Fast Spindles Research Articles

High-density EEG sleep correlates of cognitive and affective impairment at 12-month follow-up after COVID-19

ObjectiveTo disentangle the pathophysiology of cognitive/affective impairment in Coronavirus Disease-2019 (COVID-19), we studied long-term cognitive and affective sequelae and sleep high-density electroencephalography (EEG) at 12-month follow-up in people with a previous hospital admission for acute COVID-19. MethodsPeople discharged from an intensive care unit (ICU) and a sub-intensive ward (nonICU) between March and May 2020 were contacted between March and June 2021. Participants underwent cognitive, psychological, and sleep assessment. High-density EEG recording was acquired during a nap. Slow and fast spindles density/amplitude/frequency and source reconstruction in brain gray matter were extracted. The relationship between psychological and cognitive findings was explored with Pearson correlation. ResultsWe enrolled 33 participants ( 17 nonICU) and 12 controls. We observed a lower Physical Quality of Life index, higher post-traumatic stress disorder (PTSD) score, and a worse executive function performance in nonICU participants. Higher PTSD and Beck Depression Inventory scores correlated with lower executive performance. The same group showed a reorganization of spindle cortical generators. ConclusionsOur results show executive and psycho-affective deficits and spindle alterations in COVID-19 survivors – especially in nonICU participants – after 12 months from discharge. SignificanceThese findings may be suggestive of a crucial contribution of stress experienced during hospital admission on long-term cognitive functioning.

Spindle-slow oscillation coupling correlates with memory performance and connectivity changes in a hippocampal network after sleep.

After experiences are encoded, post‐encoding reactivations during sleep have been proposed to mediate long‐term memory consolidation. Spindle–slow oscillation coupling during NREM sleep is a candidate mechanism through which a hippocampal‐cortical dialogue may strengthen a newly formed memory engram. Here, we investigated the role of fast spindle‐ and slow spindle–slow oscillation coupling in the consolidation of spatial memory in humans with a virtual watermaze task involving allocentric and egocentric learning strategies. Furthermore, we analyzed how resting‐state functional connectivity evolved across learning, consolidation, and retrieval of this task using a data‐driven approach. Our results show task‐related connectivity changes in the executive control network, the default mode network, and the hippocampal network at post‐task rest. The hippocampal network could further be divided into two subnetworks of which only one showed modulation by sleep. Decreased functional connectivity in this subnetwork was associated with higher spindle–slow oscillation coupling power, which was also related to better memory performance at test. Overall, this study contributes to a more holistic understanding of the functional resting‐state networks and the mechanisms during sleep associated to spatial memory consolidation.

Topographical relocation of adolescent sleep spindles reveals a new maturational pattern in the human brain

Current theories of human neural development emphasize the posterior-to-anterior pattern of brain maturation. However, this scenario leaves out significant brain areas not directly involved with sensory input and behavioral control. Suggesting the relevance of cortical activity unrelated to sensory stimulation, such as sleep, we investigated adolescent transformations in the topography of sleep spindles. Sleep spindles are known to be involved in neural plasticity and in adults have a bimodal topography: slow spindles are frontally dominant, while fast spindles have a parietal/precuneal origin. The late functional segregation of the precuneus from the frontoparietal network during adolescence suggests that spindle topography might approach the adult state relatively late in development, and it may not be a result of the posterior-to-anterior maturational pattern. We analyzed the topographical distribution of spindle parameters in HD-EEG polysomnographic sleep recordings of adolescents and found that slow spindle duration maxima traveled from central to anterior brain regions, while fast spindle density, amplitude and frequency peaks traveled from central to more posterior brain regions. These results provide evidence for the gradual posteriorization of the anatomical localization of fast sleep spindles during adolescence and indicate the existence of an anterior-to-posterior pattern of human brain maturation.

The adolescent pattern of sleep spindle development revealed by HD-EEG.

