NREM2 and Sleep Spindles Are Instrumental to the Consolidation of Motor Sequence Memories

Although numerous studies have convincingly demonstrated that sleep plays a critical role in motor sequence learning (MSL) consolidation, the specific contribution of the different sleep stages in this type of memory consolidation is still contentious. To probe the role of stage 2 non-REM sleep (NREM2) in this process, we used a conditioning protocol in three different groups of participants who either received an odor during initial training on a motor sequence learning task and were re-exposed to this odor during different sleep stages of the post-training night (i.e., NREM2 sleep [Cond-NREM2], REM sleep [Cond-REM], or were not conditioned during learning but exposed to the odor during NREM2 [NoCond]). Results show that the Cond-NREM2 group had significantly higher gains in performance at retest than both the Cond-REM and NoCond groups. Also, only the Cond-NREM2 group yielded significant changes in sleep spindle characteristics during cueing. Finally, we found that a change in frequency of sleep spindles during cued-memory reactivation mediated the relationship between the experimental groups and gains in performance the next day. These findings strongly suggest that cued-memory reactivation during NREM2 sleep triggers an increase in sleep spindle activity that is then related to the consolidation of motor sequence memories.     

Sleep-Dependent Reactivation of Ensembles in Motor Cortex Promotes Skill Consolidation

Despite many prior studies demonstrating offline behavioral gains in motor skills after sleep, the underlying neural mechanisms remain poorly understood. To investigate the neurophysiological basis for offline gains, we performed single-unit recordings in motor cortex as rats learned a skilled upper-limb task. We found that sleep improved movement speed with preservation of accuracy. These offline improvements were linked to both replay of task-related ensembles during non-rapid eye movement (NREM) sleep and temporal shifts that more tightly bound motor cortical ensembles to movements; such offline gains and temporal shifts were not evident with sleep restriction. Interestingly, replay was linked to the coincidence of slow-wave events and bursts of spindle activity. Neurons that experienced the most consistent replay also underwent the most significant temporal shift and binding to the motor task. Significantly, replay and the associated performance gains after sleep only occurred when animals first learned the skill; continued practice during later stages of learning (i.e., after motor kinematics had stabilized) did not show evidence of replay. Our results highlight how replay of synchronous neural activity during sleep mediates large-scale neural plasticity and stabilizes kinematics during early motor learning.     

Effects of ageing on allocentric and egocentric spatial strategies in the Wistar rat

This study was designed to assess the effect of ageing on spatial (allocentric and egocentric) strategies in rats. Two different tasks were designed for this purpose: one involving Morris' circular pool (distal extramaze cues) and another using the T water maze (egocentric cues). In the first task, the aged rats showed some difficulty in acquiring allocentric spatial learning skills. After increasing the number of trials in this task, there was no significant improvement in the performance of the aged group of rats compared to the adult group. However, in the second spatial task (using egocentric cues), both age groups gave a similar performance. Therefore, the effect of ageing on spatial learning depends on the strategy required to acquire this learning.     

Ganzfeld Stimulation or Sleep Enhance Long Term Motor Memory Consolidation Compared to Normal Viewing in Saccadic Adaptation Paradigm

Adaptation of saccade amplitude in response to intra-saccadic target displacement is a type of implicit motor learning which is required to compensate for physiological changes in saccade performance. Once established trials without intra-saccadic target displacement lead to de-adaptation or extinction, which has been attributed either to extra-retinal mechanisms of spatial constancy or to the influence of the stable visual surroundings. Therefore we investigated whether visual deprivation (“Ganzfeld”-stimulation or sleep) can partially maintain this motor learning compared to free viewing of the natural surroundings. Thirty-five healthy volunteers performed two adaptation blocks of 100 inward adaptation trials – interspersed by an extinction block – which were followed by a two-hour break with or without visual deprivation (VD). Using additional adaptation and extinction blocks short and long (4 weeks) term memory of this implicit motor learning were tested. In the short term, motor memory tested immediately after free viewing was superior to adaptation performance after VD. In the long run, however, effects were opposite: motor memory and relearning of adaptation was superior in the VD conditions. This could imply independent mechanisms that underlie the short-term ability of retrieving learned saccadic gain and its long term consolidation. We suggest that subjects mainly rely on visual cues (i.e., retinal error) in the free viewing condition which makes them prone to changes of the visual stimulus in the extinction block. This indicates the role of a stable visual array for resetting adapted saccade amplitudes. In contrast, visual deprivation (GS and sleep), might train subjects to rely on extra-retinal cues, e.g., efference copy or prediction to remap their internal representations of saccade targets, thus leading to better consolidation of saccadic adaptation.     

