Hippocampal-Medial Prefrontal Event Segmentation and Integration Contribute to Episodic Memory Formation.

How do we encode our continuous life experiences for later retrieval? Theories of event segmentation and integration suggest that the hippocampus binds separately represented events into an ordered narrative. Using a functional Magnetic Resonance Imaging (fMRI) movie watching-recall dataset, we quantified two types of neural similarities (i.e., "activation pattern" similarity and within-region voxel-based "connectivity pattern" similarity) between separate events during movie watching and related them to subsequent retrieval of events as well as retrieval of sequential order. We demonstrated that compared with forgotten events, successfully remembered events were associated with distinct "activation patterns" in the hippocampus and medial prefrontal cortex. In contrast, similar "connectivity pattern" between events were associated with memory formation and were also relevant for retaining events in the correct order. We applied the same approaches to an independent movie watching fMRI dataset as validation and highlighted again the role of hippocampal activation pattern and connectivity pattern in memory formation. We propose that distinct activation patterns represent neural segmentation of events, while similar connectivity patterns encode context information and, therefore, integrate events into a narrative. Our results provide novel evidence for the role of hippocampal-medial prefrontal event segmentation and integration in episodic memory formation of real-life experience.

Splitting sleep between the night and a daytime nap reduces homeostatic sleep pressure and enhances long-term memory.

Daytime naps have been linked with enhanced memory encoding and consolidation. It remains unclear how a daily napping schedule impacts learning throughout the day, and whether these effects are the same for well-rested and sleep restricted individuals. We compared memory in 112 adolescents who underwent two simulated school weeks containing 8 or 6.5 h sleep opportunities each day. Sleep episodes were nocturnal or split between nocturnal sleep and a 90-min afternoon nap, creating four experimental groups: 8 h-continuous, 8 h-split, 6.5 h-continuous and 6.5 h-split. Declarative memory was assessed with picture encoding and an educationally realistic factual knowledge task. Splitting sleep significantly enhanced afternoon picture encoding and factual knowledge under both 6.5 h and 8 h durations. Splitting sleep also significantly reduced slow-wave energy during nocturnal sleep, suggesting lower homeostatic sleep pressure during the day. There was no negative impact of the split sleep schedule on morning performance, despite a reduction in nocturnal sleep. These findings suggest that naps could be incorporated into a daily sleep schedule that provides sufficient sleep and benefits learning.

Memory performance following napping in habitual and non-habitual nappers.

STUDY OBJECTIVES: Afternoon naps benefit memory but this may depend on whether one is a habitual napper (HN; ≥1 nap/week) or non-habitual napper (NN). Here, we investigated whether a nap would benefit HN and NN differently, as well as whether HN would be more adversely affected by nap restriction compared to NN. METHODS: Forty-six participants in the nap condition (HN-nap: n = 25, NN-nap: n = 21) took a 90-min nap (14:00-15:30 pm) on experimental days while 46 participants in the Wake condition (HN-wake: n = 24, NN-wake: n = 22) remained awake in the afternoon. Memory tasks were administered after the nap to assess short-term topographical memory and long-term memory in the form of picture encoding and factual knowledge learning respectively. RESULTS: An afternoon nap boosted picture encoding and factual knowledge learning irrespective of whether one habitually napped (main effects of condition (nap/wake): ps < 0.037). However, we found a significant interaction for the hippocampal-dependent topographical memory task (p = 0.039) wherein a nap, relative to wake, benefitted habitual nappers (HN-nap vs HN-wake: p = 0.003) compared to non-habitual nappers (NN-nap vs. NN-wake: p = 0.918). Notably for this task, habitual nappers' performance significantly declined if they were not allowed to nap (HN-wake vs NN-wake: p = 0.037). CONCLUSIONS: Contrary to concerns that napping may be disadvantageous for non-habitual nappers, we found that an afternoon nap was beneficial for long-term memory tasks even if one did not habitually nap. Naps were especially beneficial for habitual nappers performing a short-term topographical memory task, as it restored the decline that would otherwise have been incurred without a nap. CLINICAL TRIAL INFORMATION: NCT04044885.

