REM latency in neurotic and endogenous depression and the cholinergic REM induction test

Latency of rapid eye movement (REM) sleep was measured in eight healthy volunteers under baseline conditions and after administration of physostigmine. An infusion of 0.5 mg of physostigmine 5 minutes after sleep onset caused a significant shortening of REM latency in comparison with baseline conditions. In 45 patients with major depression, REM latency during baseline nights was significantly shorter than in control subjects. This shortening of the REM latency was found to be similar in endogenous, neurotic, and unclassified depressed patients. In contrast to findings in the controls, the physostigmine infusion provoked no further significant reduction of REM latency in depressed patients, but awakened the majority of patients. The data concerning spontaneous REM latency and REM latency after physostigmine do not allow a differentiation among the endogenous, neurotic, and unclassified depressed subgroups. The results of the cholinergic REM induction test do not conclusively support the hypothesis of a cholinergic hypersensitivity in depression.     

Olivo-cochlear inhibition during physostigmine-induced activity in the pontine reticular formation in the decerebrate cat

The physiological role of the olivo-cochlear pathway has been questioned recently because this pathway has never been shown to be operative under natural conditions. In this study, cochlear potentials were recorded differentially between a wire electrode placed on the round window and an indifferent electrode attached to the nuchal muscles in decerebrate, decerebellate cats. Physostigmine was used to induce bout of rapid eye movement (REM) sleep. REM bouts were verified by recording burst activity in the brain stem pontine reticular formation and the inhibition of lumbar monosynaptic reflexes. Intravenous physostigmine increased the inhibition of N₁ caused by direct electrical stimulation of the crossed olivo-cochlear bundle in the absence of REM. Olivo-cochlear system inhibition was also recruited during physostigmine-induced REM sleep. It is concluded that the brain stem reticular formation can activate the olivo-cochlear bundle and can thereby produce inhibition in the cochlea.     

EEG activities during elicited sleep onset REM and NREM periods reflect different mechanisms of dream generation. Electroencephalograms. Rapid eye movement.

OBJECTIVE: To be the first to compare EEG power spectra during sleep onset REM periods (SOREMP) and sleep onset NREM periods (NREMP) in normal individuals and relate this to dream appearance processes underlying these different types of sleep periods. METHODS: Eight healthy undergraduates spent 7 consecutive nights in the sleep lab including 4 nights for SOREMP elicitation using the Sleep Interruption Technique. This enabled us to control preceding sleep processes between SOREMP and NREMP. EEG power spectra when participants did and did not report 'dreams' were compared between both types of sleep. Sleep stages, subjective measurements including dream property scores, sleepiness, mood, and tiredness after awakenings were also examined to determine their consistency with EEG findings. RESULTS: Increased alpha EEG activities (11.72-13.67 Hz) observed mainly in the central area were related to the absence of SOREMP dreams and appearance of NREMP dreams. Analyses of sleep stages combining two studies (16 participants) also supported the Fast Fourier Transform findings, showing that when dreams were reported there were decreased amounts of stage 2 and increased stage REM in SOREMP and increased stage W in NREMP. SOREMP dreams were more bizarre than NREMP dreams. Participants felt more tired after SOREMP with dreams than without dreams, while the opposite was observed after NREMP episodes. CONCLUSIONS: EEG power spectra patterns reflected different physiological mechanisms underlying generation of SOREMP and NREMP dreams. The same relationships were also reflected by sleep stage analyses as well as subjective measurements including dream properties and tiredness obtained after awakenings. This study not only supports the hypothesized relationships between REM mechanisms and REM dreams as well as arousal processes and NREM dreams, it also provides a new perspective to dream research due to its unique techniques to awaken participants and collect REM dreams during experimentally induced SOREMP.     

La motricité redevient-elle normale en sommeil paradoxal ? Le trouble comportemental en sommeil paradoxal

