Sleep-dependent hippocampal slow activity correlates with waking memory performance in humans

The positive effect of postlearning sleep on memory consolidation as well as the relationship between sleep-related memory processes and the hippocampal formation are increasingly clarified topics in neurobiology. However, the possibility of a stable relationship between waking mnemonic performance and sleep-dependent hippocampal electric activity is unexplored. Here we report a correlative analysis between sleep-dependent parahippocampal-hippocampal (pHip-Hip) electric activity recorded by foramen ovale (FO) electrodes and different types of memory performances in epileptic patients. Psychological testing was performed days or weeks before electrophysiological recordings. The relative spectral power of the slow activity (below 1.25 Hz) during deep non-REM (NREM) sleep at the right pHip-Hip region correlated positively with the visual memory performance according to Rey-Osterrieth Complex Figure Test (ROCFT). Along the posterior-anterior direction of the hippocampal formation a linear increasing of correlations was observed. The relative power of the activity below 1.25 Hz at the left pHip-Hip during phasic REM sleep correlated positively with verbal learning performance and mnemonic retention values according to ROCFT. It is concluded that the pHip-Hip structures' capacity of producing high amplitude and synchronized slow (< 1 Hz) oscillation during deep NREM sleep is related to the functional power of these structures. We hypothesize that the asymmetric (side-specific) propagation of ponto-geniculo-occipital (PGO) activity to the pHip-Hip region is related to the memory correlates of phasic REM sleep.     

Spatial and reversal learning in the Morris water maze are largely resistant to six hours of REM sleep deprivation following training

This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair both hippocampus-dependent spatial learning and learning a new target location within a familiar environment: reversal learning. A 6-d protocol was divided into the initial spatial learning phase (3.5 d) immediately followed by the reversal phase (2.5 d). During the 6 h following four or 12 training trials/day of initial or reversal learning phases, REM sleep was eliminated and non-REM sleep left intact using the multiple inverted flowerpot method. Contrary to our hypotheses, REM sleep deprivation during four or 12 trials/day of initial spatial or reversal learning did not affect training performance. However, some probe trial measures indicated REM sleep-deprivation-associated impairment in initial spatial learning with four trials/day and enhancement of subsequent reversal learning. In naive animals, REM sleep deprivation during normal initial spatial learning was followed by a lack of preference for the subsequent reversal platform location during the probe. Our findings contradict reports that REM sleep is essential for spatial learning in the Morris water maze and newly reveal that short periods of REM sleep deprivation do not impair concurrent reversal learning. Effects on subsequent reversal learning are consistent with the idea that REM sleep serves the consolidation of incompletely learned items.     

Paradoxical sleep and information processing: exploration by inversion of the visual field

The purpose of this study was to test the potential relationship between REM sleep and information processing with inversion of the visual field. In the first experiment, four male subjects slept in the laboratory for two sessions of 6 consecutive nights: 2 adaptation nights, 2 nights of polysomnography, and 2 nights of dream collection. During the days preceding Nights 3, 4, 5, and 6 of each session, the subjects wore glasses which, during the second session, completely inverted (rotation of 180 degrees) their visual field. In a second experiment with four other male subjects, the order of conditions was reversed, and the experimental condition (visual inversion) was introduced a second time. When the data of the two experiments were combined, there was a significant (p less than .01) increase in the percentage of REM sleep from Nights 3 and 4 of the control condition to Nights 3 and 4 of the visual inversion condition, but there was no significant change in any of the other sleep stages. There was a significant decrease in horizontal (p less than .04) and vertical (p less than .005) REM density and in the density of vertical REM bursts (p less than .02). The increase in REM sleep supports the hypothesis that REM sleep contributes to information processing while the decrease in REM density suggests that this component of REM sleep may be involved in a homeostatic process of sensory input.     

