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.     

Left hemispheric dipole locations of the neuromagnetic mismatch negativity to frequency,intensity and duration deviants

The aim of the current study was to differentiate the sources of neuromagnetic mismatch negativity (MMNm) to deviants of different features. For this purpose, the MMNm of twenty-one healthy subjects (seven males) were recorded left-hemispherically. Subjects were stimulated monaurally in an oddball paradigm with standard tones of 1000 Hz and three different kinds of mismatch tones (frequency, duration and intensity deviants). Data analysis revealed mean MMNm dipole locations anterior, inferior and more medial than the N100m dipoles. The mean difference between the N100m and MMNm dipoles was in the range of up to 6 mm in one dimension. The dipole locations of all three kinds of deviants differed significantly from each other. The MMNm dipoles of both frequency and duration deviants were found to be significantly inferior to the corresponding source of intensity deviants, while the MMNm dipoles of duration and frequency deviants significantly differed in anterior-posterior direction. This differentiation between sources emphasizes the importance of feature analysis in MMN(m) generation.     

The vanishing point of the mismatch negativity at sleep onset.

OBJECTIVE: To determine when the mismatch negativity (MMN) disappears at sleep onset, event-related potentials (ERPs) were recorded continuously from wakefulness to sleep. METHODS: Ten healthy young students were told to fall asleep ignoring the tones presented through a loudspeaker above their head. Standard (1000 Hz, P=0.90), high deviant (1200 Hz, P=0.05), and low deviant (1050 Hz, P=0.05) tones were presented in a quasirandom order with a fixed stimulus onset asynchrony of 500 ms. ERP waveforms were obtained separately for 5 successive stages characterized by typical electroencephalographic (EEG) patterns of the sleep onset period. The EEG staging was made manually with very short (5 s) scoring epochs. RESULTS: The MMN appeared in wakefulness and in the early phase of stage 1 sleep (EEG stage II) but disappeared when low-voltage theta waves emerged after alpha flattening (EEG stage III). Instead, P240 and N360 developed particularly for high deviant tones. CONCLUSIONS: Concurrently with the disappearance of alpha waves, the automatic change detection system in wakefulness seems to stop operating and a different sleep-specific system becomes dominant.     

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.     

Measuring duration mismatch negativity.

OBJECTIVE: Automatic comparisons of sound duration in auditory sensory memory are typically investigated by comparing event-related potentials (ERPs) to standard and deviant stimuli presented in oddball blocks. Deviants elicit mismatch negativity (MMN). This procedure might overestimate an MMN contribution reflecting automatic sensory memory processes because of differential states of refractoriness of respectively recruited neural populations [Neuroreport 1996;7:3005; Psychophysiology 2001;38:723]. Here, memory-comparison-based Duration MMN contributions were investigated using various experimental protocols. METHODS: Memory-comparison-based first-order Duration MMN was investigated using 4 blocked conditions: (a) descending Deviant (100 ms, P=0.14), 150 ms Standard; (b) reverse ascending Deviant (150 ms), 100 ms Standard; (c) Control comprised of 7 equiprobable durations between 25 and 175 ms; and additionally (d) equiprobable tones between 100 and 400 ms. Using the former 3 conditions, Deviants, Standards and Controls were physically identical. RESULTS: Comparing Deviants and Controls excluded potential refractoriness effects, and a decomposition of memory-comparison-based MMN and residual MMN was demonstrated. Genuine Duration MMN was also obtained in the deviant-standard-reverse comparison. CONCLUSIONS: Using a blocked control condition yielded equivalent results to reversing the role of deviant and standard in two separate oddball blocks. Using the reverse ascending deviant condition is thus sufficient as a control.     

Cervical dystonia: Normal auditory mismatch negativity and abnormal somatosensory mismatch negativity

Objective

Previous electrophysiological and psychophysical tests have suggested that somatosensory integration is abnormal in dystonia. Here, we hypothesised that this abnormality could relate to a more general deficit in pre-attentive error/deviant detection in patients with dystonia. We therefore tested patients with dystonia and healthy subjects using a mismatch negativity paradigm (MMN), where evoked potentials generated in response to a standard repeated stimulus are subtracted from the responses to a rare “odd ball” stimulus.