Impaired representation of geometric relationships in humans with damage to the hippocampal formation

The pivotal role of the hippocampus for spatial memory is well-established. However, while neurophysiological and imaging studies suggest a specialization of the hippocampus for viewpoint-independent or allocentric memory, results from human lesion studies have been less conclusive. It is currently unclear whether disproportionate impairment in allocentric memory tasks reflects impairment of cognitive functions that are not sufficiently supported by regions outside the medial temporal lobe or whether the deficits observed in some studies are due to experimental factors. Here, we have investigated whether hippocampal contributions to spatial memory depend on the spatial references that are available in a certain behavioral context. Patients with medial temporal lobe lesions affecting systematically the right hippocampal formation performed a series of three oculomotor tasks that required memory of a spatial cue either in retinal coordinates or relative to a single environmental reference across a delay of 5000 ms. Stimulus displays varied the availability of spatial references and contained no complex visuo-spatial associations. Patients showed a selective impairment in a condition that critically depended on memory of the geometric relationship between spatial cue and environmental reference. We infer that regions of the medial temporal lobe, most likely the hippocampal formation, contribute to behavior in conditions that exceed the potential of viewpoint-dependent or egocentric representations. Apparently, this already applies to short-term memory of simple geometric relationships and does not necessarily depend on task difficulty or integration of landmarks into more complex representations. Deficient memory of basic geometric relationships may represent a core deficit that contributes to impaired performance in allocentric spatial memory tasks.     

Egocentric Representation Acquired from Offline Map Learning

It is widely accepted that people establish allocentric spatial representation after learning a map. However, it is unknown whether people can directly acquire egocentric representation after map learning. In two experiments, the participants learned a distal environment through a map and then performed the egocentric pointing tasks in that environment under three conditions: with the heading aligned with the learning perspective (baseline), after 240° rotation from the baseline (updating), and after disorientation (disorientation). Disorientation disrupted the internal consistency of pointing among objects when the participants learned the sequentially displayed map, on which only one object name was displayed at a time while the location of “self” remained on the screen all the time. However, disorientation did not affect the internal consistency of pointing among objects when the participants learned the simultaneously displayed map. These results suggest that the egocentric representation can be acquired from a sequentially presented map.     

Covert Reorganization of Implicit Task Representations by Slow Wave Sleep

Background

There 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.

Methodology

A 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 Findings

During 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.

Conclusions

It 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.

Significance

Original 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.     

Sleep modulates the neural substrates of both spatial and contextual memory consolidation

It is known that sleep reshapes the neural representations that subtend the memories acquired while navigating in a virtual environment. However, navigation is not process-pure, as manifold learning components contribute to performance, notably the spatial and contextual memory constituents. In this context, it remains unclear whether post-training sleep globally promotes consolidation of all of the memory components embedded in virtual navigation, or rather favors the development of specific representations. Here, we investigated the effect of post-training sleep on the neural substrates of the consolidation of spatial and contextual memories acquired while navigating in a complex 3D, naturalistic virtual town. Using fMRI, we mapped regional cerebral activity during various tasks designed to tap either the spatial or the contextual memory component, or both, 72 h after encoding with or without sleep deprivation during the first post-training night. Behavioral performance was not dependent upon post-training sleep deprivation, neither in a natural setting that engages both spatial and contextual memory processes nor when looking more specifically at each of these memory representations. At the neuronal level however, analyses that focused on contextual memory revealed distinct correlations between performance and neuronal activity in frontal areas associated with recollection processes after post-training sleep, and in the parahippocampal gyrus associated with familiarity processes in sleep-deprived participants. Likewise, efficient spatial memory was associated with posterior cortical activity after sleep whereas it correlated with parahippocampal/medial temporal activity after sleep deprivation. Finally, variations in place-finding efficiency in a natural setting encompassing spatial and contextual elements were associated with caudate activity after post-training sleep, suggesting the automation of navigation. These data indicate that post-training sleep modulates the neural substrates of the consolidation of both the spatial and contextual memories acquired during virtual navigation.     

