Off-line Memory Consolidation Research Articles

Role of cerebellum in sleep-dependent memory processes.

The activities and role of the cerebellum in sleep have, until recently, been largely ignored by both the sleep and cerebellum fields. Human sleep studies often neglect the cerebellum because it is at a position in the skull that is inaccessible to EEG electrodes. Animal neurophysiology sleep studies have focussed mainly on the neocortex, thalamus and the hippocampus. However, recent neurophysiological studies have shown that not only does the cerebellum participate in the sleep cycle, but it may also be implicated in off-line memory consolidation. Here we review the literature on cerebellar activity during sleep and the role it plays in off-line motor learning, and introduce a hypothesis whereby the cerebellum continues to compute internal models during sleep that train the neocortex.

Thalamo-hippocampal pathway regulates incidental memory capacity in mice

Incidental memory can be challenged by increasing either the retention delay or the memory load. The dorsal hippocampus (dHP) appears to help with both consolidation from short-term (STM) to long-term memory (LTM), and higher memory loads, but the mechanism is not fully understood. Here we find that female mice, despite having the same STM capacity of 6 objects and higher resistance to distraction in our different object recognition task (DOT), when tested over 1 h or 24 h delays appear to transfer to LTM only 4 objects, whereas male mice have an STM capacity of 6 objects in this task. In male mice the dHP shows greater activation (as measured by c-Fos expression), whereas female mice show greater activation of the ventral midline thalamus (VMT). Optogenetic inhibition of the VMT-dHP pathway during off-line memory consolidation enables 6-object LTM retention in females, while chemogenetic VMT-activation impairs it in males. Thus, removing or enhancing sub-cortical inhibitory control over the hippocampus leads to differences in incidental memory.

Offline memory consolidation during waking rest

Offline memory consolidation during waking rest

Sleep Deprivation Impairs Learning-Induced Increase in Hippocampal Sharp Wave Ripples and Associated Spike Dynamics during Recovery Sleep.

Sleep deprivation (SD) causes deficits in off-line memory consolidation, but the underlying network oscillation mechanisms remain unclear. Hippocampal sharp wave ripple (SWR) oscillations play a critical role in off-line memory consolidation. Therefore, we trained mice to learn a hippocampus-dependent trace eyeblink conditioning (tEBC) task and explored the influence of 1.5-h postlearning SD on hippocampal SWRs and related spike dynamics during recovery sleep. We found an increase in hippocampal SWRs during postlearning sleep, which predicted the consolidation of tEBC in conditioned mice. In contrast, sleep-deprived mice showed a loss of tEBC learning-induced increase in hippocampal SWRs during recovery sleep. Moreover, the sleep-deprived mice exhibited weaker reactivation of tEBC learning-associated pyramidal cells in hippocampal SWRs during recovery sleep. In line with these findings, tEBC consolidation was impaired in sleep-deprived mice. Furthermore, sleep-deprived mice showed augmented fast excitation from pyramidal cells to interneurons and enhanced participation of interneurons in hippocampal SWRs during recovery sleep. Among various interneurons, parvalbumin-expressing interneurons specifically exhibited overexcitation during hippocampal SWRs. Our findings suggest that altered hippocampal SWRs and associated spike dynamics during recovery sleep may be candidate network oscillation mechanisms underlying SD-induced memory deficits.

The Prospective Sleeping Brain: Age-Related Differences in Episodic Future Thinking and Frontal Sleep Spindles.

Sleep spindles are a physiological marker of off-line memory consolidation. In young adults, sleep spindles are preferentially responsive to encoded information that is tagged as having future relevance. Older adults, on the other hand, show reduced capacity for future simulation and alterations in sleep physiology. Healthy young adults (n = 38) and older adults (n = 28) completed an adaptation night, followed by two in-laboratory polysomnography nights, in which they mentally simulated future events or remembered past events, recorded via written descriptions. We quantified the degree of future/past thinking using linguistic analysis of time orientation. In young adults, greater future thinking was linked to greater spindle density, even when controlling for gender, age, and word count (rp = .370, p = .028). The opposite was true for older adults, such that greater future thinking was associated with reduced spindle density (rp = -.431, p = .031). These patterns were selective to future thinking (not observed for past thinking). The collective findings implicate an impaired interaction between future relevance tagging and sleep physiology as a mechanism by which aging compromises sleep-dependent cognitive processing.

Most hippocampal CA1 pyramidal cells in rabbits increase firing during awake sharp-wave ripples and some do so in response to external stimulation and theta.