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by violent, or potentially violent, movements during REM sleep, corresponding to enacted dreams. During sleep monitoring, there is a partial or total loss of the normal muscle atonia during REM sleep. REM sleep behavior disorder predominantly affects elderly subjects without any other disease (idiopathic RBD, a precursor of Parkinson disease and Lewy body dementia) or suffering from various neurological and neurodegenerative diseases, mainly synucleinopathies. In addition to being a treatable cause of nocturnal injury of the patients or their bed-partners, RBD is a fantastic window into motor and cognitive control during REM sleep. Notably, parkinsonism transiently disappears during RBD. The patient's voice is louder and better articulated than when awake, and movements are rapid (but jerky) suggesting that the deleterious message from the basal ganglia to the primary motor cortex is reduced or bypassed. As we observed culturally-acquired behaviors, retired patients practicing their former work with mastered gestures, as well as sentences pronounced with appropriate prosody, gesturing, fluency, and syntax during the RBD, we suggest that these behaviors are generated by the same cortical areas as during wakefulness. This model also enables the demonstration that REM during REM sleep are coded in the same direction as the arm and hand movements, as if the dreamer were scanning the dream images. This online access to the motor and verbal dream scenario (through the video and audio monitoring), and the physiological measures (via the EEG, eye movements, muscle tone, respiration, heart rate), together with the offline access to the mental content (dream report after the awakening) constitute a triangulation for validating new hypotheses about REM sleep and dreams.     

Dream experience during REM and NREM sleep of patients with complex partial seizures

This study examined the effectiveness of the cognitive processes underlying dreaming in patients with complex partial seizures (CPS), by assessing the frequency of recall and the structural organization of dreams reported after awakenings provoked alternately during REM and stage 2 NREM sleep on 12 cognitively unimpaired CPS-patients (six with epileptic focus in the right hemisphere and six in the left one). Each patient was recorded for three consecutive nights, respectively, for adaptation to the sleep laboratory context, for polysomnography and for dream collection. The frequency of dream recall was lower after stage 2 NREM sleep than REM sleep, regardless of the side of epileptic focus, while the length and structural organization of dreams did not significantly differ in REM and NREM sleep. However, the length of story-like dreams was influenced by global cognitive functioning during REM sleep. These findings indicate that in CPSs-patients the elaboration of dream experience is maintained in both REM and NREM sleep, while the access to information for conversion into dream contents and the consolidation of dream contents is much less effective during NREM rather than during REM sleep. Further studies may distinguish between these two possibilities and enlighten us as to whether the impaired memory functioning during NREM sleep is a side effect of anticonvulsant treatment.     

Dream process in asthmatic subjects with nocturnal attacks

Polygraphic sleep recordings were made and dream reports collected over 3 consecutive nights for 12 asthmatic subjects with nocturnal attacks and 12 matched normal control subjects. The asthmatic group 1) had more episodes of a vivid impression of dreaming without recollection of dream content ("white dreams") after awakening spontaneously in the morning (nights 1 and 2) and after awakening immediately following REM sleep (night 3), 2) used shorter sentences in dream narrations, and 3) had no dream recall when awakened during nocturnal asthma attacks. The authors suggest that conflictual material emerging during REM or other sleep stages may contribute to the occurrence of nocturnal attacks but is repressed on awakening.     

Neuroendocrine responses to intravenous infusion of physostigmine in patients with Alzheimer disease.

We have reported that physostigmine, a reversible cholinesterase inhibitor, enhances verbal memory in patients with Alzheimer disease (AD). To elucidate the mechanism of cognition enhancement, plasma hormones were measured during high-dose acute and low-dose chronic steady-state intravenous infusions of physostigmine in nine subjects with AD. High-dose hormone responses were measured during and for 24 h after the infusion of physostigmine 1-1.5 mg over 45-60 min. Chronic responses were measured during continuous intravenous infusions of physostigmine at doses (0.5-25 mg/day) that escalated over 2 weeks, and then during 1 week infusion of the dose that optimized cognition (2-12 mg/day) or placebo administered in a randomized, double-blind, cross-over design. A replicable improvement in verbal memory was found in five subjects. High-dose physostigmine infusion that produced noxious side effects resulted in significant elevation above baseline in plasma levels of adrenocorticotrophic hormone (ACTH) (p = 0.0001), cortisol (p = 0.0001), and beta-endorphin (p = 0.0001). Chronic physostigmine administration, in the absence of adverse effects, produced no significant elevation in ACTH (p = 0.08), cortisol (p = 0.70), or beta-endorphin (p = 0.82). These results indicate that high-dose physostigmine activates the hypothalamic-pituitary-adrenal (HPA) axis, likely representing a "stress response." In contrast, cognition-enhancing doses do not produce a peripheral corticosteroid response. Thus, physostigmine-induced memory improvement is independent of the activation of the HPA axis.     

REM ocular activity in Parkinsonian patients chronically treated with levodopa

Summary REM ocular activity of levodopa treated Parkinsonian patients was compared to REM ocular activity of normal young adults. REM densities were significantly higher in patients than in normal controls. This difference was most prominent after 10 min of REM sleep. Previous findings that levodopa treated patients reported unusually vivid and detailed dreams suggest that increase in REM ocular activity is underlying the new dreaming experiences.This study was supported in part by the Bresgin Fund.     