Reduced susceptibility to interference in the consolidation of motor memory before adolescence

Are children superior to adults in consolidating procedural memory? This notion has been tied to "critical," early life periods of increased brain plasticity. Here, using a motor sequence learning task, we show, in experiment 1, that a) the rate of learning during a training session, b) the gains accrued, without additional practice, within a 24 hours post-training interval (delayed consolidation gains), and c) the long-term retention of these gains, were as effective in 9, 12 and 17-year-olds and comparable to those reported for adults. However, a follow-up experiment showed that the establishment of a memory trace for the trained sequence of movements was significantly more susceptible to interference by a subsequent motor learning experience (practicing a reversed movement sequence) in the 17-year-olds compared to the 9 and 12-year-olds. Unlike the 17-year-olds, the younger age-groups showed significant delayed gains even after interference training. Altogether, our results indicate the existence of an effective consolidation phase in motor learning both before and after adolescence, with no childhood advantage in the learning or retention of a motor skill. However, the ability to co-consolidate different, successive motor experiences, demonstrated in both the 9 and 12-year-olds, diminishes after puberty, suggesting that a more selective memory consolidation process takes over from the childhood one. Only the adult consolidation process is gated by a recency effect, and in situations of multiple, clashing, experiences occurring within a short time-interval, adults may less effectively establish in memory experiences superseded by newer ones.     

Interaction between Hippocampal and Striatal Systems Predicts Subsequent Consolidation of Motor Sequence Memory

The development of fast and reproducible motor behavior is a crucial human capacity. The aim of the present study was to address the relationship between the implementation of consistent behavior during initial training on a sequential motor task (the Finger Tapping Task) and subsequent sleep-dependent motor sequence memory consolidation, using functional magnetic resonance imaging (fMRI) and total sleep deprivation protocol. Our behavioral results indicated significant offline gains in performance speed after sleep whereas performance was only stabilized, but not enhanced, after sleep deprivation. At the cerebral level, we previously showed that responses in the caudate nucleus increase, in parallel to a decrease in its functional connectivity with frontal areas, as performance became more consistent. Here, the strength of the competitive interaction, assessed through functional connectivity analyses, between the caudate nucleus and hippocampo-frontal areas during initial training, predicted delayed gains in performance at retest in sleepers but not in sleep-deprived subjects. Moreover, during retest, responses increased in the hippocampus and medial prefrontal cortex in sleepers whereas in sleep-deprived subjects, responses increased in the putamen and cingulate cortex. Our results suggest that the strength of the competitive interplay between the striatum and the hippocampus, participating in the implementation of consistent motor behavior during initial training, conditions subsequent motor sequence memory consolidation. The latter process appears to be supported by a reorganisation of cerebral activity in hippocampo-neocortical networks after sleep.     

Age-related changes in the circadian and homeostatic regulation of human sleep

The reduction of electroencephalographic (EEG) slow-wave activity (SWA) (EEG power density between 0.75-4.5 Hz) and spindle frequency activity, together with an increase in involuntary awakenings during sleep, represent the hallmarks of human sleep alterations with age. It has been assumed that this decrease in non-rapid eye movement (NREM) sleep consolidation reflects an age-related attenuation of the sleep homeostatic drive. To test this hypothesis, we measured sleep EEG characteristics (i.e., SWA, sleep spindles) in healthy older volunteers in response to high (sleep deprivation protocol) and low sleep pressure (nap protocol) conditions. Despite the fact that the older volunteers had impaired sleep consolidation and reduced SWA levels, their relative SWA response to both high and low sleep pressure conditions was similar to that of younger persons. Only in frontal brain regions did we find an age-related diminished SWA response to high sleep pressure. On the other hand, we have clear evidence that the circadian regulation of sleep during the 40 h nap protocol was changed such that the circadian arousal signal in the evening was weaker in the older study participants. More sleep occurred during the wake maintenance zone, and subjective sleepiness ratings in the late afternoon and evening were higher than in younger participants. In addition, we found a diminished melatonin secretion and a reduced circadian modulation of REM sleep and spindle frequency-the latter was phase-advanced relative to the circadian melatonin profile. Therefore, we favor the hypothesis that age-related changes in sleep are due to weaker circadian regulation of sleep and wakefulness. Our data suggest that manipulations of the circadian timing system, rather than the sleep homeostat, may offer a potential strategy to alleviate age-related decrements in sleep and daytime alertness levels.     