Hippocampus forms neural representations of real-life events including multimodal information of spatial and temporal context. These representations, i.e., organized sequences of neuronal firing, are repeated during following rest and sleep, especially when so-called sharp-wave ripples (SPW-Rs) characterize hippocampal local field potentials. This SPW-R -related replay is thought to underlie memory consolidation. Here, we set out to explore how hippocampal CA1 pyramidal cells respond to the conditioned stimulus during trace eyeblink conditioning and how these responses manifest during SPW-Rs in awake adult female New Zealand White rabbits. Based on reports in rodents, we expected SPW-Rs to take place in bursts, possibly according to a slow endogenous rhythm. In awake rabbits, half of all SPW-Rs took place in bursts, but no endogenous slow rhythm appeared. Conditioning trials suppressed SPW-Rs while increasing theta for a period of several seconds. As expected based on previous findings, only a quarter of the putative CA1 pyramidal cells increased firing in response to the conditioned stimulus. Compared with other cells, rate-increasing cells were more active during spontaneous epochs of hippocampal theta while response profile during conditioning did not affect firing during SPW-Rs. Taken together, CA1 pyramidal cell firing during SPW-Rs is not limited to cells that fired during the preceding experience. Furthermore, the importance of possible reactivations taking place during theta epochs on memory consolidation warrants further investigation.NEW & NOTEWORTHY We studied hippocampal sharp-wave ripples and theta and CA1 pyramidal cell activity during trace eyeblink conditioning in rabbits. Conditioning trials suppressed ripples while increasing theta for a period of several seconds. A quarter of the cells increased firing in response to the conditioned stimulus and fired extensively during endogenous theta as well as ripples. The role of endogenous theta epochs in off-line memory consolidation should be studied further.

How Bizarre: The Glitch of the Nineties as a Fantasy of New Authorship

How Bizarre: The Glitch of the Nineties as a Fantasy of New Authorship

The role of complementary learning systems in learning and consolidation in a quasi-regular domain

We examine the role of off-line memory consolidation processes in the learning and retention of a new quasi-regular linguistic system similar to the English past tense. Quasi-regular systems are characterized by a dominance of systematic, regular forms (e.g., walk-walked, jump-jumped) alongside a smaller number of high frequency irregulars (e.g., sit-sat, go-went), and are found across many cognitive domains, from spelling-sound mappings to inflectional morphology to semantic cognition. Participants were trained on the novel morphological system using an artificial language paradigm, and then tested after different delays. Based on a complementary systems account of memory, we predicted that irregular forms would show stronger off-line changes due to consolidation processes. Across two experiments, participants were tested either immediately after learning, 12 h later with or without sleep, or 24 h later. Testing involved generalization of the morphological patterns to previously unseen words (both experiments) as well as recall of the trained words (Experiment 2). In generalization, participants showed ‘default’ regularization across a range of novel forms, as well as irregularization for previously unseen items that were similar to unique high-frequency irregular trained forms. Both patterns of performance remained stable across the delays. Generalizations involving competing tendencies to regularize and irregularize were balanced between the two immediately after learning. Crucially, at both 12-h delays the tendency to irregularize in these cases was strengthened, with further strengthening after 24 h. Consolidated knowledge of both regular and irregular trained items contributed significantly to generalization performance, with evidence of strengthening of irregular forms and weakening of regular forms. We interpret these findings in the context of a complementary systems model, and discuss how maintenance, strengthening, and forgetting of the new memories across sleep and wake can play a role in acquiring quasi-regular systems.

Background matters: Minor vibratory stimulation during motor skill acquisition selectively reduces off-line memory consolidation

Although a ubiquitous situation, it is not clear how effective is a learning experience when task-irrelevant, sensory noise occurs in the background. Here, young adults were trained on the finger opposition sequence task, in a well-established training and testing protocol affording measures for online as well as off-line learning. During the training session, one group experienced a minor background vibratory stimulation to the trunk by the means of vibrating cushion, while the second group experienced recorded sound vibrations. A control group was trained with no extra sensory stimulation. Sensory stimulation during training had no effect on the online within-session gains, but dampened the expression of the off-line, consolidation phase, gains in the two sensory stimulation groups. These results suggest that background sensory stimulation can selectively modify off-line, procedural memory consolidation processes, despite well-preserved on-line learning. Classical studies have shown that neural plasticity in sensory systems is modulated by motor input. The current results extend this notion and suggest that some types of task-irrelevant sensory stimulation, concurrent with motor training, may constitute a ‘gating’ factor - modulating the triggering of long-term procedural memory consolidation processes. Thus, vibratory stimulation may be considered as a behavioral counterpart of pharmacological interventions that do not interfere with short term neural plasticity but block long-term plasticity.

