Variability and replicability of the mismatch negativity

The interindividual variation and test-retest stability of the mismatch negativity (MMN) and N1 components of the event-related potential (ERP) were investigated by presenting standard (85%) and deviant tones (15%) to 10 young subjects in 2 sessions separated by 1 month. Deviant tones in different blocks were either frequency or duration changes with interstimulus intervals (ISIS) of 0.5 and 1.5 sec. The results showed a fairly good test-retest stability of the MMN amplitude for both types of changes with each IS[ at the group level. The amplitude of the duration MMN showed significant individual test-retest stability. The N1 amplitude showed high stability at both the group and individual levels. Both the MMN and N1 showed considerable interindividual variation. The results suggest that MMN and N1 can be used in follow-up studies not only at the group level but possibly at the individual level also.     

Lexical context affects mismatch negativity caused by pseudowords

The aim of this study was to investigate the effect of lexical context on the latency and the amplitude of the mismatch negativity (MMN) brain potential caused by perception of pseudowords. The eventrelated potentials were recorded according to the multideviant passive odd-ball paradigm by using only pseudowords (control condition) or pseudowords with Russian words with different lexical frequencies (lexical context). It was found that different MMN patterns were generated when the same pseudoword was presented in different contexts. Pseudoword presentation in a context with other pseudowords resulted in a relatively small amplitude and large latency of MMN. If the same pseudoword was presented in a context with words, it induced significantly increased amplitude and reduced latency of MMN varying in the range of 100–200 ms. It is supposed that the pseudoword presented in a context with words is perceived as conceptually different stimulus, which leads to a significant increase in MMN. Moreover, our findings support the hypothesis that MMN is affected by lexical frequency. In particular, presentation of a high-frequency word induced a significantly more pronounced MMN response than a low-frequency one. High-frequency words also evoked earlier response, which indicates more rapid access to a frequently used lexical entry. More frequent use of certain words results in stronger internal connections in the corresponding memory circuit, which in turn is determined by the lexical context. We hypothesize that different intensities of activation depends on the strength of lexical representation.     

Sequential grouping of tone sequence as reflected by the mismatch negativity

The human sequential grouping that organizes parts of tones into a group was examined by the mismatch negativity (MMN), a component of event-related potentials that reveals the sensory memory process. The sequential grouping is accomplished by the combinations of some factors, e.g., temporal and frequency proximity principles. In this study, auditory oddball stimuli in which each of the stimuli consisted of series of tone bursts, were applied to the subjects, and the MMN elicited by the deviation of the frequency of the last tone in the stimulus was investigated. The relationship between the expected phenomena of sequential grouping of tones and observed magnitudes of MMN was evaluated. It was shown that the magnitudes of MMN changed according to the configuration (number of tones, frequency) of tone sequence to be stored. This result suggested that the sequential grouping of presented tones was achieved on the preattentive auditory sensory memory process. It was also shown that the relative change of MMN magnitudes corresponded to the conditions of sequential grouping, which had been proposed by the auditory psychophysical studies. The investigation of MMN properties could reveal the nature of auditory sequential grouping.This study was approved by the Ethics Committee on Clinical Investigation, Graduate School of Engineering, Tohoku University and was carried out in accordance with the policy of the Declaration of Helsinki.     

Perceptual categories for auditory motion as reflected in mismatch negativity

Auditory evoked response and mismatch negativity potential have been studied using the reversed oddball paradigm of standard and deviant stimulus presentation. In the experiments, three types of spatial sound stimuli (stationary and moving gradually or abruptly from the head midline) were presented in three configurations. In each configuration, one stimulus type served as the standard one, and the other two, as deviants. The reversal of the configuration of the presentation of the standard and deviant stimuli was shown to significantly influence the evoked response and mismatch negativity. The results are discussed as possible evidence of the categorical perception of auditory motion at early stages of sound processing in the hearing system.     

Transcriptome-wide association study reveals two genes that influence mismatch negativity

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Effects of metabotropic glutamate receptor 3 genotype on phonetic mismatch negativity

Background

The genetic and molecular basis of glutamatergic dysfunction is one key to understand schizophrenia, with the identification of an intermediate phenotype being an essential step. Mismatch negativity (MMN) or its magnetic counterpart, magnetic mismatch field (MMF) is an index of preattentive change detection processes in the auditory cortex and is generated through glutamatergic neurotransmission. We have previously shown that MMN/MMF in response to phoneme change is markedly reduced in schizophrenia. Variations in metabotropic glutamate receptor (GRM3) may be associated with schizophrenia, and has been shown to affect cortical function. Here we investigated the effect of GRM3 genotypes on phonetic MMF in healthy men.

