Slow Oscillation-spindle Coupling Research Articles

Electrophysiological Mechanisms of Memory Consolidation in Human Non-rapid Eye Movement Sleep

Abstract Purpose of Review Pioneering work in rodents has shown that the reactivation of recently acquired memories during sleep is a key mechanism underlying the beneficial effect of sleep on memory consolidation. In this review, we consider recent evidence of memory reactivation processes in human sleep. Recent Findings The precise temporal coupling of sleep spindles to slow oscillations during non-rapid eye movement sleep plays a central role in sleep-associated memory consolidation. Both correlational studies and studies directly manipulating oscillatory activity in the sleeping brain have confirmed that spindles coupled to slow oscillations are better predictors of memory than uncoupled spindles and that the greatest memory benefit comes when spindles are tightly coupled to the up-state of the slow oscillation. Recent evidence suggests that memory content is reactivated during sleep, with a functional benefit for memory performance after sleep. Reactivation events are time-locked around slow oscillation-spindle coupling events, as well as sharp-wave ripples in hippocampus. Summary Memory reactivation, which is facilitated by slow oscillation-spindle coupling events, can be observed during human sleep and shows promise as a prime mechanism underlying sleep’s beneficial effects on memory.

Sleep spindle maturity promotes slow oscillation-spindle coupling across child and adolescent development.

The synchronization of canonical fast sleep spindle activity (12.5-16 Hz, adult-like) precisely during the slow oscillation (0.5-1 Hz) up peak is considered an essential feature of adult non-rapid eye movement sleep. However, there is little knowledge on how this well-known coalescence between slow oscillations and sleep spindles develops. Leveraging individualized detection of single events, we first provide a detailed cross-sectional characterization of age-specific patterns of slow and fast sleep spindles, slow oscillations, and their coupling in children and adolescents aged 5-6, 8-11, and 14-18 years, and an adult sample of 20- to 26-year-olds. Critically, based on this, we then investigated how spindle and slow oscillation maturity substantiate age-related differences in their precise orchestration. While the predominant type of fast spindles was development-specific in that it was still nested in a frequency range below the canonical fast spindle range for the majority of children, the well-known slow oscillation-spindle coupling pattern was evident for sleep spindles in the adult-like canonical fast spindle range in all four age groups-but notably less precise in children. To corroborate these findings, we linked personalized measures of fast spindle maturity, which indicate the similarity between the prevailing development-specific and adult-like canonical fast spindles, and slow oscillation maturity, which reflects the extent to which slow oscillations show frontal dominance, with individual slow oscillation-spindle coupling patterns. Importantly, we found that fast spindle maturity was uniquely associated with enhanced slow oscillation-spindle coupling strength and temporal precision across the four age groups. Taken together, our results suggest that the increasing ability to generate adult-like canonical fast sleep spindles actuates precise slow oscillation-spindle coupling patterns from childhood through adolescence and into young adulthood.

Emotional memory consolidation during sleep is associated with slow oscillation-spindle coupling strength in young and older adults.

Emotional memories are processed during sleep; however, the specific mechanisms are unclear. Understanding such mechanisms may provide critical insight into preventing and treating mood disorders. Consolidation of neutral memories is associated with the coupling of NREM sleep slow oscillations (SOs) and sleep spindles (SPs). Whether SO-SP coupling is likewise involved in emotional memory processing is unknown. Furthermore, there is an age-related emotional valence bias such that sleep consolidates and preserves reactivity to negative but not positive emotional memories in young adults and positive but not negative emotional memories in older adults. If SO-SP coupling contributes to the effect of sleep on emotional memory, then it may selectively support negative memory in young adults and positive memory in older adults. To address these questions, we examined whether emotional memory recognition and overnight change in emotional reactivity were associated with the strength of SO-SP coupling in young (n = 22) and older (n = 32) adults. In younger adults, coupling strength predicted negative but not positive emotional memory performance after sleep. In contrast, coupling strength predicted positive but not negative emotional memory performance after sleep in older adults. Coupling strength was not associated with emotional reactivity in either age group. Our findings suggest that SO-SP coupling may play a mechanistic role in sleep-dependent consolidation of emotional memories.

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).

Theta Activity During Encoding Interacts With NREM Sleep Oscillations to Predict Memory Generalization.