Motor memory: Representation, learning and consolidation

Abstract An efficient representation of motor system is vital to robot control and its ability to learn new skills. While the increasing sensor accuracy and the speed of signal processing failed to bridge the gap between the performance of artificial and human sensorimotor systems, the motor memory architecture seems to remain neglected. Despite the advances in robot skill learning, the latter remains limited to predefined tasks and pre-specified embodiment. We propose a new motor memory architecture that enables information sharing between different skills, on-line learning and off-line memory consolidation. We develop an algorithm for learning and consolidation of motor memory and study the space complexity of the representation in the experiments with humanoid robot Nao. Finally, we propose the integration of motor memory with sensor data into a common sensorimotor memory.

Diminished Nap Effects on Memory Consolidation Are Seen Under Oral Contraceptive Use

Many young females take exogenous hormones as oral contraceptive (OC), a condition rarely controlled for in studies on sleep and memory consolidation even though sex hormones influence consolidation. This study investigated the effects of OCs on sleep-related consolidation of a motor and declarative task, utilizing a daytime nap protocol. Fifteen healthy, young females taking OCs came to the sleep lab for three different conditions: nap with previous learning, wake with previous learning and nap without learning. They underwent each condition twice, once during the ‘pill-active' weeks and once during the ‘pill-free' week, resulting in 6 visits. In all conditions, participants showed a significant off-line consolidation effect, independent of pill week or nap/wake condition. There were no significant differences in sleep stage duration, spindle activity or spectral EEG frequency bands between naps with or without the learning condition. The present data showed a significant off-line enhancement in memory irrespective of potential beneficial effects of a nap. In comparison to previous studies, this may suggest that the use of OCs may enhance off-line memory consolidation in motor and verbal tasks per se. These results stress the importance to control for the use of OCs in studies focusing on memory performance.

Impaired off-line motor skills consolidation in young primary insomniacs

Compelling evidence indicates that sleep can facilitate the off-line consolidation of declarative, perceptual, emotional and procedural memories. Here we assessed the sleep-related off-line consolidation of motor skills in 13 young primary insomniacs (23.31±2.5 yrs) compared to 13 healthy sleepers (24.31±1.6 yrs) using the sequential finger tapping task. During a training session insomniacs performed less correct sequences than controls. However, both groups exhibited similar on-line motor learning in the pre-sleep evening session. After a night of sleep, healthy controls improved their performance, indicating an overnight effect of sleep on motor skills consolidation. In contrast, insomniacs failed to exhibit a sleep-related enhancement in memory performance indicating impairment in the off-line motor skills consolidation process. Our results suggest that young adults with insomnia experience impaired off-line memory consolidation which seems not to be associated with reduced ability to acquire new motor information.

Effects of Apolipoprotein E Genotype on the Off-Line Memory Consolidation

Spontaneous brain activity or off-line activity after memory encoding is associated with memory consolidation. A few recent resting-state functional magnetic resonance imaging (RS-fMRI) studies indicate that the RS-fMRI could map off-line memory consolidation effects. However, the gene effects on memory consolidation process remain largely unknown. Here we collected two RS-fMRI sessions, one before and another after an episodic memory encoding task, from two groups of healthy young adults, one with apolipoprotein E (APOE) ε2/ε3 and the other with APOE ε3/ε4. The ratio of regional homogeneity (ReHo), a measure of local synchronization of spontaneous RS-fMRI signal, of the two sessions was used as an index of memory-consolidation. APOE ε3/ε4 group showed greater ReHo ratio within the medial temporal lobe (MTL). The ReHo ratio in MTL was significantly correlated with the recognition memory performance in the APOE ε3/ε4 group but not in ε2/ε3 group. Additionally, APOE ε3/ε4 group showed lower ReHo ratio in the occipital and parietal picture-encoding areas. Our results indicate that APOE ε3/ε4 group may have a different off-line memory consolidation process compared to ε2/ε3 group. These results may help generate future hypotheses that the off-line memory consolidation might be impaired in Alzheimer’s disease.

