Decay time of the auditory sensory memory trace during wakefulness and REM sleep

In a repetitive auditory stimulus sequence, deviant infrequent tones typically elicit a component of auditory event-related potentials termed mismatch negativity (MMN). The elicitation of MMN is assumed to reflect the existence of a memory trace of the standard stimulus that has a decay time of about 10 s and is strengthened by repetition of the standards. The main aim of the present study was to test the decay time of the sensory memory trace during rapid-eye movement (REM) sleep vs. wakefulness, as indexed by the MMN. Subjects were presented 10 tone trains, separated by 3, 6, or 9 s of silence, during waking and REM sleep. Each train consisted of 9 standards of 1000 Hz and 1 deviant of 2000 Hz that occurred at position 1, 2, 4, or 6. The waking deviants elicited a frontocentral negativity with a scalp topography equivalent to the MMN component. During REM sleep, the negative component showed the same scalp distribution only for the 3-s intertrain interval (ITI). In this brain state, the MMN amplitude was smaller and decreased with prolongation of the ITI. These results suggest a weaker sensory memory trace formation and a premature decay time of such a memory trace during REM sleep as compared with wakefulness.     

Is the failure to detect stimulus deviance during sleep due to a rapid fading of sensory memory or a degradation of stimulus encoding?

The mismatch negativity (MMN) is thought to reflect the outcome of a system responsible for the detection of change in an otherwise repetitive, homogenous acoustic environment. This process depends on the storage and maintenance of a sensory representation of the frequently presented stimulus to which the deviant stimulus is compared. Few studies have been able to record the MMN in non-rapid eye movement (NREM) sleep. This pattern of results might be explained by either a rapid fading of sensory memory or an inhibition of stimulus input prior to entry into the cortical MMN generator site. The present study used a very rapid rate of presentation in an attempt to capture mismatch-related negativity prior to the fading of sensory memory. Auditory event-related potentials were recorded from 12 subjects during a single sleep period. A 1000 Hz standard stimulus was presented every 150 ms. At random, on 6.6% of the trials, the standard was changed to either a large 2000 Hz or a small 1100 Hz deviant. In wakefulness, the large deviant elicited an extended negativity that was reduced in amplitude following the presentation of the small deviant. This negativity was also apparent during REM sleep following the presentation of the large deviant. These deviant-related negativities (DRNs) were probably a composite of N1 and MMN activity. During NREM sleep (stage 2 and slow-wave sleep), only the large deviant continued to elicit a DRN. However this DRN might be overlapped by the initial activity of a component that is unique to sleep, the N350. There was little evidence of the DRN or the MMN during sleep following the presentation of the small deviant. A rapid rate of presentation, therefore, does not preserve the MMN following small deviance within sleep. It is possible that inhibition of sensory input occurs before entry into the MMN generating system in the temporal cortex.     

Deficits in involuntary attention switching in obstructive sleep apnea syndrome

Cognitive functions are altered in patients with obstructive sleep apnea syndrome (OSAS) and it has been proposed that vigilance and attentional deficits play a pivotal role in all aspects of these deficits. One way to assess attentional system integrity is the study of event-related-potentials (ERP), but only a few ERP studies have been conducted in patients with OSAS. The aim of the study was to use ERP to further assess attentional impairments in these patients. Thirteen OSAS patients and 13 age-matched controls underwent a night of polysomnographic recording. Each subject was also tested with an ERP paradigm where standard (95%, 1000Hz), high deviant (2.5%, 1250Hz) and low deviant (2.5%, 1050Hz) tones were presented. Subjects were asked to ignore the stimuli and read during the task. Mismatch negativity (MMN) and P3a amplitudes and latencies were measured. No between-group difference was observed for sleep stages, except a lower percentage of rapid eye movement (REM) sleep in patients with OSAS (p<0.01). Moreover, the OSAS group showed a higher micro-arousal index and more sleep transitions than the control group (p<0.05). A significant group effect was found for the amplitude of the P3a component (p<0.05) that was lower in patients with OSAS for both high and low deviant tones. No between-group difference was found for the MMN and the P3a latencies. In conclusion, patients with OSAS have specific alterations of the P3a component that reflects involuntary attention switching, but automatic auditory processing assessed by MMN appears to be preserved.     

