estimate nocturnal spindle density in health and schizophrenia. Fourteen schizophrenia patients and eight healthy controls had polysomnography during two overnights and three afternoon naps. Although spindle density was lower during naps than nights, the two measures were highly correlated. For both groups, naps and nights provided highly reliable estimates of spindle density. We conclude that naps provide an accurate, reliable and morescalable alternative to measuring spindle density overnight.

Sex differences within sleep in gonadally intact rats.

Sleep impacts diverse physiological and neural processes and is itself affected by the menstrual cycle; however, few studies have examined the effects of the estrous cycle on sleep in rodents. Studies of disease mechanisms in females therefore lack critical information regarding estrous cycle influences on relevant sleep characteristics. We recorded electroencephalographic (EEG) activity from multiple brain regions to assess sleep states as well as sleep traits such as spectral power and interregional spectral coherence in freely cycling females across the estrous cycle and compared with males. Our findings show that the high hormone phase of proestrus decreases the amount of nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep and increases the amount of time spent awake compared with other estrous phases and to males. This spontaneous sleep deprivation of proestrus was followed by a sleep rebound in estrus which increased NREM and REM sleep. In proestrus, spectral power increased in the delta (0.5-4 Hz) and the gamma (30-60 Hz) ranges during NREM sleep, and increased in the theta range (5-9 Hz) during REM sleep during both proestrus and estrus. Slow-wave activity (SWA) and cortical sleep spindle density also increased in NREM sleep during proestrus. Finally, interregional NREM and REM spectral coherence increased during proestrus. This work demonstrates that the estrous cycle affects more facets of sleep than previously thought and reveals both sex differences in features of the sleep-wake cycle related to estrous phase that likely impact the myriad physiological processes influenced by sleep.

Alterations in sleep, sleep spindle, and EEG power in mGluR5 knockout mice.

The type 5 metabotropic glutamate receptor (mGluR5) represents a novel therapeutic target for schizophrenia and other disorders. Schizophrenia is associated with progressive abnormalities in cortical oscillatory processes including reduced spindles (8-15 Hz) during sleep and increased delta (0.5-4 Hz)- and gamma-band activity (30-80 Hz) during wakefulness. mGluR5 knockout (KO) mice demonstrate many schizophrenia-like behaviors, including abnormal sleep. To examine the effects of mGluR5 on the maintenance of the neocortical circuitry responsible for such neural oscillations, we analyzed sleep/wake electroencephalographic (EEG) activity of mGluR5 KO mice at baseline, after 6 h of sleep deprivation, and during a visual method of cortical entrainment (visual steady state response). We hypothesized mGluR5-KO mice would exhibit translationally relevant abnormalities in sleep and neural oscillations that mimic schizophrenia. Power spectral and spindle density analyses were performed across 24-h EEG recordings in mGluR5-KO mice and wild-type (WT) controls. Novel findings in mGluR5 KO mice include deficits in sleep spindle density, wake alpha power, and 40-Hz visual task-evoked gamma power and phase locking. Sigma power (10-15 Hz), an approximation of spindle activity, was also reduced during non-rapid eye movement sleep transitions. Our observations on abnormal sleep/wake are generally in agreement with previous reports, although we did not replicate changes in rapid eye movement sleep. The timing of these phenotypes may suggest an impaired circadian process in mGluR5 KO mice. In conclusion, EEG phenotypes in mGluR5 KO mice resemble deficits observed in patients with schizophrenia. These findings implicate mGluR5-mediated pathways in several translationally relevant phenotypes associated with schizophrenia, and suggest that agents targeting this receptor may have harmful consequences on sleep health and daily patterns of EEG power.NEW & NOTEWORTHY Metabotropic glutamate receptor type 5 (mGluR5) knockout (KO) mice show several translationally relevant abnormalities in neural oscillatory activity associated with schizophrenia. These include deficits in sleep spindle density, sigma and alpha power, and 40-Hz task-evoked gamma power. The timing of these phenotypes suggests an impaired circadian process in these mice. Previously reported rapid eye movement sleep deficits in this model were not observed. These findings suggest mGluR5-enhancing drugs may improve sleep stability and sleep spindle density, which could impact memory and cognition.

Sleep spindle density is associated with worry in children with generalized anxiety disorder and healthy controls

BackgroundChildhood generalized anxiety disorder (GAD), characterized by uncontrollable worry, is associated with long-term psychopathology risk, yet understanding of developmental trajectories is limited. Despite common complaints about sleep, ‘macro’ sleep abnormalities have not been identified. Emerging findings suggest micro-architectural features of sleep, including sleep spindles, differentiate various psychiatric populations. The current study investigated sleep spindle density during non-rapid eye movement (NREM) sleep among youth with GAD and healthy controls, including relationships with anxiety, worry, global functioning, and subjective sleep quality. Methods58 pre-pubertal children, n = 26 with GAD and n = 32 matched healthy controls, aged 7–11 years (M = 8.86, SD=1.47), completed diagnostic assessments and a week of actigraphy monitoring prior to a night of polysomnography (PSG) either at home or in a sleep laboratory. NREM spindle activity was detected in frontal and central regions. ResultsSleep spindle activity did not differ based on diagnostic group or sex. Sleep spindles were unassociated with anxiety and sleep quality but showed a significant positive association with worry in all youth. Among youth with GAD, global functioning was negatively associated with spindle density in frontal regions during NREM stage 3. Spindle density was significantly greater during in-lab compared to at-home PSG. LimitationsThe small sample size and reliance on only one night of PSG necessitate additional studies. ConclusionsThe identified link between spindle activity and worry in pre-pubertal children highlights a need for investigations on transdiagnostic features of child psychopathology rather than specific disorders. Longitudinal studies are needed to explore spindle characteristics and affective risk across development.

BDNF Val66Met polymorphism moderates the association between sleep spindles and overnight visual recognition

A common single nucleotide polymorphism (SNP) of the brain-derived neurotrophic factor (BDNF) gene, Val66Met, has been reported to impair BDNF secretion and memory function. However, few studies have investigated the interaction of BDNF genotype and sleep characteristics, such as sleep spindles, that promote long-term potentiation during sleep. In this study we compared overnight visual memory between the carriers of BDNF Met and non-carriers (Val homozygotes), and examined how sleep spindle density associated with memory performance.The sample constituted of 151 adolescents (mean age 16.9 years; 69% Val homozygotes, 31% Met carriers). The learning task contained high and low arousal pictures from Interactive Affective Picture System. The learning task and all-night polysomnography were conducted at the homes of the adolescents. Slow (10–13 Hz) and fast (13–16 Hz) spindles were detected with automated algorithm.Neither post-sleep recognition accuracy nor spindle density differed between Val homozygotes and Met carriers. While frontal slow and fast spindle densities associated with better recognition accuracy in the entire sample, examining the allelic groups separately indicated paralleling associations in Val homozygotes only. Interaction analyses revealed a significant genotype-moderated difference in the associations between frontal fast sleep spindles and high arousal pictures.In sum, sleep spindles promote or indicate visual learning in Val homozygote adolescents but not in Met carriers. The result suggests that the role of sleep spindles in visual recognition memory is not equal across individuals but moderated by a common gene variant.