Characterizing sleep spindles in 11,630 individuals from the National Sleep Research Resource.

Sleep spindles are characteristic electroencephalogram (EEG) signatures of stage 2 non-rapid eye movement sleep. Implicated in sleep regulation and cognitive functioning, spindles may represent heritable biomarkers of neuropsychiatric disease. Here we characterize spindles in 11,630 individuals aged 4 to 97 years, as a prelude to future genetic studies. Spindle properties are highly reliable but exhibit distinct developmental trajectories. Across the night, we observe complex patterns of age- and frequency-dependent dynamics, including signatures of circadian modulation. We identify previously unappreciated correlates of spindle activity, including confounding by body mass index mediated by cardiac interference in the EEG. After taking account of these confounds, genetic factors significantly contribute to spindle and spectral sleep traits. Finally, we consider topographical differences and critical measurement issues. Taken together, our findings will lead to an increased understanding of the genetic architecture of sleep spindles and their relation to behavioural and health outcomes, including neuropsychiatric disorders.

Sleep-dependent motor memory plasticity in the human brain.

Growing evidence indicates a role for sleep in off-line memory processing, specifically in post-training consolidation. In humans, sleep has been shown to trigger overnight learning on a motor-sequence memory task, while equivalent waking periods produce no such improvement. But while the behavioral characteristics of sleep-dependent motor learning become increasingly well characterized, the underlying neural basis remains unknown. Here we present functional magnetic resonance imaging data demonstrating a change in the representation of a motor memory after a night of sleep. Subjects trained on a motor-skill memory and 12 hours later, after either sleep or wake, were retested during functional magnetic resonance imaging. Following sleep relative to wake, regions of increased activation were expressed in the right primary motor cortex, medial prefrontal lobe, hippocampus and left cerebellum; changes that can support faster motor output and more precise mapping of key-press movements. In contrast, signal decreases were identified in parietal cortices, the left insular cortex, temporal pole and fronto-polar region, reflecting a reduced need for conscious spatial monitoring and a decreased emotional task burden. This evidence of an overnight, systems-level change in the representation of a motor memory holds important implications for acquiring real-life skills and in clinical rehabilitation following brain trauma, such as stroke.

Sleep, learning, and dreams: off-line memory reprocessing.

Converging evidence and new research methodologies from across the neurosciences permit the neuroscientific study of the role of sleep in off-line memory reprocessing, as well as the nature and function of dreaming. Evidence supports a role for sleep in the consolidation of an array of learning and memory tasks. In addition, new methodologies allow the experimental manipulation of dream content at sleep onset, permitting an objective and scientific study of this dream formation and a renewed search for the possible functions of dreaming and the biological processes subserving it.

Effects of fluvoxamine and paroxetine on sleep structure in normal subjects: a home-based Nightcap evaluation during drug administration and withdrawal.

BACKGROUND: Acute and chronic administration of the selective serotonin reuptake inhibitors (SSRIs) have been widely reported to disrupt sleep in laboratory studies. This study examines the naturalistic, longitudinal effects of paroxetine and fluvoxamine on sleep quality in the home setting. METHOD: Fourteen healthy volunteers free of medical and neuropsychiatric symptoms entered a 31-day protocol: 7 days of drug-free baseline (days 1-7), 19 days of drug treatment (steady state during days 18-26), and 5 days of acute withdrawal (days 27-31). On day 8, the subjects were randomly assigned to receive either 100 mg/day of fluvoxamine or 20 mg/day of paroxetine (half receiving each drug) in divided morning and evening oral doses. Investigators remained blinded to drug assignment until all sleep data had been analyzed. Sleep was monitored using the Nightcap ambulatory sleep monitor. Four standard and 3 novel measures were computed and compared using multivariate analysis of variance, analysis of variance, and Bonferroni-corrected comparison of means. RESULTS: Sleep disruption was most clearly demonstrated using the novel measures eyelid quiescence index, rhythmicity, and eyelid movements per minute in non-rapid eye movement sleep, but was also apparent as determined by standard measures of sleep efficiency, number of awakenings, and sleep onset latency. Paroxetine disrupted sleep more than fluvoxamine, and paroxetine-induced sleep disruption persisted into the withdrawal phase. Rapid eye movement sleep was suppressed during treatment (especially for fluvoxamine) and rebounded during withdrawal (especially for paroxetine). CONCLUSION: We confirm laboratory polysomnographic findings of SSRI-induced sleep quality changes and demonstrate the Nightcap's efficacy as an inexpensive longitudinal monitor for objective sleep changes induced by psychotropic medication.

