Slow Spindle Density Research Articles

Sleep-spindles as a marker of attention and intelligence in dogs

The sleep spindle-generating thalamo-cortical circuitry supports attention capacity in awake humans and animals, but using sleep spindles to predict differences in attention has not been tried in either. Of the more commonly examined cognitive correlates of spindle occurrence and amplitude, post-sleep recall, and general intelligence, only post-sleep recall had been studied in dogs, rats and mice. Here, we examined a sample of companion dogs (N = 58) for whom polysomnographic recordings and several cognitive tests were performed on two occasions each, with a three-month break in-between. Five of the tests were used to extract a factor analogous to human g (general mental ability). A sixth test in the battery measured sustained attention. Both attention and g-factor scores were predicted by higher slow spindle occurrence and absolute sigma power detected in polysomnographic recordings over the central electrode. These effects persisted across measurement occasions. Higher intrinsic spindle frequency was, in turn, linked to lower g-factor scores but displayed no relationship with attention scores. The overlap in localization and direction for the effects of slow spindle density (spindles/minute) and sigma power supports that they tap into the same underlying cognition-relevant aspects of spindling. Given earlier large sample and meta-analysis validations of sigma power as a reliable predictor of cognitive performance in humans, we thus conclude that the currently handled method for quantifying spindle density in dogs indeed measures cognition-relevant spindle activity by virtue of its agreement with the sigma power alternative.

Differences in the topographical distribution of sleep spindles among adult epilepsy with cognitive impairment.

Cognitive comorbidities are common in epilepsy; however, symptomatic treatment is currently the only available effective therapy. Sleep, cognition, and epilepsy are closely associated. Therefore, many studies on epilepsy and cognition have focused on sleep structures, such as sleep spindles, which are considered windows to understanding the sleeping brain. This study aimed to investigate the relationship between sleep spindles and the severity of cognitive impairment in adult epilepsy. Fifty-seven adults with epilepsy underwent overnight sleep electroencephalogram recordings and cognitive testing. Slow (9-12 Hz) and fast (12-15 Hz) spindle characteristics during N2 sleep were calculated using a convolutional neural network-based sleep staging system and automatic spindle detection algorithm. Repeated-measures analysis of variance was used to analyze differences in fast and slow spindle densities among subgroups of patients based on cognitive impairment severity. A significant between-group effect was observed for both slow and fast spindle densities. Multiple comparisons showed that slow and fast spindle densities of the severe cognitive impairment subgroup were lower than those of the noncognitive impairment subgroup (P < 0.05). Simple-effect analysis revealed differences in slow spindle density distributed among the EEG channels Fp1, Fp2, F3, C3, P4, O1, O2, F8, T4, T5, T6, Fz, and Cz (P < 0.05). Differences in fast spindle density were distributed among the channels Fp1, Fp2, F3, C3, O1, O2, F7, F8, T4, T5, T6, and Fz (P < 0.05). Significant differences in topographical distribution of fast and slow spindle densities were observed at the scalp level among patients with different cognitive statuses. Compared with patients with no cognitive impairment, those with severe cognitive impairment had lower slow and fast spindle densities over multiple scalp regions during N2 sleep. This study provides a reference for objective assessment of cognitive dysfunction in epilepsy patients.

Overnight declarative memory consolidation and non-rapid eye movement sleep electroencephalographic oscillations in older adults with obstructive sleep apnea.

