Fast Spindles Research Articles

Scalp and hippocampal sleep correlates of memory function in drug-resistant temporal lobe epilepsy.

Seminal animal studies demonstrated the role of sleep oscillations such as cortical slow waves, thalamocortical spindles, and hippocampal ripples in memory consolidation. In humans, whether ripples are involved in sleep-related memory processes is less clear. Here, we explored the interactions between sleep oscillations (measured as traits) and general episodic memory abilities in 26 adults with drug-resistant temporal lobe epilepsy who performed scalp-intracranial electroencephalographic recordings and neuropsychological testing, including two analogous hippocampal-dependent verbal and nonverbal memory tasks. We explored the relationships between hemispheric scalp (spindles, slow waves) and hippocampal physiological and pathological oscillations (spindles, slow waves, ripples, and epileptic spikes) and material-specific memory function. To differentiate physiological from pathological ripples, we used multiple unbiased data-driven clustering approaches. At the individual level, we found material-specific cerebral lateralization effects (left-verbal memory, right-nonverbal memory) for all scalp spindles (rs > 0.51, ps < 0.01) and fast spindles (rs > 0.61, ps < 0.002). Hippocampal epileptic spikes and short pathological ripples, but not physiological oscillations, were negatively (rs > -0.59, ps < 0.01) associated with verbal learning and retention scores, with left lateralizing and antero-posterior effects. However, data-driven clustering failed to separate the ripple events into defined clusters. Correlation analyses with the resulting clusters revealed no meaningful or significant associations with the memory scores. Our results corroborate the role of scalp spindles in memory processes in patients with drug-resistant temporal lobe epilepsy. Yet, physiological and pathological ripples were not separable when using data-driven clustering, and thus our findings do not provide support for a role of sleep ripples as trait-like characteristics of general memory abilities in epilepsy.

The influence of cognitive activity on subsequent daytime nap: A deep neural network model based on sleep spindles

ObjectivesUnderstanding the influence of cognitive activity on subsequent sleep has both theoretical and applied implications. This study aims to investigate the effect of pre-sleep cognitive activity, in the context of avoiding emotional interference, on macro-sleep and sleep spindles. MethodsIn a within-subjects design, participants’ sleep electroencephalography was collected in both the with and without pre-sleep cognitive activity conditions. Subsequent macro-sleep (i.e., sleep stage distribution and sleep parameters) and spindle characteristics (i.e., density, amplitude, duration, and frequency) were analyzed. In addition, a novel machine learning framework (i.e., deep neural network, DNN) was used to discriminate between cognitive activity and control conditions. ResultsThere were no significant differences in macro-sleep and sleep spindles between the cognitive activity and control conditions. Spindles-based DNN models achieved over 96% accuracy in differentiating between the two conditions, with fast spindles performing better than full-range and slow spindles. ConclusionsThese results suggest a weak but positive effect of pre-sleep cognitive activity on subsequent sleep. It sheds light on a possible low-cost and easily accessible sleep intervention strategy for clinical and educational purposes.

Right-lateralized sleep spindles are associated with neutral over emotional bias in picture recognition: An overnight study.

Sleep is especially important for emotional memories, although the mechanisms for prioritizing emotional content are insufficiently known. As during waking, emotional processing during sleep may be hemispherically asymmetric; right-lateralized rapid-eye movement (REM) sleep theta (~4-7 Hz) is reportedly associated with emotional memory retention. No research exists on lateralized non-REM sleep oscillations. However, sleep spindles, especially when coupled with slow oscillations (SOs), facilitate off-line memory consolidation.Our primary goal was to examine how the lateralization (right-to-left contrast) of REM theta, sleep spindles, and SO-spindle coupling is associated with overnight recognition memory in a task consisting of neutral and emotionally aversive pictures. Thirty-two healthy adults encoded 150 target pictures before overnight sleep. The recognition of target pictures among foils (discriminability, d') was tested immediately, 12 hours, and 24 hours after encoding.Recognition discriminability between targets and foils was similar for neutral and emotional pictures in immediate and 12-h retrievals. After 24 hours, emotional pictures were less accurately discriminated (p < 0.001). Emotional difference at 24-h retrieval was associated with right-to-left contrast in frontal fast spindle density (p < 0.001). The lateralization of SO-spindle coupling was associated with higher neutral versus emotional difference across all retrievals (p = 0.004).Our findings contribute to a largely unstudied area in sleep-related memory research. Hemispheric asymmetry in non-REM sleep oscillations may contribute to how neutral versus emotional information is processed. This is presumably underlain by both mechanistic offline memory consolidation and a trait-like cognitive/affective bias that influences memory encoding and retrieval. Methodological choices and participants' affective traits are likely involved.

