Differential auditory processing continues during sleep.

Auditory evoked potentials (AEPs) were used to examine selective stimulus processing in sleep. In waking, repetitive stimuli generate exogenous P1, N1 and P2 components of the auditory evoked potential (AEP). Deviant stimuli generate endogenous cognitive components including the mismatch negativity (MMN), N2 and P3 components. We examined long-latency auditory evoked potentials elicited by repetitive and deviant stimuli during waking and stage II-IV sleep to assess whether stimulus deviance is detected during sleep. The waking P1, N1b and P2 had maximal amplitudes at fronto-central scalp sites, with additional peaks (N1a, N1c) at temporal sites. Deviant tones generated a frontal maximal MMN, and complex novel tones generated an additional P3 component maximal at centro-parietal sites. During stages II-IV sleep N1a, b, c amplitudes were reduced. During stage II sleep all stimuli generated increased P2 amplitudes and a late negative component (N340). Deviant stimuli generated greater P2 and N340 amplitudes than frequent stimuli in stage II sleep, as well as an additional P420 component. In stage III-IV sleep the P420 was absent and the AEP was dominated by a negativity of long duration whose amplitude increased in response to deviant stimuli. These data indicate that auditory evoked activity changes from wakefulness to sleep. The differential response to deviant sounds observed during waking and all sleep stages supports the theory that selective processing of auditory stimuli persists during sleep.     

Sensory gating in primary insomnia

Although previous research indicates that sleep architecture is largely intact in primary insomnia (PI), the spectral content of the sleeping electroencephalographic trace and measures of brain metabolism suggest that individuals with PI are physiologically more aroused than good sleepers. Such observations imply that individuals with PI may not experience the full deactivation of sensory and cognitive processing, resulting in reduced filtering of external sensory information during sleep. To test this hypothesis, gating of sensory information during sleep was tested in participants with primary insomnia (n = 18) and good sleepers (n = 20). Sensory gating was operationally defined as (i) the difference in magnitude of evoked response potentials elicited by pairs of clicks presented during Wake and Stage II sleep, and (ii) the number of K complexes evoked by the same auditory stimulus. During wake the groups did not differ in magnitude of sensory gating. During sleep, sensory gating of the N350 component was attenuated and completely diminished in participants with insomnia. P450, which occurred only during sleep, was strongly gated in good sleepers, and less so in participants with insomnia. Additionally, participants with insomnia showed no stimulus‐related increase in K complexes. Thus, PI is potentially associated with impaired capacity to filter out external sensory information, especially during sleep. The potential of using stimulus‐evoked K complexes as a biomarker for primary insomnia is discussed.     

Effects of sleep onset on the mismatch negativity (MMN) to frequency deviants using a rapid rate of presentation

This study examined the effects of sleep onset-the transition from a waking, conscious state to one of sleep and unconsciousness-on the mismatch negativity (MMN) following frequency deviants when a rapid rate of stimulus presentation is employed. The MMN is thought to reflect a brief-lasting sensory memory. Rapid rates of stimulus presentation should guard the sensory memory from fading. A 1,000 Hz standard stimulus was presented every 150 ms. At random, on 6.6% of the trials, the standard was changed to either a large 2,000 or a small 1,100 Hz deviant. During alert wakefulness (when subject ignored the stimuli and read a book), the large deviant elicited a larger deviant related negativity (DRN) than did the small deviant. This negativity may be a composite of both N1 and MMN activity while that following the small deviant is probably a 'true' MMN. The large deviant continued to elicit a DRN in relaxed wakefulness (eyes closed) and Stages 1 and 2 of sleep, although it was much reduced in amplitude. A significant MMN was recorded for the small deviant only in alert wakefulness. The failure to observe an MMN to small deviance and the attenuation of the DRN to large deviance at sleep onset therefore is probably not due to a decay of sensory memory. It is more likely that cortical encoding of both the standard and deviant is weakened during sleep onset because of prior thalamic inhibition of sensory input.     