Is pre‐attentive processing compromised by prolonged wakefulness? Effects of total sleep deprivation on the mismatch negativity

We investigated the potential influence of sustained wakefulness on pre-attentive capacities by recording the mismatch negativity (MMN), an electrophysiological manifestation associated with nonintentional detection of auditory oddball stimuli. The MMN was elicited by pitch deviants presented to both ears via earphones, at the beginning of a total sleep deprivation session (baseline), after 24 hr, and after 36 hr of continuous controlled wakefulness. A conspicuous MMN response was elicited at all three sessions. With time, however, a small yet significant gradual reduction in the MMN amplitude was evident. Whereas previous research suggested that controlled attention-demanding tasks are hampered by sleep deprivation, the balance of the present results suggests that passive (total) sleep deprivation may also bring about some degradation in the pre-attentive detection of environmental irregularities and as a consequence may disrupt the reflexive shift of attention induced by such events.     

Comparison of sensory gating to mismatch negativity and self-reported perceptual phenomena in healthy adults

To better understand the possible functional significance of electrophysiological sensory gating measures, response suppression of midlatency auditory event related potential (ERP) components was compared to the mismatch negativity (MMN) and to self-rated indices of stimulus filtering and passive attention-switching phenomena in an age-restricted sample of healthy adults. P1 sensory gating, measured during a paired-click paradigm, was correlated with MMN amplitude, measured during an acoustic oddball paradigm (intensity deviation). Also, individuals that exhibited less robust P1 suppression endorsed higher rates of "perceptual modulation" difficulties, whereas component N1 suppression was more closely related to "over-inclusion" of irrelevant sounds into the focus of attention. These findings suggest that the ERP components investigated are not redundant, but correspond to distinct-possibly related-pre-attentive processing systems.     

What has MMN revealed about the auditory system in schizophrenia?

Evidence that deficits in early auditory processing occur in schizophrenia was first provided by an ERP study demonstrating that mismatch negativity (MMN) to duration increments is reduced in medicated patients. Our subsequent research, which is reviewed in this paper, demonstrates that duration MMN reduction cannot be attributed to neuroleptic medication, and is specific to schizophrenia. It is not dependent upon the nature of the task used to distract attention away from the auditory modality. Most importantly, a reduced duration MMN in schizophrenia is a replicable result, having been observed in multiple independently-selected groups of patients from two separate laboratories. It also occurs in unaffected first-degree relatives of patients, suggesting that it may be a vulnerability marker of the disorder. The most intriguing questions however, relate to what underpins the reduced MMN to duration increments in schizophrenia and therefore, what it reveals about the nature of the auditory system deficit in this disorder. Three hypotheses are considered here: a pervasive problem in auditory sensory memory; a specific impairment in duration processing; or an abnormality within the window of temporal integration, coincident with the early phase of auditory sensory memory. Our data so far offer preliminary support for the third hypothesis only, although the possibility of a more broadly defined deficit in temporal processing restricted to brief or rapidly-presented auditory stimuli is canvassed.     

