The mismatch negativity to frequency deviant stimuli during natural sleep

Eight subjects spent a single night in the sleep laboratory. Event-related potentials (ERPs) were recorded during the presentation of two auditory ‘oddball’ stimulus conditions in which tonal frequency was manipulated. In the first condition, 1000 Hz ‘standard’ and 2000 Hz ‘deviant’ tones were presented. In the second condition, the deviant tone was reduced to 1050 Hz. In both conditions, deviant probability was 0.2. Stimuli were presented every 600 ms during wakefulness and stages 2, 4, and REM of sleep. A distinctive N1 wave was visible in both stimulus conditions when the subject was awake. The deviant stimuli elicited a ‘mismatch negativity’ (MMN) that inverted in polarity at the mastoid. In REM sleep, an N1 and a MMN were also elicited in both conditions. In the large deviance condition, the MMN had a slightly attenuated amplitude and was shorter in duration while in the small deviant condition, its peak latency was unusually early. Neither the N1 nor the MMN could be recorded in non-REM sleep.     

Theta Oscillation Related to the Auditory Discrimination Process in Mismatch Negativity: Oddball versus Control Paradigm

Background and Purpose

The aim of this study was to identify the mechanism underlying the auditory discriminatory process reflected in mismatch negativity (MMN), using time-frequency analysis of single-trial event-related potentials (ERPs).

Methods

Two auditory tones of different probabilities (oddball paradigm) and the same probability (control paradigm) were used. The average dynamic changes in amplitude were evaluated, and the in-phase consistency of the EEG spectrum at each frequency and time window across trials, event-related spectral perturbations (ERSPs), and inter-trial phase coherence (ITC) were computed.

Results

Subtraction of the ERPs of standard stimuli from the ERPs of deviant stimuli revealed a clear MMN component in the oddball paradigm. However, no discernible MMN component was observed in the control paradigm. Statistical tests showed that in the oddball paradigm, deviant tones produced significant increases of theta ERSPs and ITC at around 250 ms as compared with the standard tone, while no significant difference between the two stimuli was observed in the control paradigm.

Conclusions

Our results confirm that the auditory discriminatory process reflected in MMN is accompanied by phase resetting and power modulation at the theta frequency.     

Auditory event-related responses in children with semi-lobar holoprosencephaly

The purpose of this study was to evaluate auditory sensory and discrimination responses in children with semi-lobar holoprosencephaly (HPE). Event-related potential (ERP) signals were recorded to tone pair stimuli at 62 electrode sites from the scalp using an oddball paradigm (a two-block design, inter-stimulus interval=70 or 300 ms; frequency of tone pair=100 vs. 100 Hz for the frequent and 100 vs. 300 Hz for the infrequent). Latencies and amplitudes of P150, N250, and mismatch negativity (MMN)-like components were compared between children with HPE and controls. Our results revealed less organized ERP waveforms to both stimuli in children with HPE, with diminished P150 and N250 components across brain area. Robust and delayed MMN-like responses were elicited from the children with HPE, with decreased MMN amplitudes in the central, parietal, occipital, and posterior temporal areas. Our results suggest that while brain sensory responses to auditory tones may be impaired in children with semi-lobar HPE, subcomponents of auditory discrimination processes remain functional.     

The effect of aging on auditory components of event-related brain potentials

OBJECTIVE: To describe auditory perceptual, pre-attentive, attention-related and cognitive processes along lifespan in normal people by a simple auditory oddball paradigm easily usable in clinical practice. METHODS: ERPs were recorded in 72 normal subjects. Four blocks of tones were delivered (20% rare 2,000 Hz and 80% frequent 1,000 Hz). In the former two blocks, subjects performed a concomitant distracting visual search task (distracted condition); in the latter two blocks, they had to attend the occurrence of the rare tones (active condition). Latency and amplitude of ERPs were analyzed according to age, gender, educational level and repetition. RESULTS: N100 amplitude was greater in active than in distracted condition. MMN amplitude decreased with age. N2b and P300 latencies increased with age, while their amplitudes decreased. Females produced greater P300 than males. In the elderly, P300 latency was found to be longer in the second block than in the first one. CONCLUSIONS: N100 and MMN were found to be less affected by age than N2b and P300. When repeated, P300 showed increased latency in elderly subjects. SIGNIFICANCE: The protocol detected the higher influence of aging on late cognitive processes than on the perceptual and pre-attentive ones. Age-adjusted normative data were produced.     