The Brain Selectively Tunes to Unfamiliar Voices during Sleep

The brain continues to respond selectively to environmental stimuli during sleep. However, the functional role of such responses, and whether they reflect information processing or rather sensory inhibition, is not fully understood. Here, we present 17 human sleepers (14 females) with their own name and two unfamiliar first names, spoken by either a familiar voice (FV) or an unfamiliar voice (UFV), while recording polysomnography during a full night of sleep. We detect K-complexes, sleep spindles, and microarousals, and assess event-related and frequency responses as well as intertrial phase synchronization to the different stimuli presented during nonrapid eye movement (NREM) sleep. We show that UFVs evoke more K-complexes and microarousals than FVs. When both stimuli evoke a K-complex, we observe larger evoked potentials, more precise time-locking of brain responses in the delta band (1–4 Hz), and stronger activity in the high frequency (>16 Hz) range, in response to UFVs relative to FVs. Crucially, these differences in brain responses disappear completely when no K-complexes are evoked by the auditory stimuli. Our findings highlight discrepancies in brain responses to auditory stimuli based on their relevance to the sleeper and propose a key role for K-complexes in the modulation of sensory processing during sleep. We argue that such content-specific, dynamic reactivity to external sensory information enables the brain to enter a sentinel processing mode in which it engages in the important internal processes that are ongoing during sleep while still maintaining the ability to process vital external sensory information.SIGNIFICANCE STATEMENT Previous research has shown that sensory processing continues during sleep. Here, we studied the capacity of the sleeping brain to extract and process relevant sensory information. We presented sleepers with their own names and unfamiliar names spoken by either an FV or a UFV. During NREM sleep, UFVs elicited more K-complexes and microarousals than FVs. By contrasting stimuli that evoked K-complexes, we demonstrate that UFVs evoked larger, more synchronized brain responses as well as stronger power at high frequencies (>16 Hz) relative to FVs. These differences in brain responses disappeared when no K-complexes were evoked. Our results suggest a pivotal role for K-complexes in the selective processing of relevant information during NREM sleep.     

The mismatch negativity to frequency deviant stimuli during natural sleep

Eight subjects spent a single night in the sleep laboratory. Event-related potentials (ERPs) were recorded during the presentation of two auditory ‘oddball’ stimulus conditions in which tonal frequency was manipulated. In the first condition, 1000 Hz ‘standard’ and 2000 Hz ‘deviant’ tones were presented. In the second condition, the deviant tone was reduced to 1050 Hz. In both conditions, deviant probability was 0.2. Stimuli were presented every 600 ms during wakefulness and stages 2, 4, and REM of sleep. A distinctive N1 wave was visible in both stimulus conditions when the subject was awake. The deviant stimuli elicited a ‘mismatch negativity’ (MMN) that inverted in polarity at the mastoid. In REM sleep, an N1 and a MMN were also elicited in both conditions. In the large deviance condition, the MMN had a slightly attenuated amplitude and was shorter in duration while in the small deviant condition, its peak latency was unusually early. Neither the N1 nor the MMN could be recorded in non-REM sleep.     

Arousal threshold determination in 1862: Kohlschütter’s Measurements on the Firmness of Sleep

A multitude of studies used external sensory stimuli to experimentally induce electroencephalographic, vegetative or behavioral reactions in the sleeping subject, either to gather information on the nature of sleep or to induce sleep fragmentation. But Ernst Otto Heinrich Kohlschütter was the first to systematically investigate the change of awakening thresholds across the night, generating a sleep depth curve for his 1862 dissertation “Measurements on the Firmness of Sleep” (“Messungen der Festigkeit des Schlafes”). For the time, his concepts of sleep and the design of his experiments were impressive. A re-analysis of his data with modern regression techniques and a comparison with a polysomnographic laboratory study on the effects of traffic noise on sleep shows that he correctly captured the typical evolution of awakening thresholds across the night, with only 74 measurements in a single subject. Nevertheless, Kohlschütter’s analyses were hypothesis driven, as he discarded almost 50% of the data points to derive what he called an “idealized curve of sleep”. This does not belittle his achievement of being the first to systematically investigate arousal thresholds across the night without the help of electrophysiologic measurement techniques.     

