Human Rapid Eye Movement Sleep Research Articles

Novel Electrophysiological Signatures of Learning and Forgetting in Human REM Sleep.

Despite the known behavioral benefits of rapid eye movement (REM) sleep, discrete neural oscillatory events in human scalp electroencephalography (EEG) linked with behavior have not been discovered. This knowledge gap hinders mechanistic understanding of the function of sleep, as well as the development of biophysical models and REM-based causal interventions. We designed a detection algorithm to identify bursts of activity in high-density, scalp EEG within theta (4-8 Hz) and alpha (8-13 Hz) bands during REM sleep. Across 38 nights of sleep, we characterized the burst events (i.e., count, duration, density, peak frequency, amplitude) in healthy, young male and female human participants (38; 21F) and investigated burst activity in relation to sleep-dependent memory tasks: hippocampal-dependent episodic verbal memory and non-hippocampal visual perceptual learning. We found greater burst count during the more REM-intensive second half of the night (p < .05), longer burst duration during the first half of the night (p < .05), but no differences across the night in density or power (p > .05). Moreover, increased alpha burst power was associated with increased overnight forgetting for episodic memory (p < .05). Furthermore, we show that increased REM theta burst activity in retinotopically specific regions was associated with better visual perceptual performance. Our work provides a critical bridge between discrete REM sleep events in human scalp EEG that support cognitive processes, and the identification of similar activity patterns in animals models that allow for further mechanistic characterization.Significance Statement Current understanding of sleep and its role cognitive processes is incomplete due to a lack of discrete electrophysiological events in human rapid eye movement (REM) sleep detectable via scalp EEG. Our work remedies this gap in knowledge by designing an open-source, computational approach to identify electrophysiological alpha and theta burst events in REM sleep. Additionally, we provide evidence that these burst events are functionally important for learning and memory. Defining burst events in human REM will contribute to the development of a comprehensive mechanistic model of how sleep as a whole, and REM specifically, facilitate cognitive processes, and provide a deeper understanding of the fundamental electrophysiological properties of REM sleep that are distinct from non-REM sleep.

Human REM sleep recalibrates neural activity in support of memory formation.

The proposed mechanisms of sleep-dependent memory consolidation involve the overnight regulation of neural activity at both synaptic and whole-network levels. Now, there is a lack of in vivo data in humans elucidating if, and how, sleep and its varied stages balance neural activity, and if such recalibration benefits memory. We combined electrophysiology with in vivo two-photon calcium imaging in rodents as well as intracranial and scalp electroencephalography (EEG) in humans to reveal a key role for non-oscillatory brain activity during rapid eye movement (REM) sleep to mediate sleep-dependent recalibration of neural population dynamics. The extent of this REM sleep recalibration predicted the success of overnight memory consolidation, expressly the modulation of hippocampal-neocortical activity, favoring remembering rather than forgetting. The findings describe a non-oscillatory mechanism how human REM sleep modulates neural population activity to enhance long-term memory.

Targeted memory reactivation in human REM sleep elicits detectable reactivation.

It is now well established that memories can reactivate during non-rapid eye movement (non-REM) sleep, but the question of whether equivalent reactivation can be detected in rapid eye movement (REM) sleep is hotly debated. To examine this, we used a technique called targeted memory reactivation (TMR) in which sounds are paired with learned material in wake, and then re-presented in subsequent sleep, in this case REM, to trigger reactivation. We then used machine learning classifiers to identify reactivation of task-related motor imagery from wake in REM sleep. Interestingly, the strength of measured reactivation positively predicted overnight performance improvement. These findings provide the first evidence for memory reactivation in human REM sleep after TMR that is directly related to brain activity during wakeful task performance.

Human REM Sleep Delta Waves and the Blurring Distinction between NREM and REM Sleep.

Sleep is universal, irresistible, and heterogeneous. In mammals, sleep is traditionally divided in to non-rapid eye movement (NREM) 1–4 and rapid eye movement (REM) stages, each with defining patterns of brain activity. Specifically, slow, synchronous delta waves, spindles, and isolated negative

Regional Delta Waves In Human Rapid Eye Movement Sleep.