The MMN amplitude increases in hypnosis: a case study

The neural mechanisms associated with hypnosis were investigated in a single highly hypnotizable subject by measuring the mismatch negativity (MMN) component of auditory ERP, reflecting the preattentive discrimination of change in stimulus flow, in normal baseline state and under hypnosis. It has been proposed that the frontal inhibition associated with hypnosis can be measured as a decrease in MMN. ERPs were elicited using the passive oddball paradigm with standard and deviant sine tone stimuli of 500 and 553Hz, respectively. The measurement was repeated in five separate sessions. In hypnosis the MMN was significantly larger compared to baseline. The results indicate that hypnosis can give rise to altered information processing in the brain even at a relatively early, i.e. preattentive level and that the larger MMN measured under hypnosis does not support frontal inhibition theory.     

Independent component analysis on the mismatch negativity in an uninterrupted sound paradigm

We compared the efficiency of the independent component analysis (ICA) decomposition procedure against the difference wave (DW) and optimal digital filtering (ODF) procedures in the analysis of the mismatch negativity (MMN). The comparison was made in a group of 54 children aged 8-16 years. The MMN was elicited in a passive oddball protocol presenting uninterrupted auditory stimulation consisting of two frequent alternating tones (600 and 800 Hz) of 100 ms duration each. Infrequently, one of the 600 Hz tones was shortened to 50 or 30 ms. The event related potentials (ERPs) were decomposed into the MMN-like and non-MMN-like independent components (ICs) through the FastICA algorithm. The ICA decomposition procedure extracted a cleaner MMN compared to the ODF or DW procedures. It extracted the MMN, whose characteristics concurred with the substantial number of publications demonstrating a significantly larger peak amplitude and shorter latency of the MMN in response to the more deviant stimulus (30 ms) compared to the less deviant stimulus (50 ms). The MMN to these two deviant stimuli did not differ in the peak amplitude or latency when it was extracted through the other two procedures. The ICA decomposition and ODF procedures, similarly, significantly improved the single trial signal-to-noise ratio (SNR) of the MMN compared to the DW procedure. Due to this improvement, the proposed ICA decomposition procedure might allow shortening of the recording session and could be used to study the MMN in paradigms similar to this with small modifications.     

Intermodal selective attention. I. Effects on event-related potentials to lateralized auditory and visual stimuli.

The effects of intermodal selective attention on event-related brain potentials (ERPs) were examined in 2 experiments. In experiment 1, auditory ERPs were compared (1) when subjects responded to easy and difficult-to-detect target tones in sequences of tone bursts; and (2) when they ignored the same auditory sequences and played a demanding video game. In experiment 2, auditory ERPs to tone bursts and visual ERPs to vertical line gratings were compared as subjects responded to difficult-to-detect targets in one modality or the other. Attention to auditory stimuli resulted in biphasic enhancements in auditory ERPs, the Nda (negative auditory difference wave, latency 120-160 msec) and the Pda (positive auditory difference wave, latency 200-240 msec) waves. These had longer latencies and somewhat different scalp distributions than N1 and P2 components evoked by non-attended tones. The Nda and Pda could be contrasted with the monophasic processing negativities typically found in dichotic selective attention tasks. Nda amplitudes were larger for difficult-to-detect targets (closely resembling standards) than for standards themselves, but no Ndas were recorded to highly deviant targets. Deviant auditory stimuli evoked mismatch negativities (MMNs) that persisted during visual attention. MMN amplitudes to difficult-to-detect deviants were enlarged with attention, but no change was found in MMN amplitudes to easy-to-detect deviants. In experiment 2 intermodal attention was associated with biphasic changes in visual ERPs over the posterior scalp: the occipital Pdv (100-130 msec), and contralateral-temporal Ndv (120-320 msec) deflections. Deviant visual stimuli also elicited mismatch negativity/N2b components, largest over the inferotemporal cortex contralateral to the stimulated visual field. Like the auditory MMN, the MMN increased in amplitude with attention, but it was also evident during attend auditory conditions. The results suggest that sustained, intermodal attention depends primarily in processing modulations in modality-specific cortex. We found no evidence of the participation of modality non-specific cortex. This excludes the possibility that intermodal attention depends on a single, supramodal attention system. The relatively long latency of intermodal effects suggests that they may depend on the reafferent (top down) modulation, and do not index "template matching" operations.     