Sleep after learning aids the consolidation of factual knowledge, but not relearning.

STUDY OBJECTIVES: Sleep strengthens and reorganizes declarative memories, but the extent to which these processes benefit subsequent relearning of the same material remains unknown. It is also unclear whether sleep-memory effects translate to educationally realistic learning tasks and improve long-term learning outcomes. METHODS: Young adults learned factual knowledge in two learning sessions that were 12 h apart and separated by either nocturnal sleep (n = 26) or daytime wakefulness (n = 26). Memory before and after the retention interval was compared to assess the effect of sleep on consolidation, while memory before and after the second learning session was compared to assess relearning. A final test 1 week later assessed whether there was any long-term advantage to sleeping between two study sessions. RESULTS: Sleep significantly enhanced consolidation of factual knowledge (p = 0.01, d = 0.72), but groups did not differ in their capacity to relearn the materials (p = 0.72, d = 0.10). After 1 week, a numerical memory advantage remained for the sleep group but was no longer significant (p = 0.21, d = 0.35). CONCLUSIONS: Reduced forgetting after sleep is a robust finding that extends to our ecologically valid learning task, but we found no evidence that sleep enhances relearning. Our findings can exclude a large effect of sleep on long-term memory after 1 week, but hint at a smaller effect, leaving open the possibility of practical benefits from organizing study sessions around nocturnal sleep. These findings highlight the importance of revisiting key sleep-memory effects to assess their relevance to long-term learning outcomes with naturalistic learning materials.

Multi-Night Sleep Restriction Impairs Long-Term Retention of Factual Knowledge in Adolescents.

PURPOSE: Sleep deprivation is associated with increased forgetting of declarative memories. Sleep restriction across multiple consecutive nights is prevalent in adolescents, but questions remain as to whether this pattern of sleep impairs memory for material typically learned in the classroom and the time course of retention beyond a few days. METHODS: Adolescents aged 15-18 years (n = 29) were given 5 hours sleep opportunity each night for 5 consecutive nights (sleep restricted group; SR), simulating a school week containing insufficient sleep. After the fourth night of restriction, participants learned detailed facts about different species of arthropod across a 6-hour period. Retention was tested 30 minutes and 3 days after learning and contrasted with a control group (n = 30) who had 9 hours sleep opportunity every night of the study. A subset of participants (SR, n = 14; control, n = 22) completed a surprise test 42 days after learning. RESULTS: Memory was significantly impaired in the SR group relative to controls, with 26% increased forgetting at the 30-minute test (t(57) = 2.54, p = .014, d = .66), 34% at the Day 3 test (t(57) = 2.65, p = .010, d = .69), and 65% at the Day 42 test (t(34) = 3.22, p = .003, d = 1.17). Vigilance was also significantly impaired after 4 nights of restricted sleep (p < .05), but did not correlate significantly with memory (p > .05). CONCLUSION: Long-term retention of classroom material is significantly compromised when adolescents learn after being sleep restricted, reinforcing the importance of keeping good sleep habits to optimize learning.

Does splitting sleep improve long-term memory in chronically sleep deprived adolescents?

Sleep aids the encoding and consolidation of declarative memories, but many adolescents do not obtain the recommended amount of sleep each night. After a normal night of sleep, there is abundant evidence that a daytime nap enhances the consolidation of material learned before sleep and also improves the encoding of new information upon waking. However, it remains unclear how learning is affected when sleep is split between nocturnal and daytime nap periods during a typical school week of restricted sleep. We compared long-term memory in 58 adolescents who underwent two simulated school weeks of suboptimal continuous (6.5 h nocturnal sleep opportunity) or split sleep (5 h nocturnal sleep +1.5 h daytime nap at 14:00). In the first week, participants encoded pictures in the late afternoon on Day 5 and were tested after 2-nights of recovery sleep. On 3 consecutive days in the second week, participants learned about six species of amphibians in the morning, and six different amphibians in the late afternoon. Testing was performed in the evening following a night of recovery sleep. In the first week, the split sleep group recognized more pictures. In the second week, they remembered more facts about species learned in the afternoon. Groups did not differ for species learned in the morning. This suggests that under conditions of sleep restriction, a split sleep schedule benefits learning after a nap opportunity without impairing morning learning, despite less preceding nocturnal sleep. While not replacing adequate nocturnal sleep, a split sleep schedule may be beneficial for chronically sleep restricted learners.

