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.     

Mismatch negativity (MMN) for sequences of auditory and visual stimuli: evidence for a mechanism specific to the auditory modality

ERPs to sequences of standard and deviant sinusoidal 100 msec tone pips, high-contrast sinusoidal gratings and to their simultaneously presented combinations were recorded. Mismatch negativity (MMN), an ERP component elicited by deviant stimuli, was estimated for the different stimulus sequences in order to find out whether it reflects modality-specific processes or non-specific attentive phenomena. In addition to the auditory modality, we studied whether the mismatch response could be evoked by a deviant visual stimulus in a visual sequence or by a deviant stimulus in either modality. The results show that only auditory stimuli produced the mismatch response, suggesting that MMN is not a manifestation of a general attentional mechanism but is probably specific to the auditory modality.     

Role of phasic changes in sound signal in localization of auditory image

The work presents experimental data on certain changes in electrical responses of the auditory system's midbrain centre in a contraphasic binaural presentation of sound impulse series. Neuronal cortical activity is selective in respect to dynamic interaural changes of signals' phasic spectre which may serve as a basis for the mechanisms of localising a moving source of sound. Human auditory evoked potentials reveal a manifestation of memorizing the auditory image movement direction as shown by appearance of stimuli deviant from standard mismatch negativity.     

Mismatch Negativity during Exposure to Acoustic Stimuli Simulating Fused Auditory Images

The authors consider the results of study of the phenomenon of mismatch negativity (MMN) during exposure to acoustic stimuli simulating fused auditory images with different spatial localization: along the head midline (a standard stimulus used in all series), near either of the ears (lateralized), and moving from the midline to or from an ear. All deviant stimuli evoked the mismatch negativity; the minimum MMN amplitude with the longest latency was observed when the stimulus simulated motion of the auditory image from the midline to either ear. When the deviant auditory images were localized on the left of the midline, the contralateral MMN dominance was more pronounced and responses to various deviant stimuli differed more than when the images were localized on the right. The mismatch negativity as a criterion of discrimination accuracy for signals with different localization features is discussed.     

Changes of evoked potentials caused by sound signals with different localization characteristics

Characteristics of the mismatch negativity (MMN) were studied by presenting the subjects with four blocks of stimuli containing standard series of clicks (90%) simulating a stationery sound image located in the head midline, and one of three different deviant series of clicks (10%) simulating either a stationary sound image located near the left ear or a moving sound image which shifted from the head midline to the left ear or in the opposite direction. All the deviant stimuli elicited the MMN with the minimal peak amplitude and the greatest latency evoked by the deviant series of clicks simulating the sound image moving from the head midline to the left ear. These findings suggest that the MMN may be considered as a pre-perceptual physiological measure of the discrimination accuracy for the sound signals with various spatial locations.     

Fast detection of unexpected sound intensity decrements as revealed by human evoked potentials

The detection of deviant sounds is a crucial function of the auditory system and is reflected by the automatically elicited mismatch negativity (MMN), an auditory evoked potential at 100 to 250 ms from stimulus onset. It has recently been shown that rarely occurring frequency and location deviants in an oddball paradigm trigger a more negative response than standard sounds at very early latencies in the middle latency response of the human auditory evoked potential. This fast and early ability of the auditory system is corroborated by the finding of neurons in the animal auditory cortex and subcortical structures, which restore their adapted responsiveness to standard sounds, when a rare change in a sound feature occurs. In this study, we investigated whether the detection of intensity deviants is also reflected at shorter latencies than those of the MMN. Auditory evoked potentials in response to click sounds were analyzed regarding the auditory brain stem response, the middle latency response (MLR) and the MMN. Rare stimuli with a lower intensity level than standard stimuli elicited (in addition to an MMN) a more negative potential in the MLR at the transition from the Na to the Pa component at circa 24 ms from stimulus onset. This finding, together with the studies about frequency and location changes, suggests that the early automatic detection of deviant sounds in an oddball paradigm is a general property of the auditory system.     

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.     

Event-related potentials in an auditory oddball situation in the rat

Evoked potentials were recorded from the auditory cortex of both freely moving and anesthetized rats when deviant sounds were presented in a homogenous series of standard sounds (oddball condition). A component of the evoked response to deviant sounds, the mismatch negativity (MMN), may underlie the ability to discriminate acoustic differences, a fundamental aspect of auditory perception. Whereas most MMN studies in animals have been done using simple sounds, this study involved a more complex set of sounds (synthesized vowels). The freely moving rats had previously undergone behavioral training in which they learned to respond differentially to these sounds. Although we found little evidence in this preparation for the typical, epidurally recorded, MMN response, a significant difference between deviant and standard evoked potentials was noted for the freely moving animals in the 100-200 ms range following stimulus onset. No such difference was found in the anesthetized animals.     

