Search activity in the context of psychosomatic disturbances,of brain monoamines and REM sleep function

The author discusses a number of controversial aspects of the search activity concept. This concept, based on an analysis of data cited by other researchers and the results of the author’s own investigation, performed together with V. V. Arshavsky, postulates that search activity raises the body’s resistance to stress and experimentally induced pathology whereas renunciation of search forms a nonspecific predisposition to somatic disturbances (e.g., psychosomatic disease). REM sleep is regarded as a specific form of search activity aimed at compensating for the state of renunciation of search in walking. In this paper the author argues that 1) renunciation of search can be accompanied either by anxiety or by depression, 2) REM sleep deprivation on a “small platform” raises the requirement in REM sleep by producing renunciation of search, 3) during search activity brain catecholamine synthesis is stimulated by catabolism whereas a state of renunciation of search upsets this feedback system. The actuation of the brain mechanisms of search in REM sleep necessitates a certain brain catecholamine level. If the brain catecholamine level is very high during waking behavior due to intensive search activity, the REM sleep requirement is low, REM sleep becoming reduced. After a moderate drop in the brain catecholamine level at the initial stage of renunciation of search the requirement in REM sleep rises and this phase grows longer. But at the late stage of renunciation of search the brain catecholamine level drops extremely, REM sleep shrinking in spite of the great appropriate requirement, and 4) the functional insufficiency of REM sleep invites various forms of pathology.     

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.     

Hemispheric lateralization of the EEG during wakefulness and REM sleep in young healthy adults

EEG recordings confirm hemispheric lateralization of brain activity during cognitive tasks. The aim of the present study was to investigate spontaneous EEG lateralization under two conditions, waking and REM sleep. Bilateral monopolar EEG was recorded in eight participants using a 12-electrode montage, before the night (5 min eyes closed) and during REM sleep. Spectral analysis (0.75-19.75 Hz) revealed left prefrontal lateralization on total spectrum amplitude power and right occipital lateralization in Delta activity during waking. In contrast, during REM sleep, right frontal lateralization in Theta and Beta activities and right lateralization in occipital Delta activity was observed. These results suggest that spontaneous EEG activities generated during waking and REM sleep are supported in part by a common thalamo-cortical neural network (right occipital Delta dominance) while additional, possibly neuro-cognitive factors modulate waking left prefrontal dominance and REM sleep right frontal dominance.     

HPA axis and sleep: identifying subtypes of major depression

It is increasingly acknowledged that the diagnosis of major depression encompasses patients who do not necessarily share the same disease biology. Though the diagnostic criteria allow the specification of different subtypes, e.g. melancholic and atypical features, a consensus still has to be reached with regard to the clinical symptoms that clearly delineate these subtypes. Beside clinical characteristics, biological markers may help to further improve identification of biologically distinct endophenotypes and, ultimately, to devise more specific treatment strategies. Alterations of the hypothalamus-pituitary-adrenal (HPA) axis and sleep architecture are not only commonly observed in patients with major depression, but the nature and extent of these alterations can help to identify distinct subtypes. Thus, a HPA overdrive, due to enhanced secretion of corticotropin-releasing hormone (CRH) and an impaired negative feedback via glucocorticoid receptors, seems to be most consistently observed in patients with melancholic features. These patients also show the clearest sleep-electroencephalogram (EEG) alterations, including disrupted sleep, low amounts of slow wave sleep (SWS), a short rapid eye movement (REM) latency and a high REM density. In contrast, patients with atypical features are characterized by reduced activity of the HPA axis and ascending noradrenergic neurons in the locus coeruleus. Though sleep-EEG alterations have been less thoroughly examined in these patients, there are data to suggest that SWS is not reduced and that REM sleep parameters are not consistently altered. While the atypical and melancholic subtypes of major depression may represent the extremes of a spectrum, the distinct clinical features provide an opportunity to further explore biological markers, as well as environmental factors, contributing to these clinical phenotypes. Moreover, dysregulations of the HPA axis and sleep-EEG alterations can also be induced in rodents, thereby allowing alignment of critical biological aspects of a human disease subtype with an animal model. Such "Translational Research" efforts should help to develop targeted therapies for distinct patient populations.     

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 imaging and the neuro-psychological assessment of dreams

Recent neuroimaging studies show that human rapid-eye-movement (REM) sleep is characterized by a specific pattern of regional brain activity. Although this is usually interpreted in relation to physiological and cellular mechanisms, the specific regional distribution of brain activity during REM sleep might also be linked to specific dream features. Remarkably, several bizarre features of normal dreams have similarities with well-known neuropsychological syndromes after brain damage, such as delusional misidentifications for faces and places. We propose that neuropsychological analysis of dream content might offer new ways of interpreting neuroimaging maps of sleep, and make specific predictions for future neuroimaging studies.     