The impact of sleep deprivation on declarative memory.

Sleep plays a crucial role in memory stabilization and integration, yet many people obtain insufficient sleep. This review assesses what is known about the level of sleep deprivation that leads to impairments during encoding, consolidation and retrieval of declarative memories, and what can be determined about the underlying neurophysiological processes. Neuroimaging studies that deprived sleep after learning have provided some of the most compelling evidence for sleep's role in the long-term reorganization of memories in the brain (systems consolidation). However, the behavioral consequences of losing sleep after learning-shown by increased forgetting-appear to recover over time and are unaffected by more common forms of partial sleep restriction across several nights. The capacity to encode new memories is the most vulnerable to sleep loss, since long-term deficits have been observed after total and partial sleep deprivation, while retrieval mechanisms are relatively unaffected. The negative impact of sleep loss on memory has been explored extensively after a night of total sleep deprivation, but further research is needed on the consequences of partial sleep loss over many days so that impairments may be generalized to more common forms of sleep loss.

A split sleep schedule rescues short-term topographical memory after multiple nights of sleep restriction.

STUDY OBJECTIVES: Chronic sleep restriction in adolescents is widespread, yet we know little about how to apportion the limited amount of sleep obtained to minimize cognitive impairment: should sleep occur only nocturnally, or be split across separate nocturnal and daytime nap periods? This is particularly relevant to hippocampal-dependent cognitive functions that underpin several aspects of learning. METHOD: We assessed hippocampal function in four groups by evaluating short-term topographical memory with the Four Mountains Test (4MT). All participants began with 9 hours nocturnal time-in-bed (TIB) for 2 days before following different sleep schedules over the next 3 days. Each day, one group had 5 hours nocturnal TIB (5.0h; n = 30), another, 6.5 hours nocturnal TIB (6.5h; n = 29), and a third had 6.5 hours split into 5 hours nocturnal TIB and a 1.5 hour TIB daytime nap (5.0 + 1.5h; n = 29). A control group maintained 9 hours nocturnal TIB (9.0h; n = 30). The 4MT was administered mid-afternoon (1.5 hours after awakening for those who napped). RESULTS: Performance of the 5.0h and 6.5h nocturnal TIB groups was significantly impaired relative to the 9.0h control group. Performance of participants on the split- sleep schedule (5.0 + 1.5h) did not significantly differ from controls. CONCLUSIONS: These findings suggest that hippocampal function is sensitive to moderate multi-night sleep restriction, but deficits can be ameliorated by splitting sleep, at least for a period after waking from a daytime nap. While this split sleep schedule should not be considered a replacement for adequate nocturnal sleep, it appears to benefit the cognitive and neurophysiological functions that underpin learning in those who are chronically sleep deprived.

The long-term memory benefits of a daytime nap compared with cramming.

Study Objectives: Daytime naps benefit long-term memory relative to taking a break and remaining awake. However, the use of naps as a practical way to improve learning has not been examined, in particular, how memory following a nap compares with spending the equivalent amount of time cramming. Methods: Young adults learned detailed factual knowledge in sessions that flanked 1 hr spent napping (n = 27), taking a break (n = 27), or cramming that information (n = 30). Recall was examined 30 min and 1 week after learning. Results: When tested 30 min after learning, cramming and napping led to significantly better memory than taking a break. After a week, napping maintained this significant advantage, but cramming did not. Conclusions: These findings demonstrate the longer-term benefits of napping for retention of memoranda akin to what students encounter daily and encourage more widespread adoption of napping in education.

