Declarative Memory Consolidation Research Articles

Scopolamine does not impact declarative and motor memory consolidation across a night of sleep or a day of wakefulness

It has been proposed that normal waking levels of acetylcholine (ACH) are important for initial memory acquisition, and that decreased ACH is critical for memory consolidation. Sleep is thought to benefit memory consolidation in part due to the predominance of low ACH levels observed during non-rapid eye movement sleep. Here we examined whether sleep and ACH suppression with the cholinergic antagonist scopolamine impact declarative and motor memory consolidation across a night of sleep or a day of wakefulness. Eighty-seven participants trained on a declarative and motor memory task in the morning or evening. Following training, participants were administered a scopolamine (0.4 mg) or placebo capsule. Participants were retested on the tasks 12 h later after a day of wake or a night of sleep. Reducing ACH levels with scopolamine provided no consolidation benefit for either task. Additionally, we found that sleep had a pronounced beneficial effect for declarative, but not motor memory consolidation. Lastly, in an exploratory analysis of the relationship between motivation and memory performance, we found that indices of intrinsic motivation were associated with improved memory acquisition and consolidation. Our findings show that reducing ACH levels after memory acquisition has no impact on the consolidation of declarative or motor memories. Additionally, sleep benefitted declarative memory but not motor memory consolidation, which highlights the interesting, though uncommon, finding that performance on some tasks might not benefit from sleep. Interestingly, the future study of intrinsic motivation may be warranted given its relationship to memory acquisition and consolidation. These findings add to our understanding of how sleep and acetylcholine impact memory consolidation, and may provide some insight about the role of ACH in memory disorders such as Alzheimer's disease.

Women with high estradiol status are protected against declarative memory impairment by pre-learning stress.

Stress is a potent modulator of learning and memory. Factors contributing to whether stress aids or impairs memory are timing of the stressor, memory stage, form of memory studied, and sex of the subjects. The female sex hormone 17-beta-estradiol (E2) has widespread effects in the brain and affects hippocampus-dependent memory in animals. In humans, the interaction between stress effects and E2 has not been widely studied. We report data from a healthy sample divided into 3 hormone-status groups: free-cycling women in the early follicular phase (EF: low E2, low progesterone [P4]), or during midcycle (MC: high E2, low P4), and men. Participants within each hormone-status group were randomly assigned to a psychosocial stressor or a control treatment 37 min before encoding a short story of neutral content. We found a Hormone status × Stress × Time (immediate, 35-min, 24-h delayed recall) interaction. Irrespective of time, hormone status mattered only after stress treatment: stressed early follicular women had poorer recall compared to stressed men and midcycle women. Only in the early follicular group, recall was negatively correlated with increases in salivary cortisol, but not with blood levels of E2 and P4. To uncover changes beyond immediate recall, we computed the individual percent change relative to immediate recall and repeated the analysis for these adjusted 35-min and 24-h data. Despite the lack of a stress effect in raw data, memory in stressed men was more stable over time (35-min and 24-h delay) than in unstressed men. In contrast, stressed EF-women (vs. control) recalled less at the 35-min and (as a trend) at the 24-h delay. Stressed MC-women (vs. control) showed less recall only at the 35-min delay while compensating this stress effect after a 24-h consolidation interval. Overall, results suggest that women in high-E2 midcycle phase could be less vulnerable to effects of pre-learning stress on declarative memory encoding and consolidation.

Sleep-dependent enhancement of emotional memory in early childhood

Naps in early childhood support declarative memory consolidation. However, emotional memories are unique in the neural basis of encoding as well as the sleep physiology underlying consolidation. Specifically, while consolidation of declarative memories has been associated with slow wave sleep, a prevailing theory suggests that REM sleep is necessary for consolidation of memories with emotional valence. Thus, we presented children (34–64 months) with faces paired with mean or nice descriptions. There were no significant main effects of emotional valence on recognition memory. Change in memory accuracy also did not differ when probed after a nap compared to the change in memory accuracy after an interval awake. However, when memory was probed again following overnight sleep, the change in memory accuracy was greater if the child napped the previous day. Greater nap slow wave activity was associated with greater memory decay during the nap. Yet nap slow wave activity also predicted greater overnight improvement in memory. These results suggest that sleep bouts can interact to benefit memory in early childhood.