Methods

MMF in response to phoneme change was recorded using magnetoencephalography in 41 right-handed healthy Japanese men. Based on previous genetic association studies in schizophrenia, 4 candidate SNPs (rs6465084, rs2299225, rs1468412, rs274622) were genotyped.

Results

GRM3 rs274622 genotype variations significantly predicted MMF strengths (p = 0.009), with C carriers exhibiting significantly larger MMF strengths in both hemispheres compared to the TT subjects.

Conclusions

These results suggest that variations in GRM3 genotype modulate the auditory cortical response to phoneme change in humans. MMN/MMF, particularly those in response to speech sounds, may be a promising and sensitive intermediate phenotype for clarifying glutamatergic dysfunction in schizophrenia.     

The mismatch negativity for duration decrement of auditory stimuli in healthy subjects

The amplitude and latency of the mismatch negativity (MMN) elicited by occasional shorter-duration tones (25 and 50 ms) in a sequence of 75 ms standard tones were studied in 40 healthy subjects (9–84 years). The replicability and age dependence of the MMN-responses were determined. The 25 ms deviant tone evoked a clear response in 39 of the subjects, while the 50 ms deviant tone evoked an observable MMN only in 32 of the subjects. The MMN peak amplitude for the 25 ms deviants was significantly larger than for the 50 ms deviants. There was no significant difference in the peak latencies (measured from stimulus offset). For the 25 ms deviant, the amplitude diminished with increasing age. The MMN curves for the 25 ms deviant, measured on separate days in 14 subjects, looked very replicable. As a result of noise and filtering effect, the product-moment correlations were poor. The results indicate that the signal-to-noise ratio for the MMN to 25 ms deviants, obtained even in a 25 min recording session, is large enough for clinical use and individual diagnostics when undetectable (or very low amplitude) MMN is used as a sign of pathology. However, judged from the low correlation coefficients, despite the good replicability in visual evaluation, better methods for MMN quantification have to be used for clinical follow-up.     

Acoustic versus phonetic representation of speech as reflected by the mismatch negativity event-related potential

The concept of categorical perception of speech and speech-like sounds has been central to models of speech perception for decades. Event-related potentials (ERPs) provide a neurophysiologic perspective of this important phenomenon. In the present experiment the mismatch negativity (MMN) event-related potential, which is sensitive to fine acoustic differences, was recorded in adults. Of interest was whether the MMN reflects the acoustic or categorical perception of speech.The MMN was elicited by stimulus pairs (along a continuum varying in place of articulation from /da/ to /ga/) which had been identified as the same phoneme /da/ (within category condition) and as different phonemes /da/ and /ga/ (across categories condition). The acoustic differences between these two pairs of stimuli were equivalent.The MMN was observed in all subjects both in the within and across category conditions. Furthermore, the MMN did not differ in latency, amplitude or area within and across categories. That is, the MMN indicated equal discrimination both across and within categories. These results suggest that the MMN appears to reflect the processing of acoustic aspects of the speech stimulus, but not phonetic processing into categories. The MMN appears to be an extremely sensitive electrophysiologic index of minimal acoustic differences in speech stimuli.     

The mismatch negativity as an index of the perception of speech sounds by the human brain

The present article outlines the contribution of the mismatch negativity (MMN), and its magnetic equivalent MMNm, to our understanding of the perception of speech sounds in the human brain. MMN data indicate that each sound, both speech and non-speech, develops its neural representation corresponding to the percept of this sound in the neurophysiological substrate of auditory sensory memory. The accuracy of this representation, determining the accuracy of the discrimination between different sounds, can be probed with MMN separately for any auditory feature or stimulus type such as phonemes. Furthermore, MMN data show that the perception of phonemes, and probably also of larger linguistic units (syllables and words), is based on language-specific phonetic traces developed in the posterior part of the left-hemisphere auditory cortex. These traces serve as recognition models for the corresponding speech sounds in listening to speech.     

Differentiation of schizophrenia patients from healthy subjects by mismatch negativity and neuropsychological tests

Background

Schizophrenia is a heterogeneous disorder with diverse presentations. The current and the proposed DSM-V diagnostic system remains phenomenologically based, despite the fact that several neurobiological and neuropsychological markers have been identified. A multivariate approach has better diagnostic utility than a single marker method. In this study, the mismatch negativity (MMN) deficit of schizophrenia was first replicated in a Han Chinese population, and then the MMN was combined with several neuropsychological measurements to differentiate schizophrenia patients from healthy subjects.