Relatively little is known regarding the interaction between encoding-related neural activity and sleep-based memory consolidation. One suggestion is that a function of encoding-related theta power may be to “tag” memories for subsequent processing during sleep. This study aimed to extend previous work on the relationships between sleep spindles, slow oscillation-spindle coupling, and task-related theta activity with a combined Deese-Roediger-McDermott (DRM) and nap paradigm. This allowed us to examine the influence of task- and sleep-related oscillatory activity on the recognition of both encoded list words and associative theme words. Thirty-three participants (29 females, mean age = 23.2 years) learned and recognised DRM lists separated by either a 2 h wake or sleep period. Mixed-effects modelling revealed the sleep condition endorsed more associative theme words and fewer list words in comparison to the wake group. Encoding-related theta power was also found to influence sleep spindle density, and this interaction was predictive of memory outcomes. The influence of encoding-related theta was specific to sleep spindle density, and did not appear to influence the strength of slow oscillation-spindle coupling as it relates to memory outcomes. The finding of interactions between wakeful and sleep oscillatory-related activity in promoting memory and learning has important implications for theoretical models of sleep-based memory consolidation.

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.

The Overnight Retention of Novel Metaphors Associates With Slow Oscillation-Spindle Coupling but Not With Respiratory Phase at Encoding.

Accumulating evidence emphasizes the relevance of oscillatory synchrony in memory consolidation during sleep. Sleep spindles promote memory retention, especially when occurring in the depolarized upstate of slow oscillation (SO). A less studied topic is the inter-spindle synchrony, i.e. the temporal overlap and phasic coherence between spindles perceived in different electroencephalography channels. In this study, we examined how synchrony between SOs and spindles, as well as between simultaneous spindles, is associated with the retention of novel verbal metaphors. Moreover, we combined the encoding of the metaphors with respiratory phase (inhalation/exhalation) with the aim of modulating the strength of memorized items, as previous studies have shown that inhalation entrains neural activity, thereby benefiting memory in a waking condition. In the current study, 27 young adults underwent a two-night mixed-design study with a 12-h delayed memory task during both sleep and waking conditions. As expected, we found better retention over the delay containing sleep, and this outcome was strongly associated with the timing of SO–spindle coupling. However, no associations were observed regarding inter-spindle synchrony or respiratory phase. These findings contribute to a better understanding of the importance of SO–spindle coupling for memory. In contrast, the observed lack of association with inter-spindle synchrony may emphasize the local nature of spindle-related plasticity.

Altered Sleep-Related Consolidation and Neurocognitive Comorbidity in CECTS.

Our aim is to use neurophysiological sleep-related consolidation (SRC) phenomena to identify putative pathophysiological mechanisms in CECTS linked to diffuse neurocognitive deficits. We argue that there are numerous studies on the association between seizure aspects and neurocognitive functioning but not as many on interictal variables and neurocognitive deficits. We suggest two additional foci. First, the interictal presentation in CECTS and second, neuronal oscillations involved in SRC processes. Existing data on mechanisms through which interictal epileptiform spikes (IES) impact upon SRC indicate that they have the potential to: (a) perturb cross-regional coupling of neuronal oscillations, (b) mimic consolidation processes, (c) alter the precision of the spatiotemporal coupling of oscillations, and (d) variably impact upon SRC performance. Sleep spindles merit systematic study in CECTS in order to clarify: (a) the state of the slow oscillations (SOs) with which they coordinate, (b) the precision of slow oscillation-spindle coupling, and (c) whether their developmental trajectories differ from those of healthy children. We subsequently review studies on the associations between IES load during NREM sleep and SRC performance in childhood epilepsy. We then use sleep consolidation neurophysiological processes and their interplay with IES to help clarify the diffuse neurocognitive deficits that have been empirically documented in CECTS. We claim that studying SRC in CECTS will help to clarify pathophysiological mechanisms toward diverse neurocognitive deficits. Future developments could include close links between the fields of epilepsy and sleep, as well as new therapeutic neurostimulation targets. At the clinical level, children diagnosed with CECTS could benefit from close monitoring with respect to epilepsy, sleep and neurocognitive functions.

Slow oscillation-spindle coupling is negatively associated with emotional memory formation following stress.