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.     

Effects of Acoustic Context on the Perceptual Differences between Spatial Sound Stimuli

We studied the effects of the acoustic context on active and passive discrimination of moving sound signals. Different contexts were created by reversing the role of standard and deviant stimuli in the oddball blocks, while their acoustical features were kept the same. Three types of sounds were used as standard or deviant stimuli in different blocks: stationary midline noises and two (smooth and abrupt) moving sounds moving to the left or right of the midline. Auditory event-related potentials (ERPs) were recorded during passive listening (the sound stimulation ignored), and mismatch negativity potentials (MMNs) were obtained. Active discrimination of sound movements was measured by the hit rate (percent correct responses) and false alarm rate, as well as the reaction time. The influence of the stimulus context on active and passive discrimination of the moving sound stimuli was reflected in the phenomenon known as the effect of deviance direction. The hit rate and MMN amplitude were higher when the deviant moved faster than the standard. The MMN amplitude was more responsive to the velocity of sound stimuli than the hit rate and false alarm rate. The psychophysical measurements in the reversed contexts suggest that smooth and abrupt sound movements may belong to the same perceptual category (moving sounds), while the stationary stimuli form another perceptual category.     

Auditory event-related potentials to deviant stimuli during drowsiness and stage 2 sleep

Twelve subjects were tested using a 3-tone auditory oddball paradigm consisting of a standard 1000 Hz tone (P = 80%) and two deviants, namely, a 1200 Hz tone and a 2000 Hz tone (both P = 10%). Testing took place in 3 conditions: (1) attend, in which the subject had to count one of the deviant tones; (2) ignore, in which the subject read a book; and (3) sleep, in which the subject was encouraged to go to sleep during presentation of the tones.In the awake conditions stimulus deviance elicited mismatch negativity (MMN) and P3. During drowsiness, no separate mismatch negativity (MMN) could be detected, but the 2000 Hz tone evoked a broad fronto-central early negative deflection, suggesting an overlap of N₁ and MMN. In the same condition, P210, N330 and P430 appeared, all being sensitive to magnitude of deviance. During stage 2, the P210, N330 and P430 amplitudes increased, most notably to the large deviant.These data indicate that differential processing of auditory inputs is maintained during drowsiness and stage 2 sleep, but do not support the notion that MMN or P3 activity comparable to the waking state occurs to oddball stimuli during this stage. It is hypothesised that during light sleep, scanning of the environment is performed by a different system than in the awake state and that during drowsiness a gradual switch between these two systems takes place.     

Human brain evoked potentials and discrimination of short acoustic stimuli with various frequency

We found that the mismatch negativity (MMM) was absent in evoked potentials in passive condition for frequency deviant acoustical stimuli when stimulus duration was only 11-30 ms. But it was shown that it is possible for participants to fairly well discriminate these stimuli and the component N2b in RP was generated without preceding MMN. Processing negativity also was absent in potentials by the minimal stimulus duration (11 ms). Auditory discrimination nevertheless was still possible, but reaction time and number of committed errors increased significantly.     

Discrimination of the dynamic properties of sound source spatial location in humans: Electrophysiology and psychophysics

The spatial resolution of the human auditory system was studied under conditions, where the location of the sound source was changed according to different temporal patterns of interaural time delay. Two experimental procedures were run in the same group of subjects: a psychophysical procedure (the transformed staircase method) and an electrophysiological one (which requires recording of mismatch negativity, the auditory evoked response component). It was established that (1) the value of the mismatch negativity reflected the degree of spatial deviation of the sound source; (2) the mismatch negativity was elicited even at minimum (20μs) interaural time delays under both temporal patterns (abrupt azimuth change and gradual sound movement at different velocities); (3) an abrupt change of the sound source azimuth resulted in a greater mismatch negativity than gradual sound movement did if the interaural time delay exceeded 40 μs; (4) the discrimination threshold values of the interaural delay obtained in the psychophysical procedure were greater than the minimum interaural delays that elicited mismatch negativity, with the exception of the expert listeners, who exhibited no significant difference.     

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.     

Mismatch negativity as a characteristic of the distinguishing locating capacity of the human auditory system

Mismatch negativity has been studied under the conditions of dichotic stimulation by deviant stimuli that either changed their azimuth from zero to 4.5°, 13.5°, and 22.5° or moved with small velocities from the head midline to one of the ears. The reference stimuli were located along the head midline. Our experiments have shown that both a discontinuous increase in the azimuth and an increase in the velocity of moving stimuli are accompanied by an increase in the amplitude of mismatch negativity. This process is more pronounced in the cases of (1) an instantaneous change in the deviant azimuth compared to its movement, (2) a longer duration of the deviant sound, (3) action of the deviant in the right hemisphere, and (4) the frontal derivation. The correlations of changes in the mismatch negativity with psychophysical data on the resolution of the human auditory system are considered.     