Post-class naps boost declarative learning in a naturalistic school setting

Laboratory evidence of a positive effect of sleep on declarative memory consolidation suggests that naps can be used to boost school learning in a scalable, low-cost manner. The few direct investigations of this hypothesis have so far upheld it, but departed from the naturalistic setting by testing non-curricular contents presented by experimenters instead of teachers. Furthermore, nap and non-nap groups were composed of different children. Here we assessed the effect of post-class naps on the retention of Science and History curricular contents presented by the regular class teacher to 24 students from 5th grade. Retention was repeatedly measured 3–4 days after content learning, with weekly group randomization over 6 consecutive weeks. Contents followed by long naps (>30 min), but not short naps (<30 min), were significantly more retained than contents followed by waking (Cohen’s d = 0.7962). The results support the use of post-class morning naps to enhance formal education.

Beneficial effects of a daytime nap on verbal memory in adolescents

This study aimed to examine the sleep-dependent memory consolidation of verbal declarative memory in Chinese adolescents in a naturalistic experimental setting. Thirty-nine healthy boarding school students (ages 15–18, 70% female) were randomized to either a one-hour afternoon nap or wake group between the baseline and the retest sessions of three verbal declarative memory tasks: a Prose Stories Recall task, a Word Pair Associates task, and Rey Auditory Verbal Learning Test. Results showed that the nap group performed better than the no-nap group on both the Prose Stories Recall task and the Word Pair Associates task, but not on list learning. Our findings suggest that napping is beneficial to verbal declarative memory in adolescents, providing ecologically-valid empirical support for the sleep-dependent memory consolidation hypothesis using a napping paradigm in participants' naturalistic habitat. Our results demonstrate the potential importance of napping as a practical mnemonic intervention/compensatory strategy for student populations.

A brief period of eyes-closed rest enhances motor skill consolidation.

Post-training sleep benefits both declarative and procedural memory consolidation. However, recent research suggests that eyes-closed waking rest may provide a similar benefit. Brokaw et al. (2016), for example, recently demonstrated that verbal declarative memory improved more following a 15 min period of waking rest, in comparison to 15 min of active wake. Here, we used the same procedures to test whether procedural memory similarly benefits from waking rest. Participants were trained on the Motor Sequence Task (MST), followed by a 15 min retention interval during which they either rested with their eyes closed or completed a distractor task. Rest significantly enhanced MST performance, mirroring the effect observed in Brokaw et al. (2016) and demonstrating that waking rest benefits the early stages of procedural memory. An additional group of participants tested 4 h later displayed no effect of rest. Overall, these results suggest that the early MST performance "boost" described in prior studies may depend on post-learning state.

0102 The Impact of Acetylcholine Levels on Declarative and Motor Memory Consolidation Following a Night of Sleep or a Day of Wake

0102 The Impact of Acetylcholine Levels on Declarative and Motor Memory Consolidation Following a Night of Sleep or a Day of Wake

目标记忆重激活对记忆巩固影响的研究综述

目标记忆重激活(Targeted memory reactivation, TMR)是一种研究记忆巩固的重要方法，通过进行记忆线索的提示诱导促进记忆的巩固。通常，发生在慢波睡眠阶段的提示可促进程序性和陈述性记忆巩固。而在清醒和快速眼动睡眠阶段进行提示对记忆巩固的效果尚无统一认识。在神经机制方面，TMR和睡眠参数有关并伴随着记忆相关脑区的激活，如海马、丘脑、前额叶皮层。TMR使用的线索材料通常为嗅觉刺激或听觉刺激，这些线索刺激呈现的时机、时长以及与目标材料之间的关系会对TMR产生影响。未来研究可以从澄清睡眠促进记忆巩固的神经机制，开发更具可操作性的TMR新技术着手，帮助大众提高学习能力、创造力和问题解决能力。 Targeted memory reactivation is a fairly important technique that has the potential to influence the course of memory formation through application of cues during imperceptible states. In gen-eral, cueing memory at the slow-wave-sleep stage can promote the consolidation of procedural and declarative memory. However, the effect of cueing memory during wake and the rapid eye move sleep has no unified. Studies have shown that TMR is associated with sleep parameters and accompanied by activation of memory related brain areas, such as Hippocampus, thalamus and the prefrontal cortex. Olfactory stimulus and auditory stimulus are adapted to TMR, which is influenced by the way the stimulus represent and the relationship of cuing materials and memory. The goal of the future study is to clear the neural mechanism of TMR and to explore safer and more effective ways of adjusting memory representations to better suit individual needs, as well as its potential applications in improving the abilities of study, creativity and problem solving.