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.

The association between sleep spindles and cognitive function in middle-aged and older men from a community-based cohort study

ObjectivesPrevious studies examining associations between sleep spindles and cognitive function attempted to account for obstructive sleep apnea without consideration for potential moderating effects. To elucidate associations between sleep spindles, cognitive function, and obstructive sleep apnea, this study of community-dwelling men examined cross-sectional associations between sleep spindle metrics and daytime cognitive function outcomes following adjustment for obstructive sleep apnea and potential obstructive sleep apnea moderating effects. MethodsFlorey Adelaide Male Ageing Study participants (n = 477, 41-87 years) reporting no previous obstructive sleep apnea diagnosis underwent home-based polysomnography (2010-2011). Cognitive testing (2007-2010) included the inspection time task (processing speed), trail-making tests A (TMT-A) (visual attention) and B (trail-making test-B) (executive function), and Fuld object memory evaluation (episodic memory). Frontal spindle metrics (F4-M1) included occurrence (count), average frequency (Hz), amplitude (µV), and overall (11-16 Hz), slow (11-13 Hz), and fast (13-16 Hz) spindle density (number/minute during N2 and N3 sleep). ResultsIn fully adjusted linear regression models, lower N2 sleep spindle occurrence was associated with longer inspection times (milliseconds) (B = −0.43, 95% confidence interval [−0.74, −0.12], p = .006), whereas higher N3 sleep fast spindle density was associated with worse TMT-B performance (seconds) (B = 18.4, 95% confidence interval [1.62, 35.2], p = .032). Effect moderator analysis revealed that in men with severe obstructive sleep apnea (apnea-hypopnea index ≥30/hour), slower N2 sleep spindle frequency was associated with worse TMT-A performance (χ2 = 12.5, p = .006). ConclusionsSpecific sleep spindle metrics were associated with cognitive function, and obstructive sleep apnea severity moderated these associations. These observations support the utility of sleep spindles as useful cognitive function markers in obstructive sleep apnea, which warrants further longitudinal investigation.

0086 Good quality sleep facilitates psychomotor learning via fast spindles among older adults

Abstract Introduction Sleep spindles are neural oscillations of frequency between 11 to 16 Hz during non rapid eye movement sleep. They are coordinated with hippocampal ripples and slow oscillations to facilitate memory consolidation by modulating synaptic plasticity. Fast spindles, predominant in central and parietal derivations of EEG during Stage 2 NREM sleep, are associated with overnight visuomotor skills enhancement, especially in the later part of the night. The relationship between fast and slow spindles during sleep and psychomotor ability has not been characterized well, particularly in older adults. The objective of this study was to study the relationship between sleep microstructure during various stages of sleep and cognition in good and poor sleepers. Methods This is a cross sectional observational study conducted on 16 male participants (age 63.6 ± 5.22 years). Good (n=9) and poor sleepers (n=7) were classified on the basis of PSQI score (&amp;lt;=5 is good). Overnight polysomnography was done and ICMR-NCTB battery was administered for assessment of cognition. In DOMINO software, after visual artifact removal, spindles were analyzed by selecting 11 - 12.99 Hz (slow) in F4, and 13 -16 Hz (fast) in C2. Statistical analysis was done using GraphPad prism (v 9.4.1). Results Fast spindle index in N2 (good sleeper: r = -0.850, p = 0.006; poor sleeper: r = 0.398, p = 0.466), fast spindle density in N2 (good sleeper: r = -0.870, p = 0.004; poor sleeper: r = -0.331, p = 0.468), total fast spindle number during deep sleep (good sleeper: r = -0.600, p = 0.031; poor sleeper: r = -0.244, p = 0.599), and total slow spindle density (good sleeper: r = -0.833, p = 0.025; poor sleeper: r = -0.080, p = 0.865) were found to be negatively correlated with psychomotor ability assessed by trail making test. Conclusion Among older adults, good sleepers, as compared to poor sleepers overall have a higher fast spindle index and density during N2 sleep and there is significant correlation with better psychomotor ability. Support (if any) All India Institute of Medical Sciences and University College of London Collaborative Grant (AIIMS-UCL 12)

Associations of Baseline Sleep Microarchitecture with Cognitive Function After 8 Years in Middle-Aged and Older Men from a Community-Based Cohort Study.