The case against memory consolidation in REM sleep

We present evidence disputing the hypothesis that memories are processed or consolidated in REM sleep. A review of REM deprivation (REMD) studies in animals shows these reports to be about equally divided in showing that REMD does, or does not, disrupt learning/memory. The studies supporting a relationship between REM sleep and memory have been strongly criticized for the confounding effects of very stressful REM deprivation techniques. The three major classes of antidepressant drugs, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), and selective serotonin reuptake inhibitors (SSRIs), profoundly suppress REM sleep. The MAOIs virtually abolish REM sleep, and the TCAs and SSRIs have been shown to produce immediate (40-85%) and sustained (30-50%) reductions in REM sleep. Despite marked suppression of REM sleep, these classes of antidepressants on the whole do not disrupt learning/memory. There have been a few reports of patients who have survived bilateral lesions of the pons with few lingering complications. Although these lesions essentially abolished REM sleep, the patients reportedly led normal lives. Recent functional imaging studies in humans have revealed patterns of brain activity in REM sleep that are consistent with dream processes but not with memory consolidation. We propose that the primary function of REM sleep is to provide periodic endogenous stimulation to the brain which serves to maintain requisite levels of central nervous system (CNS) activity throughout sleep. REM is the mechanism used by the brain to promote recovery from sleep. We believe that the cumulative evidence indicates that REM sleep serves no role in the processing or consolidation of memory.     

Brain Gene Expression During REM Sleep Depends on Prior Waking Experience

In most mammalian species studied, two distinct and successive phases of sleep, slow wave (SW), and rapid eye movement (REM), can be recognized on the basis of their EEG profiles and associated behaviors. Both phases have been implicated in the offline sensorimotor processing of daytime events, but the molecular mechanisms remain elusive. We studied brain expression of the plasticity-associated immediate-early gene (IEG) zif-268 during SW and REM sleep in rats exposed to rich sensorimotor experience in the preceding waking period. Whereas nonexposed controls show generalized zif-268 down-regulation during SW and REM sleep, zif-268 is upregulated during REM sleep in the cerebral cortex and the hippocampus of exposed animals. We suggest that this phenomenon represents a window of increased neuronal plasticity during REM sleep that follows enriched waking experience.     

Functioning of the phonological loop in auditory hallucinations

Two experiments designed to assess the functioning of the phonological store and loop were carried out with schizophrenic patients experiencing auditory hallucinations, schizophrenic patients not experiencing hallucinations and normal subjects. In the first experiment, phonological encoding was assessed. Although both groups of psychiatric patients performed more poorly overall than the normal subjects, there were no significant differences between the performances of the hallucinating and nonhallucinating patients. In the second experiment, the unattended speech effect (a phenomenon thought to reflect the functioning of the phonological store in normal subjects) was assessed in hallucinating schizophrenic patients, non-hallucinating schizophrenic patients and normal controls. The psychiatric patients performed more poorly overall than the normal subjects, but there was no evidence of abnormal functioning of the phonological store or loop in either patient group. Overall, the findings indicate that phonological store and loop abnormalities are not implicated in the experience of auditory hallucinations.     

Mood and sleep in aging women

The possible covariations of mood and sleep was examined in a group of 25 normal, aging women. Mood assessments made in the evenings of 3 consecutive days were independently related to both before and after sleep night. Only two sleep variables: sleep efficiency and latency to first rapid eye movement (REM) period--were reliably related to daytime moods. The relative paucity of relation between mood and sleep variables was interpreted as reflecting a general insulation of sleep from day-to-day mood variations.     

Misperception of sleep can adversely affect daytime functioning in insomnia

This experiment was designed to investigate the relationship between subjective perception of sleep and daytime processes in primary insomnia. Twenty-two individuals with primary insomnia received positive or negative feedback about their sleep, immediately on waking, on three consecutive mornings. The positive feedback was that last night's sleep was good quality. The negative feedback was that last night's sleep was poor quality. Objective sleep on each of the three nights was estimated by actigraphy and did not differ across the three nights or the two feedback conditions. Negative feedback (based on 32 nights of data) was associated with more negative thoughts, sleepiness, monitoring for sleep-related threat, and safety behaviours during the day, relative to positive feedback (based on 34 nights of data). These results indicate that the impaired daytime functioning reported by insomnia patients is maintained, at least in part, by subjective perception of sleep.     