Automatic auditory information processing in sleep

STUDY OBJECTIVES: The mismatch negativity (MMN) component of the event-related potentials reflects the automatic detection of sound change. Only a few researchers have investigated the MMN elicitation during sleep in adult human and some of them reported that MMN amplitude was decreased in sleep compared to in waking. However, it is not clear that the decrease of MMN amplitude was due to increased drowsiness or long-term response decrement. Two experiments were conducted to clarify whether or not the MMN was elicited in each sleep stage. We presented auditory stimuli to subjects continuously from waking until sleep state (Experiment 1). Using the same experimental condition, we examined whether or not MMN amplitude was influenced by long-term stimulus presentation (80min.) and by vigilance level (Experiment 2). DESIGN: N/A SETTING: N/A PARTICIPANTS: N/A INTERVENTIONS: N/A MEASUREMENTS & RESULTS: Experiment 1: MMN was obtained in both drowsiness and REM sleep. MMN was significantly smaller in amplitude and shorter in latency in the both stages than in the waking state. However, MMN was not found in another sleep stage. Experiment 2: Amplitudes were no different among 0-20 min., 20-40 min., 60-80 min. But it was decreased in 40-60 min. and power value of alpha-wave was decreased in 40-60 min. CONCLUSIONS: To obtain the reliable data, by using the automatic spectral analysis, we confirmed that MMN was elicited in REM sleep. MMN was not influenced by long-term stimulation. The result suggested that auditory stimuli could be processed in the pre-attentive sensory memory even in REM sleep.     

Nicotinic modulation of human auditory sensory memory: Evidence from mismatch negativity potentials.

Impairment in mismatch negativity (MMN) generation is a robust biological marker of schizophrenia. Understanding the physiological and pharmacological processes involved in its generation may therefore advance our understanding of this complex disorder. The present study tested if acute administration of nicotine modulates human auditory sensory memory as measured with MMN. ERP responses to tone duration deviants were recorded using a stimulation protocol with continuously changing (roving) standard stimuli in order to measure the effect of stimulus repetitions on encoding of new stimuli (MMN memory trace effect). Twenty healthy adult volunteers were randomly assigned to receive either a nicotine gum or placebo after a baseline ERP recording. Nicotine administration augmented MMN amplitude in the treatment group compared to the baseline recording, while no MMN change was found in the placebo group. The drug effect was due to a selective enhancement of a frontal positive potential to standard stimuli (from 80-200 ms post-stimulus), while the negativity to deviants remained unaffected. Furthermore, under nicotine stimulation this repetition positivity showed a more marked increase with stimulus repetition compared to baseline and placebo. These results have potential implications for schizophrenia by suggesting that nicotinic agonists could ameliorate patients' MMN deficits by improving stimulus encoding and sensory memory trace formation.     

Cross-modal enhancement of the MMN to speech-sounds indicates early and automatic integration of letters and speech-sounds

Recently brain imaging evidence indicated that letter/speech-sound integration, necessary for establishing fluent reading, takes place in auditory association areas and that the integration is influenced by stimulus onset asynchrony (SOA) between the letter and the speech-sound. In the present study, we used a specific ERP measure known for its automatic character, the mismatch negativity (MMN), to investigate the time course and automaticity of letter/speech-sound integration. We studied the effect of visual letters and SOA on the MMN elicited by a deviant speech-sound. We found a clear enhancement of the MMN by simultaneously presenting a letter, but without changing the auditory stimulation. This enhancement diminishes linearly with increasing SOA. These results suggest that letters and speech-sounds are processed as compound stimuli early and automatically in the auditory association cortex of fluent readers and that this processing is strongly dependent on timing.     

TrkB-deficient mice show diminished phase shifts of the circadian activity rhythm in response to light

We studied the relationship between sleep quality and quantity and subsequently recorded automatically evoked event-related potential (ERP) responses. In previous studies decrement of attentional processing has been associated with changes in sleep. Sleep is shown to associate also with ERPs elicited by unattended sound stream, however, there is no consensus on these effects. A recent study suggested that the early anterior P3a to novel stimuli in attended stream is attenuated and the late parietal P3a is strengthened by total sleep deprivation. We carried out 72-h consecutive actigraphy measurements in a naturalistic setting to collect information about variation in sleep duration, sleep onset latency, sleep efficiency, and percentage of sleep. MMN and P3a deflections to infrequent changes in sound duration and pitch in unattended sound stream were obtained in a separate recording session from the same subjects when they were awake. No significant correlations were found between sleep and MMN parameters, indicating that MMN is resistant to normal variation in sleep. However, P3a to both pitch and duration changes correlated positively with sleep onset latency, and P3a to duration changes correlated negatively with sleep efficiency and percentage of sleep. The correlation was higher in the posterior scalp areas. Our results suggest that the involuntary attention switching system, reflected by the P3a is sensitized as a function of decreased sleep quality.     