Sleep spindles are developmentally relevant cortical oscillatory patterns; however, they have mostly been studied by considering the entire spindle frequency range (11-15 Hz) without a distinction between the functionally and topographically different slow and fast spindles, using relatively few electrodes and analysing wide age-ranges. Here, we employ high-density night sleep electroencephalography in three age-groups between 12 and 20 years of age (30 females and 30 males) and analyse the adolescent developmental pattern of the four major parameters of slow and fast sleep spindles. Most of our findings corroborate those very few previous studies that also make a distinction between slow and fast spindles in their developmental analysis. We find spindle frequency increasing with age. A spindle density change is not obvious in our study. We confirm the declining tendencies for amplitude and duration, although within narrower, more specific age-windows than previously determined. Spindle frequency seems to be higher in females in the oldest age-group. Based on the pattern of our findings, we suggest that high-density electroencephalography, specifically targeting slow and fast spindle ranges and relatively narrow age-ranges would advance the understanding of both adolescent cortical maturation and development and the functional relevance of sleep spindles in general.

The association between overnight recognition accuracy and slow oscillation-spindle coupling is moderated by BDNF Val66Met

During sleep, memories are consolidated via oscillatory events that occur in temporal and phasic synchrony. Several studies show that sleep spindles peaking close to the depolarized positive peaks of slow oscillations (SO) associate with better retention of memories. The exact timing of this synchrony presumably depends on the properties of the related neural network that, in turn, is affected by certain genetic variants associated with brain development and function. Brain-derived neurotrophic factor (BDNF) Val66Met and Catechol‐O‐methyltransferase (COMT) Val158Met are repeatedly reported to implicate the structure and function of prefrontal and hippocampal areas as well as molecular events promoting synaptic plasticity. In this study, we examined with a community-based sample of 153 adolescents (~17 years) whether these variants (1) affected the coupling properties between frontal SOs and spindles and (2) moderated the association between SO-spindle coupling and overnight recognition accuracy. We found SO-upstate-coupled fast (> 13 Hz) sleep spindles to associate with better recognition in the whole sample. Additionally, Val66Met moderated this association such that SO-spindle coupling was predictive of memory outcome only in those homozygous to ValBDNF alleles but not in MetBDNF carriers. Memory outcome was not associated with the SO-coupling properties of slow spindles nor affected by the interaction between Val158Met and coupling measures. Finally, in the whole sample we found that SO-upstate-coupled fast spindles were more strongly associated with the recognition of positive, relative to neutral, pictures. In conclusion, precise coupling of SOs and fast spindles associates with overnight recognition accuracy and this association is moderated by BDNF Val66Met.

A sleep schedule incorporating naps benefits the transformation of hierarchical knowledge.

Study ObjectivesThe learning brain establishes schemas (knowledge structures) that benefit subsequent learning. We investigated how sleep and having a schema might benefit initial learning followed by rearranged and expanded memoranda. We concurrently examined the contributions of sleep spindles and slow-wave sleep to learning outcomes.MethodsFifty-three adolescents were randomly assigned to an 8 h Nap schedule (6.5 h nocturnal sleep with a 90-minute daytime nap) or an 8 h No-Nap, nocturnal-only sleep schedule. The study spanned 14 nights, simulating successive school weeks. We utilized a transitive inference task involving hierarchically ordered faces. Initial learning to set up the schema was followed by rearrangement of the hierarchy (accommodation) and hierarchy expansion (assimilation). The expanded sequence was restudied. Recall of hierarchical knowledge was tested after initial learning and at multiple points for all subsequent phases. As a control, both groups underwent a No-schema condition where the hierarchy was introduced and modified without opportunity to set up a schema. Electroencephalography accompanied the multiple sleep opportunities.ResultsThere were main effects of Nap schedule and Schema condition evidenced by superior recall of initial learning, reordered and expanded memoranda. Improved recall was consistently associated with higher fast spindle density but not slow-wave measures. This was true for both nocturnal sleep and daytime naps.ConclusionA sleep schedule incorporating regular nap opportunities compared to one that only had nocturnal sleep benefited building of robust and flexible schemas, facilitating recall of the subsequently rearranged and expanded structured knowledge. These benefits appear to be strongly associated with fast spindles.Clinical Trial registrationNCT04044885 (https://clinicaltrials.gov/ct2/show/NCT04044885).

Optimal spindle detection parameters for predicting cognitive performance.

