Attention and mismatch negativity

The mismatch negativity (MMN) component of the auditory event-related potential (ERP) is elicited by infrequent, physically deviant stimuli in a sequence of frequent homogeneous stimuli (standards). It has been suggested that the MMN is generated by an automatic (attention-independent) neural mismatch process with a memory trace that encodes the physical features of the standard stimulus. The proposed MMN independence of attention was addressed in the present study. Standard stimuli and two types of deviant stimuli, differing from standards either in frequency or intensity, were dichotically presented in random order and at a very rapid rate. The subject attended either to left-or right-ear stimuli, counting the number of a designated type of deviants in that ear. In the present conditions of very strongly focused attention, the MMN was elicited even by frequency change in the ignored input stream, and its amplitude was very similar to that of the MMN elicited by equivalent deviant stimuli (targets) in the attended input stream. In contrast, the MMN to intensity deviation was clearly attenuated in the absence of attention. This effect is, however, probably due to the attention effect on the MMN generator itself rather than the antecedent sensory-analysis and -storing functions.     

Comparison between mismatch negativity amplitude and magnetic mismatch field strength in normal adults

The auditory mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch field, MMF) has been widely used to assess the ability of stimulus-driven change detection process in humans. The authors evaluated the similarity of inter-individual variation of the response strength between MMN and MMF recordings. Three types of MMN or MMF were recorded in ten healthy subjects: change in duration of pure-tone stimuli, change in duration of the Japanese vowel /a/, and difference between the Japanese vowels /a/ and /o/. There was no significant correlation between MMN amplitude and MMF strength under any condition and in either hemisphere. These results suggest that widely used indices of MMN in the two technologies, i.e., EEG-amplitude and MEG-ECD may not be proportional in an individual. To further clarify the differential significance of recording MMN/MMF may be important to establish MMN/MMF as clinical indices of individual ability of preattentive stage of auditory processing.     

The effects of digital filtering on mismatch negativity in wakefulness and slow-wave sleep

The mismatch negativity (MMN) is a response to a deviant auditory stimulus that occurs infrequently in a sequence of otherwise repetitive, homogeneous standard auditory stimuli. The MMN is presumed automatic and independent of conscious awareness. Recording of the MMN during unconscious states may be problematic. The frequency content of the long-lasting MMN may overlap and summate with other event-related slow potentials and low-frequency background electroencephalogram (EEG) activity. The purpose of this study is to determine the optimal filter settings for recording the MMN during unconscious states. Auditory event-related potentials (ERPs) were recorded from eight subjects in an oddball paradigm during wakefulness and Stages 3 and 4 of sleep [slow-wave sleep (SWS)] using a 0.16-35 Hz analogue bandpass. Deviant probability was 0.033. Stimulus-onset asynchrony was 150 ms. The EEG data were subsequently digitally filtered in the frequency domain. The low-pass filter was set at either 24, 12 or 6 Hz, and the high-pass filter at either 1, 2, 3 or 4 Hz. Applying a low-pass filter down to 12 Hz had a minimal impact on the waking or sleeping MMN amplitude. On the other hand, increasing the high-pass setting from 2 to 3 Hz permitted the visualization of the MMN recorded during sleep. The 4 Hz filter showed a similar trend but also markedly attenuated the amplitude of the waking MMN. A high-pass setting of 3 Hz provides a reasonable compromise. It has only a slight effect on the MMN when the subject is conscious, but still attenuates most of the unwanted slow potential activity when the subject enters SWS.     

Memory reactivation or reinstatement and the mismatch negativity

Previous studies have suggested that the memory underlying the mismatch negativity (MMN) can be deactivated by a period of silence and later reactivated. An alternative is that the memory becomes inapplicable due to a period of silence and subsequently reinstated. Both interpretations rest on the absence of a MMN for a deviant in Position 1 of a train (showing deactivation or inapplicability of the memory) and the presence of a MMN in Position 2 of the train (evidencing reactivation or reinstatement of the memory). In these studies, the standards were fixed across all trains of a given condition. Hence, it is not clear if the MMN elicited in Position 2 requires presentation of multiple trains with identical standards or only a single train. Experiment 1 showed that a single train is sufficient. With data from recent studies, Experiment 2 showed that MMNs in Position 2 of trains are due to reinstatement rather than reactivation of the memory.     