Memory encoding is impaired after multiple nights of partial sleep restriction.

Sleep is important for normative cognitive functioning. A single night of total sleep deprivation can reduce the capacity to encode new memories. However, it is unclear how sleep restriction during several consecutive nights affects memory encoding. To explore this, we employed a parallel-group design with 59 adolescents randomized into sleep-restricted (SR) and control groups. Both groups were afforded 9 h time in bed (TIB) for 2 baseline nights, followed by 5 consecutive nights of 5 h TIB for the SR group (n = 29) and 9 h TIB for the control group (n = 30). Participants then performed a picture-encoding task. Encoding ability was measured with a recognition test after 3 nights of 9 h TIB recovery sleep for both groups, allowing the assessment of encoding ability without the confounding effects of fatigue at retrieval. Memory was significantly worse in the sleep-restricted group (P = 0.001), and this impairment was not correlated with decline in vigilance. We conclude that memory-encoding deteriorates after several nights of partial sleep restriction, and this typical pattern of sleep negatively affects adolescents' ability to learn declarative information.

Cued Memory Reactivation During SWS Abolishes the Beneficial Effect of Sleep on Abstraction.

Study Objectives: Extracting regularities from stimuli in our environment and generalizing these to new situations are fundamental processes in human cognition. Sleep has been shown to enhance these processes, possibly by facilitating reactivation-triggered memory reorganization. Here, we assessed whether cued reactivation during slow wave sleep (SWS) promotes the beneficial effect of sleep on abstraction of statistical regularities. Methods: We used an auditory statistical learning task, in which the benefit of sleep has been firmly established. Participants were exposed to a probabilistically determined sequence of tones and subsequently tested for recognition of novel short sequences adhering to this same statistical pattern in both immediate and delayed recall sessions. In different groups, the exposure stream was replayed during SWS in the night between the recall sessions (SWS-replay group), in wake just before sleep (presleep replay group), or not at all (control group). Results: Surprisingly, participants who received replay in sleep performed worse in the delayed recall session than the control and the presleep replay group. They also failed to show the association between SWS and task performance that has been observed in previous studies and was present in the controls. Importantly, sleep structure and sleep quality did not differ between groups, suggesting that replay during SWS did not impair sleep but rather disrupted or interfered with sleep-dependent mechanisms that underlie the extraction of the statistical pattern. Conclusions: These findings raise important questions about the scope of cued memory reactivation and the mechanisms that underlie sleep-related generalization.

Cued Reactivation of Motor Learning during Sleep Leads to Overnight Changes in Functional Brain Activity and Connectivity.

Sleep plays a role in memory consolidation. This is demonstrated by improved performance and neural plasticity underlying that improvement after sleep. Targeted memory reactivation (TMR) allows the manipulation of sleep-dependent consolidation through intentionally biasing the replay of specific memories in sleep, but the underlying neural basis of these altered memories remains unclear. We use functional magnetic resonance imaging (fMRI) to show a change in the neural representation of a motor memory after targeted reactivation in slow-wave sleep (SWS). Participants learned two serial reaction time task (SRTT) sequences associated with different auditory tones (high or low pitch). During subsequent SWS, one sequence was reactivated by replaying the associated tones. Participants were retested on both sequences the following day during fMRI. As predicted, they showed faster reaction times for the cued sequence after targeted memory reactivation. Furthermore, increased activity in bilateral caudate nucleus and hippocampus for the cued relative to uncued sequence was associated with time in SWS, while increased cerebellar and cortical motor activity was related to time in rapid eye movement (REM) sleep. Functional connectivity between the caudate nucleus and hippocampus was also increased after targeted memory reactivation. These findings suggest that the offline performance gains associated with memory reactivation are supported by altered functional activity in key cognitive and motor networks, and that this consolidation is differentially mediated by both REM sleep and SWS.