SSRI treatment suppresses dream recall frequency but increases subjective dream intensity in normal subjects.

Clinical lore and a small number of published studies report that the selective serotonin reuptake inhibitors (SSRIs) intensify dreaming. This study examines the dream effects of paroxetine and fluvoxamine in order to both increase clinical knowledge of these agents and to test an important potential method for probing the relationship between REM sleep neurobiology and dreaming in humans. Fourteen normal, paid volunteers (4 males, 10 females; mean age 27.4 year, range 22--39) free of medical or neuropsychiatric symptoms as well as of psychotropic or sleep affecting drugs completed a 31-day home-based study consisting of: 7 days drug-free baseline; 19 days on either 100 mg fluvoxamine (7 Ss) or 20 mg paroxetine (7 Ss) in divided morning and evening doses; and 5 days acute discontinuation. Upon awakening, subjects wrote dream reports, self-scored specific emotions in their reports and rated seven general dream characteristics using 5-point Likert scales. Dream reports were independently scored for bizarreness, movement and number of visual nouns by three judges. REM sleep-related measures were obtained using the Nightcap ambulatory sleep monitor. Mean dream recall frequency decreased during treatment compared with baseline. Dream report length and judge-rated bizarreness were greater during acute discontinuation compared with both baseline and treatment and this effect was a result of the fluvoxamine-treated subjects. The subjective intensity of dreaming increased during both treatment and acute discontinuation compared with baseline. Propensity to enter REM sleep was decreased during treatment compared with baseline and acute discontinuation and the intensity of REM sleep increased during acute discontinuation compared with baseline and treatment. The decrease in dream frequency during SSRI treatment may reflect serotonergic REM suppression while the augmented report length and bizarreness during acute SSRI discontinuation may reflect cholinergic rebound from serotonergic suppression.

Watching the sleeping brain watch us - sensory processing during sleep.

Presentation of auditory stimuli to sleeping subjects produced distinct fMRI activation patterns. Whereas pure tones activated auditory processing regions, subjects' names additionally activated language centers as well as the left amygdala and prefrontal cortex. These studies open the way for crucial studies of sleep-dependent cognitive processing.

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-mind states: I. Longitudinal field study of sleep/wake factors influencing mentation report length.

STUDY OBJECTIVES: To collect and analyze reports of mental activity across sleep/wake states. DESIGN: Mentation reports were collected in a longitudinal design by combining our Nightcap sleep monitor with daytime experience sampling techniques. Reports were collected over 14 days and nights from active and quiet wake, after instrumental awakenings at sleep onset, and after both spontaneous and instrumental awakenings from REM and NREM sleep. SETTING: All reports were collected in the normal home, work and school environments of the subjects. PARTICIPANTS: Subjects included 8 male and 8 female undergraduate students (19-26 years of age). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: A total of 1,748 reports, averaging 109 per subject, were collected from active wake across the day (n=894), from quiet wake in the pre-sleep onset period (n=58), from sleep onset (n=280), and from later REM (n=269) and nonREM (n=247) awakenings. Median report lengths varied more than 2-fold, in the order REM > active wake > quiet wake > NREM = sleep onset. The extended protocol allowed many novel comparisons between conditions. In addition, while spontaneous REM reports were longer than those from forced awakenings, the difference was explained by the time within the REM period at which the awakenings occurred. Finally, intersubject differences in REM report lengths were correlated with similar differences in waking report lengths. CONCLUSIONS: The use of the Nightcap sleep monitoring system along with waking experience sampling permits a more complete sampling and analysis of mental activity across the sleep/wake cycle than has been previously possible.

Finding the stuff that dreams are made of.

The scientific study of dreams has had a long but tortured history. While the discovery of REM sleep in 1953 and its strong correlation with dreaming led to a renewed hope that the study of dreaming could be moved to a solidly scientific and physiological base, such studies have provided only mixed success. In 1977, Hobson and McCarley proposed the activation-synthesis model for dream construction based on the physiological features of REM sleep, but since then the field has shown surprisingly little progress.

The mind in REM sleep: reports of emotional experience.