Prospective studies examining associations between baseline sleep microarchitecture and future cognitive function recruited from small samples with predominantly short follow-up. This study examined sleep microarchitecture predictors of cognitive function (visual attention, processing speed, and executive function) after 8 years in community-dwelling men. Florey Adelaide Male Ageing Study participants (n=477) underwent home-based polysomnography (2010-2011), with 157 completing baseline (2007-2010) and follow-up (2018-2019) cognitive assessments (trail-making tests A [TMT-A] and B [TMT-B] and the standardized mini-mental state examination [SMMSE]). Whole-night F4-M1 sleep EEG recordings were processed following artifact exclusion, and quantitative EEG characteristics were obtained using validated algorithms. Associations between baseline sleep microarchitecture and future cognitive function (visual attention, processing speed, and executive function) were examined using linear regression models adjusted for baseline obstructive sleep apnoea, other risk factors, and cognition. The final sample included men aged (mean [SD]) 58.9 (8.9) years at baseline, overweight (BMI 28.5 [4.2] kg/m2), and well educated (75.2% ≥Bachelor, Certificate, or Trade), with majorly normal baseline cognition. Median (IQR) follow-up was 8.3 (7.9, 8.6) years. In adjusted analyses, NREM and REM sleep EEG spectral power was not associated with TMT-A, TMT-B, or SMMSE performance (all p>0.05). A significant association of higher N3 sleep fast spindle density with worse TMT-B performance (B=1.06, 95% CI [0.13, 2.00], p=0.026) did not persist following adjustment for baseline TMT-B performance. In this sample of community-dwelling men, sleep microarchitecture was not independently associated with visual attention, processing speed, or executive function after 8 years.

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.

Bridging the Gap between Psychiatry and Neurology: Alzheimer's disease- symptoms beyond memory impairment

It is increasingly recognized that there is significant heterogeneity in phenotype and clinical trajectories in Alzheimer's disease.Up to 25% of Alzheimer's disease (AD) cases do not show the typical neuropathology. Recently subtypes and atypical non-amnestic AD presentations have been formalized in the International Working Group (IWG) clinical diagnosis criteria. Clinical diagnosis of atypical AD has significantly been improved by the availability of biomarkers, including cerebrospinal fluid levels of Aβ42, total tau (t-tau) and phosphorylated tau181 (p-tau), MRI volumetric estimation of hippocampal and medial temporal atrophy, and amyloid brain PET imaging. Special attention will be given to language variant of Alzheimer's disease. A predominant deficit in the language domain is a key feature of primary progressive aphasia but language impairment is commonly present in Alzheimer's disease. International diagnostic criteria for PPA and its three variants (agrammatic, logopenic, semantic) were published in 2011. Since then, studies have investigated the validity of these criteria in classifying patients which includes clinical symptoms, neurocognitive presentations, distinct MRI signatures, and neuropathological differences. In this session special attention will be given of logopenic PPA a syndrome frequently seen in atypical Alzheimer's disease. Even though Alzheimer's disease is most notable for memory impairment, language impairments are also found early in the disease course. Indeed, neuropsychological testing shows changes in confrontation naming and semantic fluency. However, there is an additional body of research that shows that changes in spontaneous language, including idea density, speech quantity, fluency, and tempo can differentiate between normal aging and Alzheimer's disease.A physiologic sleep pattern is essential in the process of memory formation. Inadequate sleep results in cognitive impairment. MCI has an increased rate of sleeping problems compared to healthy people of the same age. In MCI, primary sleep disorders like sleep-disordered breathing, PLMS, RLS, RBD are more common, and also associated with a high rate of progression from MCI to AD. MCI also showed shorter total sleep time (longer in non-amnestic MCI), sleep efficiency, and cyclic alternating pattern. There is increased nighttime behavior. EEG power in amnestic MCI showed a reduction in the power of delta and theta frequency. There is a reduction in fast spindle counts on frontal location. Blunted and delayed onset with a duration of REM sleep reduced. A growing body of evidence supports the hypothesis that people with sleep disorders have a higher risk of developing Alzheimer's disease AD. Insomnia, self-reported sleep disturbances, decline in sleep duration, impaired sleep consolidation, delayed or decreased circadian rhythms and sleep-disordered breathing have been shown to increase AD risk, supporting the hypothesis that a chronically disrupted sleep-wake cycle can drive AD pathogenesis. Associations of sleep disorders and neurodegeneration in Alzheimer's are complex. Its understanding however is crucial for proper AD prevention, diagnosis, as well as management.Psychosis is a core syndrome in other than Alzheimer's disease and neurodegenerative disorders. It is however present in a large percentage of patients with AD. Psychosis most commonly presents as a delusional process and is linked to disruptive behavior, rapid progression, and overall morbidity. Psychotic syndromes in AD are complex but necessary to be diagnosed and managed properly.