Language learning efficiency, dreams and REM sleep

As a follow-up from a previous study, four subjects taking a 6-week French language immersion program maintained a dream diary starting 2 weeks before until 2 weeks after the course. They also slept in the laboratory during four series of nights: one before the course, two during the course and one after the course. Confirming previous observations, it was observed that those subjects who made significant progress in French learning, experienced French incorporations into dreams earlier and had more verbal communication in their dreams during the language training than those who made little progress. Combining these results with those of the earlier study revealed significant positive correlations between language learning efficiency and both increases in REM sleep percentages, and verbal communication in dreams, as well as a negative correlation with latency to the first French incorporation in dreams. These results support the notion that REM sleep and dreaming are related to waking cognitive processes.     

Sleep and dreams in Korsakoff's amnesia due to alcoholism

Sleep and dreams in 15 chronic alcoholic patients with amnesia were compared with sleep and dreams of 15 age- and sex-adjusted normal subjects. The patients were subjected to psychological tests in order to determine their I.Q. and their memory disturbances. All subjects had two nights of polygraphic recordings; the first tested the natural sleep organization. During the second night, they were awakened 7 min after the onset of each REM sleep episode, and, at least once, 20 min after the onset of a stage II episode, in order to record on a tape their dream reports according to a standardized protocol. The sleep patterns of the amnesic patients did not show any significant alteration. However, after wakening during the night, patients exhibited a higher tendency to return to REMS than controls. There was still some dream activity in those patients, although noticeably less frequently, and their dream activity had a very poor verbal expression. However, there was no change with respect to the spatio-temporal organization, sensorial perceptions, motor activity and verbalizations during their dreams.     

Visual hallucinations as REM sleep behavior disorders in patients with Parkinson's disease.

To clarify whether visual hallucinations in patients with Parkinson's disease (PD) are related to rapid eye movement (REM) sleep, nocturnal polysomnographic variables were compared between a group with hallucinations (hallucinators, n = 14) and a group without hallucinations (nonhallucinators, n = 8). A multiple sleep latency test (MSLT) was performed on 3 hallucinators, and the content of dreams during daytime REM sleep was investigated. The efficacy of clonazepam, a standard treatment choice for REM sleep behavior disorders, was investigated in 8 hallucinators. Nocturnal polysomnograms of the hallucinators showed a higher amount of stage 1-REM sleep with tonic electromyogram (stage 1-REM) than the nonhallucinators, and the reported occurrences of nocturnal hallucinations corresponded with the periods of stage REM or stage 1-REM in most hallucinators. The frequency of sleep onset REM periods (SOREMP) on the MSLT were pathologically high in the hallucinators, and the content of the dreams during the MSLT period was quite similar to their hallucinations. During clonazepam treatment, the frequency of hallucinatory symptoms decreased in 5 of 8 hallucinators. These results indicate that visual hallucinations in PD are likely to be related to a REM sleep disorder manifested as the appearance of both stage 1-REM during the night and SOREMP in the daytime.     

Dreams and hallucinations: A common neurochemical mechanism mediating their phenomenological similarities

Dreams and drug-induced hallucinations have several phenomenological similarities, especially with respect to their visual and emotive components. This similarity is hypothesized to be due to a neurochemical mechanism which is common to both states: the inactivation of the brain serotonin system. This is supported by electrophysiological data indicating that the activity of serotonin-containing neurons is depressed during both dreaming (in REM and non-REM sleep) and in response to hallucinogenic drugs. Further support for the hypothesis derives from neuropharmacological data demonstrating that decreases in synaptic serotonin are associated with increased hallucinatory-like behavior or hallucinatory experience during waking, and increased duration of REM periods during sleep. Reciprocally, increases in synaptic serotonin are associated with decreased hallucinatory-like behavior or hallucinatory experience, and with decreased REM sleep time and dream reports. Neuroanatomical evidence that serotonin is heavily concentrated in brain areas which mediate visual perception and emotive experience is consonant with the strong visual and emotive components of dreams and hallucinations. When these data are considered in conjunction with the exclusively inhibitory synaptic action of serotonin in the forebrain, an explicit hypothesis can be formulated: A cessation, or decrease, in the discharge rate of serotonin-containing neurons, either spontaneously during REM and non-REM sleep, or in response to drugs such as LSD, precipitates, through disinhibition, a dramatic increase in activity of their target neurons in brain areas mediating visual sensation and emotional experience. These latter neural events are a primary physiological substrate for the emergence of strong sensory and emotive processes during dreams and drug-induced hallucinations.     