STUDY OBJECTIVES: No consensus has been reached on the characteristics of emotional experience during rapid eye movement sleep (REM). Thus, the relationship between the emotional brain activation and mental activity in REM remains unclear. Our objective is to characterize emotional experience in REM in order to facilitate understanding of brain-mind correlations in this state. DESIGN: We combined instrumental awakenings from REM with the subjects' own ratings of the occurrence and intensity of discrete emotion types for each line in their REM mentation reports. SETTING: The study was performed in the subjects' own homes over three consecutive nights using ambulatory polysomnography. PARTICIPANTS: Nine normal healthy subjects, age 31-60 (mean=43.0). INTERVENTIONS: Awakenings 5-15 minutes into REM periods across the night. MEASUREMENTS AND RESULTS: Emotions were found in 74% of 88 mentation reports, with a balanced proportion of positive and negative emotions. Among the reports scored for emotions, 14% contained one emotion and 86% contained two or more different emotion types. Joy/elation was the most frequent emotion, found in 36% of the reports, followed by surprise (24%), anger (17%), anxiety/fear (11%), and sadness (10%). Anxiety/fear was significantly less intense than joy/elation, anger, and surprise. Except for surprise, no specific emotion type changed from the first to the second half of the night. Negative emotions and surprise but not positive emotions varied significantly across subjects. CONCLUSIONS: The analysis of subject reports of emotions following instrumental awakenings demonstrate a balanced and widespread occurrence of both positive and negative emotions in REM sleep dreams. Emotions in REM are likely to be powerfully modulated by the neurobiological processes which differentiate REM from waking.

Replaying the game: hypnagogic images in normals and amnesics.

Participants playing the computer game Tetris reported intrusive, stereotypical, visual images of the game at sleep onset. Three amnesic patients with extensive bilateral medial temporal lobe damage produced similar hypnagogic reports despite being unable to recall playing the game, suggesting that such imagery may arise without important contribution from the declarative memory system. In addition, control participants reported images from previously played versions of the game, demonstrating that remote memories can influence the images from recent waking experience.

Visual discrimination task improvement: A multi-step process occurring during sleep.

Performance on a visual discrimination task shows long-term improvement after a single training session. When tested within 24 hr of training, improvement was not observed unless subjects obtained at least 6 hr of posttraining sleep prior to retesting, in which case improvement was proportional to the amount of sleep in excess of 6 hr. For subjects averaging 8 hr of sleep, overnight improvement was proportional to the amount of slow wave sleep (SWS) in the first quarter of the night, as well as the amount of rapid eye movement sleep (REM) in the last quarter. REM during the intervening 4 hr did not appear to contribute to improvement. A two-step process, modeling throughput as the product of the amount of early SWS and late REM, accounts for 80 percent of intersubject variance. These results suggest that, in the case of this visual discrimination task, both SWS and REM are required to consolidate experience-dependent neuronal changes into a form that supports improved task performance.

Dreaming and the brain: toward a cognitive neuroscience of conscious states.

Sleep researchers in different disciplines disagree about how fully dreaming can be explained in terms of brain physiology. Debate has focused on whether REM sleep dreaming is qualitatively different from nonREM (NREM) sleep and waking. A review of psychophysiological studies shows clear quantitative differences between REM and NREM mentation and between REM and waking mentation. Recent neuroimaging and neurophysiological studies also differentiate REM, NREM, and waking in features with phenomenological implications. Both evidence and theory suggest that there are isomorphisms between the phenomenology and the physiology of dreams. We present a three-dimensional model with specific examples from normally and abnormally changing conscious states.

Dreaming and waking consciousness: a character recognition study.

The formal features of dream characters were studied in a sample of 320 dream reports submitted by 33 adult subjects (13 male, 20 female) of varying ages in a university extension course. Subjects were queried by questionnaire about dream characters immediately after recording their dreams upon awakening in their normal home setting. It was found that 48% of characters represented a named personage known to the dreamer, 35% were generically identified by their social role (e.g., policeman) or abstract relation to the dreamer (e.g., a friend) while only 16% were wholly novel. Seventy-seven percent of characters were pseudosensorily present in the dream whereas 23% were present only by mention or thought. Subjects were allowed to endorse one or more of four bases of recognition and, among named characters, 32% were identified by 'appearance', 21% by 'behavior', 45% by 'face', and 44% by 'just knowing' (with the respective percentages for generic characters being 39%, 38%, 9% and 40%). Fourteen percent of named and generic characters had associated some element of bizarreness most frequently consisting of an incongruous feature. Comparing the 25 longest and 25 shortest reports, named subjects were significantly more common in the shortest reports whereas generic and unknown characters were more common in the longest reports. Results are interpreted in neurocognitive terms as possibly reflecting a decrease during dreaming relative to waking in the exchange of information between inferotemporal face identification areas and prefrontal areas subserving logic and working memory.