Dissociable learning-dependent changes in REM and non-REM sleep in declarative and procedural memory systems

Sleep spindles and rapid eye movements have been found to increase following an intense period of learning on a combination of procedural memory tasks. It is not clear whether these changes are task specific, or the result of learning in general. The current study investigated changes in spindles, rapid eye movements, K-complexes and EEG spectral power following learning in good sleepers randomly assigned to one of four learning conditions: Pursuit Rotor (n=9), Mirror Tracing (n=9), Paired Associates (n=9), and non-learning controls (n=9). Following Pursuit Rotor learning, there was an increase in the duration of Stage 2 sleep, spindle density (number of spindles/min), average spindle duration, and an increase in low frequency sigma power (12-14Hz) at occipital regions during SWS and at frontal regions during Stage 2 sleep in the second half of the night. These findings are consistent with previous findings that Pursuit Rotor learning is consolidated during Stage 2 sleep, and provide additional data to suggest that spindles across all non-REM stages may be a mechanism for brain plasticity. Following Paired Associates learning, theta power increased significantly at central regions during REM sleep. This study provides the first evidence that REM sleep theta activity is involved in declarative memory consolidation. Together, these findings support the hypothesis that brain plasticity during sleep does not involve a unitary process; that is, different types of learning have unique sleep-related memory consolidation mechanisms that act in dissociable brain regions at different times throughout the night.     

The novelty P3: an event-related brain potential (ERP) sign of the brain's evaluation of novelty.

A review of the literature that examines event-related brain potentials (ERPs) and novelty processing reveals that the orienting response engendered by deviant or unexpected events consists of a characteristic ERP pattern, comprised sequentially of the mismatch negativity (MMN) and the novelty P3 or P3a. A wide variety of evidence suggests that the MMN reflects the detection of deviant events, whereas the P3a is associated more with the evaluation of those events for subsequent behavioral action. On the scalp, the novelty P3a is comprised of at least two aspects, one frontal the other posterior, each with different cognitive (and presumably neurologic) correlates. Intracranial ERP investigations and studies of patients with localized brain lesions (and, to some extent, fMRI data) converge with the scalp-recorded data in suggesting a widespread neural network, the different aspects of which respond differentially to stimulus and task characteristics.     

Modulation of mismatch negativity by stimulus deviance and modality of attention

We studied the effect of attention on the processing of auditory sensory inputs by means of the mismatch negativity (MMN) potential, which can be derived from event-related EEG. A series of frequent standard and rare deviant auditory stimuli were presented to 20 healthy subjects in two recording sessions about five weeks apart. Deviant stimuli were either low or highly deviant as compared to the standard stimulus. While MMN was recorded, subjects were performing a visual and, subsequently, an auditory discrimination task. Directing attention towards the auditory task was associated with increased MMN amplitude only in response to low deviant stimuli and only in the first recording session. No change of MMN amplitude was found when directing attention towards the visual task or when MMN was recorded in response to highly deviant auditory stimuli. The latter may trigger an involuntary switch of attention, thereby overwriting the effect of task-directed attention. Conversely, the effects of attention on the processing of low deviant stimuli appear to be fragile and diminish with increasing automaticity of task execution.     

Abnormal mismatch negativity in women with sexual assault-related posttraumatic stress disorder.

BACKGROUND: Disturbances in sensory processing have been hypothesized in individuals with posttraumatic stress disorder (PTSD). The authors investigated this possibility by using mismatch negativity (MMN), an event-related potential (ERP) that reflects the operation of a preconscious cortical detector of stimulus change. METHODS: Thirteen medication-free women with sexual assault-related PTSD were compared with 16 age-matched, healthy comparison women without PTSD. ERPs were elicited by regularly presented "standard" auditory stimuli and by infrequently occurring "deviant" auditory stimuli, which differed slightly in frequency. The MMN was identified in the subtraction waveforms as the difference between ERPs elicited by the deviant and standard stimuli. Group comparisons of P50, N1, P2, and N2 to the standard and to the deviant stimuli, and of the MMN in the subtraction waveform were performed. RESULTS: The amplitude of the MMN was significantly greater in the PTSD compared to the non-PTSD women. MMN was significantly correlated with the total Mississippi PTSD Symptom Scale score in the PTSD group. No significant group differences were noted in P50, N1, or P2 responding. Significant group differences in N2 were due to the increased MMN in PTSD subjects. CONCLUSIONS: The data provide evidence for abnormalities in preconscious auditory sensory memory in PTSD, whereas earlier studies have reported abnormalities in conscious processing. These data suggest an increased sensitivity to stimulus changes in PTSD and implicate the auditory cortex in the pathophysiology of the disorder.     