To compare overnight declarative memory consolidation and non-rapid eye movement (NREM) sleep electroencephalogram (EEG) oscillations in older adults with obstructive sleep apnea (OSA) to a control group and assess slow-wave activity (SWA) and sleep spindles as correlates of memory consolidation. Forty-six older adults (24 without OSA and 22 with OSA) completed a word-pair associate's declarative memory task before and after polysomnography. Recall and recognition were expressed as a percentage of the morning relative to evening scores. Power spectral analysis was performed on EEG recorded at frontal (F3-M2, F4-M1) and central (C3-M2, C4-M1) sites. We calculated NREM absolute slow oscillation (0.25-1 Hz) and delta (0.5-4.5 Hz) EEG power, and slow (11-13 Hz) spindle density (number of events per minute of N2 sleep) and fast (13-16 Hz) spindle density. There were no significant differences in overnight recall and recognition between OSA (mean age 58.7 ± 7.1 years, apnea-hypopnea index (AHI) 41.9 ± 29.7 events/hour) and non-OSA (age 61.1 ± 10.3 years, AHI 6.6 ± 4.2 events/hour) groups. The OSA group had lower fast spindle density in the frontal region (p = 0.007). No between-group differences in SWA were observed. In the Control group, overnight recognition positively correlated with slow spindle density in frontal (rho = 0.555, p = 0.020) and central regions (rho = 0.490, p = 0.046). Overnight recall was not related to SWA or spindle measures in either group. Older adults with OSA had deficits in fast sleep spindles but showed preserved overnight declarative memory consolidation. It is possible that compensatory mechanisms are being recruited by OSA patients to preserve declarative memory consolidation despite the presence of sleep spindle deficits.

Sleep spindles changes in people with previous COVID-19 infection.

Stage 2 sleep spindles are considered useful biomarkers for the integrity of the central nervous system and for cognitive and memory skills. We investigated sleep spindles patterns in subjects after 12 months of their hospitalization in the intensive care unit (ICU) of the Padova Teaching Hospital due to COVID-19 between March and November 2020. Before the nap, participants (13 hospitalized in ICU - ICU; 9 hospitalized who received noninvasive ventilation - nonlCU; 9 age and sex-matched healthy controls - CTRL, i.e., not infected by COVID-19) underwent a cognitive and psychological as-sessment. During the nap, high-density electroencephalography (EEG) recordings were acquired. Slow (i.e., [9]-[12] Hz) and fast (i.e.,]12-16] Hz) spindles were automatically detected. Spindle density and spindle source reconstruction in brain grey matter were extracted. The psychological assessment revealed a statistical difference comparing CTRL and nonlCU in Beck Depression Inventory score and in the Physical Quality of Life index (pvalue = 0.03). The cognitive assessment revealed a trend of worsening results in executive functions in COVID-19 survivors. Slow spindle density significantly decreased comparing CTRL to COVID-19 survivors (pvalue= 0.001). There were statistically significant differences in EEG source-waveforms fast spindle amplitude onset among the three groups, mainly between CTRL and nonlCU. Clinical Relevance- Our results suggest that nonlCU were more susceptible to the hospitalization experience than ICU participants with a slight effect on cognitive tests. This impacted the spindle generation revealing a decreased density of slow spindles and affecting the generators of fast spindles in COVID-19 survivors especially in nonlCU.

The association between obstructive sleep apnea and sleep spindles in middle-aged and older men: a community-based cohort study.

Sleep spindles show morphological changes in obstructive sleep apnea (OSA). However, previous small studies have limited generalizability, leaving associations between OSA severity measures and spindle metrics uncertain. This study examined cross-sectional associations between OSA severity measures and spindle metrics among a large population-based sample of men. Community-dwelling men with no previous OSA diagnosis underwent home-based polysomnography. All-night EEG (F4-M1) recordings were processed for artifacts and spindle events identified using previously validated algorithms. Spindle metrics of interest included frequency (Hz), amplitude (µV2), overall density (11-16 Hz), slow density (11-13 Hz), and fast density (13-16 Hz) (number/minute). Multivariable linear regression models controlling for demographic, biomedical, and behavioral confounders were used to examine cross-sectional associations between OSA severity measures and spindle metrics. In adjusted analyses, higher apnea-hypopnea index (AHI/h, as a continuous variable) and percentage total sleep time with oxygen saturation <90% (TST90) were associated with decreased slow spindle density (AHI, B = -0.003, p = 0.032; TST90, B = -0.004, p = 0.047) but increased frequency (AHI, B = 0.002, p = 0.009; TST90, B = 0.002, p = 0.043). Higher TST90 was also associated with greater spindle amplitude (N2 sleep, B = 0.04, p = 0.011; N3 sleep, B = 0.11, p < 0.001). Furthermore, higher arousal index was associated with greater spindle amplitude during N2 sleep (B = 0.31, p < 0.001) but decreased overall density (B = -1.27, p = 0.030) and fast density (B = -4.36, p = 0.028) during N3 sleep. Among this large population-based sample of men, OSA severity measures were independently associated with spindle abnormalities. Further population studies are needed to determine associations between spindle metrics and functional outcomes.