The limbic-reticular coupling theory of memory processing in the brain and its greater compatibility over other theories.

The limbic-reticular coupling theory suggests that the hippocampus and amygdala regulate such descending limbic structures as the mammillary bodies, septum, hypothalamus and epithalamus to regulate the ascending noradrenergic, serotonergic, dopaminergic and cholinergic systems, performing declarative memory consolidation and recall. Recent studies have revealed that, less sensitive to familiarity, the hippocampus functions via the fornix, mammillary bodies and hypothalamus for memory recall. Lesions to the thalamic nuclei were complicated with damage to adjacent fornix, stria medullaris and habenula, simultaneously destroying two kinds of structures respectively for familiarity and recall. Furthermore, the orbitofrontal cortex was shown to be clinically irrelevant for memory recall. Electrophysiologically, the hippocampus regulates the raphe nuclei in complex ways, and the hippocampal theta wave activates the dopaminergic cells in ventral tegmental area and cholinergic neurons in basal forebrain, while cholinergic-modulated theta-gamma coupling mediates cortical recall. These concurrent advances support the limbic-reticular coupling theory for elucidation of memory recall.

The effect of daytime napping and full-night sleep on the consolidation of declarative and procedural information.

SummaryMany studies investigating sleep and memory consolidation have evaluated full‐night sleep rather than alternative sleep periods such as daytime naps. This multi‐centre study followed up on, and was compared with, an earlier full‐night study (Schabus et al., 2004) investigating the relevance of daytime naps for the consolidation of declarative and procedural memory. Seventy‐six participants were randomly assigned to a nap or wake group, and performed a declarative word‐pair association or procedural mirror‐tracing task. Performance changes from before to after a 90‐min retention interval filled with sleep or quiet wakefulness were evaluated between groups. Associations between performance changes, sleep architecture, spindles, and slow oscillations were investigated. For the declarative task we observed a trend towards stronger forgetting across a wake period compared with a nap period, and a trend towards memory increase over the full‐night. For the procedural task, accuracy was significantly decreased following daytime wakefulness, showed a trend to increase with a daytime nap, and significantly increased across full‐night sleep. For the nap protocol, neither sleep stages, spindles, nor slow oscillations predicted performance changes. A direct comparison of day and nighttime sleep revealed that daytime naps are characterized by significantly lower spindle density, but higher spindle activity and amplitude compared with full‐night sleep. In summary, data indicate that daytime naps protect procedural memories from deterioration, whereas full‐night sleep improves performance. Given behavioural and physiological differences between day and nighttime sleep, future studies should try to characterize potential differential effects of full‐night and daytime sleep with regard to sleep‐dependent memory consolidation.

Sleep in Humans Stabilizes Pattern Separation Performance.