An infant sleep electroencephalographic marker of thalamocortical connectivity predicts behavioral outcome in late infancy

Infancy represents a critical period during which thalamocortical brain connections develop and mature. Deviations in the maturation of thalamocortical connectivity are linked to neurodevelopmental disorders. There is a lack of early biomarkers to detect and localize neuromaturational deviations, which can be overcome with mapping through high-density electroencephalography (hdEEG) assessed in sleep. Specifically, slow waves and spindles in non-rapid eye movement (NREM) sleep are generated by the thalamocortical system, and their characteristics, slow wave slope and spindle density, are closely related to neuroplasticity and learning. Spindles are often subdivided into slow (11.0-13.0 Hz) and fast (13.5-16.0 Hz) frequencies, for which not only different functions have been proposed, but for which also distinctive developmental trajectories have been reported across the first years of life. Recent studies further suggest that information processing during sleep underlying sleep-dependent learning is promoted by the temporal coupling of slow waves and spindles, yet slow wave-spindle coupling remains unexplored in infancy. Thus, we evaluated three potential biomarkers: 1) slow wave slope, 2) spindle density, and 3) the temporal coupling of slow waves with spindles. We use hdEEG to first examine the occurrence and spatial distribution of these three EEG features in healthy infants and second to evaluate a predictive relationship with later behavioral outcomes. We report four key findings: First, infants’ EEG features appear locally: slow wave slope is maximal in occipital and frontal areas, whereas slow and fast spindle density is most pronounced frontocentrally. Second, slow waves and spindles are temporally coupled in infancy, with maximal coupling strength in the occipital areas of the brain. Third, slow wave slope, fast spindle density, and slow wave-spindle coupling are not associated with concurrent behavioral status (6 months). Fourth, fast spindle density in central and frontocentral regions at age 6 months predicts overall developmental status at age 12 months, and motor skills at age 12 and 24 months. Neither slow wave slope nor slow wave-spindle coupling predict later behavioral development. We further identified spindle frequency as a determinant of slow and fast spindle density, which accordingly, also predicts motor skills at 24 months. Our results propose fast spindle density, or alternatively spindle frequency, as early EEG biomarker for identifying thalamocortical maturation, which can potentially be used for early diagnosis of neurodevelopmental disorders in infants. These findings are in support of a role of sleep spindles in sensorimotor microcircuitry development. A crucial next step will be to evaluate whether early therapeutic interventions may be effective to reverse deviations in identified individuals at risk.

Sleep electroencephalogram (EEG) oscillations and associated memory processing during childhood and early adolescence.

The architecture of sleep undergoes distinct changes during childhood and early adolescence. Slow wave sleep is involved in memory processing and may support active consolidation of newly encoded representations to support the formation of abstracted "gist" memories. Here, we examined sleep and overnight memory formation in German school children (n = 33) between 7 and 15 years of age, after the encoding phase of a verbal Deese-Roediger-McDermott (DRM) task. Effects of age were analyzed on sleep electroencephalogram (EEG) signatures of memory processing during nonrapid eye movement (NonREM) sleep, and the overnight formation of veridical and gist-based memories. Increasing age decreases time spent in slow wave sleep, and slow wave activity, whereas density and amplitude of fast sleep spindles in NonREM sleep were increased. Moreover, fast spindles were more consistently and more closely coupled to the upstate of the slow oscillation in the older children. Also, veridical and gist-based recall of words after sleep increased with age. Notably, a closer slow oscillation upstate-fast spindle coupling predicted veridical recall of words, and this relationship was found independent of age. Memory performance in the sleeping children did not differ from that of an age-matched control group (n = 32) tested over a daytime wake retention interval, with adolescents even showing superior veridical recall after wake. Our findings suggest that slow oscillation-spindle coupling as a mechanism of sleep-dependent memory formation becomes increasingly relevant during childhood and early adolescence. However, wake-associated mechanisms similarly effective in forming medium-term memory exist in this age as well. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Sleep spindles in the healthy brain from birth through 18 years.