Although the EEG slow wave of sleep is typically considered to be a hallmark of nonrapid eye movement (NREM) sleep, recent work in mice has shown that slow waves can also occur in REM sleep. Here, we investigated the presence and cortical distribution of negative delta (1-4 Hz) waves in human REM sleep by analyzing high-density EEG sleep recordings obtained in 28 healthy subjects. We identified two clusters of delta waves with distinctive properties: (1) a frontal-central cluster characterized by ∼2.5-3.0 Hz, relatively large, notched delta waves (so-called "sawtooth waves") that tended to occur in bursts, were associated with increased gamma activity and rapid eye movements (EMs), and upon source modeling displayed an occipital-temporal and a frontal-central component and (2) a medial-occipital cluster characterized by more isolated, slower (<2 Hz), and smaller waves that were not associated with rapid EMs, displayed a negative correlation with gamma activity, and were also found in NREM sleep. Therefore, delta waves are an integral part of REM sleep in humans and the two identified subtypes (sawtooth and medial-occipital slow waves) may reflect distinct generation mechanisms and functional roles. Sawtooth waves, which are exclusive to REM sleep, share many characteristics with ponto-geniculo-occipital waves described in animals and may represent the human equivalent or a closely related event, whereas medial-occipital slow waves appear similar to NREM sleep slow waves.SIGNIFICANCE STATEMENT The EEG slow wave is typically considered a hallmark of nonrapid eye movement (NREM) sleep, but recent work in mice has shown that it can also occur in REM sleep. By analyzing high-density EEG recordings collected in healthy adult individuals, we show that REM sleep is characterized by prominent delta waves also in humans. In particular, we identified two distinctive clusters of delta waves with different properties: a frontal-central cluster characterized by faster, activating "sawtooth waves" that share many characteristics with ponto-geniculo-occipital waves described in animals and a medial-occipital cluster containing slow waves that are more similar to NREM sleep slow waves. These findings indicate that REM sleep is a spatially and temporally heterogeneous state and may contribute to explaining its known functional and phenomenological properties.

Human Rapid Eye Movement Sleep Shows Local Increases in Low-Frequency Oscillations and Global Decreases in High-Frequency Oscillations Compared to Resting Wakefulness.

It is often assumed that during rapid eye movement (REM) sleep the cerebral cortex homogenously shows electroencephalogram (EEG) activity highly similar to wakefulness. However, to date no studies have compared neural oscillatory activity in human REM sleep to resting wakefulness with high spatial sampling. In the current study, we evaluated high-resolution topographical changes in neural oscillatory power between both early and late naturalistic REM sleep and resting wakefulness in adult humans. All-night recordings with 256-channel high-density EEG (hd-EEG) were collected in healthy volunteers (N = 12). Topographic analysis revealed that, compared to wake, both the first and last cycle of REM sleep were associated with increased low-frequency oscillations in local central and occipital regions. In contrast, high-frequency activity in both α and β bands (8–20 Hz) was globally decreased during both early and late REM sleep cycles compared to wakefulness. No significant differences in topographic power in any frequency band were observed between REM sleep cycles occurring early and late in the night. We replicated these findings in an independent dataset (N = 33). Together, our findings show that human REM sleep shows consistent topographical changes in oscillatory power across both early and late sleep cycles compared to resting wakefulness.

Effect of Sleep State and Position on Obstructive Respiratory Events Distribution in Adolescent Children.

This study aimed to examine the effect of sleep state (rapid eye movement [REM] versus non-rapid eye movement [NREM]) and position (supine versus non-supine position) on obstructive respiratory events distribution in adolescent population (ages 12 to 18 y). This was a retrospective study that included 150 subjects between the ages of 12 to 18 y with an apnea-hypopnea index (AHI) > 1/h. Subjects using REM sleep-suppressant medications and subjects with history of genetic anomalies or craniofacial syndromes were excluded. The median age was 14 y with interquartile range (IQR) of 13 to 16 y, 56% of patients were males and the median body mass index (BMI) z-score was 2.35 (IQR: 1.71-2.59) with 77.3% of patients fulfilling obesity criteria. Respiratory obstructive events were more common in REM sleep. The median REM obstructive AHI (OAHI) was 8.9 events per hour (IQR: 2.74-22.8), whereas the median NREM OAHI was 3.2 events per hour (IQR: 1.44-8.29; p < 0.001). African American adolescents had more REM obstructive events with median REM OAHI of 13.2 events per hour (IQR: 4.88-30.6), which was significantly higher than median REM OAHI of 4.94 (IQR: 2.05-11.36; p = 0.004) in white adolescents. Obstructive events were more common in supine position with higher median supine OAHI of 6.55 (IQR: 4-17.73) when compared to median non-supine OAHI of 2.94 (IQR: 1-6.54; p < 0.001). This study shows that sleep related obstructive respiratory events in the adolescents (12 to 18 y of age) occur predominantly in REM sleep and in supine position.