Replay of hippocampal neural representations during sleep is thought to promote systems consolidation of declarative memory. How this reprocessing of memory during sleep affects the hippocampal representation itself, is unclear. Here we tested hippocampal stimulus processing (i.e., pattern separation) before and after periods of sleep and wakefulness in humans (female and male participants). Pattern separation deteriorated across the wake period but remained stable across sleep (p = 0.013) with this sleep-wake difference being most pronounced for stimuli with low similarity to targets (p = 0.006). Stimuli with the highest similarity showed a reversed pattern with reduced pattern separation performance after sleep (p = 0.038). Pattern separation performance was positively correlated with sleep spindle density, slow oscillation density, and theta power phase-locked to slow oscillations. Sleep, presumably by neural memory replay, shapes hippocampal representations and enhances computations of pattern separation to subsequent presentation of similar stimuli.SIGNIFICANCE STATEMENT The consolidation of hippocampus-dependent memories is causally related to reactivation during sleep of previously encoded representations. Here, we show that reactivation-based consolidation processes during sleep shape the hippocampal representation itself. We studied the effect of sleep and wakefulness on pattern separation (i.e., orthogonalization of similar representations) and completion performance (i.e., recall of a memory in light of noisy input) that are essential cognitive elements of encoding and retrieval of information by the hippocampus. Our results demonstrate that pattern separation was stabilized after sleep but diminished after wakefulness. We further showed that pattern separation was related to EEG oscillatory parameters of non-REM sleep serving as markers of sleep-dependent memory consolidation and hippocampal reactivation.

Impaired memory consolidation in children with obstructive sleep disordered breathing.

Memory consolidation is stabilized and even enhanced by sleep (and particularly by 12–15 Hz sleep spindles in NREM stage 2 sleep) in healthy children but it is unclear what happens to these processes when sleep is disturbed by obstructive sleep disordered breathing. This cross-sectional study investigates differences in declarative memory consolidation among children with primary snoring (PS) and obstructive sleep apnea (OSA) compared to controls. We further investigate whether memory consolidation group differences are associated with NREM stage 2 (N2) sigma (12–15 Hz) or NREM slow oscillation (0.5–1 Hz) spectral power bands. In this study, we trained and tested participants on a spatial declarative memory task with cued recall. Retest occurred after a period of daytime wake (Wake) or a night of sleep (Sleep) with in-lab polysomnography. 36 participants ages 5–9 years completed the protocol: 14 with OSA as defined by respiratory disturbance index (RDI) > 1/hour, 12 with primary snoring (PS) and 10 controls. OSA participants had poorer overall memory consolidation than controls across Wake and Sleep conditions [OSA: mean = -18.7% (5.8), controls: mean = 1.9% (7.2), t = -2.20, P = 0.04]. In contrast, PS participants and controls had comparable memory consolidation across conditions (t = 0.41; P = 0.38). We did not detect a main effect for condition (Sleep, Wake) or group x condition interaction on memory consolidation. OSA participants had lower N2 sigma power than PS (P = 0.03) and controls (P = 0.004) and N2 sigma power inversely correlated with percentage of time snoring on the study night (r = -0.33, P<0.05). Across all participants, N2 sigma power modestly correlated with memory consolidation in both Sleep (r = 0.37, P = 0.03) and Wake conditions (r = 0.44, P = 0.009). Further observed variable path analysis showed that N2 sigma power mediated the relationship between group and mean memory consolidation across Sleep and Wake states [Bindirect = 6.76(3.5), z = 2.03, P = 0.04]. NREM slow oscillation power did not correlate with memory consolidation. All results retained significance after controlling for age and BMI. In sum, participants with mild OSA had impaired memory consolidation and results were mediated by N2 sigma power. These results suggest that N2 sigma power could serve as biomarker of risk for cognitive dysfunction in children with sleep disordered breathing.

Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus.

Consolidation of declarative memories requires hippocampal-neocortical communication. Although experimental evidence supports the role of sharp-wave ripples in transferring hippocampal information to the neocortex, the exact cortical destinations and the physiological mechanisms of such transfer are not known. We used a conducting polymer-based conformable microelectrode array (NeuroGrid) to record local field potentials and neural spiking across the dorsal cortical surface of the rat brain, combined with silicon probe recordings in the hippocampus, to identify candidate physiological patterns. Parietal, midline, and prefrontal, but not primary cortical areas, displayed localized ripple (100 to 150 hertz) oscillations during sleep, concurrent with hippocampal ripples. Coupling between hippocampal and neocortical ripples was strengthened during sleep following learning. These findings suggest that ripple-ripple coupling supports hippocampal-association cortical transfer of memory traces.