The study of mismatch negativity]

We studied age related correlations of mismatch negativity (MMN) auditory event-related potentials (ERPs) using odd ball paradigm in 121 normal subjects (from 6 months to 43 years) and 33 mentally retarded subjects (from 2 to 18 years). The subject was instructed to read a book in order to ignore the stimulus during the experiment, or no specific task was imposed on young child. The MMN wave form was clearly obtained in normal 6 month old subjects. As the age advanced from 6-months, the latencies of MMN progressively shortened till about 7 years, when the latency reached adult level. One-third of mentally retarded patients had prolonged MMN than that normal age-matched subjects. Reliable recording of P300 requires subject's cooperation and attentiveness, which are difficult to achieve in young children or mentally retarded patients. MMN may be utilized in children to evaluate the development of the cognitive function.     

Evoked potential correlates of stimulus deviance during wakefulness and sleep in cat--animal model of mismatch negativity

Auditory evoked potentials (EPs) elicited by standard (STs) and deviant tones (DTs) of different probabilities were studied in freely moving cats during wakefulness and sleep. A large double peaked negativity, so-called mismatch negativity (MMN), was evoked by the unattended low probability DTs. The EPs recorded from the AI and AII areas of the auditory cortex showed more dynamic changes than the vertex and association cortical responses. The amplitude of the MMN was inversely proportional to the probability of DTs. The latency of the MMN showed dependence both on the location of the recording site and on the probability of DTs. During slow wave sleep (SWS) the MMN of increased latency could be evoked only at the lowest probabilities. The cortical distribution of the MMN changed in the SWS.     

The mismatch negativity: A review of underlying mechanisms

The mismatch negativity (MMN) is a brain response to violations of a rule, established by a sequence of sensory stimuli (typically in the auditory domain) [Näätänen R. Attention and brain function. Hillsdale, NJ: Lawrence Erlbaum; 1992]. The MMN reflects the brain’s ability to perform automatic comparisons between consecutive stimuli and provides an electrophysiological index of sensory learning and perceptual accuracy. Although the MMN has been studied extensively, the neurophysiological mechanisms underlying the MMN are not well understood. Several hypotheses have been put forward to explain the generation of the MMN; amongst these accounts, the “adaptation hypothesis” and the “model adjustment hypothesis” have received the most attention. This paper presents a review of studies that focus on neuronal mechanisms underlying the MMN generation, discusses the two major explanatory hypotheses, and proposes predictive coding as a general framework that attempts to unify both.     

The disruptive effect of chronic pain on mismatch negativity.

OBJECTIVE: To investigate the effect of chronic pain on processes that generate the mismatch negativity (MMN). METHODS: Twelve participants with a diagnosis of chronic intractable pain were tested before and after pain treatment. During testing, event-related potentials were recorded while participants performed tasks of varying difficulty. RESULTS: The amplitude of the MMN was found to be greater following a nerve block procedure compared to MMN amplitude when participants were experiencing chronic pain. This effect was found to occur in the MMN for difficult-to-detect tones elicited while participants were performing a simultaneous cognitively demanding visual task. MMN amplitude was found to be greater with attention to difficult-to-detect deviants during pain but not in no pain conditions. CONCLUSIONS: These results provide an electrophysiological correlate of previous findings that high levels of pain disrupt cognition during the performance of demanding tasks.     

Duration and frequency mismatch negativity in schizophrenia.

OBJECTIVES: The aim of the present study was to elucidate the reasons for apparent inconsistencies in the schizophrenia literature with respect to the mismatch negativity (MMN) waveform of the event-related potential (ERP). While most previous research has shown that MMN is reduced in schizophrenia, there are a small number of studies reporting that frequency MMN is not reduced. METHODS: We recorded ERPs to auditory stimuli with different frequencies and durations from patients with schizophrenia (N = 14) and control subjects (N = 17) of similar age and sex. MMNs to small but discriminable frequency deviants were contrasted with large frequency deviants and duration deviants. RESULTS: Only the MMN to duration deviants was significantly reduced in patients, although there was evidence of a similar trend for large frequency deviants. CONCLUSIONS: The results together with a review of the frequency MMN literature suggest that there are 3 variables which are important in determining whether patients exhibit a reduced MMN to frequency deviants: deviant probability, degree of deviance and interstimulus interval. The results also indicated that patients with schizophrenia may have particular deficits in processing the temporal properties of auditory stimuli. This finding has implications for the pathophysiology of the disorder as time-dependent processing is reliant on the integrity of an extensive network of brain areas consisting of auditory cortex, areas of pre-frontal cortex, the basal ganglia and cerebellum.     