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.     

Mismatch negativity in the auditory event-related potentials in response to abrupt and smooth displacements of virtual sound source

The work investigated event-related potentials, mismatch negativity (MMN), and P3a component under dichotic stimulation with deviant stimuli simulating abrupt or smooth displacement of auditory images to the left or to the right from the head midline by means of interaural time delay introduced into the deviant stimuli. Repetitive standard stimuli were localized near the head midline. All deviant stimuli elicited mismatch negativity and P3a component. It was shown the MMN for smooth deviant motion was lower than that for the abrupt deviant displacement. MMN amplitude for both deviant types obviously depended on interaural time delay, which confirms that MMN might be considered as a measure of the auditory system spatial discriminative ability. The P3a component demonstrated the same amplitude dependences as the MMN. The results obtained are discussed in respect to manifestation of the processes underlying the auditory motion detection in the event-related potentials.     

The orienting response, and future directions of its development

The orienting response (OR) is a specific behavioral act directed towards extraction of information from the environment. Head and eye movements represent only the tip of the iceberg of internal responses, which includes vascular modifications, EEG changes, and event-related potentials. Two mechanisms of the OR have to be differentiated: voluntary and involuntary. In the event-related potential, such a differentiation is expressed in mismatch negativity (involuntary effect) and processing negativity (voluntary effect). Single unit studies have shown that hippocampal neurones are simulating specific features of the OR as a response to novelty. Repeated presentation of stimuli results in a selective habituation of novelty detectors in hippocampus and of the OR. The trace of a standard stimulus formed at the level of hippocampal neurones matches the features of the standard stimulus and can be called a "neuronal model of the stimulus." The OR is triggered by mismatch between the test stimulus and the elaborated neuronal model, and is activated by verbal instruction, by reinforcement during the initial stage of conditioned reflex elaboration, and by differentiation of signal and non-signal stimuli. A promising new area of practical application of the OR lies in the evaluation of a corridor of optimal functional state for efficient computer-based learning. Registration of the OR and defensive responses can be used for an objective evaluation of the functional state of the student, or, in a wider sense, of the industrial operator. New avenues of OR research are opened by recent techniques that isolate single-trial event related potentials, and their correlation with autonomic and behavioral manifestations of the OR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Moving sound source discrimination in humans: Mismatch negativity and psychophysics

The ability to discriminate moving sounds sources with different dynamic properties was studied in humans. Mismatch negativity was studied in an experiment on dichotic stimulation, with deviant stimuli simulating the instantaneous movement of the auditory image to the right or left of the head midline in the horizontal plane. Standard stimuli simulated continuous movement of the sound source to the right or to the left to the same angular distances. It was also established that both deviant stimuli caused mismatch negativity, its parameters being independent on the direction of sound movement. Psychophysical testing of the same group of subjects showed that discrimination between the stimuli was below the psychophysical threshold. The results obtained are discussed from the point of view of current theories of moving sound localization. The correlation between the objective and subjective levels of discrimination of moving auditory images are discussed.     

Preattentive auditory information processing under exposure to the 902 MHz GSM mobile phone electromagnetic field: A mismatch negativity (MMN) study

Previous studies on the effects of the mobile phone electromagnetic field (EMF) on various event‐related potential (ERP) components have yielded inconsistent and even contradictory results, and often failed in replication. The mismatch negativity (MMN) is an auditory ERP component elicited by infrequent (deviant) stimuli differing in some physical features from the repetitive frequent (standard) stimuli in a sound sequence. The MMN provides a sensitive measure for cortical auditory stimulus feature discrimination, regardless of attention and other contaminating factors. In this study, MMN responses to duration, intensity, frequency, and gap changes were recorded in healthy young adults (n = 17), using a multifeature paradigm including several types of auditory change in the same stimulus sequence, while a GSM mobile phone was placed on either ear with the EMF (902 MHz pulsed at 217 Hz; SAR_1g = 1.14 W/kg, SAR_10g = 0.82 W/kg, peak value = 1.21 W/kg, measured with an SAM phantom) on or off. An MMN was elicited by all deviant types, while its amplitude and latency showed no significant differences due to EMF exposure for any deviant types. In the present study, we found no conclusive evidence that acute exposure to GSM mobile phone EMF affects cortical auditory change detection processing reflected by the MMN. Bioelectromagnetics 30:241–248, 2009. © 2009 Wiley‐Liss, Inc.