Both stress and sleep enhance emotional memory. They also interact, with the largest effect of sleep on emotional memory being seen when stress occurs shortly before or after encoding. Slow wave sleep (SWS) is critical for long-term episodic memory, facilitated by the temporal coupling of slow oscillations and sleep spindles. Prior work in humans has shown these associations for neutral information in non-stressed participants. Whether coupling interacts with stress to facilitate emotional memory formation is unknown. Here, we addressed this question by reanalyzing an existing dataset of 64 individuals. Participants underwent a psychosocial stressor (32) or comparable control (32) prior to the encoding of 150-line drawings of neutral, positive, and negative images. All participants slept overnight with polysomnography, before being given a surprise memory test the following day. In the stress group, time spent in SWS was positively correlated with memory for images of all valences. Results were driven by those who showed a high cortisol response to the stressor, compared to low responders. The amount of slow oscillation-spindle coupling during SWS was negatively associated with neutral and emotional memory in the stress group only. The association with emotional memory was significantly stronger than for neutral memory within the stress group. These results suggest that stress around the time of initial memory formation impacts the relationship between slow wave sleep and memory.

Memory-relevant nap sleep physiology in healthy and pathological aging.

Aging is associated with detrimental changes in sleep physiology, a process accelerated in Alzheimer's disease. Fine-tuned temporal interactions of non-rapid eye movement slow oscillations and spindles were shown to be particularly important for memory consolidation, and to deteriorate in healthy older adults. Whether this oscillatory interaction further decline in early stages of Alzheimer's disease such as mild cognitive impairment has not been investigated to date, but may have important therapeutic implications. Here, we assessed differences in sleep architecture and memory-relevant slow oscillation, sleep spindles and their functional coupling during a 90-min nap between healthy young and older adults, and in older patients with mild cognitive impairment. Furthermore, associations of nap-sleep characteristics with sleep-dependent memory performance change were evaluated. We found significant differences between young and older healthy adults, and between young adults and patients with mild cognitive impairment, but not between healthy older adults and patients for several sleep metrics, including slow oscillation-spindle coupling. Moreover, sleep-dependent retention of verbal memories was significantly higher in young healthy adults versus older adults with and without mild cognitive impairment, but no difference between the two older groups was observed. Associations with sleep metrics were only found for pre-nap memory performances. In conclusion, our results indicate changes in nap sleep physiology and sleep-related memory consolidation in older adults with and without mild cognitive impairment. Thus, interventions targeted at improving sleep physiology may help to reduce memory decline in both groups, but our study does not indicate additional benefits for patients with mild cognitive impairment. Effects of Brain Stimulation During Daytime Nap on Memory Consolidation in Younger, Healthy Subjects: https://clinicaltrials.gov/ct2/show/NCT01840865; NCT01840865. Effects of Brain Stimulation During a Daytime Nap on Memory Consolidation in Older Adults; https://clinicaltrials.gov/ct2/show/study/NCT01840839?term=01840839&draw=2&rank=1; NCT01840839. Effects of Brain Stimulation During a Daytime Nap on Memory Consolidation in Patients With Mild Cognitive Impairment; https://clinicaltrials.gov/ct2/show/NCT01782365?term=01782365&draw=2&rank=1; NCT01782365.

How do children with autism spectrum disorder form gist memory during sleep? A study of slow oscillation-spindle coupling.

Sleep is assumed to support memory through an active systems consolidation process that does not only strengthen newly encoded representations but also facilitates the formation of more abstract gist memories. Studies in humans and rodents indicate a key role of the precise temporal coupling of sleep slow oscillations (SO) and spindles in this process. The present study aimed at bolstering these findings in typically developing (TD) children, and at dissecting particularities in SO-spindle coupling underlying signs of enhanced gist memory formation during sleep found in a foregoing study in children with autism spectrum disorder (ASD) without intellectual impairment. Sleep data from 19 boys with ASD and 20 TD boys (9–12 years) were analyzed. Children performed a picture-recognition task and the Deese–Roediger–McDermott (DRM) task before nocturnal sleep (encoding) and in the next morning (retrieval). Sleep-dependent benefits for visual-recognition memory were comparable between groups but were greater for gist abstraction (recall of DRM critical lure words) in ASD than TD children. Both groups showed a closely comparable SO-spindle coupling, with fast spindle activity nesting in SO-upstates, suggesting that a key mechanism of memory processing during sleep is fully functioning already at childhood. Picture-recognition at retrieval after sleep was positively correlated to frontocortical SO-fast-spindle coupling in TD children, and less in ASD children. Critical lure recall did not correlate with SO-spindle coupling in TD children but showed a negative correlation (r = −.64, p = .003) with parietal SO-fast-spindle coupling in ASD children, suggesting other mechanisms specifically conveying gist abstraction, that may even compete with SO-spindle coupling.