Cognitive and emotional processes during dreaming: a neuroimaging view

Dream is a state of consciousness characterized by internally-generated sensory, cognitive and emotional experiences occurring during sleep. Dream reports tend to be particularly abundant, with complex, emotional, and perceptually vivid experiences after awakenings from rapid eye movement (REM) sleep. This is why our current knowledge of the cerebral correlates of dreaming, mainly derives from studies of REM sleep. Neuroimaging results show that REM sleep is characterized by a specific pattern of regional brain activity. We demonstrate that this heterogeneous distribution of brain activity during sleep explains many typical features in dreams. Reciprocally, specific dream characteristics suggest the activation of selective brain regions during sleep. Such an integration of neuroimaging data of human sleep, mental imagery, and the content of dreams is critical for current models of dreaming; it also provides neurobiological support for an implication of sleep and dreaming in some important functions such as emotional regulation.     

Dreaming,cognition, and physical illness: Part I

Part I of a two part article on the effect upon dreaming on physical illness briefly explores the historical medico-philosophical antecedents of the notion that dreams can be diagnostic of bodily disease. Modern sleep research findings relating REM sleep to physiologic changes are also explored. The controversy of whether dreams are merely the consequence of random brain activity or whether they are a valid psychological phenomenon is discussed. Six contemporary views of the function of REM sleep are outlined. A seventh view of dreaming, that of a “cognitive monitoring system” is suggested. Like earlier historical notions, it is suggested that dreaming is a cognitive activity that processes bodily cues indicating illness or disease. Part II. presents a clinical compendium of dreams relating to Part I.     

REM mentation in narcoleptics and normals: an empirical test of two neurocognitive theories

This study tested the two main neurocognitive models of dreaming by using cognitive data elicited from REM sleep in normals and narcoleptics. The two models were the "activation-only" view which holds that, in the context of sleep, overall activation of the brain is sufficient for consciousness to proceed in the manner of dreaming (e.g., Antrobus, 1991; Foulkes, 1993; Vogel, 1978); and the Activation, Input source, Modulation (AIM model), which predicts that not only brain activation level but also neurochemical modulatory systems exert widespread effects upon dreaming (Hobson & McCarley, 1977; Hobson, Pace-Schott, & Stickgold, 2000). Mental activity was studied in nocturnal REM in 15 narcoleptics and 9 normal healthy persons and in REM at the onset of daytime naps and nighttime sleep (SOREM) in narcoleptics. The study was performed in the subjects' homes, using instrumental awakenings and ambulatory polysomnographic techniques, and focused upon visual vividness, mentation report length, improbable and discontinuous bizarre features, and reflective consciousness. Within each subject group, most cognitive variables tended to fluctuate in line with expected variations in circadian activation level. When comparing the cognitive variables between the two groups, reflective consciousness was clearly highest in narcoleptics, whereas improbabilities and discontinuities were lower, with mentation report length and visual vividness differing less between the groups. These findings are consistent with the AIM model of sleep mentation, but not with the activation-only model.     

William James''s The Fringe of Consciousness REM Mentation in Narcoleptics and Normals: Reply to Tore Nielsen

This study tested the two main neurocognitive models of dreaming by using cognitive data elicited from REM sleep in normals and narcoleptics. The two models were the "activation-only" view which holds that, in the context of sleep, overall activation of the brain is sufficient for consciousness to proceed in the manner of dreaming (e.g., Antrobus, 1991; Foulkes, 1993; Vogel, 1978); and the Activation, Input source, Modulation (AIM model), which predicts that not only brain activation level but also neurochemical modulatory systems exert widespread effects upon dreaming (Hobson & McCarley, 1977; Hobson, Pace-Schott, & Stickgold, 2000). Mental activity was studied in nocturnal REM in 15 narcoleptics and 9 normal healthy persons and in REM at the onset of daytime naps and nighttime sleep (SOREM) in narcoleptics. The study was performed in the subjects' homes, using instrumental awakenings and ambulatory polysomnographic techniques, and focused upon visual vividness, mentation report length, improbable and discontinuous bizarre features, and reflective consciousness. Within each subject group, most cognitive variables tended to fluctuate in line with expected variations in circadian activation level. When comparing the cognitive variables between the two groups, reflective consciousness was clearly highest in narcoleptics, whereas improbabilities and discontinuities were lower, with mentation report length and visual vividness differing less between the groups. These findings are consistent with the AIM model of sleep mentation, but not with the activation-only model.     