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

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

Magnetic Resonance Imaging and Anatomical Correlation of Human Temporal Lobe Landmarks, in 3D Euclidean Space: A Study of Control and Alzheimer's Disease Subjects.

The medial temporal lobe (MTL), and in particular the hippocampal formation, is essential in the processing and consolidation of declarative memory. The 3D environment of the anatomical structures contained in the MTL is an important issue. Our aim was to explore the spatial relationship of the anatomical structures of the MTL and changes in aging and/or Alzheimer's disease (AD). MTL anatomical landmarks are identified and registered to create a 3D network. The brain network is quantitatively described as a plane, rostrocaudally-oriented, and presenting Euclidean/real distances. Correspondence between 1.5T RM, 3T RM, and histological sections were assessed to determine the most important recognizable changes in AD, based on statistical significance. In both 1.5T and 3T RM images and histology, inter-rater reliability was high. Sex and hemisphere had no influence on network pattern. Minor changes were found in relation to aging. Distances from the temporal pole to the dentate gyrus showed the most significant differences when comparing control and AD groups. The best discriminative distance between control and AD cases was found in the temporal pole/dentate gyrus rostrocaudal length in histological sections. Moreover, more distances between landmarks were required to obtain 100% discrimination between control (divided into <65 years or >65 years) and AD cases. Changes in the distance between MTL anatomical landmarks can successfully be detected by using measurements of 3D network patterns in control and AD cases.

Individual baseline memory performance and its significance for sleep-dependent memory consolidation

Today, there is little doubt concerning the significance of sleep for memory consolidation. Some studies have suggested, however, that overnight memory consolidation as well as their underpinning neural mechanisms might be modulated by general cognitive abilities. In this paper, we used a more specific trait measure of declarative word-pair encoding efficiency, namely “baseline memory performance (BMP).” We explored its relation to consolidation and stabilization of declarative memories overnight as well as its relationship to sleep mechanisms. We included healthy subjects and insomnia patients from two studies with slightly differing demands on declarative memory. In the first study, an insomnia sample (N = 21) performed a declarative word-pair association task with pre- and post-sleep retrieval sessions and recorded 8 hr of nocturnal sleep following learning. In the second study, insomnia (N = 24) as well as sex-and-age-matched control (N = 29) subjects underwent a similar task but with an additional in...

P112 Investigations of general cognitive ability on the efficiency of slow oscillatory-tDCS

Introduction Application of SO-tDCS during NREM sleep has shown to be beneficial for consolidation of declarative memories, although contradictory reports also exist ( Barham et al., 1974 ). Specifically the disparate results of individual studies led us to investigate task and trait-dependent effects of SO-tDCS on modulating endogenous brain rhythms and its impact on memory consolidation. Objectives The aim of the present study is to determine the interaction between general cognitive abilities and the efficiency of SO-tDCS on manipulating endogenous EEG activity and memory performance. Methods Young healthy students (n = 14, 8 females) participated in three experimental sessions of nocturnal sleep with EEG, EOG and EMG recordings: Stimulation, Sham and one Baseline session without learning. Five different tasks were to be learned prior to sleep and contents recalled the following morning. SO-tDCS (0.8 Hz) was applied during a stimulation period within early NREM sleep. This stimulation consisted five 5-min blocks of SO-tDCS followed each by a 60-s stimulation free interval. IQ performance was tested 7 days after the last sleep session. Results Participants improved on the figural paired-associate task significantly during the stimulation condition as compared to sham (p Summary Our study suggests that externally applied electric fields during NREM sleep can alter endogenous oscillations in the hours following stimulation and this favours the consolidation of a declarative memory. Furthermore, the correlation with IQ performance suggests SO-tDCS efficiency is dependent upon interactions with non-task and or non-state dependent features.