A modified oddball paradigm "cross-modal delayed response" and the research on mismatch negativity

A modified oddball paradigm was developed to facilitate the focus of attention and to minimize target effects on deviant-related components of auditory and visual event-related potentials (ERPs) elicited with long interstimulus intervals. Subjects were required to focus on either the visual or auditory stimulus in each stimulus block. Deviant-related components were obtained by subtracting ERPs of the standard stimulus from that of the deviant stimulus for each modality with each stimulus condition. Results showed that auditory mismatch negativity (MMN) and a visual early deviant related negativity (DRN1) were elicited both when stimuli were attended and unattended. In contrast, N2b and P3 were produced only under the attended condition. In comparison of attended MMN and unattended MMN at three time windows (100-150 ms, 150-200 ms, and 200-250 ms) of MMN zone, different scalp distributions were shown, depending on the time windows. This result suggests that the attended auditory MMN is a mixed wave, consisting of genuine MMN, N2b, and possible P165. The effect of attention on MMN may stem from the contamination of these overlapping components. With the present paradigm, at least three sensory memory traces have to be maintained simultaneously in multiple sensory modalities to support automatic processing.     

Therapeutic use of sleep deprivation in depression

Total sleep deprivation (TSD) for one whole night improves depressive symptoms in 40-60% of treatments. The degree of clinical change spans a continuum from complete remission to worsening (in 2-7%). Other side effects are sleepiness and (hypo-) mania. Sleep deprivation (SD) response shows up in the SD night or on the following day. Ten to 15% of patients respond after recovery sleep only. After recovery sleep 50-80% of day 1 responders suffer a complete or partial relapse; but improvement can last for weeks. Sleep seems to lead to relapse although this is not necessarily the case. Treatment effects may be stabilised by antidepressant drugs, lithium, shifting of sleep time or light therapy. The best predictor of a therapeutic effect is a large variability of mood. Current opinion is that partial sleep deprivation (PSD) in the second half of the night is equally effective as TSD. There are, however, indications that TSD is superior. Early PSD (i.e. sleeping between 3:00 and 6:00) has the same effect as late PSD given equal sleep duration. New data cast doubt on the time-honoured conviction that REM sleep deprivation is more effective than non-REM SD. Both may work by reducing total sleep time. SD is an unspecific therapy. The main indication is the depressive syndrome. Some studies show positive effects in Parkinson's disease. It is still unknown how sleep deprivation works.     

Response of polygraphic sleep to phenytoin treatment for epilepsy. A longitudinal study of immediate, short- and long-term effects

Report on a prospective longitudinal study of alterations in polygraphic sleep by phenytoin monotherapy for epilepsy. A first dose of 100mg already caused abbreviation of sleep latency and an increase of slow-wave sleep in the first NREM-REM cycle. In the course of adjustments to steady state, an increase of Stage 3 + 4 sleep in the later REM cycles developed, such that the percentage of slow-wave sleep for the whole night was also augmented, whereas the percentage of light sleep decreased. Sleep structure was affected particularly in the third NREM-REM cycle. With continuing therapy, however, these effects were reversed. The only permanent effect was an abbreviated sleep latency. There were only minimal differences in the response of generalized and of localization-related epilepsies. Serum drug levels had only a very limited influence, seizure control and length of follow-up had no influence on the results. As a collateral finding, a delayed further decrease of epileptic discharges during sleep was observed under long-term conditions in patients who were seizure-free and had been so since adjustment to the steady state.     