Sleep spindles are present from birth and reflect cognitive functions across the lifespan, but normative values for this cognitive biomarker across development are lacking. This study aims to establish normative spindle features over development. All available normal 19-channel electroencephalograms from developmentally normal children between February 2002 and June 2021 in the MGH EEG lab were analyzed. Approximately, 20 000 spindles were hand-marked to train and validate an automated spindle detector across ages. Normative values for spindle rate, duration, frequency, refractory period, and interhemispheric lag are provided for each channel and each age. Sleep EEGs from 567 developmentally normal children (range 0 days to 18 years) were included. The detector had excellent performance (F1 = 0.47). Maximal spindle activity is seen over central regions during infancy and adolescence and frontopolar regions during childhood. Spindle rate and duration increase nonlinearly, with the most rapid changes during the first 4 months of life and between ages 3 and 14 years. Peak spindle frequency follows a U-shaped curve and discrete frontal slow and central fast spindles are evident by 18 months. Spindle refractory periods decrease between ages 1 and 14 years while interhemispheric asynchrony decreases over the first 3 months of life and between ages 1 and 14 years. These data provide age- and region-specific normative values for sleep spindles across development, where measures that deviate from these values can be considered pathological. As spindles provide a noninvasive biomarker for cognitive function across the lifespan, these normative measures can accelerate the discovery and diagnosis in neurodevelopmental disorders.

Differential thalamocortical interactions in slow and fast spindle generation: A computational model.

Cortical slow oscillations (SOs) and thalamocortical sleep spindles are two prominent EEG rhythms of slow wave sleep. These EEG rhythms play an essential role in memory consolidation. In humans, sleep spindles are categorized into slow spindles (8-12 Hz) and fast spindles (12-16 Hz), with different properties. Slow spindles that couple with the up-to-down phase of the SO require more experimental and computational investigation to disclose their origin, functional relevance and most importantly their relation with SOs regarding memory consolidation. To examine slow spindles, we propose a biophysical thalamocortical model with two independent thalamic networks (one for slow and the other for fast spindles). Our modeling results show that fast spindles lead to faster cortical cell firing, and subsequently increase the amplitude of the cortical local field potential (LFP) during the SO down-to-up phase. Slow spindles also facilitate cortical cell firing, but the response is slower, thereby increasing the cortical LFP amplitude later, at the SO up-to-down phase of the SO cycle. Neither the SO rhythm nor the duration of the SO down state is affected by slow spindle activity. Furthermore, at a more hyperpolarized membrane potential level of fast thalamic subnetwork cells, the activity of fast spindles decreases, while the slow spindles activity increases. Together, our model results suggest that slow spindles may facilitate the initiation of the following SO cycle, without however affecting expression of the SO Up and Down states.

Age-related changes in fast spindle clustering during non-rapid eye movement sleep and their relevance for memory consolidation.

Sleep plays a crucial role in memory consolidation. Recent data in rodents and young adults revealed that fast spindle band power fluctuates at a 0.02-Hz infraslow scale during non-rapid eye movement (NREM) sleep. These fluctuations result from a periodic temporal clustering of spindles and may modulate sleep maintenance and memory consolidation. With age, sleep undergoes substantial changes but age-related changes in spindle clustering have never been investigated. Polysomnography data were collected in 147 older (mean age ± SD: 69.3 ± 4.1 years) and 32 young-middle aged (34.5 ± 10.9 years) adults. Sleep-dependent memory consolidation was assessed in a subsample of 57 older adults using a visuospatial memory task. We analyzed power fluctuations in fast spindle frequency band, detected fast spindles, and quantified their clustering during the night separating encoding and retrieval. Fast spindle band power fluctuated at a 0.02-Hz infraslow scale in young-middle aged and older adults. However, the proportion of clustered fast spindles decreased non-linearly with age (p < .001). This effect was not mediated by NREM sleep fragmentation. The clustering level of fast spindles modulated their characteristics (p < .001). Finally, the mean size of spindle clusters was positively associated with memory consolidation (p = .036) and negatively with NREM sleep micro-arousal density (p = .033). These results suggest that clusters of fast spindles may constitute stable sleep periods promoting off-line processes such as memory consolidation. We emphasize the relevance of considering spindle dynamics, obviously impaired during aging, to understand the impact of age-related sleep changes on memory. Clinical Trial Information: Name: Study in Cognitively Intact Seniors Aiming to Assess the Effects of Meditation Training (Age-Well). URL: https://clinicaltrials.gov/ct2/show/NCT02977819?term=Age-Well&draw=2&rank=1. See STROBE_statement_AGEWELL.doc in supplementary material. Registration: EudraCT: 2016-002441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819.