A systematic review of the mismatch negativity as an index for auditory sensory memory: From basic research to clinical and developmental perspectives

Auditory sensory memory is an important ability for successful language acquisition and processing. The mismatch negativity (MMN) in response to auditory stimuli has been proposed as an objective tool to measure the existence of auditory sensory memory traces. By increasing interstimulus intervals, attenuation of MMN peak amplitude and increased MMN peak latency have been suggested to reflect duration and decay of sensory memory traces. The aim of the present study is to conduct a systematic review of studies investigating sensory memory duration with MMN. Searches of electronic databases yielded 743 articles. Of these, 37 studies met final eligibility criteria. Results point to maturational changes in the time span of auditory sensory memory from birth on with a peak in young adulthood, as well as to a decrease of sensory memory duration in healthy aging. Furthermore, this review suggests that sensory memory decline is related to diverse neurological, psychiatric, and pediatric diseases, including Alzheimer's disease, alcohol abuse, schizophrenia, and language disorders. This review underlines that the MMN provides a unique window to the cognitive processes of auditory sensory memory. However, further studies combining electrophysiological and behavioral data, and further studies in clinical populations are needed, also on individual levels, to validate the MMN as a clinical tool for the assessment of sensory memory duration.     

Interactions between sleep and sensory physiology

The processing of sensory information is definitely present during sleep, however, profound modifications occur. All sensory systems reviewed (visual, auditory, vestibular, somesthetic and olfactory) demonstrate some influence on sleep and, at the same time, sensory systems undergo changes that depend on the sleep or waking state of the brain. Thus, different sensory modalities encoded by their specific receptors and pathways may not only alter the sleep and waking physiology, but also the sleeping brain imposes ‘rules’ on the incoming information. It is suggested that the neural networks responsible for sleep and waking control are actively modulated by sensory inputs in order to enter and maintain normal sleep and wakefulness. Furthermore, both sensory stimulation and deprivation may induce changes in sleep/waking neural networks. This leads to the conclusion that the central nervous system and sensory input have reciprocal interactions, on which normal sleep/waking cycling and behaviour depends.     

Processing of auditory stimuli during tonic and phasic periods of REM sleep as revealed by event-related brain potentials

SUMMARY The brain has been reported to be more preoccupied with dreams during phasic than during tonic REM sleep. Whether these periods also differ in terms of the processing of external stimuli was examined. Event-related brain potentials (ERPs) to a frequent standard tone of 1000 Hz ( P = 97%) and infrequent deviant tones of 1100 and 2000 Hz ( P = 1.5% for each) were recorded ( n = 13) during wakefulness and nocturnal sleep. An ERP wave (called REM-P3) resembling a waking P3 wave was larger for the 2000 Hz deviant during tonic than during phasic REM sleep. Also the P210 wave was larger during tonic than during phasic REM sleep. A reliable mismatch negativity component appeared only in wakefulness. In summary, these results support the hypothesis that the brain is more 'open' for changes in an auditory input during tonic than phasic REM sleep.     

Of dreaming and wakefulness.