Long-term habituation of the speech-elicited mismatch negativity

A significant issue in the use of the mismatch negativity evoked potential (MMN) concerns its low signal-to-noise ratio (SNR). One can improve the noise level by increasing the number of samples included in the averaged response. However, improvement achieved in this way assumes that the signal, the MMN, remains stable for extended test times, an assumption which has not been tested. If the MMN is not stable, or exhibits habituation over the test session, then SNR would be adversely affected. MMN response magnitude was measured in 5-min intervals over the course of a test session in response to various speech syllable contrasts. Significant long-term habituation of MMN was observed for all three subject populations tested: young adults, school-age children, and guinea pigs. The time course of the habituation and the stimulus conditions under which it occurs have important implications for research and clinical applications of the MMN. Recording procedures that minimize habituation effects may be used to advantage to improve the signal-to-noise ratio of the MMN.     

First‐impression bias effects on mismatch negativity to auditory spatial deviants

Internal models of regularities in the world serve to facilitate perception as redundant input can be predicted and neural resources conserved for that which is new or unexpected. In the auditory system, this is reflected in an evoked potential component known as mismatch negativity (MMN). MMN is elicited by the violation of an established regularity to signal the inaccuracy of the current model and direct resources to the unexpected event. Prevailing accounts suggest that MMN amplitude will increase with stability in regularity; however, observations of first‐impression bias contradict stability effects. If tones rotate probabilities as a rare deviant (p = .125) and common standard (p = .875), MMN elicited to the initial deviant tone reaches maximal amplitude faster than MMN to the first standard when later encountered as deviant—a differential pattern that persists throughout rotations. Sensory inference is therefore biased by longer‐term contextual information beyond local probability statistics. Using the same multicontext sequence structure, we examined whether this bias generalizes to MMN elicited by spatial sound cues using monaural sounds (n = 19, right first deviant and n = 22, left first deviant) and binaural sounds (n = 19, right first deviant). The characteristic differential modulation of MMN to the two tones was observed in two of three groups, providing partial support for the generalization of first‐impression bias to spatially deviant sounds. We discuss possible explanations for its absence when the initial deviant was delivered monaurally to the right ear.     

Dissociation of the mismatch negativity and processing negativity attentional waveforms with nitrous oxide.

In Näätänen's model of early attention, the role of arousal in influencing the permanent feature detection system (indexed by mismatch negativity [MMN]) and the temporary feature-detection system (indexed by processing negativity [PN]) is unclear. To address this question, we investigated the effects of the anesthetic gas nitrous oxide (N₂O) on the MMN and PN. Ten subjects performed a dichotic listening task in which discrimination difficulty and breathing mixture (air or 25% N₂O) were manipulated factorially. MMN, PN, N1 and P300 at Fz, Cz, and Pz, as well as reaction time (RT), were measured. N₂O had no effect on the PN, but decreased MMN amplitude. As expected, N₂O decreased the amplitude of the N1 and P300 and increased the latency of the P300 and RT. The dissociation of MMN and PN by N₂O suggests that this agent decreases the ability to detect automatic stimulus change without affecting voluntary selective attention. We interpret these results as indicating that arousal has multidimensional effects on early attentional mechanisms. These dimensions can be differentiated chemically by neurotransmitters in the reticular formation of the brain.     

Genetic overlap between P300, P50, and duration mismatch negativity.

Mismatch Negativity (MMN), P300, and P50 suppression event-related potential (ERP) components measure intermediate stages of information processing but little is known of how they relate to each other genetically. The present study used multivariate genetic model fitting analytic techniques in 46 monozygotic and 32 dizygotic twin pairs. P300, P50 suppression, and MMN were recorded using a 19-channel electroencephalograph (EEG). Zygosity was determined using DNA genotyping. Little evidence for either genetic or environmental association between each of the three ERP paradigms was found. This result suggests that P300, MMN, and P50 suppression serve to evaluate different brain information processing functions that may be mediated by distinct neurobiological mechanisms which in turn are influenced by different sets of genes. Within paradigm, P300 amplitude and latency shared about half of their genetic effects.     

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.     