Remembering specific features of emotional events across time: The role of REM sleep and prefrontal theta oscillations

When an episode of emotional significance is encountered, it often results in the formation of a highly resistant memory representation that is easily retrieved for many succeeding years. Recent research shows that beyond generic consolidation processes, rapid eye movement (REM) sleep importantly contributes to this effect. However, the boundary conditions of consolidation processes during REM sleep, specifically whether these extend to source memory, have not been examined extensively. The current study tested the effects of putative consolidation processes emerging during REM sleep and slow wave sleep (SWS) on item and source memory of negative and neutral images, respectively. Results demonstrate superior emotional relative to neutral item memory retention after both late night REM sleep and early night SWS. Emotional source memory, on the other hand, exhibited an attenuated decline following late night REM sleep, whereas neutral source memory was selectively preserved across early night SWS. This pattern of results suggests a selective preservation of emotional source memory during REM sleep that is functionally dissociable from SWS-dependent reprocessing of neutral source memory. This was further substantiated by a neurophysiological dissociation: Postsleep emotional source memory was selectively correlated with frontal theta lateralization (REM sleep), whereas postsleep neutral item memory was correlated with SWS spindle power. As such, the present results contribute to a more comprehensive characterization of sleep-related consolidation mechanisms underlying emotional and neutral memory retention. Subsidiary analysis of emotional reactivity to previously encoded material revealed an enhancing rather than attenuating effect of late night REM sleep on emotional responses.     

睡眠对恐惧学习的影响及其认知神经机制

睡眠问题可能会诱发恐惧相关情绪障碍(焦虑、创伤性应激障碍、恐怖症等),研究睡眠影响恐惧学习的认知神经机制,有助于增强对恐惧相关情绪障碍的预测、诊断和治疗。以往研究表明睡眠剥夺影响恐惧习得和消退主要是通过抑制vmPFC活动,阻碍其与杏仁核的功能连接,从而导致恐惧习得增强或是消退学习受损。进一步研究发现睡眠不同阶段对恐惧学习相关脑区有独特的影响:剥夺(缺乏)快速眼动睡眠会抑制vmPFC活动、增强杏仁核、海马激活,导致恐惧习得增强,消退学习受损,此外边缘皮层的功能连接减少破坏了记忆巩固(恐惧记忆和消退记忆);而慢波睡眠主要与海马变化有关,慢波睡眠期间进行目标记忆重激活可促进恐惧消退学习。未来研究需要增加睡眠影响恐惧泛化的神经机制研究、及昼夜节律中断对恐惧消退的影响,以及关注动物睡眠研究向人类睡眠研究转化中存在的问题。     

Sleep physiology and psychological aspects of the fibrositis (fibromyalgia) syndrome

Fibrositis (fibromyalgia) patients were compared with normal controls in terms of electrophysiology (EEG), self-report indicants of awakening, quality of sleep, behaviourally signalled awakenings, and Symptom Check List 90R (SCL-90R) scores. The results differentiated fibrositis patients from normal controls in terms of SCL-90R scores, with fibrositis patients showing significantly more psychopathology. Fibrositis patients had more alpha EEG sleep and less REM and Stage 1 sleep. They were better able to recall their behaviourally signalled awakenings the following morning and reported qualitatively less satisfying sleep than the normal controls. The alpha EEG sleep anomaly may reflect a vigilant arousal state during nocturnal sleep and result in the daytime experience of unrefreshing sleep, psychologic distress, that re-enforces the perpetuation of the sleep-related symptoms.     

Memory consolidation during sleep: interactive effects of sleep stages and HPA regulation

