Effects of physiological aging on mismatch negativity: A meta-analysis

Mismatch negativity (MMN) is a promising window on how the functional integrity of auditory sensory memory and change discrimination is modulated by age and relevant clinical conditions. However, the effects of aging on MMN have remained somewhat elusive, particularly at short interstimulus intervals (ISIs). We performed a meta-analysis of peer-reviewed MMN studies that had targeted both young and elderly adults to estimate the mean effect size. Nine studies, consisting of 29 individual investigations, were included and the final total study population consisted of 182 young and 165 elderly subjects. The effects of different deviant types and duration of ISIs on the effect size were assessed. The overall mean effect size was 0.63 (95% CI at 0.43–0.82). The effect sizes for long ISI (> 2 s, effect size 0.68, 95% CI at 0.31–1.06) and short ISI (< 2 s, effect size 0.61, 95% CI at 0.39–0.84) were both considered moderate. A further analysis showed a prominent aging-related decrease in MMN responses to duration and frequency changes at short ISIs. It was also interesting to note that the effect size was about 25% larger for duration deviant condition compared to the frequency deviant condition. In conclusion, a reduced MMN response to duration and frequency deviants is a robust feature among the aged adults, which suggests that there has been a decline in the functional integrity of central auditory processing in this population.     

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.     

Sensory memory during physiological aging indexed by mismatch negativity (MMN)

Physiological aging affects early sensory-perceptual processes. The aim of this experiment was to evaluate changes in auditory sensory memory in physiological aging using the Mismatch Negativity (MMN) paradigm as index. The MMN is a marker recorded through the electroencephalogram and is used to evaluate the integrity of the memory system. We adopted a new, faster paradigm to look for differences between 3 groups of subjects of different ages (young, middle age and older adults) as a function of short or long intervals between stimuli. We found that older adults did not show MMN at long interval condition and that the duration of MMN varied according to the participants' age. The current study provides electrophysiological evidence supporting the theory that the encoding of stimuli is preserved during normal aging, whereas the maintenance of sensory memory is impaired. Considering the advantage offered by the MMN paradigm used here, these data might be a useful reference point for the assessment of auditory sensory memory in pathological aging (e.g., in neurodegenerative diseases).     

Auditory sensory memory and language abilities in former late talkers: A mismatch negativity study

The present study investigated whether (a) a reduced duration of auditory sensory memory is found in late talking children and (b) whether deficits of sensory memory are linked to persistent difficulties in language acquisition. Former late talkers and children without delayed language development were examined at the age of 4 years and 7 months using mismatch negativity (MMN) with interstimulus intervals (ISIs) of 500 ms and 2000 ms. Additionally, short‐term memory, language skills, and nonverbal intelligence were assessed. MMN mean amplitude was reduced for the ISI of 2000 ms in former late talking children both with and without persistent language deficits. In summary, our findings suggest that late talkers are characterized by a reduced duration of auditory sensory memory. However, deficits in auditory sensory memory are not sufficient for persistent language difficulties and may be compensated for by some children.     

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.     

Representation of harmonic frequencies in auditory memory: a mismatch negativity study

Most natural sounds are composed of a mixture of frequencies, which activate separate neurons in the tonotopic auditory cortex. Nevertheless, we perceive this mixture as an integrated sound with unique acoustic properties. We used the Mismatch Negativity (MMN), a marker of auditory change detection, to determine whether individual harmonics are represented in sensory memory. The MMN elicited by duration and pitch deviations were compared for harmonic and pure tones. Controlled for acoustic differences between standards and deviants and their relative probabilities, the MMN was larger for harmonic than pure tones for duration but not for pitch deviance. Because the magnitude of the MMN reflects the number of concurrent changes in the acoustic input relative to a preexistent acoustic representation, these results suggest that duration is represented and compared separately for individual frequencies, whereas pitch comparison occurs after integration.     

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

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

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.     

Effects of auditory hallucinations on the mismatch negativity (MMN) in schizophrenia as measured by a modified ‘optimal’ multi-feature paradigm

The recently developed Optimal-3 multi-feature MMN paradigm, a shortened version of the ‘optimal’ multi-feature MMN paradigm, allows for the focused recording of the most widely reported MMN deviants (frequency, duration, intensity) within an efficient and time-saving paradigm. The objective of this study was to examine MMN acoustic change detection in schizophrenia (SZ), and elucidate its association with auditory verbal hallucinations (AH), using the Optimal-3.