O005 Overnight consolidation of spatial navigation memories is impaired in Mild Cognitive Impairment and is associated with loss of sleep spindles and hippocampal subfield volumes

Abstract Introduction Allocentric spatial navigation (SN) is considered a measure for conversion from mild cognitive impairment (MCI) to Alzheimer’s disease. NREM sleep slow waves and spindles, and hippocampal volume (HV) are impaired in MCI, however their relationship with SN overnight memory consolidation (OMC) is unknown. This study aimed to examine: 1) SN OMC in MCI, and, 2) associations between SN OMC and NREM oscillations and HV. Methods Cognitively-intact (n=25), non-amnestic MCI (naMCI, n=22) and amnestic-MCI (aMCI, n=10) older adults completed neuropsychological assessment, neuroimaging, overnight routine and high-density EEG polysomnography (hdEEG subset; controls=17, MCI=8). Slow oscillations, slow wave activity, slow and fast spindle density and power were computed. OMC% was calculated by: ([post-sleep error score/pre-sleep error score]*100) from a familiar and novel (allocentric) location. Right CA1, dentate gyrus (DG) and entorhinal cortex were computed using ASHS software. Results MCI performed worse on familiar location-OMC% compared to controls (Cohens d= -.67, p= .016). aMCI performed worse on allocentric-OMC% compared to controls (omega2= .09, p= .032). Reduced spindles were associated with worse allocentric-OMC% in aMCI (frontal-slow spindles [rho= -.782 p= .008], parietal-fast spindles [rho= -.576, p= .082]). Using hdEEG, widespread fast spindle and allocentric-OMC% associations were indicated in MCI. Reduced right HV (DG [r= -.453, p= .023], CA1 [r= -.426, p= .068]) was related to worse allocentric-OMC% in MCI. Discussion In MCI, SN OMC is impaired, with worse consolidation associated with spindle and right HV loss. Future studies should examine whether SN OMC and spindles capture conversion to Alzheimer’s disease in ‘at-risk’ older adults.

O070 Longitudinal associations of sleep microarchitecture with future cognitive function in middle-aged and older men from a community-based cohort study

Abstract Study objectives Prospective studies examining associations of sleep microarchitecture with future cognitive function predominantly recruited from small samples with relatively short follow-up. Therefore, this study examined sleep microarchitecture predictors of cognitive function (visual attention, processing speed, and executive function) after 8–10 years in community-dwelling middle-aged and older men. Methods Of 433 Florey Adelaide Male Ageing Study participants who underwent home-based polysomnography (2010–2011), 157 completed baseline and follow-up cognitive testing. Whole-night F4-M1 sleep EEG recordings were processed following artefact exclusion, and quantitative EEG features obtained using validated algorithms. Trail-making tests A (TMT-A) and B (TMT-B) were administered at baseline (2007–2010) and follow-up (2018–2019) examinations. Linear regression models were adjusted for baseline obstructive sleep apnea, demographic, biomedical, and behavioural factors, and cognitive performance. Results At baseline, participants were aged mean (SD) 58.9 (8.9) years with normal cognition. In unadjusted models only, lower REM sleep delta and higher alpha power were associated with worse TMT-A performance at follow-up (delta, B= -0.02, 95% CI [-0.04, -0.001], p=0.042; alpha, B=0.08, 95% CI [0.01, 0.15], p=0.024). Lower overall and slow sleep spindle density in N2 and N3 were associated with worse TMT-A performance at follow-up (all p&amp;lt;0.05). The association of higher fast spindle density in N3 with worse TMT-B performance (B =1.06, 95% CI [0.13, 2.00], p=0.026) was not significant after adjustment for baseline cognition. Conclusions In this sample of community-dwelling middle-aged and older men with normal baseline cognition, sleep microarchitecture parameters were not independently associated with cognitive function after 8–10 years.