Methodology/Principal Findings

120 schizophrenia patients and 76 healthy controls were recruited. Each subject received examinations for duration MMN, Continuous Performance Test, Wisconsin Card Sorting Test, and Wechsler Adult Intelligence Scale Third Edition (WAIS-III). The MMN was compared between cases and controls, and important covariates were investigated. Schizophrenia patients had significantly reduced MMN amplitudes, and MMN decreased with increasing age in both patient and control groups. None of the neuropsychological indices correlated with MMN. Predictive multivariate logistic regression models using the MMN and neuropsychological measurements as predictors were developed. Four predictors, including MMN at electrode FCz and three scores from the WAIS-III (Arithmetic, Block Design, and Performance IQ) were retained in the final predictive model. The model performed well in differentiating patients from healthy subjects (percentage of concordant pairs: 90.5%).

Conclusions/Significance

MMN deficits were found in Han Chinese schizophrenia patients. The multivariate approach combining biomarkers from different modalities such as electrophysiology and neuropsychology had a better diagnostic utility.     

Integration of consonant and pitch processing as revealed by the absence of additivity in mismatch negativity

Consonants, unlike vowels, are thought to be speech specific and therefore no interactions would be expected between consonants and pitch, a basic element for musical tones. The present study used an electrophysiological approach to investigate whether, contrary to this view, there is integrative processing of consonants and pitch by measuring additivity of changes in the mismatch negativity (MMN) of evoked potentials. The MMN is elicited by discriminable variations occurring in a sequence of repetitive, homogeneous sounds. In the experiment, event-related potentials (ERPs) were recorded while participants heard frequently sung consonant-vowel syllables and rare stimuli deviating in either consonant identity only, pitch only, or in both dimensions. Every type of deviation elicited a reliable MMN. As expected, the two single-deviant MMNs had similar amplitudes, but that of the double-deviant MMN was also not significantly different from them. This absence of additivity in the double-deviant MMN suggests that consonant and pitch variations are processed, at least at a pre-attentive level, in an integrated rather than independent way. Domain-specificity of consonants may depend on higher-level processes in the hierarchy of speech perception.     

A mismatch negativity elicited with stationary and moving auditory images of different azimuth positions

Characteristics of mismatch negativity elicited by dichotic stimulation were examined using deviant stimuli simulating movement of fused auditory images towards the standard stimuli or in the reverse direction. The effect of stationary deviants localized at 90 degrees in respect to standards was also measured. The standard stimuli were localized near either of ears or along the head midline. The spatial locations were produced by introducing interaural time differences into the click trains. All deviant stimuli evoked the mismatch negativity. The deviants moving from standards seem to evoke the lowest mismatch negativity with the longest latency at all azimuthal locations of standard stimuli. Besides, the deviant shift from standards proved to be the only direction at which the characteristics of mismatch negativity depended upon the standard's azimuth. It is seems that the discrimination of interaural time delay is essentially dependent on the pattern of interaural delay changes at the moment when the deviant occurs.     

Allocentric or craniocentric representation of acoustic space: an electrotomography study using mismatch negativity

The world around us appears stable in spite of our constantly moving head, eyes, and body. How this is achieved by our brain is hardly understood and even less so in the auditory domain. Using electroencephalography and the so-called mismatch negativity, we investigated whether auditory space is encoded in an allocentric (referenced to the environment) or craniocentric representation (referenced to the head). Fourteen subjects were presented with noise bursts from loudspeakers in an anechoic environment. Occasionally, subjects were cued to rotate their heads and a deviant sound burst occurred, that deviated from the preceding standard stimulus either in terms of an allocentric or craniocentric frame of reference. We observed a significant mismatch negativity, i.e., a more negative response to deviants with reference to standard stimuli from about 136 to 188 ms after stimulus onset in the craniocentric deviant condition only. Distributed source modeling with sLORETA revealed an involvement of lateral superior temporal gyrus and inferior parietal lobule in the underlying neural processes. These findings suggested a craniocentric, rather than allocentric, representation of auditory space at the level of the mismatch negativity.     

Mechanisms of generation of mismatch negativity and their role in discrimination of short acoustical stimuli

The effect of stimulus duration on the mismatch negativity in the auditory event-related potentials was used to study the role of mismatch negativity (MMN) in discrimination of short acoustical stimuli. We compared discrimination of different short acoustical stimuli in active variant of "odd ball" paradigm. It was shown that it is possible to discriminate between standard and deviant acoustical stimuli which do not produce MMN in passive condition. It makes possible to estimate behavioural significance of MMN in active discrimination task. If the MMN had not been recorded in passive condition, that leads to an increase of reaction time in active paradigm approximately by 50 ms.     