Visual performance fields: frames of reference

Performance in most visual discrimination tasks is better along the horizontal than the vertical meridian (Horizontal-Vertical Anisotropy, HVA), and along the lower than the upper vertical meridian (Vertical Meridian Asymmetry, VMA), with intermediate performance at intercardinal locations. As these inhomogeneities are prevalent throughout visual tasks, it is important to understand the perceptual consequences of dissociating spatial reference frames. In all studies of performance fields so far, allocentric environmental references and egocentric observer reference frames were aligned. Here we quantified the effects of manipulating head-centric and retinotopic coordinates on the shape of visual performance fields. When observers viewed briefly presented radial arrays of Gabors and discriminated the tilt of a target relative to homogeneously oriented distractors, performance fields shifted with head tilt (Experiment 1), and fixation (Experiment 2). These results show that performance fields shift in-line with egocentric referents, corresponding to the retinal location of the stimulus.     

Memory for events and their spatial context: models and experiments

The computational role of the hippocampus in memory has been characterized as: (i) an index to disparate neocortical storage sites; (ii) a time-limited store supporting neocortical long-term memory; and (iii) a content-addressable associative memory. These ideas are reviewed and related to several general aspects of episodic memory, including the differences between episodic, recognition and semantic memory, and whether hippocampal lesions differentially affect recent or remote memories. Some outstanding questions remain, such as: what characterizes episodic retrieval as opposed to other forms of read-out from memory; what triggers the storage of an event memory; and what are the neural mechanisms involved? To address these questions a neural-level model of the medial temporal and parietal roles in retrieval of the spatial context of an event is presented. This model combines the idea that retrieval of the rich context of real-life events is a central characteristic of episodic memory, and the idea that medial temporal allocentric representations are used in long-term storage while parietal egocentric representations are used to imagine, manipulate and re-experience the products of retrieval. The model is consistent with the known neural representation of spatial information in the brain, and provides an explanation for the involvement of Papez''s circuit in both the representation of heading direction and in the recollection of episodic information. Two experiments relating to the model are briefly described. A functional neuroimaging study of memory for the spatial context of life-like events in virtual reality provides support for the model''s functional localization. A neuropsychological experiment suggests that the hippocampus does store an allocentric representation of spatial locations.     

Vision and the representation of the surroundings in spatial memory

One of the paradoxes of vision is that the world as it appears to us and the image on the retina at any moment are not much like each other. The visual world seems to be extensive and continuous across time. However, the manner in which we sample the visual environment is neither extensive nor continuous. How does the brain reconcile these differences? Here, we consider existing evidence from both static and dynamic viewing paradigms together with the logical requirements of any representational scheme that would be able to support active behaviour. While static scene viewing paradigms favour extensive, but perhaps abstracted, memory representations, dynamic settings suggest sparser and task-selective representation. We suggest that in dynamic settings where movement within extended environments is required to complete a task, the combination of visual input, egocentric and allocentric representations work together to allow efficient behaviour. The egocentric model serves as a coding scheme in which actions can be planned, but also offers a potential means of providing the perceptual stability that we experience.     

Age‐related Changes in the Circadian and Homeostatic Regulation of Human Sleep

The reduction of electroencephalographic (EEG) slow‐wave activity (SWA) (EEG power density between 0.75–4.5 Hz) and spindle frequency activity, together with an increase in involuntary awakenings during sleep, represent the hallmarks of human sleep alterations with age. It has been assumed that this decrease in non‐rapid eye movement (NREM) sleep consolidation reflects an age‐related attenuation of the sleep homeostatic drive. To test this hypothesis, we measured sleep EEG characteristics (i.e., SWA, sleep spindles) in healthy older volunteers in response to high (sleep deprivation protocol) and low sleep pressure (nap protocol) conditions. Despite the fact that the older volunteers had impaired sleep consolidation and reduced SWA levels, their relative SWA response to both high and low sleep pressure conditions was similar to that of younger persons. Only in frontal brain regions did we find an age‐related diminished SWA response to high sleep pressure. On the other hand, we have clear evidence that the circadian regulation of sleep during the 40 h nap protocol was changed such that the circadian arousal signal in the evening was weaker in the older study participants. More sleep occurred during the wake maintenance zone, and subjective sleepiness ratings in the late afternoon and evening were higher than in younger participants. In addition, we found a diminished melatonin secretion and a reduced circadian modulation of REM sleep and spindle frequency—the latter was phase‐advanced relative to the circadian melatonin profile. Therefore, we favor the hypothesis that age‐related changes in sleep are due to weaker circadian regulation of sleep and wakefulness. Our data suggest that manipulations of the circadian timing system, rather than the sleep homeostat, may offer a potential strategy to alleviate age‐related decrements in sleep and daytime alertness levels.     