Wakefulness-sleep transition: emerging electroencephalographic similarities with the rapid eye movement phase

The covert-rapid eye movement (REM) sleep hypothesis of dreaming suggests that elements of REM sleep emerge during sleep onset, leading to vivid hypnagogic imagery. We tested the physiological part of this hypothesis by analysing scalp-recorded electroencephalograms of 15 human subjects during wake–sleep transition and subsequent night time sleep. Wake–sleep transition was categorised semi-automatically as alpha activity, alpha dropout and as early Stage 2 sleep. The slow oscillation, the slow and the fast subdivisions of the delta and the theta frequencies respectively, as well as alpha and sigma bands were analysed. The similarity of individual-specific wake–sleep transition periods and the whole night Stage 2 or REM sleep periods was expressed in a composite similarity measure covering the spectral power of all analysed frequency bands and in frequency-specific similarities related to power values in single bands. A significant increase in composite similarity with the whole night REM sleep emerged in the period of alpha dropout and diminished in early Stage 2 sleep. The alpha dropout period was more similar to whole night REM sleep than to whole night Stage 2 sleep. These region-independent effects were mirrored in region-specific manner by frequency bands of the delta-slow theta range. Findings are in accordance with the covert REM sleep hypothesis, with previous electrocorticographic results and with the frequency range of the sawtooth waves in humans.     

Complex sound processing during human REM sleep by recovering information from long-term memory as revealed by the mismatch negativity (MMN)

Perceptual learning is thought to be the result of neural changes that take place over a period of several hours or days, allowing information to be transferred to long-term memory. Evidence suggests that contents of long-term memory may improve attentive and pre-attentive sensory processing. Therefore, it is plausible to hypothesize that learning-induced neural changes that develop during wakefulness could improve automatic information processing during human REM sleep. The MMN, an objective measure of the automatic change detection in auditory cortex, was used to evaluate long-term learning effects on pre-attentive processing during wakefulness and REM sleep. When subjects learned to discriminate two complex auditory patterns in wakefulness, an increase in the MMN was obtained in both wake and REM states. The automatic detection of the infrequent complex auditory pattern may therefore be improved in both brain states by reactivating information from long-term memory. These findings suggest that long-term learning-related neural changes are accessible during REM sleep as well.     

Dreaming and Offline Memory Consolidation

Converging evidence suggests that dreaming is influenced by the consolidation of memory during sleep. Following encoding, recently formed memory traces are gradually stabilized and reorganized into a more permanent form of long-term storage. Sleep provides an optimal neurophysiological state to facilitate this process, allowing memory networks to be repeatedly reactivated in the absence of new sensory input. The process of memory reactivation and consolidation in the sleeping brain appears to influence conscious experience during sleep, contributing to dream content recalled on awakening. This article outlines several lines of evidence in support of this hypothesis, and responds to some common objections.     

Event-related potential indices of auditory vowel processing in 3-year-old children

Objective: To determine the ERP characteristics and ERP indices of central speech sound encoding and discrimination in young children.Methods: Auditory sensory event-related potentials (ERPs) and the ERP index of auditory sensory discrimination (the mismatch negativity, MMN) were elicited by vowel stimuli in 3-year-old children. In an oddball paradigm, the standard stimulus was vowel /a/, one deviant stimulus was vowel /o/ (the across-category change), and the other was nasalized vowel /a/ (within-category change). In addition, the ERP changes occurring during the 14 min uninterrupted recording were examined.Results: As indexed by the sensory P1, N2, and N4 peaks, the 3-year-old children's transient neural encoding of vowels was comparable to that earlier registered in 1-year-old children but also showed vowel-specific characteristics observed in school-age children. The 3-year-old's MMN was comparable in amplitude to the school-age children's MMN and appeared to be sensitive to the across-category aspects of vowel changes. However, its latency was longer in the 3-year-olds than in school-age children. Among the sensory ERPs, only the N4 peak showed significant diminution during the experiment. The across-category change MMN diminished after 10 min of the recording, however, over the frontal areas only.Conclusions: In the 3-year-old children, the sensory processing of vowels exhibited transitional characteristics between those observed in infants and school-age children. The auditory sensory discrimination in the 3-year-olds appeared to be sensitive to the phonemic aspects of stimulus change. The frontally-predominant MMN diminution during the experiment might indicate the greater refractoriness of its frontal-lobe generators. In general, the auditory sensory ERPs show distinct maturational profiles from that of the MMN.     