Quantifying signal-to-noise ratio of mismatch negativity in humans

Mismatch negativity (MMN) is thought to represent a neurophysiological index of auditory information processing that is independent of attention. Because this measure does not require an overt behavioral response, MMN has potential to evaluate higher order perceptual abilities in infants, young children and difficult-to-test populations, thereby extending results obtained from more basic physiologic and electroacoustic measures (auditory brainstem responses, ABRs; otoacoustic emissions, OAEs). Whereas the basic tenet of MMN is appealing, several issues-of-contention remain to be solved before this event related potential (ERP) can be applicable for routine clinical use. These issues include the consistent identification of MMN within individuals (vs. groups), its stability over time, and its reportedly poor signal-to-noise ratio (SNR). Herein, we focus on the issue of SNR, by comparing and contrasting SNR of MMN with other long latency auditory ERPs.     

Detecting violation in abstract pitch patterns with mismatch negativity

The human brain automatically extracts regularities embedded in environmental auditory events. This study investigated the extraction of abstract patterns by measuring mismatch negativity (MMN). Participants watched a silent subtitled movie and ignored a sequence of auditory events comprising frequent standards and rare deviants presented in the background. Tone triplets with varying pitch (first‐order property) served as the auditory events. The pitch intervals (interval 1 and interval 2) between the tones in a triplet and the ratio of interval 1 and 2 were considered second‐ and third‐order properties, respectively. Both second‐ and third‐order properties of the standards were kept constant in the mixed patterns block, while only the third‐order property was kept constant in the ratio pattern block. Four sets of tone triplets violating the interval and ratio patterns with different deviance levels were presented as deviants in both blocks, and subtracted with physically identical stimuli in a control block to isolate the MMNs. Interval and ratio pattern deviants elicited MMNs in the mixed patterns block while only ratio pattern deviants elicited MMNs in the ratio pattern block. Larger MMNs were elicited by large deviants as compared to small deviants. These results suggest that the change detection system is sensitive to the violation of both second‐ and third‐order abstract patterns. In addition to regularities in the abstract properties of auditory events, regularities in the relationships between abstract properties can also be extracted. This ability plays an important role in music and language perception.     

Word-specific cortical activity as revealed by the mismatch negativity

Neurophysiological brain activity evoked by individual spoken words and pseudowords was recorded and the mismatch negativity (MMN), an automatic index of experience-dependent auditory memory traces, was calculated. Consistent with earlier reported results, the MMN response to word-final syllables was enhanced compared with that elicited by the same syllables placed in a pseudoword context. Here we now demonstrate that the enhancement of the MMN elicited by two individual words showed different scalp topographies. The early word-specific brain activity is consistent with the assumption that the memory traces activated by individual words are carried by large neuronal ensembles that differ in their distributions over the cortex. Current source estimates localized the between-word differences in the right hemisphere and in parieto-occipital left-hemispheric areas. The differential brain responses to individual words appeared as early as ∼100 ms after the recognition points of the words, suggesting that their specific memory traces become active almost immediately after the information in the acoustic input is sufficient for word identification.     

The effect of perceptual grouping on the mismatch negativity

The mismatch negativity (MMN) was used as a probe to evaluate changes, with age, of transient auditory memory. Subjects were 16 young (M = 23 years) and 16 old (M = 72 years) people. Standard auditory stimuli were presented in trains of eight tones (1000 Hz) with either a I-s or 8-s intertrain interval (ITI). Occasionally, the first stimulus of a train was replaced with a 1200 Hz tone (deviant). The MMN was recorded while subjects watched a silent movie and ignored the sounds. Both groups of subjects showed an MMN response to deviant stimuli under the 1-s ITI condition, but MMNs were only seen for some subjects under the 8-s ITI condition. After MMN recording, subjects performed a discrimination task to the tones used for recording MMNs. Accuracy for both groups was near 100% at both ITIs. These results suggest that generation of MMN is a function of the perceptual grouping of the acoustical stimuli and that the integrity of perceptual grouping may be maintained with increased age.     