Alterations in sleep spindles have been linked to cognitive impairment. This finding has contributed to a growing interest in identifying sleep-based biomarkers of cognition and neurodegeneration, including sleep spindles. However, flexibility surrounding spindle definitions and algorithm parameter settings present a methodological challenge. The aim of this study was to characterize how spindle detection parameter settings influence the association between spindle features and cognition and to identify parameters with the strongest association with cognition. Adult patients (n = 167, 49 ± 18 years) completed the NIH Toolbox Cognition Battery after undergoing overnight diagnostic polysomnography recordings for suspected sleep disorders. We explored 1000 combinations across seven parameters in Luna, an open-source spindle detector, and used four features of detected spindles (amplitude, density, duration, and peak frequency) to fit linear multiple regression models to predict cognitive scores. Spindle features (amplitude, density, duration, and mean frequency) were associated with the ability to predict raw fluid cognition scores (r = 0.503) and age-adjusted fluid cognition scores (r = 0.315) with the best spindle parameters. Fast spindle features generally showed better performance relative to slow spindle features. Spindle features weakly predicted total cognition and poorly predicted crystallized cognition regardless of parameter settings. Our exploration of spindle detection parameters identified optimal parameters for studies of fluid cognition and revealed the role of parameter interactions for both slow and fast spindles. Our findings support sleep spindles as a sleep-based biomarker of fluid cognition.

Slow waves contribute to memory consolidation only in older adults without sleep‐disordered breathing

AbstractBackgroundSleep‐dependent memory consolidation, which is thought to rely on the dialogue between the hippocampus and the medial prefrontal cortex (mPFC) during NREM sleep, is mediated by slow waves (SW) and sleep spindles. Some studies indicate that this process is impaired in ageing but also in sleep‐disordered breathing (SDB), a very common sleep disorder in ageing. In this study, we investigated sleep‐dependent memory consolidation in older adults with or without SDB and explored the underlying mechanisms.MethodBaseline data of 57 cognitively unimpaired older adults (mean age ± SD: 68.6 ± 3.3 years) from the Age‐Well cohort were analysed. Participants underwent a structural MRI scan to obtain mPFC and hippocampal grey matter volumes, and performed a visuospatial memory task until reaching a learning criterion of 66.6% of correct answers. Post‐learning sleep was monitored using polysomnography, and delayed recall was probed the next morning. An overnight change in memory performance (OCMP) was computed as follows: (recall performance – learning performance) / learning performance. SW, slow and fast spindles during N2 and N3 sleep were automatically detected using the SleepTrip toolbox. Based on the standard apnea‐hypopnea index (AHI) cutoff of 15 events/h, participants were classified as having SDB (SDB+, n=47) or not (SDB‐, n=10).ResultThere was no between‐group difference in OCMP, as well as in amplitude, duration and frequency of SW, slow and fast spindles (p>0.05). However, we found a significant group by SW density interaction after controlling for age, sex, education, total sleep time and trait‐anxiety (p=0.03). Thus, a positive association was only found between SW density and OCMP in the SDB‐ group (p=0.02; Fig 1). No correlation was found between slow or fast spindle density and OCMP in either group. Finally, mPFC and hippocampal volumes did not differ between SDB+ and SDB‐ participants (p>0.05), but SW density positively correlated with the volume of the mPFC (p=0.01; Fig 2).ConclusionOur findings suggest that the contribution of SW to sleep‐dependent memory consolidation is impaired in participants with SDB and incriminate the mPFC. We plan to conduct connectivity and SW‐spindle coupling analyses to unravel the functional substrates of this deficit.

A role for inflammaging in α-synuclein-associated breakdown of local sleep in the elderly.