Following a set of studies concerning the intrinsic electrophysiology of mammalian central neurons in relation to global brain function, we reach the following conclusions: (i) the main difference between wakefulness and paradoxical sleep lies in the weight given to sensory afferents in cognitive images; (ii) otherwise, wakefulness and paradoxical sleep are fundamentally equivalent brain states probably subserved by an intrinsic thalamo-cortical loop. From this assumption, we conclude that wakefulness is an intrinsic functional realm, modulated by sensory parameters. In support of this hypothesis, we review morphological studies of the thalamocortical system, which indicate that only a minor part of its connectivity is devoted to the transfer of direct sensory input. Rather, most of the connectivity is geared to the generation of internal functional modes, which may, in principle, operate in the presence or absence of sensory activation. These considerations lead us to challenge the traditional Jamesian view of brain function according to which consciousness is generated as an exclusive by-product of sensory input. Instead, we argue that consciousness is fundamentally a closed-loop property, in which the ability of cells to be intrinsically active plays a central role. We further discuss the importance of spatial and temporal mapping in the elaboration of cognitive and perceptual constructs.     

Event-related potential measures of the inhibition of information processing: II. The sleep onset period.

The loss of consciousness during the sleep onset period is associated with dramatic changes in information processing. Human event-related potentials (ERPs) reflect these changes. Short- and mid-latency ERPs are only minimally affected by sleep onset. On the other hand, long-latency ERPs are very much affected. A negative wave, N1, peaking at approximately 100 ms gradually decreases in amplitude until it reaches baseline level during definitive stage 2 sleep. The changes in N1 are especially apparent when the subject no longer signals awareness of the external stimulus or when stage 1 is dominated by theta activity in the EEG. The positive peaks, P1 and P2, peaking at approximately 50 and 180 ms, respectively, may appear to increase in amplitude (i.e. also be less negative). A long-lasting processing negativity (PN) may overlap and summate with these peaks during the waking state. During sleep onset, the PN dissipates, thus explaining the apparent positive baseline shift in the ERP waveform. In an oddball task, when an alert and awake subject detects a rare, relevant stimulus, a large positive wave, P300, maximum over parietal areas of the scalp, is observed. This P300 is, however, widely dispersed and can be observed over frontal areas of the scalp. When the subject no longer signals detection of this target stimulus, P300 can no longer be recorded. During stage 1, the parietal P300 remains large, providing the subject overtly detects the target. The amplitude of the frontal aspect of P300 is much reduced as response times slow. This may reflect deactivation of the frontal lobes during the sleep onset period. The infrequent change of an otherwise rapidly presented homogenous train of stimuli is associated with another long-lasting negativity, the mismatch negativity (MMN). The MMN also decreases in amplitude during the sleep onset period, reaching baseline level during definitive sleep. The vertex sharp wave (VSW) becomes apparent during the sleep onset period. Associated with the VSW is a late negative ERP, sometimes called the sleep N2 or the N350, peaking between 300 and 350 ms. It is unique to the sleep onset and sleep periods, becoming very large during stage 1-theta or when the subject no longer shows signs of awareness of the external stimulus.     

Visual mismatch negativity and unintentional temporal-context-based prediction in vision

Since the discovery of an event-related brain potential (ERP) component, auditory mismatch negativity (auditory MMN), there has been a long-lasting debate regarding the existence of its counterparts in other sensory modalities. Over the past few decades, several studies have confirmed the existence of mismatch negativity in the visual modality (visual MMN) and have revealed the various characteristics of visual MMN. In the present review, a full range of visual MMN studies are overviewed from the perspective of the predictive framework of visual MMN recently proposed by Kimura et al. (2011b). In the first half, the nature of visual MMN is reviewed in terms of (1) typical paradigm and morphologies, (2) underlying processes, (3) neural generators, and (4) functional significance. The main message in this part is that visual MMN is closely associated with the unintentional prediction of forthcoming visual sensory events on the basis of abstract sequential rules embedded in the temporal context of visual stimulation (i.e., "unintentional temporal-context-based prediction in vision"). In the second half, the nature of the unintentional prediction is discussed in terms of (1) behavioral indicators, (2) cognitive properties, and (3) neural substrates and mechanisms. As the main message in this part, I put forward a hypothetical model, which suggests that the unintentional prediction might be implemented by a bi-directional cortical network that includes the visual and prefrontal areas.     