Sleep Spindle Density Predicts the Effect of Prior Knowledge on Memory Consolidation.

Information that relates to a prior knowledge schema is remembered better and consolidates more rapidly than information that does not. Another factor that influences memory consolidation is sleep and growing evidence suggests that sleep-related processing is important for integration with existing knowledge. Here, we perform an examination of how sleep-related mechanisms interact with schema-dependent memory advantage. Participants first established a schema over 2 weeks. Next, they encoded new facts, which were either related to the schema or completely unrelated. After a 24 h retention interval, including a night of sleep, which we monitored with polysomnography, participants encoded a second set of facts. Finally, memory for all facts was tested in a functional magnetic resonance imaging scanner. Behaviorally, sleep spindle density predicted an increase of the schema benefit to memory across the retention interval. Higher spindle densities were associated with reduced decay of schema-related memories. Functionally, spindle density predicted increased disengagement of the hippocampus across 24 h for schema-related memories only. Together, these results suggest that sleep spindle activity is associated with the effect of prior knowledge on memory consolidation. SIGNIFICANCE STATEMENT: Episodic memories are gradually assimilated into long-term memory and this process is strongly influenced by sleep. The consolidation of new information is also influenced by its relationship to existing knowledge structures, or schemas, but the role of sleep in such schema-related consolidation is unknown. We show that sleep spindle density predicts the extent to which schemas influence the consolidation of related facts. This is the first evidence that sleep is associated with the interaction between prior knowledge and long-term memory formation.

Cued memory reactivation during slow-wave sleep promotes explicit knowledge of a motor sequence.

Memories are gradually consolidated after initial encoding, and this can sometimes lead to a transition from implicit to explicit knowledge. The exact physiological processes underlying this reorganization remain unclear. Here, we used a serial reaction time task to determine whether targeted memory reactivation (TMR) of specific memory traces during slow-wave sleep promotes the emergence of explicit knowledge. Human participants learned two 12-item sequences of button presses (A and B). These differed in both cue order and in the auditory tones associated with each of the four fingers (one sequence had four higher-pitched tones). Subsequent overnight sleep was monitored, and the tones associated with one learned sequence were replayed during slow-wave sleep. After waking, participants demonstrated greater explicit knowledge (p = 0.005) and more improved procedural skill (p = 0.04) for the cued sequence relative to the uncued sequence. Furthermore, fast spindles (13.5-15 Hz) at task-related motor regions predicted overnight enhancement in procedural skill (r = 0.71, p = 0.01). Auditory cues had no effect on post-sleep memory performance in a control group who received TMR before sleep. These findings suggest that TMR during sleep can alter memory representations and promote the emergence of explicit knowledge, supporting the notion that reactivation during sleep is a key mechanism in this process.

Time- but not sleep-dependent consolidation promotes the emergence of cross-modal conceptual representations.

Conceptual knowledge about objects comprises a diverse set of multi-modal and generalisable information, which allows us to bring meaning to the stimuli in our environment. The formation of conceptual representations requires two key computational challenges: integrating information from different sensory modalities and abstracting statistical regularities across exemplars. Although these processes are thought to be facilitated by offline memory consolidation, investigations into how cross-modal concepts evolve offline, over time, rather than with continuous category exposure are still missing. Here, we aimed to mimic the formation of new conceptual representations by reducing this process to its two key computational challenges and exploring its evolution over an offline retention period. Participants learned to distinguish between members of two abstract categories based on a simple one-dimensional visual rule. Underlying the task was a more complex hidden indicator of category structure, which required the integration of information across two sensory modalities. In two experiments we investigated the impact of time- and sleep-dependent consolidation on category learning. Our results show that offline memory consolidation facilitated cross-modal category learning. Surprisingly, consolidation across wake, but not across sleep showed this beneficial effect. By demonstrating the importance of offline consolidation the current study provided further insights into the processes that underlie the formation of conceptual representations.