Inflammatory cascades accompany α-synuclein overexpression in brain aging. Sleep spindles, neural oscillations supporting memory and neuroplasticity, are also vulnerable to the effects of aging. However, relationships between α-synuclein, chronic central inflammation, and age-related sleep spindle deficits remain unexplored. Here, we examined relationships between glial activation, α-synuclein, and local sleep spindle expression during non-rapid eye movement (NREM) sleep. Polysomnography with 256-channel electroencephalography (EEG) was conducted on 58 cognitively unimpaired older adults (61.4±6.3 years, 38 female). Absolute fast spindle power (FSP; 13-16Hz) during NREM sleep was obtained from EEG data using multitaper spectral analysis. Cerebrospinal fluid (CSF) biomarkers were measured using exploratory Roche NeuroToolKit assays (automated robust prototype immunoassays, Roche Diagnostics International Ltd). Measurements of soluble triggering receptor expressed on myeloid cells 2 (sTREM2, denoting microglial activation), α-synuclein (denoting neurodegeneration), and glial fibrillary acidic protein (GFAP, denoting astrocytic activation) were correlated with FSP across scalp topography, after normalizing sTREM2 (log(x)) and α-synuclein (1/x). These correlations were corrected for multiple comparisons using threshold-free cluster enhancement (TFCE; 5000 permutations). PROCESSv3.5 (model 6, SPSS) was used to test indirect effects of age, inflammation, and α-synuclein on FSP, controlling for apnea-hypopnea index (AHI), sex, and time between CSF draw and sleep study. FSP was correlated with GFAP (Pearson's r=-0.325, p<0.05), log10(sTREM2) (r=-0.327, p<0.05), and 1/α-synuclein (r=0.503, p<0.001), with associations overlapping at 13 fronto-central derivations [Fig. 1-3]. This overlap was unique and specific to the 13-16Hz range. Supporting the association between α-synuclein and synaptic degeneration, log10(neurogranin), a marker of synaptic integrity, was associated with both 1/α-synuclein (r=-0.821, p<0.001) and FSP (r=-0.421, p=0.001). A serial mediation modeled from age to GFAP, 1/α-synuclein, and averaged FSP [Fig. 4], showed a significant, unstandardized indirect effect of -0.00186310 (5000-sample bootstrapped 99% confidence interval [-0.00518986, -0.00004027]). Another serial mediation modeled from age to log10(sTREM2), 1/α-synuclein, and averaged FSP [Fig. 4], revealed a significant, unstandardized indirect effect of -0.00298193 (bootstrapped 99% confidence interval [-0.00732707, -0.00015208]). Microglial and astrocytic activation in aging may disrupt fronto-central fast spindle expression through individual associations with α-synuclein-related synaptic degeneration. Contextualizing these findings with age-related accumulation of other neuropathologies, and associated cognitive impairments, requires further work. Support: R56AG052698, P50AG033514.

P.0490 Lower fast spindle density is associated with insomnia with short sleep duration (

P.0490 Lower fast spindle density is associated with insomnia with short sleep duration (<6 hours) and poorer executive functioning

Altered sleep spindles and slow waves during space shuttle missions

Sleep deficiencies and associated performance decrements are common among astronauts during spaceflight missions. Previously, sleep in space was analyzed with a focus on global measures while the intricate structure of sleep oscillations remains largely unexplored. This study extends previous findings by analyzing how spaceflight affects characteristics of sleep spindles and slow waves, two sleep oscillations associated with sleep quality and quantity, in four astronauts before, during and after two Space Shuttle missions. Analysis of these oscillations revealed significantly increased fast spindle density, elevated slow spindle frequency, and decreased slow wave amplitude in space compared to on Earth. These results reflect sleep characteristics during spaceflight on a finer electrophysiological scale and provide an opportunity for further research on sleep in space.

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.

Motor Learning Promotes the Coupling between Fast Spindles and Slow Oscillations Locally over the Contralateral Motor Network.

Recent studies from us and others suggest that traditionally declarative structures mediate some aspects of the encoding and consolidation of procedural memories. This evidence points to the existence of converging physiological pathways across memory systems. Here, we examined whether the coupling between slow oscillations (SO) and spindles, a mechanism well established in the consolidation of declarative memories, is relevant for the stabilization of human motor memories. To this aim, we conducted an electroencephalography study in which we quantified various parameters of these oscillations during a night of sleep that took place immediately after learning a visuomotor adaptation (VMA) task. We found that VMA increased the overall density of fast (≥12Hz), but not slow (<12Hz), spindles during nonrapid eye movement sleep, stage 3 (NREM3). This modulation occurred rather locally over the hemisphere contralateral to the trained hand. Although adaptation learning did not affect the density of SOs, it substantially enhanced the number of fast spindles locked to the active phase of SOs. The fact that only coupled spindles predicted overnight memory retention points to the relevance of this association in motor memory consolidation. Our work provides evidence in favor of a common mechanism at the basis of the stabilization of declarative and motor memories.