Do the eyes scan dream images during rapid eye movement sleep? Evidence from the rapid eye movement sleep behaviour disorder model

Rapid eye movements and complex visual dreams are salient features of human rapid eye movement sleep. However, it remains to be elucidated whether the eyes scan dream images, despite studies that have retrospectively compared the direction of rapid eye movements to the dream recall recorded after having awakened the sleeper. We used the model of rapid eye movement sleep behaviour disorder (when patients enact their dreams by persistence of muscle tone) to determine directly whether the eyes move in the same directions as the head and limbs. In 56 patients with rapid eye movement sleep behaviour disorder and 17 healthy matched controls, the eye movements were monitored by electrooculography in four (right, left, up and down) directions, calibrated with a target and synchronized with video and sleep monitoring. The rapid eye movement sleep behaviour disorder-associated behaviours occurred 2.1 times more frequently during rapid eye movement sleep with than without rapid eye movements, and more often during or after rapid eye movements than before. Rapid eye movement density, index and complexity were similar in patients with rapid eye movement sleep behaviour disorder and controls. When rapid eye movements accompanied goal-oriented motor behaviour during rapid eye movement sleep behaviour disorder (e.g. grabbing a fictive object, hand greetings, climbing a ladder), which happened in 19 sequences, 82% were directed towards the action of the patient (same plane and direction). When restricted to the determinant rapid eye movements, the concordance increased to 90%. Rapid eye movements were absent in 38-42% of behaviours. This directional coherence between limbs, head and eye movements during rapid eye movement sleep behaviour disorder suggests that, when present, rapid eye movements imitate the scanning of the dream scene. Since the rapid eye movements are similar in subjects with and without rapid eye movement sleep behaviour disorder, this concordance can be extended to normal rapid eye movement sleep.

Selective enhancement of rapid eye movement sleep by deep brain stimulation of the human pons

Animal studies suggest that rapid eye movement (REM) sleep is governed by the interaction of REM-promoting and REM-inhibiting nuclei in the pontomesencephalic tegmentum. The pedunculopontine nucleus is proposed to be REM promoting. Using polysomnography, we studied sleep in five parkinsonian patients undergoing unilateral pedunculopontine nucleus deep brain stimulation (DBS). We demonstrated a near doubling of nocturnal REM sleep between the DBS "off" and DBS "on" states, without significant changes in other sleep states. This represents the first demonstration that DBS can selectively modulate human sleep, and it supports an important role for the pedunculopontine nucleus region in modulating human REM sleep. Ann Neurol 2009;66:110-114.

Using Magnetic Resonance Spectroscopy in Narcolepsy to Study the Limbic Mechanisms of Cataplexy

Using Magnetic Resonance Spectroscopy in Narcolepsy to Study the Limbic Mechanisms of Cataplexy

Brain potentials related to rapid eye movements and dreaming during REM sleep: A short review of psychophysiological correlates

Many sleep researchers have examined dream image-generation, which occurs during rapid eye movement (REM) sleep. Furthermore, activation of brain regions related to rapid eye movements during human REM sleep has been reported. Although recent brain imaging techniques have high spatial resolution, their temporal resolution is limited. Consequently, the spatio-temporal structures of brain activities related to rapid eye movement remain largely unknown. This article presents a short review of findings of recent studies that have used brain potentials related to rapid eye movement to examine dream image-generation processes. Brain potentials related to rapid eye movement are obtained using averaged electroencephalography (EEG) that is time-locked to the onset or offset of rapid eye movement. First, based on findings related to presaccadic and pre-REM brain potentials, we discuss why eyes move during REM sleep. Second, the relationship of lambda-like potentials, which occur immediately after the cessation of rapid eye movement, to generation of visual dream images, is discussed. Third, enhancement of gamma-band EEG activity occurring immediately after the offset of rapid eye movement is discussed in terms of information-binding of dream images. Finally in this review, preparatory activation of emotion and memory circuits before the onset of rapid eye movement is discussed in terms of contextual setting of the dream story.