Hippocampal–cortical interaction during periods of subcortical silence

Hippocampal ripples, episodic high-frequency field-potential oscillations primarily occurring during sleep and calmness, have been described in mice, rats, rabbits, monkeys and humans, and so far they have been associated with retention of previously acquired awake experience. Although hippocampal ripples have been studied in detail using neurophysiological methods, the global effects of ripples on the entire brain remain elusive, primarily owing to a lack of methodologies permitting concurrent hippocampal recordings and whole-brain activity mapping. By combining electrophysiological recordings in hippocampus with ripple-triggered functional magnetic resonance imaging, here we show that most of the cerebral cortex is selectively activated during the ripples, whereas most diencephalic, midbrain and brainstem regions are strongly and consistently inhibited. Analysis of regional temporal response patterns indicates that thalamic activity suppression precedes the hippocampal population burst, which itself is temporally bounded by massive activations of association and primary cortical areas. These findings suggest that during off-line memory consolidation, synergistic thalamocortical activity may be orchestrating a privileged interaction state between hippocampus and cortex by silencing the output of subcortical centres involved in sensory processing or potentially mediating procedural learning. Such a mechanism would cause minimal interference, enabling consolidation of hippocampus-dependent memory.

Increased local synchronization of resting-state fMRI signal after episodic memory encoding reflects off-line memory consolidation

The changes of spontaneous activity from before and after a memory or learning task had been considered to be related to off-line memory consolidation process in human brain by using resting-state functional connectivity (RSFC) MRI (fMRI). However, RSFC reflects temporal synchronization of timecourses of spatially distinct brain regions and therefore could not determine which specific brain region is involved in the memory consolidation process. Here we used regional homogeneity (ReHo), a method for measuring local synchronization, to link the local spontaneous activity change to off-line episodic memory consolidation. We hypothesized that the spontaneous activity change would be different between people with better memory performance and those with worse performance in memory-related regions. All participants completed two resting-state sessions, that is, before (REST-1) and after (REST-2) an episodic memory encoding task (picture indoor or outdoor judgment). Then, based on the d' of a later surprise memory retrieval test, a high-performance group and a low-performance group, each consisting of 16 participants, were chosen from whole 58 participants. We defined a ReHo ratio, that is, ReHo of REST-2 divided by ReHo of REST-1, as a change induced by memory consolidation. The high-performance group showed a significant higher ReHo ratio than low-performance group in medial temporal lobe (MTL) including parahippocampal and anterior temporal regions. The current results provide neuroimaging evidence supporting that the MTL is involved in off-line memory consolidation of episodic memory. Moreover, this study may provide a paradigm for understanding of episodic memory deficit in Alzheimer's disease.

The Memory Function of Noradrenergic Activity in Non-REM Sleep

There is a long-standing assumption that low noradrenergic activity during sleep reflects mainly the low arousal during this brain state. Nevertheless, recent research has demonstrated that the locus coeruleus, which is the main source of cortical noradrenaline, displays discrete periods of intense firing during non-REM sleep, without any signs of awakening. This transient locus coeruleus activation during sleep seems to occur in response to preceding learning-related episodes. In the present study, we manipulate noradrenergic activity during sleep in humans with either the α2-autoreceptor agonist clonidine or the noradrenaline reuptake inhibitor reboxetine. We show that reducing noradrenergic activity during sleep, but not during wakefulness, impairs subsequent memory performance in an odor recognition task. Increasing noradrenergic availability during sleep, in contrast, enhances memory retention. We conclude that noradrenergic activity during non-REM sleep interacts with other sleep-related mechanisms to functionally contribute to off-line memory consolidation.

A double dissociation of memory impairments in major depression

Sleep benefits the consolidation of both declarative and nondeclarative memories, however the question if these two memory systems profit from sleep in more or less similar ways is still under debate. Studying the on-line and off-line consolidation of declarative and nondeclarative memory tasks in depressed patients and healthy controls, we here present a clear double dissociation between memory systems and consolidation phases, suggesting radically different ways how sleep benefits memory consolidation. 37 medicated inpatients with an acute episode of major depression and 31 healthy controls were assessed using a nondeclarative (sequential finger tapping) memory task before and after a night with polysomnography, 27 of the depressed and 22 of the control subjects additionally performed a declarative (paired associates) task. Although depressed patients and control subjects did not differ in practice-dependent learning of the nondeclarative motor task in the wake state, healthy subjects showed overnight improvements in tapping performance of 11.4%, while the patients’ performance decreased overnight by 11.5%. This pattern was reversed for the declarative task: While patients learned 33.5% less word pairs than controls in the wake state, overnight changes did not differ between the two groups. These results suggest a double dissociation of memory consolidation processes in major depression: Off-line memory consolidation in major depression is impaired for nondeclarative, but not declarative tasks. The same tasks in the wake state show a reversed pattern, with performance in declarative but not nondeclarative tasks being impaired in major depression.