Sleep is critically involved in the consolidation of previously acquired memory traces. However, nocturnal sleep is not uniform but is subject to distinct changes in electrophysiological and neuroendocrine activity. Specifically, the first half of the night is dominated by slow wave sleep (SWS), whereas rapid eye movement (REM) sleep prevails in the second half. Concomitantly, hypothalamo-pituitary-adrenal (HPA) activity as indicated by cortisol release is suppressed to a minimum during early sleep, while drastically increasing during late sleep. We have shown that the different sleep stages and the concomitant glucocorticoid release are interactively involved in the consolidation of different types of memories. SWS-rich early sleep has been demonstrated to benefit mainly the consolidation of hippocampus-dependent declarative memories (i.e. facts and episodes). In contrast, REM sleep-rich late sleep was shown to improve in particular emotional memories involving amygdalar function, as well as procedural memories (for skills) not depending on hippocampal or amygdalar function. Enhancing plasma glucocorticoid concentrations during SWS-rich early sleep counteracted hippocampus-dependent declarative memory consolidation, but did not affect hippocampus-independent procedural memory. Preventing the increase in cortisol during late REM sleep-rich sleep by administration of metyrapone impaired hippocampus-dependent declarative memory but enhanced amygdala-dependent emotional aspects of memory. The data underscore the importance of pituitary-adrenal inhibition during early SWS-rich sleep for efficient consolidation of declarative memory. The increase in cortisol release during late REM sleep-rich sleep may counteract an overshooting consolidation of emotional memories.     

Posttraining increases in REM sleep intensity implicate REM sleep in memory processing and provide a biological marker of learning potential

Posttraining rapid eye movement (REM) sleep has been reported to be important for efficient memory consolidation. The present results demonstrate increases in the intensity of REM sleep during the night of sleep following cognitive procedural/implicit task acquisition. These REM increases manifest as increases in total number of rapid eye movements (REMs) and REM densities, whereas the actual time spent in REM sleep did not change. Further, the participants with the higher intelligence (IQ) scores showed superior task acquisition scores as well as larger posttraining increases in number of REMs and REM density. No other sleep state changes were observed. None of the pretraining baseline measures of REM sleep were correlated with either measured IQ or task performance. Posttraining increases in REM sleep intensity implicate REM sleep mechanisms in further off-line memory processing, and provide a biological marker of learning potential.     

Immediate as well as delayed post learning sleep but not wakefulness enhances declarative memory consolidation in children

While there is mounting evidence for the importance of sleep for declarative memory consolidation in adults, so far this issue has not been investigated in children despite considerable differences in sleep duration and sleep architecture between children and adults. Here, 27 children (aged between 9 and 12yr) were examined on two conditions: on the Sleep-Wake condition, subjects learned word pairs in the evening and delayed recall was tested first in the next morning after sleep and then again in the following evening after daytime wakefulness. On the Wake-Sleep condition, learning took place in the morning and delayed recall was tested in the evening of the same day and again in the next morning after sleep. In both conditions retention of declarative memory was significantly increased only after an interval of sleep that either followed immediately after learning (as in the Sleep-Wake condition) or that followed after daytime wakefulness (as in the Wake-Sleep condition), respectively. The results support the hypothesis that sleep plays an active role in declarative memory consolidation even if delayed and further show for the first time the importance of sleep for declarative memory consolidation during childhood.     

Implicit learning of complex information in amnesia

Implicit learning abilities of nine amnesic patients were explored by using an artificial grammar learning task in which the test strings were constructed in such a way that grammaticality judgments could not be based on a simple knowledge of bigrams and trigrams (chunks). Results show that amnesic patients and controls performed at the same level during the classification task, whereas amnesic patients performed worse than controls in an explicit generation task. Moreover, there was no correlation between the implicit and explicit measures. These results are compatible with the existence of two kinds of representation intervening in artificial grammar learning. The first one based on processes leading to fragment-specific knowledge (the chunks, which can be accessed explicitly), and the second based on the learning of simple associations and more complex conditional relations between elements.     

The role of sleep in changing our minds: a psychologist's discussion of papers on memory reactivation and consolidation in sleep

The group of papers on memory reactivation and consolidation during sleep included in this volume represents cutting edge work in both animals and humans. They support that the two types of sleep serve different necessary functions. The role of slow wave sleep (SWS) is reactivation of the hippocampal-neocortical circuits activated during a waking learning period, while REM sleep is responsible for the consolidation of this new learning into long-term memory. These studies provide further insights into mechanisms involved in brain plasticity. Robeiro has demonstrated the upregulation of an immediate-early gene (IEG zif 268) to waking levels, which occurs only in REM and only in connection with new learning. McNaughton and his group have identified electrical indicators that the hippocampus and neocortex are talking to each other by testing the coactivation of hippocampal sharp wave bursts in SWS and shifts from down to up states of activation in the neocortex. In human studies Smith's group reports work on individual differences such as intelligence and presleep alcohol that affect postsleep performance, and Stickgold and collaborators report that a short nap will improve performance if it contains REM sleep. Payne and Nadel suggest that the recall benefit associated with REM sleep may be due to its association with increased cortisol levels. These papers are important not only in their individual contributions but also in revitalizing the work coordinating waking and sleep. This promises to further the understanding of how our unique capacity to learn from experience and modify our behavior takes place.     