Sleep-induced changes in associative memory.

The notion that dreaming might alter the strength of associative links in memory was first proposed almost 200 years ago. But no strong evidence of such altered associative links has been obtained. Semantic priming can be used to quantify the strength of associative links between pairs of words; it is thought to measure the automatic spread of activation from a "node" representing one word to nodes representing semantically related words. Semantic priming could thus be used to test for global alterations in the strengths of associative links across the wake-sleep cycle. Awakenings from REM and nonREM (NREM) sleep produce a period of state carry-over during which performance is altered as a result of the brain's slow transition to full wakefulness, and cognitive testing in this period can provide information about the functioning of the brain during the prior sleep period. When subjects were tested across the night--before and after a night's sleep as well as immediately following forced awakenings from REM and NREM sleep--weak priming (e. g., thief-wrong) was found to be state dependent (p = 0.016), whereas strong priming (e.g., hot-cold) was not (p = 0.89). Weak primes were most effective in the presleep and REM sleep conditions and least effective in NREM and postsleep conditions. Most striking are analyses comparing weak and strong priming within each wake-sleep state. Contrary to the normal pattern of priming, subjects awakened from REM sleep showed greater priming by weak primes than by strong primes (p = 0.01). This result was seen in each of three protocols. In contrast, strong priming exceeded weak priming in NREM sleep. The shift in weak priming seen after REM sleep awakenings suggests that cognition during REM sleep is qualitatively different from that of waking and NREM sleep and may reflect a shift in associative memory systems, a shift that we hypothesize underlies the bizarre and hyperassociative character of REM-sleep dreaming. Known changes in brainstem activity that control the transition into and maintenance of REM sleep provide a possible explanation of this shift.

To dream or not to dream? Relevant data from new neuroimaging and electrophysiological studies.

The study of sleep and dreams has enjoyed a major breakthrough with recent findings from brain imaging studies in humans. Several independent groups have shown global deactivation of the brain during non rapid eye movement sleep and a regionally selective reactivation during rapid eye movement sleep. These results are complemented by new brain lesion and electrophysiological recording data to give a detailed picture of the brain dynamics of changes in conscious state.

Eyelid movements and mental activity at sleep onset.

The nature and time course of sleep onset (hypnagogic) mentation was studied in the home environment using the Nightcap, a reliable, cost-effective, and relatively noninvasive sleep monitor. The Nightcap, linked to a personal computer, reliably identified sleep onset according to changes in perceived sleepiness and the appearance of hypnagogic dream features. Awakenings were performed by the computer after 15 s to 5 min of sleep as defined by eyelid quiescence. Awakenings from longer periods of sleep were associated with (1) an increase in reported sleepiness, (2) a decrease in the length of mentation reports, (3) a decrease in the frequency of reports of normal, wake-like thoughts, (4) an increase in the frequency of "unusual thoughts," and (5) increased frequencies of formal dream features, including visual hallucination, self-representation, fictive movement, narrative plot, and bizarreness. While sleep-onset reports can include all features of rapid eye movement (REM) dream reports, the number of such features is markedly reduced at sleep onset, suggesting that this mentation is a greatly diminished version of REM dreaming.

The neuropsychology of REM sleep dreaming.

Recent PET imaging and brain lesion studies in humans are integrated with new basic research findings at the cellular level in animals to explain how the formal cognitive features of dreaming may be the combined product of a shift in neuromodulatory balance of the brain and a related redistribution of regional blood flow. The human PET data indicate a preferential activation in REM of the pontine brain stem and of limbic and paralimbic cortical structures involved in mediating emotion and a corresponding deactivation of dorsolateral prefrontal cortical structures involved in the executive and mnemonic aspects of cognition. The pontine brainstem mechanisms controlling the neuromodulatory balance of the brain in rats and cats include noradrenergic and serotonergic influences which enhance waking and impede REM via anticholinergic mechanisms and cholinergic mechanisms which are essential to REM sleep and only come into full play when the serotonergic and noradrenergic systems are inhibited. In REM, the brain thus becomes activated but processes its internally generated data in a manner quite different from that of waking.