Methods

MMN to duration, frequency and intensity deviants were recorded in 12 SZ outpatients (SZs) with persistent AHs and 12 matched healthy controls (HC). Electrical activity was recorded from 32 scalp electrodes; MMN amplitudes and latencies for each deviant were compared between groups and were correlated with trait (PSYRATS) and state measures of AH severity and Positive and Negative Syndrome Scale (PANSS) ratings in SZs.

Results

SZs showed a significantly smaller duration MMN compared to HCs. Furthermore, in SZs attenuated duration MMN amplitudes were correlated with increased PSYRATS scores, as well as increased PANSS positive symptom, hallucination item and general psychoticism ratings, while attenuated intensity MMN amplitudes were correlated with increased PSYRATS scores.

Conclusions

This is the first study to examine MMN in SZ within the modified (Optimal-3) multi-feature MMN paradigm. This study corroborates previous research reporting a robust duration MMN deficit in SZ and supports previous findings suggesting that AHs may contribute to MMN deficits in SZ.     

Effect of deviance direction and calculation method on duration and frequency mismatch negativity (MMN)

The mismatch negativity (MMN) component of the auditory event-related potential (ERP) reflects the process of change detection in the auditory system. The present study investigated the effect of deviance direction (increment vs. decrement) and calculation method (traditional vs. same-stimulus) on the amplitude of MMN. MMN was recorded for increments and decrements in frequency and duration in 20 adults. The stimuli (standard/deviant) were 250 Hz/350 Hz (frequency MMN) and 200 ms/300 ms (duration MMN) for increment MMN and vice versa for decrement MMN. Amplitude of MMN was calculated in two ways: the traditional method (subtracting ERP to the standard from the deviant presented in the same block) and the same-stimulus method (subtracting ERP to identical stimuli presented as standard in one block and deviant in another block). We found that increments in frequency produced higher MMN amplitudes compared to decrements for both methods of calculation. For duration deviance, the decrement MMN was absent in the traditional method, while the decrement and increment MMN did not differ for the same-stimulus method. These findings suggest that the brain processes frequency increments and decrements in different ways. The results also suggest the use of same-stimulus method for the calculation of duration MMN when long duration stimuli are used.     

Representation of the standard: stimulus context effects on the process generating the mismatch negativity component of event-related brain potentials

In the auditory oddball paradigm, the frequent occurrence of a sound (the "standard") forms the basis of deviance detection. The incoming sounds are compared with the cortical representation of the standard and those sounds that do not match it elicit the mismatch negativity (MMN) event-related brain potential. Here we address the issue of whether the relative probability of the sounds in a sequence was a critical factor influencing which sounds would be represented as standards in the deviant comparison process. One frequent (F1) and two infrequent (D1 and D2) sounds that differed only in duration were presented in a sequence. D1 occurred proportionally as frequently with respect to D2 as F1 occurred with respect to D1. If the proportional relationship of sounds were critical then D1 could serve as a "standard" to D2 and thus D2 should elicit two MMNs. However, D2 elicited MMN only with respect to F1. This result as well as those obtained in two control conditions suggests that "standards" are not established on the basis of relative probability; they emerge as a result of global characteristics, the longer-term context, of the sound sequence.     

Finding the missing stimulus mismatch negativity (MMN): emitted MMN to violations of an auditory gestalt

Deviations from repetitive auditory stimuli evoke a mismatch negativity (MMN). Counterintuitively, omissions of repetitive stimuli do not. Violations of patterns reflecting complex rules also evoke MMN. To detect a MMN to missing stimuli, we developed an auditory gestalt task using one stimulus. Groups of six pips (50 ms duration, 330 ms stimulus onset asynchrony [SOA], 400 trials), were presented with an intertrial interval (ITI) of 750 ms while subjects (n=16) watched a silent video. Occasional deviant groups had missing 4th or 6th tones (50 trials each). Missing stimuli evoked a MMN (p<.05). The missing 4th (-0.8 μV, p<.01) and the missing 6th stimuli (-1.1 μV, p<.05) were more negative than standard 6th stimuli (0.3 μV). MMN can be elicited by a missing stimulus at long SOAs by violation of a gestalt grouping rule. Patterned stimuli appear more sensitive to omissions and ITI than homogenous streams.     