REM sleep and the analytic process: a psychophysiologic bridge.

Recent research on the physiology of REM sleep has supported the hypothesis that it serves processes of psychologic adaptation. This study examines the relationship between physiologic parameters of REM sleep and evidence in analytic material of the need for adaptation. Significant correlations were found between defensive strain before sleep and REM latency, and between change in defensive strain from evening to morning and total REM time.     

Associative relationships between pre-sleep sentence stimuli and reports of mental sleep experience

The aim of this experiment was to study some linguistic relationships between pre-sleep verbal stimuli and contents of reports of mental experience during sleep. In 4 weekly sessions 16 subjects listened before sleep to a sentence stimulus, which was either semantically acceptable (SEM+) or not (SEM-), and were told to retain it for a recall test after awakening; they were awakened once each night during NREM or REM sleep and asked to report their mental experience during sleep. The relationships between the stimulus and the contents of the reports were classified using Clark's (1970) associative rules. Both pre-sleep sentence stimuli were frequently incorporated into contents of NREM and REM reports, without significant differences between the two types of sleep. The SEM+ sentence led prevalently to incorporations through paradigmatic associative relationships, while the SEM- sentence led to incorporations through both paradigmatic and syntagmatic relationships. It appears that all the features of the lexical constituents of the stimulus may be involved in the processing leading to incorporation.     

Testing the involvement of the prefrontal cortex in lucid dreaming: A tDCS study

Recent studies suggest that lucid dreaming (awareness of dreaming while dreaming) might be associated with increased brain activity over frontal regions during rapid eye movement (REM) sleep. By applying transcranial direct current stimulation (tDCS), we aimed to manipulate the activation of the dorsolateral prefrontal cortex (DLPFC) during REM sleep to increase dream lucidity. Nineteen participants spent three consecutive nights in a sleep laboratory. On the second and third nights they randomly received either 1 mA tDCS for 10 min or sham stimulation during each REM period starting with the second one. According to the participants’ self-ratings, tDCS over the DLPFC during REM sleep increased lucidity in dreams. The effects, however, were not strong and found only in frequent lucid dreamers. While this indicates some preliminary support for the involvement of the DLPFC in lucid dreaming, further research, controlling for indirect effects of stimulation and including other brain regions, is needed.     

Interhemispheric EEG coherence during sleep and wakefulness in left- and right-handed subjects

REM sleep is associated with the production of complex imagery sequences. Yet research is divided as to whether different brain regions are more or less coordinated in their functioning at this time. Some research suggests that there may occur a functional disconnection of the left and right cerebral hemispheres during REM sleep which is similar to the disconnection syndrome seen after corpus callosotomy. Other research suggests that an increase in interhemispheric coordination occurs. On the assumption that hemispheric coordination is reflected in the EEG coherence measure, we explored differences in interhemispheric coherence recorded in six left- and six right-handed normal subjects during periods of wakefulness, stage REM, stage 2, and stage 3/4 sleep. Strong evidence was found that mean EEG coherence values are larger during sleep than during waking and that they are approximately equal for the different stages of sleep. Frontal electrode placements demonstrated a slightly different pattern of coherence than central, parietal, or occipital placements. Furthermore, coherence values were larger for left-handed subjects over the occipital region during wakefulness, stage 2, and stage REM sleep, but not during stage 3/4 sleep. Coherence was not different for male and female subjects. These findings oppose the interpretation that a functional disconnection of hemispheres occurs during REM sleep and favor the interpretation that sleep in general is a state of heightened cortical coordination. Moreover, greater interhemispheric coherence over occipital brain regions in left-handed subjects suggests possible differences in the cognitive processes of these subjects during waking and dreaming states.