Role of REM sleep and dream variables in the prediction of remission from depression

To test the hypothesis that REM sleep and/or dreams contribute to overnight mood regulation, 61 subjects were tested on the Beck Depression Inventory (BDI), and for 3 nights of monitored sleep on two occasions, once close to, and 1 year after, a marital separation. Forty-nine percent of the variance in the follow-up BDI could be accounted for by the initial BDI score, and three sleep and dream variables associated with the mood regulatory hypothesis: eye movement density in the first REM, strength of the affect in the first dream and total number of negative dreams recalled from REM awakenings. Among the 39 who met BDI depression criteria initially, 71.8% could be classified correctly as remitted or not remitted at follow-up by discriminant function analysis based on the presence of negative dreams the first vs. second half of the night. Subjects reporting more negative dreams at the beginning and fewer at the night's end were more likely to be in remission 1 year later than were those with fewer negative dreams at the beginning and more at the end of the night. Early negative dreams may reflect a within-sleep mood regulation process taking place, while those that occur later may indicate a failure in the completion of this process.     

Human regional cerebral blood flow during rapid-eye-movement sleep

Owing to the coupling between CBF and neuronal activity, regional CBF is a reflection of neural activity in different brain regions. In this study we measured regional CBF during polysomnographically well-defined rapid-eye-movement (REM) sleep by the use of single photon emission computerized tomography and the new tracer 99mTc-dl-hexamethylpropyleneamine. Eleven healthy volunteers aged between 22 and 27 years were studied. CBF was measured on separate nights during REM sleep and during EEG-verified wakefulness. On awakening from REM sleep, all subjects reported visual dreams. During REM sleep CBF increased by 4% (p less than 0.01) in the associative visual area, while it decreased by 9% (p less than 0.01) in the inferior frontal cortex. The CBF increase in the associative visual area suggests that activation of cerebral structures processing complex visual material is correlated to visual dream experiences. On the other hand, the reduced involvement of the inferior frontal cortex observed during REM sleep might explain the poor temporal organization and bizarreness often experienced in dreams.     

Case Report of Rapid-eye-movement(REM) sleep behavior disorder

Summary

A 23-year-old female student presented with a five-year history of abnormal sleep in which she would sit up or stand up for brief periods in the early morning, talk loudly for a couple of minutes and then lie back down. When woken by family members she would remember vivid dreams and nightmares. In one episode she had a fall that resulted in a subdural hematoma. On presentation at the psychiatric hospital she had a normal mental status exam except for being mildly depressed and anxious about the chronic fatigue from poor sleep. Overnight polysomnography (PSG) showed multiple waking periods each night, poor sleep efficiency and a lack of normal muscle paralysis during REM sleep. The patient was diagnosed with REM Sleep Behavior Disorder and treated with 1 mg clonazepam nightly. Her sleep improved dramatically and remained better at a six-month follow-up, but repeat PSG exam found that the lack of muscle paralysis during REM sleep remained.     

Cholinergic and noradrenergic neurotransmission: impact on REM sleep regulation in healthy subjects and depressed patients.

The reciprocal interaction model of NonREM- and REM sleep regulation suggests that the cycling alternating pattern of Non-REM- and REM sleep is under the control of noradrenergic/serotonergic and cholinergic neuronal networks. This model was tested in healthy humans by administration of cholinergic agonists/antagonists and noradrenergic antagonists prior to or during sleep. Cholinomimetics like physostigmine, RS 86 and galanthamine provoked an earlier onset of REM sleep, whereas subchronic treatment with scopolamine, a cholinergic antagonist, only led to a heightening of REM density. Simultaneous administration of noradrenergic antagonists with a cholinergic agonist did not provoke a more pronounced REM sleep advance. Comparative studies with the cholinergic agonist RS 86 in depressed patients, schizophrenic patients and patients with other psychiatric disorders revealed the most pronounced REM sleep response in the depressed group. The REM sleep response to cholinergic stimulation in depression did however not predict the treatment response to a differential-therapeutic strategy.     