Discrimination of auditory motion patterns: The mismatch negativity study

The aim of the present study is to test whether mismatch negativity (MMN) response can be elicited by changes in auditory motion dynamics. The discrimination of auditory motion patterns was investigated using psychophysical and electrophysiological methods in the same group of subjects. Auditory event-related potentials (ERP) were recorded for stationary midline noises and moving noises shifting to the left/right from the head midline. Two patterns of auditory motion were used with gradual (Motion) and stepwise (Step) movements which started and ended at the same loci. Auditory motion was produced by linear and abrupt changes of interaural time differences (ITD) in binaurally presented stimuli. In Experiment 1, ERPs were recorded for stationary midline standards and for Motion and Step deviants. It was found that Step deviants result in larger MMN amplitudes than Motion deviants with the same distance travelled, which implies that information contained in the stimulus midportion could be involved in the processing of the auditory motion. The threshold ITD values for the detection of Step and Motion stimuli displacement obtained during psychoacoustic tests were greater than the minimal ITD changes which elicited significant MMN. Experiment 2 demonstrated that Step deviants elicited significant MMNs in the context of Motion standards, although these stimuli could not be discriminated behaviourally. MMNs elicited by Step deviants in different acoustic contexts are discussed from the viewpoint of different brain processes underlying the discrimination of the abrupt ITD change. These results suggest that the early cortical mechanism of auditory motion processing reflected by MMN could not be considered as a spatial discriminator of the onset/offset stimulus positions, that is, a simple onset-offset detector. Combining psychoacoustic data with MMN results we may conclude that motion discrimination in auditory system might be better at the preattentive level.     

Finding the right control: The mismatch negativity under investigation

ObjectiveWhen investigating auditory perceptual regularity processing, mismatch negativity (MMN) is commonly used. MMN is computed as a difference signal between the event-related potentials (ERPs) elicited by repeated standard tones and rarely occurring deviant tones. This procedure leads to an underestimation of the N1 component elicited by standards compared to the N1 to deviants which might affect the MMN. Consequently, a random control design was previously introduced. This design, however, overestimates the N1 to the deviant. Here, we developed a new paradigm that avoids previous drawbacks.MethodsWe designed a regular cascadic sequence as a control to the deviant. ERPs were measured while presenting conventional oddball blocks (standards, deviants), random control blocks and a cascadic control block.ResultsMMN was observed in each difference signal. Regarding the N1, standards elicited smallest amplitudes. The N1 for the deviant and the cascadic control was comparable. The largest N1 was elicited by the random control.ConclusionStandards underestimate N1 refractoriness effects in the responses to deviants, while random control tones overestimate. Cascadic control tones, however, provide a reasonable estimation for the N1.SignificanceThe new cascadic control design is suitable to investigate auditory perceptual regularity processes while controlling for N1 refractoriness effects.     

Demonstration of mismatch negativity in the monkey.

In humans, deviant auditory stimuli elicit an event-related potential (ERP) component, termed "mismatch negativity" (MMN), that reflects the operation of a cortical detector of infrequent stimulus change. Epidural auditory ERPs were recorded from 3 cynomolgous monkeys in response to soft and loud clicks. "Oddball" loud or soft stimuli elicited a long-duration frontocentral negativity, peaking at approximately 85 msec, that was superimposed upon cortically generated obligatory ERP components. These data suggest that monkeys might serve as a heuristically valuable system in which to study the neurochemical and neuroanatomical substrates of early context-dependent ERP generation.     

Detection of cognitive impairment in patients with obstructive sleep apnea hypopnea syndrome using mismatch negativity

In this experiment,97 patients with obstructive sleep apnea hypopnea syndrome were divided into three groups(mild,moderate,severe) according to minimum oxygen saturation,and 35 healthy subjects were examined as controls.Cognitive function was determined using the mismatch negativity paradigm and the Montreal Cognitive Assessment.The results revealed that as the disease worsened,the mismatch negativity latency was gradually extended,and the amplitude gradually declined in patients with obstructive sleep apnea hypopnea syndrome.Importantly,mismatch negativity latency in severe patients with a persistent time of minimum oxygen saturation < 60 seconds was significantly shorter than that with a persistent time of minimum oxygen saturation > 60 seconds.Correlation analysis revealed a negative correlation between minimum oxygen saturation latency and Montreal Cognitive Assessment scores.These findings indicate that intermittent night-time hypoxemia affects mismatch negativity waveforms and Montreal Cognitive Assessment scores.As indicators for detecting the cognitive functional status of obstructive sleep apnea hypopnea syndrome patients,the sensitivity of mismatch negativity is 82.93%,the specificity is 73.33%,the accuracy rate is 81.52%,the positive predictive value is 85.00%,the negative predictive value is 70.21%,the positive likelihood ratio is 3,and the negative likelihood ratio is 0.23.These results indicate that mismatch negativity can be used as an effective tool for diagnosis of cognitive dysfunction in obstructive sleep apnea hypopnea syndrome patients.     

