Human REM sleep recalibrates neural activity in support of memory formation.

The proposed mechanisms of sleep-dependent memory consolidation involve the overnight regulation of neural activity at both synaptic and whole-network levels. Now, there is a lack of in vivo data in humans elucidating if, and how, sleep and its varied stages balance neural activity, and if such recalibration benefits memory. We combined electrophysiology with in vivo two-photon calcium imaging in rodents as well as intracranial and scalp electroencephalography (EEG) in humans to reveal a key role for non-oscillatory brain activity during rapid eye movement (REM) sleep to mediate sleep-dependent recalibration of neural population dynamics. The extent of this REM sleep recalibration predicted the success of overnight memory consolidation, expressly the modulation of hippocampal-neocortical activity, favoring remembering rather than forgetting. The findings describe a non-oscillatory mechanism how human REM sleep modulates neural population activity to enhance long-term memory.

An evolutionary conserved division-of-labor between archicortical and neocortical ripples organizes information transfer during sleep.

Systems-level memory consolidation during sleep depends on the temporally precise interplay between cardinal sleep oscillations. Specifically, hippocampal ripples constitute a key substrate of the hippocampal-neocortical dialog underlying memory formation. Recently, it became evident that ripples are not unique to archicortex, but constitute a wide-spread neocortical phenomenon. To date, little is known about the morphological similarities between archi- and neocortical ripples. Moreover, it remains undetermined if neocortical ripples fulfill distinct functional roles. Leveraging intracranial recordings from the human medial temporal lobe (MTL) and neocortex during sleep, our results reveal region-specific functional specializations, albeit a near-uniform morphology. While MTL ripples synchronize the memory network to trigger directional MTL-to-neocortical information flow, neocortical ripples reduce information flow to minimize interference. At the population level, MTL ripples confined population dynamics to a low-dimensional subspace, while neocortical ripples diversified the population response; thus, constituting an effective mechanism to functionally uncouple the MTL-neocortical network. Critically, we replicated the key findings in rodents, where the same division-of-labor between archi- and neocortical ripples was evident. In sum, these results uncover an evolutionary preserved mechanism where the precisely coordinated interplay between MTL and neocortical ripples temporally segregates MTL information transfer from subsequent neocortical processing during sleep.

Investigating the Effects of Seizures on Procedural Memory Performance in Patients with Epilepsy.

Memory complaints are frequently reported by patients with epilepsy and are associated with seizure occurrence. Yet, the direct effects of seizures on memory retention are difficult to assess given their unpredictability. Furthermore, previous investigations have predominantly assessed declarative memory. This study evaluated within-subject effects of seizure occurrence on retention and consolidation of a procedural motor sequence learning task in patients with epilepsy undergoing continuous monitoring for five consecutive days. Of the total sample of patients considered for analyses (N = 53, Mage = 32.92 ± 13.80 y, range = 18-66 y; 43% male), 15 patients experienced seizures and were used for within-patient analyses. Within-patient contrasts showed general improvements over seizure-free (day + night) and seizure-affected retention periods. Yet, exploratory within-subject contrasts for patients diagnosed with temporal lobe epilepsy (n = 10) showed that only seizure-free retention periods resulted in significant improvements, as no performance changes were observed following seizure-affected retention. These results indicate general performance improvements and offline consolidation of procedural memory during the day and night. Furthermore, these results suggest the relevance of healthy temporal lobe functioning for successful consolidation of procedural information, as well as the importance of seizure control for effective retention and consolidation of procedural memory.

Procedural memory consolidation is associated with heart rate variability and sleep spindles.