Gamma band EEG activity is enhanced after the occurrence of rapid eye movement during human REM sleep

This study investigated changes in gamma band (35–44 Hz) EEG activity associated with rapid eye movement (REM) during human REM sleep. Polysomnograms of eight healthy young volunteers were recorded during their normal nocturnal sleep using 26 scalp electrode sites. The recordings were analyzed for changes in gamma band EEG activity as a function of four sleep states (slow wave sleep, stage 2, tonic and phasic periods of the REM stage), electrode sites (six midline sites) and the time of occurrence (before and after rapid eye movement). The findings revealed that gamma band EEG activity is enhanced during REM sleep, particularly in the prefrontal regions during phasic periods of the REM stage, even after excluding the possible effects of peri-orbital activity. This result suggests that the prefrontal brain area is activated during the phasic periods of the REM stage. Moreover, results of this study show that the gamma band EEG activity is enhanced following the onset of REM. Taken together, these results suggest that enhancement of gamma band EEG activity is caused by processes such as ponto-geniculo-occipital activity, a lambda-like response and corollary discharge associated with REM.

Functional microstates within human REM sleep: first evidence from fMRI of a thalamocortical network specific for phasic REM periods

High thalamocortical neuronal activity characterizes both, wakefulness and rapid eye movement (REM) sleep, but apparently this network fulfills other roles than processing external information during REM sleep. To investigate thalamic and cortical reactivity during human REM sleep, we used functional magnetic resonance imaging with simultaneous polysomnographic recordings while applying acoustic stimulation. Our observations indicate two distinct functional substates within general REM sleep. Acoustic stimulation elicited a residual activation of the auditory cortex during tonic REM sleep background without rapid eye movements. By contrast, periods containing bursts of phasic activity such as rapid eye movements appear characterized by a lack of reactivity to sensory stimuli. We report a thalamocortical network including limbic and parahippocampal areas specifically active during phasic REM periods. Thus, REM sleep has to be subdivided into tonic REM sleep with residual alertness, and phasic REM sleep with the brain acting as a functionally isolated and closed intrinsic loop.

Rapid eye movement-related brain activation in human sleep: a functional magnetic resonance imaging study

In animal models, ponto-geniculo-occipital waves appear as an early sign of rapid eye movement sleep and may be functionally significant for brain plasticity processes. In this pilot study, we use a combined polysomnographic and functional magnetic resonance imaging approach, and show distinct magnetic resonance imaging signal increases in the posterior thalamus and occipital cortex in close temporal relationship to rapid eye movements during human rapid eye movement sleep. These findings are consistent with cell recordings in animal experiments and demonstrate that functional magnetic resonance imaging can be utilized to detect ponto-geniculo-occipital-like activity in humans. Studying intact neuronal networks underlying sleep regulation is no longer confined to animal models, but has been shown to be feasible in humans by a combined functional magnetic resonance imaging and electroencephalograph approach.

The effects of isolated brainstem lesions on human REM sleep

Background: Clinical and electrophysiologic data support the role of multiple brainstem structures responsible for sleep architecture. To determine if patients with isolated brainstem lesions have detectable abnormalities of sleep architecture with polysomnography (PSG). Method: The objective of this study is to determine if patients with isolated brainstem lesions defined by magnetic resonance imaging (MRI), and without sleep complaints, underwent PSG. The data was compared to age-matched controls. Eight patients met inclusion criteria. Of the eight locations, one was midbrain, two were pontomesencephalic, four were pontine and one was pontomedullary. Results: Four of the eight patients had a decreased percentage of Rapid Eye Movement (REM) sleep. The abnormal studies occurred in patients with a right paramedian pontine infarct, a left pontomedullary cavernous hemangioma (CH), a left pontine CH, and a right pontomesencephalic CH. REM sleep, as a percentage of total bed time, was 8.7, 12.3, 14.8, and 16.7%, respectively. Conclusion: These findings concur with non-human data that depict pontine structures as the major generators of REM sleep.