Noradrenergic Neurons of the Locus Coeruleus Are Phase Locked to Cortical Up-Down States during Sleep

Nonrapid eye movement (NREM) sleep is characterized by periodic changes in cortical excitability that are reflected in the electroencephalography (EEG) as high-amplitude slow oscillations, indicative of cortical Up/Down states. These slow oscillations are thought to be involved in NREM sleep-dependent memory consolidation. Although the locus coeruleus (LC) noradrenergic system is known to play a role in off-line memory consolidation (that may occur during NREM sleep), cortico-coerulear interactions during NREM sleep have not yet been studied in detail. Here, we investigated the timing of LC spikes as a function of sleep-associated slow oscillations. Cortical EEG was monitored, along with activity of LC neurons recorded extracellularly, in nonanesthetized naturally sleeping rats. LC spike-triggered averaging of EEG, together with phase-locking analysis, revealed preferential firing of LC neurons along the ascending edge of the EEG slow oscillation, correlating with Down-to-Up state transition. LC neurons were locked best when spikes were shifted forward ∼50 ms in time with respect to the EEG slow oscillation. These results suggest that during NREM sleep, firing of LC neurons may contribute to the rising phase of the EEG slow wave by providing a neuromodulatory input that increases cortical excitability, thereby promoting plasticity within these circuits.

Off-line memory consolidation impairments in multiple sclerosis patients receiving high-dose corticosteroid treatment mirror consolidation impairments in depression

Sleep supports the consolidation of procedural memory, however patients with major depression show impaired motor memory performance after a night of sleep. It was hypothesized that this impairment is related to hypothalamic-pituitary-adrenal (HPA) axis dysfunction. We tested if high-dose administration of corticosteroids impairs off-line motor memory consolidation in patients with multiple sclerosis (MS). Nine patients with MS receiving high-dose corticosteroid therapy (methylprednisolone) and nine MS patients receiving alternative therapy (mitoxantrone) were assessed using a sequential finger tapping task before and after a night with polysomnography. In addition, nine patients with major depression (MD) receiving antidepressants and nine healthy controls were assessed. Although the four groups did not differ in practice-dependent learning, healthy subjects and MS patients receiving mitoxantrone showed markedly overnight-improvements in tapping performance of 17% and 24% while MS patients receiving high-dose corticosteroid therapy and depressed patients showed -9% and -10% overnight decrease. MS patients with and without corticosteroid therapy did not differ in their amount of REM sleep, nor did MD patients and healthy controls. In addition, we did not find any correlation between REM sleep and memory consolidation. Our results show that a strong intervention into the HPA system like in MS high-dose corticosteroid therapy impairs off-line motor memory consolidation comparable to the impairments seen in depressed patients. We propose therefore that depression-related changes in plasma corticosteroid levels rather than in sleep per se underlie off-line memory consolidation impairments in MD.

Covert Reorganization of Implicit Task Representations by Slow Wave Sleep

BackgroundThere is evidence that slow wave sleep (SWS) promotes the consolidation of memories that are subserved by mediotemporal- and hippocampo-cortical neural networks. In contrast to implicit memories, explicit memories are accompanied by conscious (attentive and controlled) processing. Awareness at pre-sleep encoding has been recognized as critical for the off-line memory consolidation. The present study elucidated the role of task-dependent cortical activation guided by attentional control at pre-sleep encoding for the consolidation of hippocampus-dependent memories during sleep.MethodologyA task with a hidden regularity was used (Number Reduction Task, NRT), in which the responses that can be implicitly predicted by the hidden regularity activate hippocampo-cortical networks more strongly than responses that cannot be predicted. Task performance was evaluated before and after early-night sleep, rich in SWS, and late-night sleep, rich in rapid eye movement (REM) sleep. In implicit conditions, slow cortical potentials (SPs) were analyzed to reflect the amount of controlled processing and the localization of activated neural task representations.Principal FindingsDuring implicit learning before sleep, the amount of controlled processing did not differ between unpredictable and predictable responses, nor between early- and late-night sleep groups. A topographic re-distribution of SPs indicating a spatial reorganization occurred only after early, not after late sleep, and only for predictable responses. These SP changes correlated with the amount of SWS and were covert because off-line RT decrease did not differentiate response types or sleep groups.ConclusionsIt is concluded that SWS promotes the neural reorganization of task representations that rely on the hippocampal system despite absence of conscious access to these representations.SignificanceOriginal neurophysiologic evidence is provided for the role of SWS in the consolidation of memories encoded with hippocampo-cortical interaction before sleep. It is demonstrated that this SWS-mediated mechanism does not depend critically on explicitness at learning nor on the amount of controlled executive processing during pre-sleep encoding.