Slow oscillation-spindle coupling predicts enhanced memory formation from childhood to adolescence.

Precise temporal coordination of slow oscillations (SO) and sleep spindles is a fundamental mechanism of sleep-dependent memory consolidation. SO and spindle morphology changes considerably throughout development. Critically, it remains unknown how the precise temporal coordination of these two sleep oscillations develops during brain maturation and whether their synchronization indexes the development of memory networks. Here, we use a longitudinal study design spanning from childhood to adolescence, where participants underwent polysomnography and performed a declarative word-pair learning task. Performance on the memory task was better during adolescence. After disentangling oscillatory components from 1/f activity, we found frequency shifts within SO and spindle frequency bands. Consequently, we devised an individualized cross-frequency coupling approach, which demonstrates that SO-spindle coupling strength increases during maturation. Critically, this increase indicated enhanced memory formation from childhood to adolescence. Our results provide evidence that improved coordination between SOs and spindles indexes the development of sleep-dependent memory networks.

Weakly encoded memories due to acute sleep restriction can be rescued after one night of recovery sleep

Sleep is thought to play a complementary role in human memory processing: sleep loss impairs the formation of new memories during the following awake period and, conversely, normal sleep promotes the strengthening of the already encoded memories. However, whether sleep can strengthen deteriorated memories caused by insufficient sleep remains unknown. Here, we showed that sleep restriction in a group of participants caused a reduction in the stability of EEG activity patterns across multiple encoding of the same event during awake, compared with a group of participants that got a full night’s sleep. The decrease of neural stability patterns in the sleep-restricted group was associated with higher slow oscillation-spindle coupling during a subsequent night of normal sleep duration, thereby suggesting the instantiation of restorative neural mechanisms adaptively supporting cognition and memory. Importantly, upon awaking, the two groups of participants showed equivalent retrieval accuracy supported by subtle differences in the reinstatement of encoding-related activity: it was longer lasting in sleep-restricted individuals than in controls. In addition, sustained reinstatement over time was associated with increased coupling between spindles and slow oscillations. Taken together, these results suggest that the strength of prior encoding might be an important moderator of memory consolidation during sleep. Supporting this view, spindles nesting in the slow oscillation increased the probability of correct recognition only for weakly encoded memories. Current results demonstrate the benefit that a full night’s sleep can induce to impaired memory traces caused by an inadequate amount of sleep.

Large-scale structure and individual fingerprints of locally coupled sleep oscillations

Slow oscillations and sleep spindles, the canonical electrophysiological oscillations of nonrapid eye movement sleep, are thought to gate incoming sensory information, underlie processes of sleep-dependent memory consolidation, and are altered in various neuropsychiatric disorders. Accumulating evidence of the predominantly local expression of these individual oscillatory rhythms suggests that their cross-frequency interactions may have a similar local component. However, it is unclear whether locally coordinated sleep oscillations exist across the cortex, and whether and how these dynamics differ between fast and slow spindles, and sleep stages. Moreover, substantial individual variability in the expression of both spindles and slow oscillations raises the possibility that their temporal organization shows similar individual differences. Using two nights of multichannel electroencephalography recordings from 24 healthy individuals, we characterized the topography of slow oscillation-spindle coupling. We found that while slow oscillations are highly restricted in spatial extent, the phase of the local slow oscillation modulates local spindle activity at virtually every cortical site. However, coupling dynamics varied with spindle class, sleep stage, and cortical region. Moreover, the slow oscillation phase at which spindles were maximally expressed differed markedly across individuals while remaining stable across nights. These findings both add an important spatial aspect to our understanding of the temporal coupling of sleep oscillations and demonstrate the heterogeneity of coupling dynamics, which must be taken into account when formulating mechanistic accounts of sleep-related memory processing.