Two-minute rapid eye movement (REM) density fluctuations in human REM sleep

Rapid eye movement (REM) density fluctuations during REM sleep were studied in five healthy young adults (23–26 years of age). Appropriate electro-oculographic (EOG) montage and automated EOG analysis enabled the detection of horizontal, vertical, and oblique REMs. REM density time series based on these REMs were formed for all the REM periods of the subjects. Autoregressive (AR) spectral analysis of the REM density time series estimated periodicities in the range of 1.7–2.4 min for 14 of the 16 REM periods analyzed, regardless of duration or number of REMs. Four subjects had such periodicities in each of their REM periods and the fifth subject had such periodicities in half the REM periods. This REM density fluctuation at a periodicity of about 2 min may relate to an important ‘rhythmic’ component of the REM generating mechanism(s).

Experience-dependent changes in cerebral functional connectivity during human rapid eye movement sleep

One function of sleep is hypothesized to be the reprocessing and consolidation of memory traces ( Smith, 1995; Gais et al., 2000; McGaugh, 2000; Stickgold et al., 2000). At the cellular level, neuronal reactivations during post-training sleep in animals have been observed in hippocampal ( Wilson and McNaughton, 1994) and cortical ( Amzica et al., 1997) neuronal populations. At the systems level, using positron emission tomography, we have recently shown that some brain areas reactivated during rapid-eye-movement sleep in human subjects previously trained on an implicit learning task (a serial reaction time task) ( Maquet et al., 2000). These cortical reactivations, located in the left premotor area and bilateral cuneus, were thought to reflect the reprocessing – possibly the consolidation – of memory traces during post-training rapid-eye-movement sleep. Here, the experience-dependent functional connectivity of these brain regions is examined. It is shown that the left premotor cortex is functionally more correlated with the left posterior parietal cortex and bilateral pre-supplementary motor area during rapid-eye-movement sleep of subjects previously trained to the reaction time task compared to rapid-eye-movement sleep of untrained subjects. The increase in functional connectivity during post-training rapid-eye-movement sleep suggests that the brain areas reactivated during post-training rapid-eye-movement sleep participate in the optimization of the network that subtends subject’s visuo–motor response. The optimization of this visuo–motor network during sleep could explain the gain in performance observed during the following day.

Experience-dependent changes in cerebral functional connectivity during human rapid eye movement sleep

Experience-dependent changes in cerebral functional connectivity during human rapid eye movement sleep

Rhythmic hippocampal slow oscillation characterizes REM sleep in humans

Hippocampal rhythmic slow activity (RSA) is a well-known electrophysiological feature of exploratory behavior, spatial cognition, and rapid eye movement (REM) sleep in several mammalian species. Recently, RSA in humans during spatial navigation was reported, but systematic data regarding human REM sleep are lacking. Using mesio-temporal corticography with foramen ovale electrodes in epileptic patients, we report the presence of a 1.5-3-Hz synchronous rhythmic hippocampal oscillation seemingly specific to REM sleep. This oscillation is continuous during whole REM periods, is clearly observable by visual inspection, and appears in tonic and phasic REM sleep episodes equally. Quantitative analysis proved that this 1.5-3-Hz frequency band significantly differentiates REM sleep from waking and slow-wake sleep (SWS). No other frequency band proved to be significant or showed this high rhythmicity. Even in temporo-lateral surface recordings, although visually much less striking, the relative power of the 1.5-3-Hz frequency band differentiates REM sleep from other states with statistical significance. This could mean that the 1.5-3-Hz hippocampal RSA spreads over other cortical areas in humans as in other mammals. We suggest that this oscillation is the counterpart of the hippocampal theta of mammalian REM sleep, and that the 1.5-3-Hz delta EEG activity is a basic neurophysiological feature of human REM sleep.

Experience-dependent changes in cerebral activation during human REM sleep.

The function of rapid-eye-movement (REM) sleep is still unknown. One prevailing hypothesis suggests that REM sleep is important in processing memory traces. Here, using positron emission tomography (PET) and regional cerebral blood flow measurements, we show that waking experience influences regional brain activity during subsequent sleep. Several brain areas activated during the execution of a serial reaction time task during wakefulness were significantly more active during REM sleep in subjects previously trained on the task than in non-trained subjects. These results support the hypothesis that memory traces are processed during REM sleep in humans.