Functional and physical interaction between the mismatch repair and FA-BRCA pathways

Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure and an increased risk for leukemia and cancer. Fifteen proteins thought to function in the repair of DNA interstrand crosslinks (ICLs) comprise what is known as the FA-BRCA pathway. Activation of this pathway leads to the monoubiquitylation and chromatin localization of FANCD2 and FANCI. It has previously been shown that FANCJ interacts with the mismatch repair (MMR) complex MutLα. Here we show that FANCD2 interacts with the MMR proteins MSH2 and MLH1. FANCD2 monoubiquitylation, foci formation and chromatin loading are greatly diminished in MSH2-deficient cells. Human or mouse cells lacking MSH2 or MLH1 display increased sensitivity and radial formation in response to treatment with DNA crosslinking agents. Studies in human cell lines and Drosophila mutants suggest an epistatic relationship between FANCD2, MSH2 and MLH1 with regard to ICL repair. Surprisingly, the interaction between MSH2 and MLH1 is compromised in multiple FA cell lines, and FA cell lines exhibit deficient MMR. These results suggest a significant role for MMR proteins in the activation of the FA pathway and repair of ICLs. In addition, we provide the first evidence for a defect in MMR in FA cell lines.     

Attentional modulation of the mismatch negativity elicited by frequency differences between binaurally presented tone bursts

We examined the attentional sensitivity of the frequency-change mismatch negativity (MMN). Subjects listened to a binaural mixture of a narrative and a series of tone bursts that included 1200-Hz standards and two deviants (1000 and 1400 Hz). In the attend-tones condition, subjects responded to one deviant and ignored the narrative. In the attend-words condition, subjects responded to target words in the narrative and ignored the tones. Event-related potentials (ERPs) were recorded for the tones, and differences waves (deviant ERPs minus standard ERPs) were computed. Two negative peaks in the difference waves, DNI (100–180 ms) and DN2 (200–300 ms), overlapped the known scalp distribution and latency of the MMN. Mean DN1 and DN2 amplitudes were greater in the attend-tones condition than in the attend-words condition. These data suggest that the frequency-change MMN is modulated by nonspatial shifts of auditory attention.     

Loudness summation and the mismatch negativity event-related brain potential in humans

Abstract Infrequently omitting a sound from a repetitive sequence elicits the mismatch negativity (MMN) ERP response when the stimulus onset asynchrony (SOA) is less than 200 ms. We contrasted two alternative explanations of omission MMN. (1) Each sound starts a separate temporal integration process. Omissions violate the constancy of the temporal structure within the integration window. (2) Sounds preceding an omission are perceived to be louder than those followed by a sound within the integration period, because omissions allow the full stimulus aftereffect to be included in perceived loudness. We varied the SOA between 117 and 217 ms. For this case, the temporal structure explanation predicts that no MMN will be elicited, whereas the loudness summation explanation predicts that MMN will be elicited. MMN was elicited by tone omissions with random SOA, suggesting that loudness summation plays an important role in the elicitation of omission MMN.     

Differential changes in frontal and sub-temporal components of mismatch negativity.

Novel evidence is reported showing changes in the mismatch negativity (MMN) event-related potential (ERP) that followed a different time course in frontal and sub-temporal (mastoid) electrodes. MMN recorded in frontal electrode sites, assumed to originate predominantly in the superior temporal gyrus, showed amplitude enhancement from the first to the second recording block. In contrast, the amplitude of the sub-temporal, mastoid component (termed mismatch positivity, MMP) diminished. In addition to these changes in the MMN elicited by tone duration deviants, there were also significant changes in the ERP to the standard stimulus. The positivity in the standard ERP between 50 and 150 ms increased in bilateral mastoid electrodes but showed no reliable change in frontal electrodes. This suggests that more than one generator underpins the two mismatch components, and that the sub-temporal mismatch component does not only represent a polarity reversal of the main MMN component in the superior temporal gyrus.     

Visual mismatch negativity elicited by facial expressions under non-attentional condition

A modified "cross-modal delayed response" paradigm was used to investigate putative processing of face expression in the absence of focused attention to the face. Neutral, happy and sad faces were presented during intervals occurring between a tone and a response imperative signal (a faint click), while subjects were instructed to discriminate the location of the tone as quickly and accurately as possible and to ignore the faces. A neutral face was presented in 80% of the trials whereas the happy and sad faces were presented in the remaining trials - 10%, respectively. Expression mismatch negativity (EMMN) was obtained by subtracting the ERP elicited by neutral faces from that elicited by sad faces or happy faces. The EMMN started from around 120 ms (sad) and 110 ms (happy) lasting up to 430 ms (sad) and 360 ms (happy) post-stimulus. The EMMN elicited by sad faces was more negative than that elicited by happy faces. Both EMMNs distributed over posterior areas and covered larger areas in the right than in the left hemisphere sites (especially for happy EMMN).