P143 Sleep-dependent declarative memory consolidation and NREM sleep EEG oscillations in older adults with obstructive sleep apnea

Abstract Objectives To compare overnight declarative memory consolidation and NREM sleep EEG oscillations in older adults with OSA to an age-matched control group, and to assess the quantitative sleep EEG features as correlates of memory consolidation. Methods 46 participants (24 without OSA and 22 patients with OSA) were recruited. Participants completed a word-paired associates declarative memory task before and after an 8-hour sleep opportunity with full polysomnography. Power spectral analysis was performed on all-night EEG recorded at frontal and central electrode sites. We calculated slow wave activity (slow oscillations absolute power 0.25–1 Hz; and delta EEG power (0.5–4.5 Hz) in NREM sleep. Slow spindle density (11–13 Hz, events p/min) and fast spindle density (13–16 Hz, events p/min) in stage N2 was derived using an automated spindle detection algorithm. Results Patients with OSA showed no significant differences in overnight memory recall and recognition compared to individuals without OSA. The OSA group showed reduced slow spindle density at the central region and fast spindle density at the frontal region relative to controls. No differences were observed in SWA. Within group correlations showed slow and fast spindle density were correlated to percent recognition in the control group. Conclusion Older adults with OSA had deficits in slow and fast sleep spindles compared to controls. OSA patients showed preserved sleep-dependent declarative memory consolidation despite sleep fragmentation and intermittent hypoxemia. Sleep spindles were positively correlated with overnight memory consolidation in controls but not OSA patients. Targeted interventions to boost spindles may enhance memory consolidation in older adults.

P110 The association between sleep spindles and cognitive function in middle-aged and older men: A community-based study

Abstract Introduction The association between sleep spindles and cognitive function and the potential confounding influence of obstructive sleep apnea (OSA) remains uncertain. This study examined cross-sectional associations between sleep spindle metrics and cognitive function outcomes in community-dwelling men. Methods Men, Androgen, Inflammation, Lifestyle, Environment, and Stress (MAILES) study participants (n=477) underwent home-based polysomnography between 2010–2011 and completed the inspection time task, trail-making test A (TMT-A) and B (TMT-B), and Fuld object memory evaluation. Frontal spindle metrics derived from sleep electroencephalography included occurrence (total no. of sleep spindle events) and slow (11–13 Hz) and fast (13–16 Hz) spindle density (no./min) during N2 and N3 sleep. Results Men with OSA (any OSA and severe OSA) had significantly impaired sleep spindles (reduced occurrence and densities). In the complete study sample, higher spindle occurrence during N2 sleep was independently associated with faster inspection time (B= -0.44, 95% CI [-0.87, -0.02], p=0.041), whereas higher fast spindle density during N3 sleep was independently associated with worse TMT-B performance (B=20.7, 95% CI [0.55, 40.9], p=0.044). Furthermore, in men with severe OSA (apnea-hypopnea index ≥30/h), higher slow spindle density during N2 sleep was independently associated with worse TMT-A and TMT-B performance, whereas only higher spindle occurrence during N2 sleep was independently associated with worse TMT-A performance (all p&amp;lt;0.05). Discussion Specific spindle metrics during N2 and N3 sleep are independently associated with cognitive function in an unselected population of men and men with undiagnosed severe OSA. The utility of sleep spindles for predicting cognitive dysfunction and decline requires further investigation.