A daytime nap containing solely non-REM sleep enhances declarative but not procedural memory

The specialized role that sleep-specific brain physiology plays in memory processing is being rapidly clarified with a greater understanding of the dynamic, complex, and exquisitely orchestrated brain state that emerges during sleep. Behaviorally, the facilitative role of non-REM (NREM) sleep (primarily slow wave sleep) for declarative but not procedural memory performance in humans has been demonstrated in a number of nocturnal sleep studies. However, subjects in these studies were tested after periods of sleep that contained REM sleep in addition to NREM sleep, and comparison wake groups were subjected to mild sleep deprivation. To add some clarity to the findings of these nocturnal studies, we assessed performance on declarative and procedural memory tasks following a daytime training-retest interval containing either a short nap that included NREM without REM sleep, or wakefulness. Consistent with previous findings we show that, after a comparatively brief sleep episode, subjects that take a nap improve more on a declarative memory task than subjects that stay awake, but that improvement on a procedural memory task is the same regardless of whether subjects take a nap or remain awake. Slow wave sleep was the only sleep parameter to correlate positively with declarative memory improvement. These findings are discussed with reference to the general benefits of napping and within the broader context of a growing literature suggesting a role for NREM-specific physiology for the processing of declarative memory.     

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.     

The prefrontal cortex in sleep

Experimental data indicate a role for the prefrontal cortex in mediating normal sleep physiology, dreaming and sleep-deprivation phenomena. During nonrandom-eye-movement (NREM) sleep, frontal cortical activity is characterized by the highest voltage and the slowest brain waves compared to other cortical regions. The differences between the self-awareness experienced in waking and its diminution in dreaming can be explained by deactivation of the dorsolateral prefrontal cortex during REM sleep. Here, we propose that this deactivation results from a direct inhibition of the dorsolateral prefrontal cortical neurons by acetylcholine, the release of which is enhanced during REM sleep. Sleep deprivation influences frontal executive functions in particular, which further emphasizes the sensitivity of the prefrontal cortex to 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.     

原发性失眠对睡眠依赖性记忆巩固的影响及机制

现代社会的失眠问题异常突出,其对睡眠依赖性记忆巩固（SDC）的影响日益引起重视。目前,原发性失眠（PI）对陈述性及程序性记忆SDC的影响存在分歧。梳理以往研究发现,系统巩固假说和突触稳态假说所支持的睡眠结构紊乱及脑结构异常可能是PI患者SDC损伤的潜在脑机制。未来研究可考虑同步采集行为、脑电和脑成像数据,深入探究PI影响SDC的脑机制,并验证上述假说;还可尝试通过经颅电/磁刺激和目标记忆重激活等无创性干预措施改善PI患者的SDC效应。     

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.     

Social factors and the psychobiology of depression: relations between life stress and rapid eye movement sleep latency.

We examined psychosocial factors (i.e., life stress) and biological factors (i.e., REM sleep latency) that are hypothesized to be of complementary importance for defining depressive subtypes in a sample of 61 nonpsychotic, endogenous major depressives. Subjects were evaluated on several diagnostic scales for life stress, on electroencephalographic sleep data, and on 2 symptom measures for depression. As predicted, persons with severe stress that occurred shortly before depression onset had essentially normal REM latency values; patients without such stress had reduced REM latency values. Both stress and REM latency were also associated with greater severity of self-reported depressive symptoms. Alternative explanations of these findings are discussed, with particular emphasis on different roles of pre-onset and post-onset stressors.     

Motivation and affect in REM sleep and the mentation reporting process

Although the emotional and motivational characteristics of dreaming have figured prominently in folk and psychoanalytic conceptions of dream production, emotions have rarely been systematically studied, and motivation, never. Because emotions during sleep lack the somatic components of waking emotions, and they change as the sleeper awakens, their properties are difficult to assess. Recent evidence of limbic system activation during REM sleep suggests a basis in brain architecture for the interaction of motivational and cognitive properties in dreaming. Motivational and emotional content in REM and NREM laboratory mentation reports from 25 participants were compared. Motivational and emotional content was significantly greater in REM than NREM sleep, even after controlling for the greater word count of REM reports.     

Brain-mind states: reciprocal variation in thoughts and hallucinations

The exclusion of thinking from recent studies of sleep mentation has hindered a full appreciation of how cognitive activity differs across the states of waking and sleep. To overcome this limitation, this study investigated thoughts and hallucinations using experience sampling, home-based sleep-wake monitoring, and formal analyses of the psychological data. The prevalence of thoughts decreased gradually from waking through sleep onset and non-REM sleep, to reach its nadir in REM sleep, whereas hallucinations increased sharply across these states. Furthermore, multiple occurrences of hallucinations but not of thoughts increased significantly from sleep onset through non-REM sleep, to a peak in REM sleep. This reciprocity in thoughts and hallucinations might reflect a progressive shift from high to low aminergic-to-cholinergic neuromodulatory ratios across wake-sleep states, accompanied by an array of changes in the regional activation patterns of the brain.     

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.