Optimized mismatch negativity paradigm reflects deficits in schizophrenia patients. A combined EEG and MEG study

Mismatch negativity (MMN) and its neuromagnetic analog (MMNm) are event-related brain responses elicited by changes in a sequence of auditory events and indexes early cognitive processing. It consistently detects neural processing deficits in schizophrenia. So far MMN is assessed with different methods (electroencephalography, EEG; magnetoencephalography, MEG) and with different paradigms: the "traditional" oddball design with rare deviants (20%) or the "optimum" design with 50% deviants varying in one of five parameters each. These MMN measures may not reflect one unitary mechanism which is equally affected in schizophrenia. We compared both designs in 12 patients with schizophrenia and controls using MEG and EEG. Automated, observer-independent data analysis rendered the procedures suitable for clinical applications. The optimum design was fastest to detect MMN and MEG had the best signal-to-noise ratio. In addition MMN was mostly reduced in schizophrenia if measured with MEG in the optimum paradigm. Optimized paradigms improve sensitivity and speed for the detection of schizophrenia endophenotypes. Dysfunctions in this disorder may lie primarily in the fast and automatic encoding of stimulus features at the auditory cortex.     

Memory-based or afferent processes in mismatch negativity (MMN): a review of the evidence

The mismatch negativity (MMN) is an electromagnetic response to any discriminable change in regular auditory input. This response is usually interpreted as being generated by an automatic cortical change‐detection process in which a difference is found between the current input and the representation of the regular aspects of the preceding auditory input. Recently, this interpretation was questioned by Jääskeläinen et al. (2004) who proposed that the MMN is a product of an N1 (N1a) difference wave emerging in the subtraction procedure used to visualize and quantify the MMN. We now evaluate this “adaptation hypothesis” of the MMN in the light of the available data. It is shown that the MMN cannot be accounted for by differential activation of the afferent N1 transient detectors by repetitive (“standard”) stimuli and deviant (“novel”) stimuli and that the presence of a memory representation of the standard is required for the elicitation of MMN.     

Units of sound representation and temporal integration: A mismatch negativity study

Two acoustic events occurring successively within 200 ms are processed as a single event when the first event predicts the occurrence of the second, but are processed as two separate events when the two events can also occur independently of each other and thus the second event provides new information. However, if the two events are carried by the same stimulus, they are always processed as a single event. This was shown by studies using the mismatch negativity (MMN) event-related potential (ERP). The current study was aimed at investigating the acoustic parameters that determine the integration of successive events within the putative temporal window of integration (TWI). The results demonstrate that temporal grouping (achieved here by presenting sounds in pairs) of the acoustic events within the TWI creates strong unitization, which is not broken up by higher level contingencies of the sound sequence, such as the predictability of the second successive event.     

N1 and the mismatch negativity are spatiotemporally distinct ERP components: disruption of immediate memory by auditory distraction can be related to N1

Event-related potentials (ERPs) were recorded for ignored tones presented during the retention interval of a delayed serial recall task. The mismatch negativity (MMN) and N1 ERP components were measured to discern spatiotemporal and functional properties of their generation. A nine-token sequence with nine different tone pitches was more disruptive than an oddball (two-token) sequence, yet this oddball sequence was no more disruptive than a single repeating tone (one-token). Tones of the nine-token sequence elicited augmented N1 amplitudes compared to identical tones delivered in the one-token sequence, yet deviants elicited an additional component (MMN) with distinct temporal properties and topography. These results suggested that MMN and N1 are separate, functionally distinct components. Implications are discussed for the N1 hypothesis and the changing-state hypothesis of the disruption of serial recall performance by auditory distraction.     

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.     

Age-related ERP differences at retrieval persist despite age-invariant performance and left-frontal negativity during encoding

Although it has been reported repeatedly that retrieval-related processes decline with aging, the influence of well-documented age-related encoding deficiencies on the observed changes at retrieval have not been ruled out as a contributing factor. Here, we disentangle this confound by using a serendipitous finding reported by Nessler et al. [D. Nessler, R. Johnson Jr., M. Bersick, D. Friedman, On why the elderly have normal semantic retrieval but deficient episodic encoding: a study of left inferior frontal ERP activity, Neuroimage 30 (2006) 299–312]. In that study, age-related differences in the magnitude of left inferior frontal brain activity at encoding and subsequent recognition memory performance were eliminated when a deeper level of semantic encoding in the older adults was compared with a shallow level in the young. Based on this earlier result, the present paper is concerned with the question of whether the matched recognition performance resulting from age-equivalent ERP encoding activity was also accompanied by age-invariant retrieval-related brain activity. The results in the young were consistent with dual-process models of recognition memory due to the presence of ERP activity linked previously to familiarity (frontal EM effect) and recollection (parietal EM effect). By contrast the older adults only showed evidence of familiarity-based processes. Thus, despite age-equivalent brain activity at encoding and subsequent recognition performance, older relative to young adults appeared to base their old–new decisions on a qualitatively different pattern of retrieval processes (i.e., more on familiarity and less on recollection). Consequently, these data suggest that the age-related changes in retrieval observed here are independent of, and likely occur in addition to, any age-related changes in encoding processes.     

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.     

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.