Sleep and memory studies often focus on overnight rather than long-term memory changes, traditionally associating overnight memory change (OMC) with sleep architecture and sleep patterns such as spindles. In addition, (para-)sympathetic innervation has been associated with OMC after a daytime nap using heart rate variability (HRV). In this study we investigated overnight and long-term performance changes for procedural memory and evaluated associations with sleep architecture, spindle activity (SpA) and HRV measures (R-R interval [RRI], standard deviation of R-R intervals [SDNN], as well as spectral power for low [LF] and high frequencies [HF]). All participants (N = 20, Mage  = 23.40 ± 2.78 years) were trained on a mirror-tracing task and completed a control (normal vision) and learning (mirrored vision) condition. Performance was evaluated after training (R1), after a full-night sleep (R2) and 7 days thereafter (R3). Overnight changes (R2-R1) indicated significantly higher accuracy after sleep, whereas a significant long-term (R3-R2) improvement was only observed for tracing speed. Sleep architecture measures were not associated with OMC after correcting for multiple comparisons. However, individual SpA change from the control to the learning night indicated that only "SpA enhancers" exhibited overnight improvements for accuracy and long-term improvements for speed. HRV analyses revealed that lower SDNN and LF power was associated with better OMC for the procedural speed measure. Altogether, this study indicates that overnight improvement for procedural memory is specific for spindle enhancers, and is associated with HRV during sleep following procedural learning.

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

Many 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.

The impact of sleep characteristics and epilepsy variables on memory performance in patients with focal seizures.

Disturbed sleep can negatively affect overnight memory retention as well as new learning the subsequent day. In healthy participants, positive associations between memory performance and sleep characteristics (e.g., time spent in slow-wave sleep [SWS]) have been detected. In a previous study, we found that SWS was much reduced in patients with focal seizures, but when correlations between memory complaints and various sleep characteristics were considered, the only significant relationship was with the time to onset of rapid eye movement (REM) sleep (i.e., REM latency). In this study, we investigated the relationships between sleep, epilepsy, and objective memory performance variables. Twenty-five patients with focal seizures had their memory tested while undergoing a two-day ambulatory electroencephalography (EEG). The sleep variables of interest were the percentage of time spent in SWS (%SWS) and REM latency. Epilepsy variables included the presence of (1) seizures, (2) interictal epileptiform discharges, and/or (3) hippocampal lesions as well as site of seizure origin (temporal vs extratemporal). Overnight retention (of autobiographical events, a story, and a complex geometric figure) and the ability to learn a word list on day 2 were the measures of memory. A significant positive correlation was found between word-list learning and %SWS during the previous night. A significant negative correlation was observed between REM latency and overnight retention of autobiographical events. Overnight retention scores for the story and geometric figure were not related to sleep characteristics but were negatively affected by the presence of epileptiform activity. Story retention was also worse for temporal lobe epilepsy (TLE) than for patients with extratemporal epilepsy (ETE). Those with hippocampal lesions were more impaired than those without lesions on word-list learning, autobiographical events' retention, and story retention. When multiple contributing factors were entered into regression analyses, %SWS was found to be the best predictor of subsequent word-list learning, whereas the presence of a hippocampal lesion was the best predictor of overnight retention of autobiographical events and a story. These findings provide further evidence of the ways in which particular sleep characteristics are associated with memory and suggest that treatment of sleep disturbances in patients with epilepsy might be helpful for improving their performance.

Effects of Arc/Arg3.1 gene deletion on rhythmic synchronization of hippocampal CA1 neurons during locomotor activity and sleep.

The activity-regulated cytoskeletal-associated protein/activity regulated gene (Arc/Arg3.1) is crucial for long-term synaptic plasticity and memory formation. However, the neurophysiological substrates of memory deficits occurring in the absence of Arc/Arg3.1 are unknown. We compared hippocampal CA1 single-unit and local field potential (LFP) activity in Arc/Arg3.1 knockout and wild-type mice during track running and flanking sleep periods. Locomotor activity, basic firing and spatial coding properties of CA1 cells in knockout mice were not different from wild-type mice. During active behavior, however, knockout animals showed a significantly shifted balance in LFP power, with a relative loss in high-frequency (beta-2 and gamma) bands compared to low-frequency bands. Moreover, during track-running, knockout mice showed a decrease in phase locking of spiking activity to LFP oscillations in theta, beta and gamma bands. Sleep architecture in knockout mice was not grossly abnormal. Sharp-wave ripples, which have been associated with memory consolidation and replay, showed only minor differences in dynamics and amplitude. Altogether, these findings suggest that Arc/Arg3.1 effects on memory formation are not only manifested at the level of molecular pathways regulating synaptic plasticity, but also at the systems level. The disrupted power balance in theta, beta and gamma rhythmicity and concomitant loss of spike-field phase locking may affect memory encoding during initial storage and memory consolidation stages.