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.

P051 SLEEP SPINDLES AND SWA DIFFERENTIALLY CORRELATE WITH OVERNIGHT EPISODIC AND VISUOSPATIAL MEMORY CONSOLIDATION IN OLDER ADULTS WITH AND WITHOUT MILD COGNITIVE IMPAIRMENT

Abstract Introduction Sleep microarchitecture disruption is a feature of ageing that is further altered in neurodegenerative disorders. Sleep-memory links in younger adults have been established, however mechanistic pathways of this uncoupling in ageing is poorly understood. Method Our sample consisted of n=46 mild cognitively impaired (MCI) older adults and n=32 cognitively-intact controls who underwent overnight polysomnography and episodic (Rey Auditory Verbal Learning test) and visuospatial (Rey-Osterrieth Complex Figure task) memory tasks that were administered before and after sleep. We examined group differences in overnight memory % retention and associations with NREM slow oscillations (SO, 0.25–1 Hz), delta power (0.5–4 Hz), N2 spindle events (occurrence [11–16 Hz] and slow [11–13 Hz] and fast [13–16 Hz] spindle density p/min) and REM theta power (4.5–8 Hz). Results Repeated measures ANCOVA, controlling for age, indicated greater memory scores in Controls compared to MCI on the episodic task, F=6.7 (p=.01), and no group differences in the visuospatial task (F=1.8, p=.17). In Controls, greater delta power was associated with increased episodic memory retention (r=.515, p=.006). In the MCI group, episodic memory was associated with fast spindle density (r=-.352, p=.04), and visuospatial memory was also associated with fast spindle density (r=-.385, p=.01) and spindle occurrence (r=-.479, p=.003). Conclusion Sleep spindles appear to be negatively associated with memory retention, specifically in MCI. However, given the heterogeneity of MCI, further analysis of its cognitive subtypes is warranted. Comprehensive cognitive and neural pathophysiology profiling are required to better delineate the function of spindles in ageing.

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.

The effect of zolpidem on targeted memory reactivation during sleep.

According to the active system consolidation theory, memory consolidation during sleep relies on the reactivation of newly encoded memory representations. This reactivation is orchestrated by the interplay of sleep slow oscillations, spindles, and theta, which are in turn modulated by certain neurotransmitters like GABA to enable long-lasting plastic changes in the memory store. Here we asked whether the GABAergic system and associated changes in sleep oscillations are functionally related to memory reactivation during sleep. We administered the GABAA agonist zolpidem (10 mg) in a double-blind placebo-controlled study. To specifically focus on the effects on memory reactivation during sleep, we experimentally induced such reactivations by targeted memory reactivation (TMR) with learning-associated reminder cues presented during post-learning slow-wave sleep (SWS). Zolpidem significantly enhanced memory performance with TMR during sleep compared with placebo. Zolpidem also increased the coupling of fast spindles and theta to slow oscillations, although overall the power of slow spindles and theta was reduced compared with placebo. In an uncorrected exploratory analysis, memory performance was associated with slow spindle responses to TMR in the zolpidem condition, whereas it was associated with fast spindle responses in placebo. These findings provide tentative first evidence that GABAergic activity may be functionally implicated in memory reactivation processes during sleep, possibly via its effects on slow oscillations, spindles and theta as well as their interplay.

Sleep and Inhibitory Control Over Mood-Congruent Information in Emerging Adults With Depressive Disorder.