Preattentive sensory processing as indexed by the MMN and P3a brain responses is associated with cognitive and psychosocial functioning in healthy adults

Understanding the basic neural processes that underlie complex higher order cognitive operations and psychosocial functioning is a fundamental goal of cognitive neuroscience. Event-related potentials allow investigators to probe the earliest stages of information processing. Mismatch negativity (MMN) and P3a are auditory event-related potential components that reflect automatic sensory discrimination. The aim of the present study was to determine if MMN and P3a are associated with higher order cognitive operations and psychosocial functioning in clinically normal healthy subjects. Twenty adults were assessed using standardized clinical, cognitive, and psychosocial functional instruments. All individuals were within the normal range on cognitive tests and functional ratings. Participants were also tested on a duration-deviant MMN/P3a paradigm (50-msec standard tones, p = .90; 100-msec deviant tones, p = .10; stimulus onset asynchrony [SOA] = 505 msec). Across fronto-central electrode regions, significant correlations were observed between psychosocial functioning and MMN (r = -.62, p < .01) and P3a (r = .63, p < .01) amplitudes. P3a amplitude was also highly associated with immediate and delayed recall of verbal information with robust correlations widely distributed across fronto-central recording areas (e.g., r = .72, p < .001). The latency of the P3a response was significantly associated with both working memory performance (r = -.53, p < .05) and functional ratings (r = -.48, p < .05). Neurophysiological measures of relatively automatic auditory sensory information processing are associated with higher order cognitive abilities and psychosocial functioning in normal subjects. Efficiency at elementary levels of information processing may underlie the successful encoding, retrieval, and discrimination of task-relevant information, which, in turn, facilitates the iterative and responsive processing necessary for adaptive cognitive and social functioning.     

Changes in sensitivity to stimulus deviance in Alzheimer's disease: an ERP perspective

The mismatch negativity (MMN) of the event-related brain potential (ERP) reflects the storage of information in sensory memory. MMNs were recorded from eight patients with Alzheimer's disease (AD) and eight controls to small (delta50 Hz), large (delta300 Hz), and a variety of highly deviant, environmental sounds. Both old controls and patients showed robust MMNs to all three classes of deviant events, and robust P3 compounds (indicative of active attention) to the environmental sounds. The data suggest that patients with mild AD have an intact sensory memory mechanism that responds similarly to that of controls to systematic increases in deviance. However, for both older controls and patients, only highly deviant acoustic events are likely to involuntary capture attention.     

Effects of waking-auditory stimulation on human sleep architecture.

Evidence suggests that sleep architecture is affected by endogenous homeostatic mechanisms as well as by behavioral and sensory demands during the prior wakefulness. Regarding the auditory system, sensory deprivation has shown to drastically modify the sleep structure, stressing the relevance of such sensory system for sleep organization. Changes in sleep architecture following prolonged auditory stimulation during prior wakefulness would provide additional support to this hypothesis. In the present study, auditory stimulation was administered over a 6 h period prior to sleep. Sleep parameters obtained from visual scoring were quantified across the total sleep period, for each sleep cycle, and for the two halves of the night, separately. Results showed that 6 h of waking-auditory stimulation were followed by an increase in the duration of slow wave sleep, a shortening of the latency between slow wave sleep periods, and a longer sleep onset latency as compared with the baseline night. In contrast, REM sleep parameters were unaffected by the pre-sleep auditory stimulation. These results indicate that sleep architecture depends on auditory demands during the prior wakefulness, suggesting that the local neural activation underlying auditory stimulation may trigger brain control mechanisms selectively involved in both the slow wave sleep maintenance and organization.