Spatial Hyperschematia without Spatial Neglect after Insulo-Thalamic Disconnection

Different spatial representations are not stored as a single multipurpose map in the brain. Right brain-damaged patients can show a distortion, a compression of peripersonal and extrapersonal space. Here we report the case of a patient with a right insulo-thalamic disconnection without spatial neglect. The patient, compared with 10 healthy control subjects, showed a constant and reliable increase of her peripersonal and extrapersonal egocentric space representations - that we named spatial hyperschematia - yet left her allocentric space representations intact. This striking dissociation shows that our interactions with the surrounding world are represented and processed modularly in the human brain, depending on their frame of reference.     

My Hand or Yours? Markedly Different Sensitivity to Egocentric and Allocentric Views in the Hand Laterality Task

In the hand laterality task participants judge the handedness of visually presented stimuli--images of hands shown in a variety of postures and views--and indicate whether they perceive a right or left hand. The task engages kinaesthetic and sensorimotor processes and is considered a standard example of motor imagery. However, in this study we find that while motor imagery holds across egocentric views of the stimuli (where the hands are likely to be one's own), it does not appear to hold across allocentric views (where the hands are likely to be another person's). First, we find that psychophysical sensitivity, d', is clearly demarcated between egocentric and allocentric views, being high for the former and low for the latter. Secondly, using mixed effects methods to analyse the chronometric data, we find high positive correlation between response times across egocentric views, suggesting a common use of motor imagery across these views. Correlations are, however, considerably lower between egocentric and allocentric views, suggesting a switch from motor imagery across these perspectives. We relate these findings to research showing that the extrastriate body area discriminates egocentric ('self') and allocentric ('other') views of the human body and of body parts, including hands.     

Sequence specific motor performance gains after memory consolidation in children and adolescents

Memory consolidation for a trained sequence of finger opposition movements, in 9- and 12-year-old children, was recently found to be significantly less susceptible to interference by a subsequent training experience, compared to that of 17-year-olds. It was suggested that, in children, the experience of training on any sequence of finger movements may affect the performance of the sequence elements, component movements, rather than the sequence as a unit; the latter has been implicated in the learning of the task by adults. This hypothesis implied a possible childhood advantage in the ability to transfer the gains from a trained to the reversed, untrained, sequence of movements. Here we report the results of transfer tests undertaken to test this proposal in 9-, 12-, and 17-year-olds after training in the finger-to-thumb opposition sequence (FOS) learning task. Our results show that the performance gains in the trained sequence partially transferred from the left, trained hand, to the untrained hand at 48-hours after a single training session in the three age-groups tested. However, there was very little transfer of the gains from the trained to the untrained, reversed, sequence performed by either hand. The results indicate sequence specific post-training gains in FOS performance, as opposed to a general improvement in performance of the individual, component, movements that comprised both the trained and untrained sequences. These results do not support the proposal that the reduced susceptibility to interference, in children before adolescence, reflects a difference in movement syntax representation after training.     

After Being Challenged by a Video Game Problem,Sleep Increases the Chance to Solve It

In the past years many studies have demonstrated the role of sleep on memory consolidation. It is known that sleeping after learning a declarative or non-declarative task, is better than remaining awake. Furthermore, there are reports of a possible role for dreams in consolidation of declarative memories. Other studies have reported the effect of naps on memory consolidation. With similar protocols, another set of studies indicated that sleep has a role in creativity and problem-solving. Here we hypothesised that sleep can increase the likelihood of solving problems. After struggling to solve a video game problem, subjects who took a nap (n = 14) were almost twice as likely to solve it when compared to the wake control group (n = 15). It is interesting to note that, in the nap group 9 out 14 subjects engaged in slow-wave sleep (SWS) and all solved the problem. Surprisingly, we did not find a significant involvement of Rapid Eye Movement (REM) sleep in this task. Slow-wave sleep is believed to be crucial for the transfer of memory-related information to the neocortex and implement intentions. Sleep can benefit problem-solving through the generalisation of newly encoded information and abstraction of the gist. In conclusion, our results indicate that sleep, even a nap, can potentiate the solution of problems that involve logical reasoning. Thus, sleep''s function seems to go beyond memory consolidation to include managing of everyday-life events.