Accumulating evidence has suggested bidirectionality between sleep problems and depression, but the underlying mechanism is unclear. We assessed the role of sleep in inhibitory control ability with emotional stimuli, which has been shown to be suboptimal among individuals with depression and proposed to perpetuate depressive symptoms. Emerging adults (aged 18-25 years, 64.6% female) were screened for depressive and other mental disorders by structured clinical interview and questionnaire. Individuals with depressive disorders were assigned to have a polysomnography-monitored daytime sleep opportunity (Sleep-Dep, n = 20), whereas nondepressed individuals were randomized to either have daytime sleep (Sleep-Ctrl, n = 27) or stay awake (Wake-Ctrl, n = 18). Participants completed the Affective Go/No-Go Task two times, separated by experimental conditions. A factorial model with a between-subject factor (Sleep-Dep/Sleep-Ctrl/Wake-Ctrl) and a within-subject factor (test 1/test 2) was used to assess if the groups differed in inhibitory control across test sessions, as inferred by changes in d-prime and false alarm rates (FA). Results from mixed factorial models showed a significant interaction effect between time and group on FA in the block with neutral faces as the target and happy faces as the nontarget (F(2,61) = 5.15, pfdr = .045). Although Sleep-Dep had decreased FA after sleep (t(19) = 2.94, pfdr = .050), Sleep-Ctrl and Wake-Ctrl had no significant between-session changes (p values > .05). Postsleep improvement in FA in Sleep-Dep correlated with longer stage 2 sleep (r(20) = 0.788, pfdr < .001) and stage 2 fast spindle number at O1 (r(18) = 0.692, pfdr = .015). Sleep gain, particularly stage 2 sleep and related physiology, potentially enhances inhibitory control ability responding to emotional information among individuals with depressive disorders.

Changes in sleep structure and sleep spindles are associated with the neuropsychiatric profile in paradoxical insomnia

AimSleep spindles have an important role in the pathophysiology and perception of sleep. We aimed to investigate the link between sleep spindles and microstructural architecture of sleep in regard to psychiatric characteristics in paradoxical insomnia. MethodA total of 40 participants (20 with paradoxical insomnia, 20 healthy controls) were included in the study. All participants were evaluated by somnologists and undergone a full-night polysomnography at sleep laboratory. In addition, psychiatric interview was made by the same psychiatrist, and questionnaires were performed to assess the dimensions of the personality such as the neuroticism or extroversion (Eysenck Personality Questionnaire, EPQR-A); to evaluate the tendency to exaggerate somatic perceptions (Somatosensory Amplification Scale, SSAS), somatic parts of dissociation (Somatoform Dissociation Questionnaire, SDQ-20), and somatization (Somatization Scale, SS); to measure participants' feelings about their health and disease anxiety (Health Anxiety Inventory, HAI-18), and the level of uncontrollable and persistent anxiety (Penn State Worry Questionnaire, PSWQ); to investigate the tendency to ruminative thinking (Ruminative Thought Style Questionnaire, RTSQ), alexithymia (Toronto Alexithymia Scale, TAS-20); and to define the presence and the severity of depressive symptoms (Beck Depression Inventory, BDI). ResultsThe duration and frequency of the sleep spindles were similar between two groups, while the density was significantly decreased in paradoxical insomnia. The duration of sleep spindles, on the other hand, showed positive correlations with the extroversion dimension scores of EPQR-A and PSWQ scores. DiscussionSleep protective mechanisms are disturbed in paradoxical insomnia as shown by the lower density of sleep spindles. In addition, fast spindle activity is associated with the personality traits, characterized by an increase in the expression of feelings and the level of anxiety.

Increased spindle density correlates with sleep continuity improvements following an eight-week course of a melatonin agonist in people with depression: A proof-of-concept study with agomelatine.

Sleep fragmentation and reductions in sleep spindles have been observed in individuals with depression. Sleep spindles are known to play a protective role for sleep, and there are indications that melatonin agents can enhance spindles in healthy people. Whether agomelatine, a melatonin agonist indicated for the treatment of depression, may increase spindle density sufficiently to impact sleep continuity in people with depression remains unknown. This proof-of-concept study investigated changes in spindles following agomelatine intake in young adults with depression and assessed how they may relate to potential changes in sleep continuity and depressive symptoms. This study was based on an open-label design. Fifteen participants between 17 and 28years of age (mean=22.2; standard deviation [SD]=3.4) with a diagnosis of a depressive disorder underwent polysomnography before and after an intervention including a 1hr psychoeducation session centered on sleep and circadian rhythms, and an 8-week course of agomelatine (25-50mg) with a guided sleep phase advance. Fast spindle density significantly increased from pre- to post-intervention. This increase in spindle density significantly correlated with a reduction in wake after sleep onset, and a similar trend was found with increased sleep efficiency. There was no significant correlation between spindle parameters and depressive symptoms. These findings suggest that agomelatine may contribute to enhanced sleep consolidation, possibly in part through the modulation of spindle production. This should be confirmed by larger randomized control trials.