Auditory stimulus discrimination recorded in dogs, as indicated by mismatch negativity (MMN)

Dog cognition research tends to rely on behavioural response, which can be confounded by obedience or motivation, as the primary means of indexing dog cognitive abilities. A physiological method of measuring dog cognitive processing would be instructive and could complement behavioural response. Electroencephalogram (EEG) has been used in humans to study stimulus processing, which results in waveforms called event-related potentials (ERPs). One ERP component, mismatch negativity (MMN), is a negative deflection approximately 160-200 ms after stimulus onset, which may be related to change detection from echoic sensory memory. We adapted a minimally invasive technique to record MMN in dogs. Dogs were exposed to an auditory oddball paradigm in which deviant tones (10% probability) were pseudo-randomly interspersed throughout an 8 min sequence of standard tones (90% probability). A significant difference in MMN ERP amplitude was observed after the deviant tone in comparison to the standard tone, t₅ = −2.98, p = 0.03. This difference, attributed to discrimination of an unexpected stimulus in a series of expected stimuli, was not observed when both tones occurred 50% of the time, t₁ = −0.82, p > 0.05. Dogs showed no evidence of pain or distress at any point. We believe this is the first illustration of MMN in a group of dogs and anticipate that this technique may provide valuable insights in cognitive tasks such as object discrimination.     

Preattentive extraction of abstract auditory rules in speech sound stream: a mismatch negativity study using lexical tones

Background

Extraction of linguistically relevant auditory features is critical for speech comprehension in complex auditory environments, in which the relationships between acoustic stimuli are often abstract and constant while the stimuli per se are varying. These relationships are referred to as the abstract auditory rule in speech and have been investigated for their underlying neural mechanisms at an attentive stage. However, the issue of whether or not there is a sensory intelligence that enables one to automatically encode abstract auditory rules in speech at a preattentive stage has not yet been thoroughly addressed.

Methodology/Principal Findings

We chose Chinese lexical tones for the current study because they help to define word meaning and hence facilitate the fabrication of an abstract auditory rule in a speech sound stream. We continuously presented native Chinese speakers with Chinese vowels differing in formant, intensity, and level of pitch to construct a complex and varying auditory stream. In this stream, most of the sounds shared flat lexical tones to form an embedded abstract auditory rule. Occasionally the rule was randomly violated by those with a rising or falling lexical tone. The results showed that the violation of the abstract auditory rule of lexical tones evoked a robust preattentive auditory response, as revealed by whole-head electrical recordings of the mismatch negativity (MMN), though none of the subjects acquired explicit knowledge of the rule or became aware of the violation.

Conclusions/Significance

Our results demonstrate that there is an auditory sensory intelligence in the perception of Chinese lexical tones. The existence of this intelligence suggests that the humans can automatically extract abstract auditory rules in speech at a preattentive stage to ensure speech communication in complex and noisy auditory environments without drawing on conscious resources.     

Integrated mismatch negativity (MMNi): a noise-free representation of evoked responses allowing single-point distribution-free statistical tests

If the repeated presentation of a single (standard) auditory stimulus is randomly interspersed with a second acoustically different (deviant) stimulus, the cortical activity evoked by the deviant stimulus can contain a negative component known as the mismatch negativity (MMN). The MMN is derived by subtracting the averaged response evoked by the standard stimulus from that evoked by the deviant stimulus. When the magnitude of the response is small or the signal-to-noise ratio is poor, it is difficult to judge the presence or absence of the MMN simply by visual inspection, and statistical detection techniques become necessary. A method of analysis is proposed to quantify the magnitude and statistically evaluate the presence of the MMN based on time-integrated evoked responses. This paper demonstrates the use of this integrated mismatch negativity (MMN_i) analysis to detect the MMN evoked by stimulus contrasts near the perceptual threshold of two subjects. The MMN_i, by virtue of being equivalent to a low-pass filtered response, presents an almost noise-free estimate of MMN magnitude. A single measure of the integrated evoked response at a fixed time point is used in a distribution-free statistic that compares the magnitude of the averaged response evoked by the deviant stimulus with a magnitude distribution derived from 200 subaveraged responses to the standard stimulus (with the number of sweeps per average equal to that of the deviant stimulus). This allows a calculation of the exact probability for the null hypothesis that the negative magnitude of the response evoked by the deviant stimulus is drawn from the magnitude distribution of responses evoked by the standard stimulus. Rejection of this hypothesis provides objective evidence of the presence of the MMN.