0672 The Effect Of Armodafinil On Sleep Spindles In Obstructive Sleep Apnea: Secondary Analysis Of A Randomized Placebo-controlled Trial

Abstract Introduction Armodafinil has been trialed in OSA patients to promote wakefulness and simulated driving performance. We have previously completed a 6-month trial of 150mg of armodafinil vs placebo in moderate-severe OSA patients not using CPAP (ACTRN# 12611000847910) observing that participants on armodafinil learned to perform better across a 90-minute driving simulator task faster than those on placebo. It is possible that this reduction in time-on-task decrement may have been due to increased learning on armodafinil. Sleep spindles have previously been implicated in procedural learning and neurobehavioral performance. We hypothesized that armodafinil increases sleep spindle events during NREM sleep to enhance learning. Methods Sixty-three overweight severe OSA patients (mean BMI: 32.3kg/m2 (26.1-42.5); age 53.1 years (28-71), 52 males) underwent overnight in-lab polysomnography at baseline (0 months) and at a 6-month follow-up. All-night EEG signals were analyzed using a previously validated automated spindle detection algorithm. EEG recordings were visually inspected by an experienced sleep physician (LE), who was blinded to drug allocation. To minimize the likelihood of type 1 error we selected three key spindle variables detected at Cz for analysis of change between 0 and 6 months: 1) total number of spindle events (11-16 Hz) in NREM sleep 2) density of slow spindles (≥11 to ≤ 13Hz) per minute of NREM sleep, and 3) fast spindle density in NREM (&amp;gt;13 to ≤ 16Hz). Results The change in total spindle count in NREM sleep (armodafinil=11.6 vs Placebo =-17.1, p=0.57), fast spindle density (armodafinil=0.06 vs Placebo =-0.02, p=0.63) and slow spindle density (armodafinil=-0.00 vs. Placebo =-0.03, p=0.74) were not increased by armodafinil. Conclusion If armodafinil enhances simulated driving performance in a way that suppresses time-on-task effects it does not appear to be through a sleep spindle enhancing mechanism. Armodafinil is probably not a pharmacological method of enhancing sleep spindles. Support World Sleep Society (International Sleep Research Training Program)CIRUS, Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, University of Sydney

Age-related differences and sexual dimorphism in canine sleep spindles

Non-REM bursts of activity in the sigma range (9–16 Hz) typical of sleep spindles predict learning in dogs, similar to humans and rats. Little is known, however, about the age-related changes in amplitude, density (spindles/minute) and frequency (waves/second) of canine spindles. We investigated a large sample (N = 155) of intact and neutered pet dogs of both sexes, varying in breed and age, searching for spindles in segments of non-REM sleep. We recorded EEG from both a frontal midline electrode (Fz) and a central midline electrode (Cz) in 55.5% of the dogs, in the remaining animals only the Fz electrode was active (bipolar derivation). A similar topography was observed for fast (≥13 Hz) spindle occurrence as in humans (fast spindle number, density on Cz > Fz). For fast spindles, density was higher in females, and increased with age. These effects were more pronounced among intact animals and on Fz. Slow spindle density declined and fast spindle frequency increased with age on Cz, while on Fz age-related amplitude decline was observed. The frequency of fast spindles on Fz and slow spindles on Cz was linked to both sex and neutering, suggesting modulation by sexual hormones. Intact females displayed higher frequencies than males and neutered females. Our findings support the argument that sigma bursts in the canine non-REM sleep are analogous to human sleep spindles, and suggest that slow and fast spindles display different trajectories related to age, of which an increase in frontal fast spindles is unique to dogs.