Analysis of slow and fast sleep spindle properties in Parkinson's disease – A comparative EEG study

Study objectivesSleep disturbances and altered sleep macrostructure are common in Parkinson's disease (PD). Few studies have addressed the changes in sleep spindle (SS) properties in this movement disorder so far. SS seem to be fundamental of both sleep architecture and memory consolidation. The aim of our comparative study was to investigate the changes of SS characteristics in PD, and reveal the relationship between SS properties and cognitive function. MethodsWe investigated 20 PD patients and 18 age-matched controls. All participants underwent a 24-hour-long polygraphic EEG recording after extensive clinical investigation. We detected slow and fast SS properties automatically using individual adjusting method (IAM). The data were statistically evaluated. ResultsWe found significantly lower fast spindle amplitude in PD comparing with controls. We did not find significant differences in SS densities, duration and oscillatory frequency between the groups. We detected significant positive correlation between fast SS amplitude and memory in PD, and between fast SS density and retrograde memory in controls. The total Addenbrooke's cognitive score correlated negatively with slow SS density and duration in controls. ConclusionsBy the time clinical diagnosis of PD is established, the pathological process is already spreading. Changes in sleep macrostructure and SS properties might become a useful biomarker of the neurodegenerative process in PD. In addition, decreased fast SS amplitude might predict further cognitive deterioration and indicate early involvement of corresponding cortical area. Our study results strengthen the importance of EEG examination in PD, and the use of IAM method in SS analysis.

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.

Focal epilepsy disrupts spindle structure and function

Sleep spindles are the hallmark of N2 sleep and are attributed a key role in cognition. Little is known about the impact of epilepsy on sleep oscillations underlying sleep-related functions. This study assessed changes in the global spindle rate in patients with epilepsy, analysed the distribution of spindles in relation to the epileptic focus, and performed correlations with neurocognitive function. Twenty-one patients with drug-resistant focal epilepsy (12 females; mean age 32.6 ± 10.7 years [mean ± SD]) and 12 healthy controls (3 females; 24.5 ± 3.3 years) underwent combined whole-night high-density electroencephalography and polysomnography. Global spindle rates during N2 were lower in epilepsy patients compared to controls (mean = 5.78/min ± 0.72 vs. 6.49/min ± 0.71, p = 0.02, d = − 0.70). Within epilepsy patients, spindle rates were lower in the region of the epileptic focus compared to the contralateral region (median = 4.77/min [range 2.53–6.18] vs. 5.26/min [2.53–6.56], p = 0.02, rank biserial correlation RC = − 0.57). This decrease was driven by fast spindles (12–16 Hz) (1.50/min [0.62–4.08] vs. 1.65/min [0.51–4.28], p = 0.002, RC = − 0.76). The focal reduction in spindles was negatively correlated with two scales of attention (r = − 0.54, p = 0.01; r = − 0.51, p = 0.025). Patients with focal epilepsy show a reduction in global and local spindle rates dependent on the region of the epileptic focus. This may play a role in impaired cognitive functioning. Future work will show if the local reduction in spindles can be used as potential marker of the epileptic focus.

Association of polygenic risk for schizophrenia with fast sleep spindle density depends on pro-cognitive variants

Cognitive impairment is a common feature in schizophrenia and the strongest prognostic factor for long-term outcome. Identifying a trait associated with the genetic background for cognitive outcome in schizophrenia may aid in a deeper understanding of clinical disease subtypes. Fast sleep spindles may represent such a biomarker as they are strongly genetically determined, associated with cognitive functioning and impaired in schizophrenia and unaffected relatives. We measured fast sleep spindle density in 150 healthy adults and investigated its association with a genome-wide polygenic score for schizophrenia (SCZ-PGS). The association between SCZ-PGS and fast spindle density was further characterized by stratifying it to the genetic background of intelligence. SCZ-PGS was positively associated with fast spindle density. This association mainly depended on pro-cognitive genetic variants. Our results strengthen the evidence for a genetic background of spindle abnormalities in schizophrenia. Spindle density might represent an easily accessible marker for a favourable cognitive outcome which should be further investigated in clinical samples.