Linear and nonlinear auditory response properties of interneurons in a high-order avian vocal motor nucleus during wakefulness

Motor-related forebrain areas in higher vertebrates also show responses to passively presented sensory stimuli. However, sensory tuning properties in these areas, especially during wakefulness, and their relation to perception, are poorly understood. In the avian song system, HVC (proper name) is a vocal-motor structure with auditory responses well defined under anesthesia but poorly characterized during wakefulness. We used a large set of stimuli including the bird's own song (BOS) and many conspecific songs (CON) to characterize auditory tuning properties in putative interneurons (HVC(IN)) during wakefulness. Our findings suggest that HVC contains a diversity of responses that vary in overall excitability to auditory stimuli, as well as bias in spike rate increases to BOS over CON. We used statistical tests to classify cells in order to further probe auditory responses, yielding one-third of neurons that were either unresponsive or suppressed and two-thirds with excitatory responses to one or more stimuli. A subset of excitatory neurons were tuned exclusively to BOS and showed very low linearity as measured by spectrotemporal receptive field analysis (STRF). The remaining excitatory neurons responded well to CON stimuli, although many cells still expressed a bias toward BOS. These findings suggest the concurrent presence of a nonlinear and a linear component to responses in HVC, even within the same neuron. These characteristics are consistent with perceptual deficits in distinguishing BOS from CON stimuli following lesions of HVC and other song nuclei and suggest mirror neuronlike qualities in which "self" (here BOS) is used as a referent to judge "other" (here CON).     

The Mechanisms and Meaning of the Mismatch Negativity

The mismatch negativity (MMN) is a pre-attentive auditory event-related potential (ERP) component that is elicited by a change in a repetitive acoustic pattern. It is obtained by subtracting responses evoked by frequent ‘standard’ sounds from responses evoked by infrequent ‘deviant’ sounds that differ from the standards along some acoustic dimension, e.g., frequency, intensity, or duration, or abstract feature. The MMN has been attributed to neural generators within the temporal and frontal lobes. The mechanisms and meaning of the MMN continue to be debated. Two dominant explanations for the MMN have been proposed. According to the “neural adaptation” hypothesis, repeated presentation of the standards results in adapted (i.e., attenuated) responses of feature-selective neurons in auditory cortex. Rare deviant sounds activate neurons that are less adapted than those stimulated by the frequent standard sounds, and thus elicit a larger ‘obligatory’ response, which yields the MMN following the subtraction procedure. In contrast, according to the “sensory memory” hypothesis, the MMN is a ‘novel’ (non-obligatory) ERP component that reflects a deviation between properties of an incoming sound and those of a neural ‘memory trace’ established by the preceding standard sounds. Here, we provide a selective review of studies which are relevant to the controversy between proponents of these two interpretations of the MMN. We also present preliminary neurophysiological data from monkey auditory cortex with potential implications for the debate. We conclude that the mechanisms and meaning of the MMN are still unresolved and offer remarks on how to make progress on these important issues.     

Electrophysiological evidence for the hierarchical organization of auditory change detection in the human brain

Auditory change detection has been associated with mismatch negativity (MMN), an event‐related potential (ERP) occurring at 100–250 ms after the onset of an acoustic change. Yet, single‐unit recordings in animals suggest much faster novelty‐specific responses in the auditory system. To investigate change detection in a corresponding early time range in humans, we measured the Middle Latency Response (MLR) and MMN during a controlled frequency oddball paradigm. In addition to MMN, an early effect of change detection was observed at about 40 ms after change onset reflected in an enhancement of the Nb component of the MLR. Both MMN and the Nb effect were shown to be free from confounding influences such as differences in refractoriness. This finding implies that early change detection processes exist in humans upstream of MMN generation, which supports the emerging view of a hierarchical organization of change detection expanding along multiple levels of the auditory pathway.