Association of inattention with slow-spindle density in sleep EEG of children with attention deficit-hyperactivity disorder

ObjectiveWe evaluated the power of slow sleep spindles during sleep stage 2 to clarify their relationship with executive function, especially with attention, in children with attention deficit-hyperactivity disorder (ADHD). MethodsSubjects were 21 children with ADHD and 18 aged-matched, typically developing children (TDC). ADHD subjects were divided into groups of only ADHD and ADHD + autism spectrum disorder (ASD). We employed the Continuous Performance Test (CPT) to measure attention. We focused on sleep spindle frequencies (12–14 Hz) in sleep stage 2 and performed a power spectral analysis using fast Fourier transform techniques and compared sleep spindles with the variability of reaction time in CPT. ResultsIn the CPT, reaction variabilities in ADHD and ADHD + ASD significantly differed from those in TDC. Twelve-hertz spindles were mainly distributed in the frontal pole and frontal area and 14-Hz spindles in the central area. The ratio of 12-Hz frontal spindle power was higher in ADHD than in TDC, especially in ADHD + ASD. Significant correlation between the ratio of 12-Hz spindles and reaction time variability was observed. ConclusionsTwelve-hertz frontal spindle EEG activity may have positive associations with sustained attention function. Slow frontal spindles may be useful as a biomarker of inattention in children with ADHD.

Early childhood adversity associations with nightmare severity and sleep spindles

ObjectiveChildhood adversity figures prominently in the clinical histories of children and adolescents suffering from a panoply of physical, mental or sleep disorders, including posttraumatic stress disorder. But the nature and prevalence of early adversity in the case of idiopathic nightmare-prone individuals have received little study. We characterize the types and frequencies of self-reported childhood adversity for nightmare-prone individuals using the developmentally sensitive Traumatic Antecedents Questionnaire (TAQ) and assess relationships between separation adversity and sleep spindles. MethodThe TAQ was administered to 73 non-treatment-seeking volunteers with frequent idiopathic nightmares and 67 healthy controls. Nightmare severity, anxiety, depression, alexithymia and past and present sleep disorders were also assessed. Sleep was recorded with polysomnography (PSG) for 90 participants and sleep spindles were assessed for 63. ResultsNightmare-prone participants scored higher on most TAQ measures, including adversity at 0–6 years of age. TAQ-derived scales assessing traumatic and nontraumatic forms of adversity were both elevated for nightmare-prone participants; for 0–6 year estimates, nontraumatic adversity was associated with nightmares independent of trauma adversity. Group differences were only partially mediated by current psychopathology symptoms and were largely independent of nightmare frequency but not of nightmare distress. Adversity/nightmare relationships were graded differentially for the two study groups. Separation adversity at 0–6 years of age correlated with current sleep spindle anomalies—in particular, lower slow spindle density—an anomaly known to index both psychopathology and early nightmare-onset. ConclusionsSelf-reported adversity occurring as young as 0–6 years of age is associated with nightmare severity and sleep spindle anomalies. Adversity-linked nightmares may reflect pathophysiological mechanisms common also to the nightmares of pre-clinical and full-blown post-traumatic stress disorder.

Developmental changes of sleep spindles and their impact on sleep-dependent memory consolidation and general cognitive abilities: A longitudinal approach.

Sleep spindles are related to sleep‐dependent memory consolidation and general cognitive abilities. However, they undergo drastic maturational changes during adolescence. Here we used a longitudinal approach (across 7 years) to explore whether developmental changes in sleep spindle density can explain individual differences in sleep‐dependent memory consolidation and general cognitive abilities. Ambulatory polysomnography was recorded during four nights in 34 healthy subjects (24 female) with two nights (baseline and experimental) at initial recording (age range 8–11 years) and two nights at follow‐up recording (age range 14–18 years). For declarative learning, participants encoded word pairs with a subsequent recall before and after sleep. General cognitive abilities were measured by the Wechsler Intelligence Scale. Higher slow (11–13 Hz) than fast (13–15 Hz) spindle density at frontal, central, and parietal sites during initial recordings, followed by a shift to higher fast than slow spindle density at central and parietal sites during follow‐up recordings, suggest that mature spindle topography develops throughout adolescence. Fast spindle density increases from baseline to experimental night were positively related to sleep‐dependent memory consolidation. In addition, we found that the development of fast spindles predicted the improvement in memory consolidation across the two longitudinal measurements, a finding that underlines a crucial role for mature fast spindles for sleep‐dependent memory consolidation. Furthermore, slow spindle changes across adolescence were related to general cognitive abilities, a relationship that could indicate the maturation of frontal networks relevant for efficient cognitive processing. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=7NXJzm8HbIw and https://www.youtube.com/watch?v=iuMQY1OIJ0s

Sleep spindles are altered in early- but not late-onset nightmare recallers

Nightmares are a common sleep disorder, defined as highly disturbing mentation which usually awakens the individual from rapid eye movement (REM) sleep. While nightmares are mainly a REM sleep phenomenon, Picard-Deland et al., (2017) recently showed an association between nightmare recall and sleep spindles, which are a non-rapid eye movement (NREM) oscillatory feature. Their results pointed to fewer slow spindles and a higher oscillatory frequency for fast spindles among frequent nightmare recallers compared with controls. To test the suggestion that nightmares stem from changes to emotional neural circuits arising in early childhood (Nielsen, 2017), including early changes in sleep spindles (Scholle et al., 2007), we investigated if the spindle features of early-onset nightmare recallers (ie, recalling nightmares since childhood) (N = 22), differed from those of late-onset nightmare recallers (ie, since adolescence or adulthood) (N = 11), or from those of controls (N = 23). A retrospective analysis of the sleep spindles of 56 participants who had undergone a polysomnographically-recorded morning nap revealed that Early starters uniquely exhibited lower slow spindle densities in five of six derivations (all p < 0.045) and higher fast spindle frequencies in all six derivations (all p < 0.015). These results add precision to previously reported findings for Nightmare recallers: spindle differences are shown to hold only for Early starters. The lifelong occurrence of nightmares may be closely tied to disruptions in the normal development of spindle generation processes occurring early in development.

Reliability of sleep spindle measurements in adolescents: How many nights are necessary?

Evidence of night-to-night variation in adolescent sleep spindle characteristics is lacking. Twelve adolescents (M=15.8±0.8years, eight males) participated in a laboratory study involving 9 nights with 10hr sleep opportunity. Sleep electroencephalograph was analysed and intra-class coefficients calculated to determine the reliability of sleep spindles across multiple nights of recording. Slow spindle amplitude and fast spindle density, duration and amplitude characteristics all had acceptable reliability within a single night of sleep recording. Slow spindle density and duration measurements needed a minimum of 4 and 2 nights, respectively, for reliable estimation. Theoretical and methodological implications are discussed.

Efficacy of slow oscillatory-transcranial direct current stimulation on EEG and memory - contribution of an inter-individual factor.

Despite many reports on beneficial effects of anodal slow oscillatory-transcranial direct current stimulation (so-tDCS) during non-rapid eye movement (NREM) sleep on memory consolidation, frequent negative outcomes have also been observed. Our working hypothesis is that so-tDCS efficacy is strongly dependent upon the susceptibility of the underlying network. One component determining susceptibility of the network is hypothesized to be reflected in learning or 'task-induced' plastic changes. Another component is hypothesized to represent inter-individual confounds. Twenty-five (15 female) healthy students participated in two learning conditions with and without so-tDCS during early nocturnal NREM sleep and in one control condition without learning tasks. So-tDCS was applied in five 5-min blocks. EEG was assessed during two time windows: an acute period with five 1-min epochs after each stimulation block and a 150-min post-stimulation time period. Inter-individual differences were assessed by a memory quotient (MQ) and subjects classified into high- vs. low-scoring groups. Although so-tDCS was efficient in enhancing fast spindle parameters in the 150-min time period in all subjects, so-tDCS failed to modulate memory consolidation. In contrast, in subjects with a high MQ, memory retention on a figural paired-associate task was significantly increased after so-tDCS. Task-induced slow spindle density was modulated in the opposite direction in subjects with high vs. low MQ being increased in the high-MQ group only. Effects of so-tDCS on EEG were limited to fast spindle modulations in both time windows. These results reveal that inter-individual confound can impact so-tDCS efficacy, suggesting potential use of such factors as biomarkers.

Investigation of sleep spindle activity and morphology as predictors of neurocognitive functioning in medicated patients with schizophrenia.

Neurocognitive impairment is a trait marker of schizophrenia, but no effective treatment has yet been identified. Sleep spindle deficits have been associated with diminished sleep-dependent memory learning. We examined whether this link could be extended into various cognitive domains by investigating the association of a neurocognitive test battery (the Brief Assessment of Cognition in Schizophrenia) with sleep spindle activity and morphology. We examined 37 outpatients diagnosed with schizophrenia and medicated with both antipsychotics and benzodiazepines. Participants underwent 1 night polysomnography and test of neurocognitive functioning. We identified and analysed sleep spindles in all non-rapid eye movement sleep and in non-rapid eye movement sleep stage 2 in a central electroencephalography channel using an automatic sleep spindle detector previously validated. Slow sleep spindle density was computed from a frontal electroencephalography channel as well. We found no association between cognitive functioning and sleep spindle density or sleep spindle morphology for spindles in non-rapid eye movement sleep when controlling for gender, age, symptom severity, and daily dose of antipsychotics and benzodiazepines. For spindles in non-rapid eye movement sleep stage 2, we found that motor speed was associated with frontal slow sleep spindle density. We conclude that frontal slow spindle density might predict motor speed in medicated patients with schizophrenia, but that no other sleep spindle activity or sleep spindle morphology measures were predictors of neurocognitive functioning.

Fast sleep spindle density is associated with rs4680 (Val108/158Met) genotype of catechol-O-methyltransferase (COMT).

Sleep spindles are a hallmark of NREM stage 2 sleep. Fast sleep spindles correlate with cognitive functioning and are reduced in schizophrenia. Although spindles are highly genetically determined, distinct genetic mechanisms influencing sleep spindle activity have not been identified so far. Spindles are generated within a thalamocortical network. Dopaminergic neurotransmission modulates activity within this network and importantly depends on activity of catechol-O-methyltransferase (COMT). We aimed at testing whether the common functional rs4680 (Val108/158Met) polymorphism of COMT modulates fast spindle activity in healthy participants. In 150 healthy participants (93 women, 57 men; mean age 30.9 ± 11.6 years) sleep spindle density was analyzed during the second of two nights of polysomnography. We investigated the effect of the COMT Val108/158Met genotype on fast spindle density in whole-night NREM sleep stages N2 and N3. As predicted, higher Val allele dose correlates with reduced fast spindle density. Additional exploratory analysis of the effect of COMT genotype revealed that slow spindle density in heterozygote participants was lower than that of both homozygote groups. Morphological characteristics of fast and slow spindles did not show significant differences between genotypes. COMT genotype had also no significant effect on measures of general sleep quality. This is the first report of a distinct gene effect on sleep spindle density in humans. As variation in the COMT Val108/158Met polymorphism is associated with differential expression of fast spindles in healthy participants, genetically determined dopaminergic neurotransmission may modulate spindle oscillations during NREM sleep. DRKS00008902.

Sleep spindle and psychopathology characteristics of frequent nightmare recallers