Event-related potentials in response to 3-D auditory stimuli

To evaluate auditory spatial cognitive function, age correlations for event-related potentials (ERPs) in response to auditory stimuli with a Doppler effect were studied in normal children. A sound with a Doppler effect is perceived as a moving audio image. A total of 99 normal subjects (age range, 4–21 years) were tested. In the task-relevant oddball paradigm, P300 and key-press reaction time were elicited using auditory stimuli (1000 Hz fixed and enlarged tones with a Doppler effect). From the age of 4 years, the P300 latency for the enlarged tone with a Doppler effect shortened more rapidly with age than did the P300 latency for tone-pips, and the latencies for the different conditions became similar towards the late teens. The P300 of auditory stimuli with a Doppler effect may be used to evaluate auditory spatial cognitive function in children.     

Electrophysiological evidence implicates automatic low-level feature detectors in perceptual asymmetry

Perceptual asymmetry has been demonstrated behaviorally using frequency modulated (FM) stimuli: a modulated tone is easier to detect among unmodulated distracters than the converse. We demonstrate perceptual asymmetry for FM tones in the mismatch negativity (MMN) component of the event-related potential, regardless of whether the participant attends to the tones. These results suggest that perceptual asymmetry reflects the automatic activation of low-level feature detectors in the auditory system.     

The mismatch negativity and the P3a components of the auditory event-related potentials in autistic low-functioning subjects.

OBJECTIVE: In order to understand better the psychophysiological basis of auditory processing abnormalities in autism, we decided to study two automatic components of the auditory event-related potentials (ERPs): the mismatch negativity (MMN)--a component of the ERP which is recorded when, during repetitive auditory stimulation, rare changes are introduced--and the novelty-related P3a which is recorded as a response to unexpected novel events occurring in a sequence of repetitive stimuli. METHODS: Ten male subjects, mean age 12.3 years (SD 4.95), affected by autism and mental retardation were admitted to this study. All patients were also mentally retarded. Ten normal male subjects, mean age 12.2 years (SD 3.94), were used as controls. Auditory evoked potentials were recorded from 19 scalp electrodes (10-20 system), and stimuli were presented in sequences consisting of 2000 tones (70 dB, ISI=800 ms). Three types of stimuli were presented: (1) standard stimuli (1000 Hz tones, 80% of total stimuli), (2) deviant stimuli (1300 Hz tones, 10% of total stimuli), and (3) novel stimuli (complex and non-monotonal, 10% of total stimuli). To quantify the MMN, the evoked response to the standard tones was subtracted from the corresponding deviant stimulus response and its amplitude and latency at peak were measured over Fz, Cz and Pz; similarly, the P3a component of the ERP was obtained by subtracting the response to the standard tone from that to the novel stimuli and its amplitude and latency at peak were measured over Fz, Cz and Pz. Also, the amplitude and latency at peak for the N1 component of the auditory evoked potential obtained with the standard stimuli were measured over Fz, Cz and Pz. The correlation between age and MMN and P3a amplitude was also analyzed. RESULTS: N1 showed significantly shorter latencies in the autistic groups. MMN elicited by deviant stimuli, but not that elicited by novel stimuli, was found to be significantly larger in autistic children than in normal controls. P3a showed higher amplitude in autistic subjects than in normal controls during childhood; the opposite was observed during young adulthood. DISCUSSION: Our findings indicate that significant changes in ERPs can also be seen in non-cooperative individuals with autism and mental retardation, which might be different from the changes already reported for high-functioning autistic subjects and deserve further insight. These changes show developmental modifications that should be taken into consideration when analyzing data from autistic subjects.     

Auditory selective attention in middle-aged and elderly subjects: an event-related brain potential study.

Reaction times (RTs) and event-related brain potentials (ERPs) were recorded in middle-aged (MA) and elderly (ELD) subjects performing an auditory selective attention task. Subjects attended to tone bursts of a specified pitch and ear of delivery and responded to occasional longer duration target tones (75 vs. 25 msec). Infrequent novel stimuli (computer synthesized sounds and digitized environmental noises) were also included in the stimulus sequence. No significant age-related differences were found in the speed or accuracy of target detection. However, in both groups, RTs were delayed (by more than 300 msec) to targets that followed novel sounds. The prolongation was greater following novel sounds in the attended ear, particularly in the ELD group. The effects of selective attention on ERPs to standard tones were isolated as negative difference waves (Nds) by substracting ERPs to non-attended stimuli from ERPs to the same signals when attended. Nds had similar amplitudes, latencies of onset (60 msec), and distributions in ELD and MA groups. In both groups, