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.     

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.     

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.     

Short-term replicability of the mismatch negativity

The short-term replicability of the mismatch negativity (MMN) between two recording sessions spaced 2 h apart was evaluated at individual and group levels in a sample of 11 healthy adults. Subjects were presented with a random sequence of 1000 Hz standard (92%) and 1100 Hz deviant (8%) tones while they were reading a book. The N1 and P2 exogenous components to standard tones showed a fairly good individual and group replicability. There were no significant differences in the MMN amplitude and latency between the two sessions in the group of subjects as a whole. The individual replicability of the MMN was not as good as for the N1 to standards, reaching significance in only some of the electrodes. This result was, however, similar to that obtained for the N1 after deviant tones. The results indicate that the MMN has good replicability at the group level, and further that at the individual level, MMN replicability is similar to that of the N1 to deviants. This suggests that the number of summations should be increased in order to improve the clinical usefulness of the MMN.     

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.     

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.     

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.     

Brain mechanism of selective listening reflected by event-related potentials

Stimulus selection during selective listening on the basis of simple physical stimulus features is reflected by an event-related potential (ERP) component called the processing negativity (PN). PN has been proposed to indicate a matching or comparison process between the physical features of the stimulus and an ‘attentional trace’, an actively formed and maintained temporary neuronal representation of the features defining the relevant stimuli. According to this theory, the smaller is the difference between the eliciting stimulus and that represented by the attentional trace, the longer time is the stimulus processed, and thus the larger in amplitude and longer in duration is the PN elicited. The relevant stimuli, perfectly matching with the attentional trace, and therefore eliciting the largest and longest-duration PN, are selected for further processing. In the present study, the relevant and irrelevant stimuli differed in pitch, and the magnitude of this pitch separation was varied between different stimulus blocks. The results support the afore-mentioned matching or comparison hypothesis of selective attention by showing that PN is not elicited only by the relevant stimuli but even by irrelevant stimuli, and further that the latter PN is larger in amplitude and longer in duration the more similar the irrelevant stimuli are to the relevant stimuli. This PN, however, was smaller than that to the relevant stimuli even for very small separations, reflecting high accuracy of the discrimination function of the attentional trace mechanism proposed to underly selective listening. The termination of the PN to the irrelevant stimuli was followed by a positivity which thus partly explained the difference (Nd) between the ERPs to the relevant and irrelevant stimuli.     

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.     

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.     

Effects of pre- and postnatal exposure to extremely low-frequency electric fields on mismatch negativity component of the auditory event-related potentials: Relation to oxidative stress

ABSTRACT

In our previous study, the developmental effects of extremely low-frequency electric fields (ELF-EF) on visual and somatosensory evoked potentials in adult rats were studied. There is no study so far examining the effects of 50 Hz electric field (EF) on mismatch negativity (MMN) recordings after exposure of rats during development. Therefore, our present study aimed to investigate MMN and oxidative brain damage in rats exposed to EF (12 kV/m, 1 h/day). Rats were divided into four groups, namely control (C), prenatal (Pr), postnatal (Po), and prenatal+postnatal (PP). Pregnant rats of Pr and PP groups were exposed to EF during pregnancy. Following birth, rats of PP and Po groups were exposed to EF for three months. After exposure to EF, MMN was recorded by electrodes positioned stereotaxically to the surface of the dura, and then brain tissues were removed for histological and biochemical analyses. The MMN amplitude was higher to deviant tones than to standard tones. It was decreased in all experimental groups compared with the C group. 4-Hydroxy-2-nonenal (4-HNE) levels were significantly increased in the Po group with respect to the C group, whereas they were significantly decreased in the PP group compared with Pr and Po groups. Protein carbonyl levels were significantly decreased in the PP group compared with C, Pr, and Po groups. EF decreased MMN amplitudes were possibly induced by lipid peroxidation.     

Acoustic signal patterns as reflected in the frequency following response of the cat auditory system

In the source of experiments on unanesthetized cats it was shown that all the essential qualities of acoustic stimuli are expressed in the frequency following response (FFR) peculiar to the lower regions of the auditory system (the inferior colliculus included). Amplitude and wave-form of response largely depend on the frequency and intensity of stimulation, frequency and phasic spectra bands for complex signals, together with their wave form and periodicity, acoustic masking of the "useful" signal, and finally interaural differences in stimulation modelling different spatial positions of the sound source.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 19, No. 1, pp. 67–74, January–February, 1987.     

Dissociation of category versus item priming in face processing: an event-related potential study

The underlying specificity of visual object categorization and discrimination can be elucidated by studying different types of repetition priming. Here we focused on this issue in face processing. We investigated category priming (i.e. the prime and target stimuli represent different exemplars of the same object category) and item priming (i.e. the prime and target stimuli are exactly the same image), using an immediate repetition paradigm. Twenty-three subjects were asked to respond as fast and accurately as possible to categorize whether the target stimulus was a face or a building image, but to ignore the prime stimulus. We recorded event-related potentials (ERPs) and reaction times (RTs) simultaneously. The RT data showed significant effects of category priming in both face trials and building trials, as well as a significant effect of item priming in face trials. With respect to the ERPs, in face trials, no priming effect was observed at the P100 stage, whereas a category priming effect emerged at the N170 stage, and an item priming effect at the P200 stage. In contrast, in building trials, priming effects occurred already at the P100 stage. Our results indicated that distinct neural mechanisms underlie separable kinds of immediate repetition priming in face processing.     

Genetic structure of wild emmer wheat populations as reflected by transcribed versus anonymous SSR markers.

Simple sequence repeat (SSR) markers have become a major tool in population genetic analyses. The anonymous genomic SSRs (gSSRs) have been recently supplemented with expressed sequence tag (EST) derived SSRs (eSSRs), which represent the transcribed regions of the genome. In the present study, we used 8 populations of wild emmer wheat (Triticum turgidum subsp. dicoccoides) to compare the usefulness of the two types of SSR markers in assessing allelic diversity and population structure. gSSRs revealed significantly higher diversity than eSSRs in terms of average number of alleles (14.92 vs. 7.4, respectively), polymorphic information content (0.87 vs. 0.68, respectively), and gene diversity (He; 0.55 vs. 0.38, respectively). Despite the overall differences in the level of diversity, Mantel tests for correlations between eSSR and gSSR pairwise genetic distances were found to be significant for each population as well as for all accessions jointly (RM=0.54, p=0.01). Various genetic structure analyses (AMOVA, PCoA, STRUCTURE, unrooted UPGMA tree) revealed a better capacity of eSSRs to distinguish between populations, while gSSRs showed a higher proportion of intrapopulation (among accessions) diversity. We conclude that eSSR and gSSR markers should be employed in conjunction to obtain a high inter- and intra-specific (or inter- and intra-varietal) distinctness.     

Laterality of the olfactory event-related potential response

In experimental practice, odors are commonly applied to only one nostril for recordings of olfactory event-related potentials (OERPs), but the lateralization aspect of the OERP response is unclear regarding both stimulated nostril and cortical topography. The purpose of the present study was to investigate whether stimulated-nostril side affects OERP amplitudes and latencies and whether these potentials indicate lateralization of brain response in healthy, right-handed, young adults. OERPs were recorded from nine electrode sites in response to monorhinal stimulation with amyl acetate in 28 participants. The results showed a general increase in amplitude from frontal to parietal electrode sites (in particular for N1/P3) and generally larger amplitudes on the left hemisphere and midline than on the right hemisphere. There was no main effect of stimulated-nostril side on amplitude. Interactions indicated that N1/P2 amplitude was larger for left- than right-nostril stimulation and larger on the left hemisphere and midline than on the right hemisphere in left-nostril stimulation. No main effect or interactions of stimulated-nostril side over latencies were found and no effects on latencies of sagittal or coronal sites. These findings suggest a general parietal, left-hemisphere predominance in response amplitude to odorous stimulation and imply that either the left or the right nostril may be sufficient for accurate assessment of OERP latency in right-handed, young adults.