P193 Effect of transcranial direct current stimulation (tDCS) on sleep-dependent memory consolidation in healthy young subjects

Transcranial direct current stimulation (tDCS) is a method to stimulate the brain in a noninvasive manner leading either to an increased (anodal stimulation) or a decreased (cathodal stimulation) excitability of cortical neurons. Slow oscillations with a frequency below 1 Hz are assumed to be associated with sleep-dependent consolidation of declarative memories by exerting a temporal synchronizing influence on hippocampal reactivations and thalamic spindle activity. Many studies have revealed that offline consolidation during sleep varies with age showing better performances in the young compared to the elderly. A study in young subjects provided evidence of a beneficial impact of an anodal slow oscillation tDCS (0.75 Hz) during early SWS-rich on declarative memory but not on procedural memory. These results could not be confirmed in a study on elderly subjects (Eggert et al., 2013). The present study aims to replicate the results, which have been observed in younger subjects (Marshal et al., 2006). To be able to test an effect of 0.65 with a power of 0.8 and a double-sided alpha 2 ) is triggered after the first 8 consecutive epochs of NREM sleep 2 immediately before the first occurrence of slow wave sleep. The total 25 ′ 8 ″ stimulation period is divided into five 5 ′ 16 ″ intervals, each of them followed by 1 min break without stimulation. To test for a stimulation-dependent effect on offline consolidation during sleep a declarative memory task (word pair test) and a procedural memory task (finger-tapping) have to be completed before sleep and after awakening. Furthermore, sleep stages were scored and EEG power and spindle densities were computed. Statistical analysis was based upon comparisons between the tDCS and the sham stimulation condition. Currently 18 subjects (10 males and 8 females) are already enrolled. First results will be presented at the meeting.

Sleep-Dependent Consolidation of Rewarded Behavior Is Diminished in Children with Attention Deficit Hyperactivity Disorder and a Comorbid Disorder of Social Behavior.

Children suffering from attention-deficit hyperactivity disorder (ADHD) often also display impaired learning and memory. Previous research has documented aberrant reward processing in ADHD as well as impaired sleep-dependent consolidation of declarative memory. We investigated whether sleep also fosters the consolidation of behavior learned by probabilistic reward and whether ADHD patients with a comorbid disorder of social behavior show deficits in this memory domain, too. A group of 17 ADHD patients with comorbid disorders of social behavior aged 8–12 years and healthy controls matched for age, IQ, and handedness took part in the experiment. During the encoding task, children worked on a probabilistic learning task acquiring behavioral preferences for stimuli rewarded most often. After a 12-hr retention interval of either sleep at night or wakefulness during the day, a reversal task was presented where the contingencies were reversed. Consolidation of rewarded behavior is indicated by greater resistance to reversal learning. We found that healthy children consolidate rewarded behavior better during a night of sleep than during a day awake and that the sleep-dependent consolidation of rewarded behavior by trend correlates with non-REM sleep but not with REM sleep. In contrast, children with ADHD and comorbid disorders of social behavior do not show sleep-dependent consolidation of rewarded behavior. Moreover, their consolidation of rewarded behavior does not correlate with sleep. The results indicate that dysfunctional sleep in children suffering from ADHD and disorders of social behavior might be a crucial factor in the consolidation of behavior learned by reward.

Age-related differences in sleep-based memory consolidation: A meta-analysis

A period of post-learning sleep benefits memory consolidation compared with an equal-length wake interval. However, whether this sleep-based memory consolidation changes as a function of age remains controversial. Here we report a meta-analysis that investigates the age differences in the sleep-based memory consolidation in two types of memory: declarative memory and procedural memory. The meta-analysis included 22 comparisons of the performance between young adults (N =640) and older adults (N =529) on behavioral tasks measuring sleep-based memory consolidation. Our results showed a significant overall sleep-based beneficial effect in young adults but not in older adults. However, further analyses suggested that the age differences were mainly manifested in sleep-based declarative memory consolidation but not in procedural memory consolidation. We discussed the possible underlying mechanisms for the age-related degradation in sleep-based memory consolidation. Further research is needed to determine the crucial components for sleep-related memory consolidation in older adults such as age-related changes in neurobiological and cardiovascular functions, which may play an important role in this context and have the potential to delineate the interrelationships between age-related changes in sleep and memory.