Determining the relationship between sleep architecture, seizure variables and memory in patients with focal epilepsy.

Sleep has been shown to be important to memory. Both sleep and memory have been found to be abnormal in patients with epilepsy. In this study, we explored the effects that nocturnal epileptiform discharges and the presence of a hippocampal lesion have on sleep patterns and memory. Twenty-five patients with focal epilepsy who underwent a 24-hr ambulatory EEG also completed the Everyday Memory Questionnaire (EMQ). The EEG record was scored for length of time spent in the various sleep stages, time spent awake after sleep onset, and rapid eye movement (REM) latency. Of these sleep variables, only REM latency differed when the epilepsy patients were divided on the bases of either presence/absence of nocturnal discharges or presence/absence of a hippocampal lesion. In both cases, presence of the abnormality was associated with longer latency. Furthermore, longer REM latency was found to be a better predictor of EMQ score than either number of discharges or presence of a hippocampal lesion. Longer REM latency was associated with a smaller percentage of time spent in slow-wave sleep in the early part of the night and may serve as a particularly sensitive marker to disturbances in sleep architecture. (PsycINFO Database Record

The role of sleep timing in children's observational learning.

Acquisition of information can be facilitated through different learning strategies, classically associated with either declarative or procedural memory modalities. The consolidation of the acquired information has been positively associated with sleep. In addition, subsequent performance was better when acquisition was quickly followed by sleep, rather than daytime wakefulness. Prior studies with adults have indicated the viability of the alternative learning strategy of observational learning for motor skill acquisition, as well as the importance of sleep and sleep timing. However, relatively little research has been dedicated to studying the importance of sleep for the consolidation of procedural memory in children. Therefore, this study investigated whether children could encode procedural information through observational learning, and whether sleep timing could affect subsequent consolidation and performance. School-aged children aged 9-12years (N=86, 43% male, Mage=10.64years, SD=.85) were trained on a procedural fingertapping task through observation, either in the morning or evening; creating immediate wake and immediate sleep groups, respectively. Performance was evaluated the subsequent evening or morning on either a congruent or incongruent task version. Observation and task execution was conducted using an online interface, allowing for remote participation. Performance of the immediate wake group was lower for a congruent version, expressed by a higher error rate, opposed to an incongruent version; an effect not observed in the immediate sleep group. This finding showed that observational learning did not improve performance in children. Yet, immediate sleep prevented performance reduction on the previously observed task. These results support a benefit of sleep in observational learning in children, but in a way different from that seen in adults, where sleep enhanced performance after learning by observation.

Social support moderates the effects of stress on sleep in adolescents.

Academic expectations and demands become primary sources of stress during adolescence, negatively affecting sleep. To cope with stress, adolescents may turn to social support figures. The present study tested the extent of main and moderating effects of various sources of social support on the association between stress and sleep. Adolescents (n = 202, meanage 14.6 years, standard deviation = 0.71) reported on academic stress, sleep, and support using questionnaires during a low- and high-stress period, defined by the absence or presence of examinations, respectively. Inquiries were made regarding social support from parents, friends, and class supervisor. During both stress periods, academic stress was associated negatively with sleep quality and positively with sleep reduction. Social support increased sleep quality and lowered sleep reduction. In addition, social support moderated the effects of academic stress on sleep, thus improving sleep quality and lowering sleep reduction. Moderating effects were stronger during a period of high stress. The present study showed that adolescents can benefit from stress moderation through social support by improvements of sleep quality and sleep reduction. Such moderating effects should be taken into account when studying stress and sleep. Implications and recommendations based on these findings are discussed.