Idiopathic nightmares are a common disturbance of rapid eye movement sleep (REM) sleep, but studies of comorbid pathologies and sleep architecture suggest that non-REM (NREM) sleep is also affected. Sleep spindles are a NREM sleep characteristic associated with both pathophysiology and sleep-dependent memory consolidation, yet they have not been evaluated in frequent nightmare recallers. The morning naps of 38 participants with frequent idiopathic nightmares (mean age: 23.7 ± 3.78 years) and 25 age- and sex-matched controls (23.9 ± 3.65 years) were recorded and their sleep evaluated. A custom spindle detector assessed NREM sleep stage 2 (N2) sleep spindles on six electroencephalogram (EEG) derivations (F3, F4, C3, C4, O1, and O2) for density (number spindles/N2 time), mean frequency, and amplitude. Total spindles (10–16 Hertz (Hz) range), slow spindles (10–12.79 Hz), and fast spindles (12.8–16 Hz) were all assessed separately. Compared with the Control group, the Nightmare group had longer N2 sleep latency and a marginally greater %N2 sleep. The Nightmare group also had a lower than normal density of slow spindles in most EEG derivations, a higher density of fast spindles in frontal derivations, and an elevated fast spindle oscillatory frequency—“faster fast” spindles—mainly in central derivations. These differences withstood controls for pre-existing group differences in depression. Correlational analyses demonstrated a further pattern of group differences by which higher pathology scores were associated with higher slow spindle densities and slower spindle frequencies for the Nightmare but not the Control group. A similar pattern was observed for some dream content measures, ie, the Nightmare group showed positive correlations of slow spindle density with dreamed fear and word count and negative correlations with dreamed positive emotion. Conversely, the Control group showed opposite trends. Results thus demonstrate abnormalities in the composition of N2 sleep—and especially in N2 spindles—among frequent nightmare recallers and link these abnormalities to both trait (psychopathology) and state (dream content) factors. Spindle findings for psychopathology resemble, but are not identical with, previous findings for patients with major depression, social anxiety, and schizophrenia and are thus consistent with an explanation implicating spindles as trait markers of psychopathology. Correlational analyses go beyond a trait explanation to suggest several possible state-based explanations involving memory consolidation mechanisms, specifically, the possibility that spindles index either emotional or verbal task-based processes.

P384 The role of sleep spindles in overnight verbal memory consolidation in temporal lobe epilepsy patients

Introduction Declarative memory performance and hippocampal functioning are highly associated. Learning induced memory consolidation results in an increased coupling between mesial temporal lobe, thalamus and frontal areas during sleep, resulting in the increase of sleep spindles and slow wave sleep. Our aim was to investigate the modulatory effect of learning on sleep spindles in temporal lobe epilepsy (TLE) patients and to see whether the association between declarative memory consolidation and sleep parameters are altered. Materials and methods We administered three modified versions of the Rey Auditory Verbal Learning Task to TLE patients (n = 22) on three consecutive nights undergoing video-EEG monitoring. Delayed recall was measured 30 min after learning, memory retention was measured in the following morning. Sleep stages were detected manually, sleep spindles were detected with an automated threshold-cutting method based on individually adjusted slow and fast sleep spindle frequency values. Fast and slow sleep spindle density, duration and amplitude were correlated with both online and offline learning. Results Online learning scores showed positive correlation with slow spindle duration, density and amplitude, and a negative correlation with fast spindle density and duration. On the contrary, memory retention scores showed a negative relationship with slow spindle density, duration and amplitude. Conclusion Our results indicate that learning and overnight memory consolidation related sleep spindles are compromised by the pathological process.

NREM sleep spindles are associated with dream recall

Both rapid eye movement (REM) sleep dreaming and non-rapid eye movement (NREM) sleep spindles have been linked to processes of memory consolidation. However, relationships between the two phenomena have yet to be explored. In a heterogeneous sample of 53 healthy subjects who had participated in a memory consolidation protocol and who varied in their self-reported recall of dreams and nightmares, we assessed overnight polysomnography, N2 sleep spindle density, REM dream word count, and retrospective estimates of how often they recall dreams, bad dreams (dysphoric dreams, no awakening), and nightmares (dysphoric dreams, with awakenings). Fast spindle density positively correlated with all measures of dream recall but was most robustly associated with bad dream recall and REM dream word count. Correlations with bad dream recall were particularly strong for spindles occurring in sleep cycles 2 and 3 and correlations with word count for cycles 1, 4, and 5. While slow spindle density showed opposite correlation...