Visual mismatch negativity: the detection of stimulus change

Mismatch negativity is an event related potential generated by a mechanism which detects stimulus change. Such a mechanism is important to enable attention to be switched to important changes in the environment. The effect has been extensively studied in the auditory modality. The present investigation was designed to establish whether the enhanced negativity in the visual event related potential evoked by deviant stimuli presented infrequently among a sequence of repeated standard stimuli is really associated with the detection of stimulus change. The experiment set out to distinguish effects associated with stimulus change from those related to the physical attributes of the stimuli or to differences in the refractory state of receptors or neurons. The findings support the hypothesis that deviance-related negativity reflects the operation of a change detection mechanism and not the refractory state of elements of the visual system.     

Phonological categorization of vowels: a mismatch negativity study

There is electrophysiological evidence that phonological categorization has occurred within 100-200 ms post stimulus onset for the syllables /tae/ and /dae/, which vary in voice onset time. Using a similar paradigm, this study investigated when phonological categorization occurred for the contrast between /I/ and /epsilon/, using synthesized speech tokens that differed in the frequency of the first formant. Here we show that phonological categorization of these tokens has not occurred 100-200 ms after stimulus onset. However, the presence of a late mismatch negativity (350 ms after stimulus onset) indicated that phonological categorization had taken place by this time.     

The individual replicability of mismatch negativity at short and long inter-stimulus intervals.

OBJECTIVES: The individual replicability of the mismatch negativity (MMN) event-related brain potential (ERP) was studied at two different inter-stimulus intervals (ISIs), to establish its potential value for routine clinical evaluation of sound discrimination and auditory sensory memory. METHODS: Ten healthy young subjects were presented sequences of 3 stimulus trains, in two recording sessions approximately 1 month apart. The stimuli in the trains were delivered at an ISI of 300 ms, whereas the inter-train intervals (ITIs) were 0.4 s and 4.0 s in different blocks. ERPs were averaged to standard (75 ms) and deviant (25 ms) tones started equiprobably the stimulus trains. RESULTS: Significant Pearson product-moment correlations coefficients were found between sessions at all scalp locations for the short ITI, when the MMN was quantified as the mean amplitude in the 100-200 ms latency window around its peak. However, none of the correlations reached significance for the longer ITI. CONCLUSIONS: MMN appears to be a reliable measure for single-case assessment and follow-ups when obtained at short ISIs and quantified as an integrated window of neuroelectric activation over a temporal span.     

Using mismatch negativity to measure auditory temporal resolution thresholds.

It has been hypothesized that poor auditory temporal resolution is related to language-learning problems in children as well as problems with speech perception in noise in the elderly. We show that the presence of occasional silent gaps between short tone pips elicits mismatch negativity (MMN) in young adults. We also measured gap-detection thresholds with MMN that agree well with behavioural thresholds. Near threshold, the MMN increases as the gap size increases millisecond by millisecond. The MMN methodology for measuring temporal resolution is not only robust, but can be applied identically across the life span as it does not require the attention of participants or a behavioural response. We are now in a position to examine temporal resolution in infancy.     

Functional characterization of mismatch negativity to a visual stimulus.

OBJECTIVE: To record mismatch negativity (MMN) to a visual stimulus fulfilling similar criteria to those of auditory MMN (A-MMN). METHODS: Twelve normal adults were instructed to simultaneously listen to a story and to pay attention to a visual target. Three windmill patterns that differed in the number of vanes (standard, deviant, or target) were used as visual stimuli, and were randomly presented. To ensure endogeneity, standard and deviant stimuli were alternated. To vary differences between frequent (standard) and infrequent (deviant) stimuli, deviants were changed by modulating the number of vanes. To examine effects of physical features of the target stimulus on changes in detection, two target conditions were used. The deviant-related component (DRC) was obtained by subtracting event-related potentials (ERPs) to the deviant stimulus from those to the standard stimulus. RESULTS: Seven subjects completed all phases of the experiment. Behavioral performances indicated that subjects' attention was directed by auditory context and identification of the target stimulus. Visual DRC appeared 150-300 ms after stimulus onset, and consisted of an early (DRN1) and a late (DRN2) component. Magnitude of deviancy from standard stimulus significantly influenced latency of DRN2 but not its magnitude, while changes in target stimulus affected latencies of both DRN1 and DRN2. CONCLUSIONS: Our DRCs satisfied criteria for A-MMN. In contrast to A-MMN, only latency of the DRC was associated with visual sensory discrimination and attentional reorienting. SIGNIFICANCE: It is possible to record valid MMN to a visual stimulus, which allows the study of preattentive visual information processing.