Effect of illicit recreational drugs upon sleep: cocaine, ecstasy and marijuana

The illicit recreational drugs cocaine, ecstasy and marijuana have pronounced effects upon sleep. Administration of cocaine increases wakefulness and suppresses REM sleep. Acute cocaine withdrawal is often associated with sleep disturbances and unpleasant dreams. Studies have revealed that polysomnographically assessed sleep parameters deteriorate even further during sustained abstinence, although patients report that sleep quality remains unchanged or improves. This deterioration of objective sleep measures is associated with a worsening in sleep-related cognitive performance. Like cocaine, 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") is a substance with arousing properties. Heavy MDMA consumption is often associated with persistent sleep disturbances. Polysomnography (PSG) studies have demonstrated altered sleep architecture in abstinent heavy MDMA users. Smoked marijuana and oral Delta-9-tetrahydrocannabinol (THC) reduce REM sleep. Moreover, acute administration of cannabis appears to facilitate falling asleep and to increase Stage 4 sleep. Difficulty sleeping and strange dreams are among the most consistently reported symptoms of acute and subacute cannabis withdrawal. Longer sleep onset latency, reduced slow wave sleep and a REM rebound can be observed. Prospective studies are needed in order to verify whether sleep disturbances during cocaine and cannabis withdrawal predict treatment outcome.     

Michel Jouvet: an explorer of dreams and a great storyteller

In the late 50s Michel Jouvet discovered the presence of muscle atonia during REM sleep in cats and created the first model of REM sleep behavior disorder. He built and led in Lyon, France, the “Laboratory of Molecular Dream Science” (a merry oxymoron to silently protest against the research policy of favoring molecular biology over physiology), where in the late 80s, you could cross people who had worked on sleep in the python, tench fish, tortoise, iguana, hen, lamb, mouse, rat and cat. This brilliant physiologist was also a great storyteller with a very good sense of humor. He supported the theory that dreaming is equivalent to REM sleep (which he called “paradoxical sleep”), kept his own dream diary, and imagined that the ponto-geniculo-occipital waves during REM sleep could compose the song sheet of dreams. He wrote several books published in French on dreams and dreaming.     

Pontine control of rapid eye movement sleep and fear memory

Aims

We often experience dreams of strong irrational and negative emotional contents with postural muscle paralysis during rapid eye movement (REM) sleep, but how REM sleep is generated and its function remain unclear. In this study, we investigate whether the dorsal pontine sub-laterodorsal tegmental nucleus (SLD) is necessary and sufficient for REM sleep and whether REM sleep elimination alters fear memory.

Methods

To investigate whether activation of SLD neurons is sufficient for REM sleep induction, we expressed channelrhodopsin-2 (ChR2) in SLD neurons by bilaterally injecting AAV1-hSyn-ChR2-YFP in rats. We next selectively ablated either glutamatergic or GABAergic neurons from the SLD in mice in order to identify the neuronal subset crucial for REM sleep. We finally  investigated the role of REM sleep in consolidation of fear memory using rat model with complete SLD lesions.

Results

We demonstrate the sufficiency of the SLD for REM sleep by showing that photo-activation of ChR2 transfected SLD neurons selectively promotes transitions from non-REM (NREM) sleep to REM sleep in rats. Diphtheria toxin-A (DTA) induced lesions of the SLD in rats or specific deletion of SLD glutamatergic neurons but not GABAergic neurons in mice completely abolish REM sleep, demonstrating the necessity of SLD glutamatergic neurons for REM sleep. We then show that REM sleep elimination by SLD lesions in rats significantly enhances contextual and cued fear memory consolidation by 2.5 and 1.0 folds, respectively, for at least 9 months. Conversely, fear conditioning and fear memory trigger doubled amounts of REM sleep in the following night, and chemo-activation of SLD neurons projecting to the medial septum (MS) selectively enhances hippocampal theta activity in REM sleep; this stimulation immediately after fear acquisition reduces contextual and cued fear memory consolidation by 60% and 30%, respectively.

Conclusion

SLD glutamatergic neurons generate REM sleep and REM sleep and SLD via the hippocampus particularly down-regulate contextual fear memory.     

REM sleep behavior disorder in Parkinson's disease and dementia with Lewy bodies

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested by vivid, often frightening dreams associated with simple or complex motor behavior during REM sleep. Patients appear to "act out their dreams," in which the exhibited behaviors mirror the content of the dreams. Management of RBD involves counseling about safety measures in the sleep environment; in those at risk for injury, clonazepam and/or melatonin is usually effective. In this article, the authors present a detailed review of the clinical and polysomnographic features, differential diagnosis, diagnostic criteria, management strategies, and pathophysiologic mechanisms of RBD. They then review the literature and their institutional experience of RBD associated with neurodegenerative disease, particularly Parkinson's disease and dementia with Lewy bodies. The evolving data suggests that RBD may have clinical diagnostic and pathophysiologic significance in isolation and when associated with neurodegenerative disease.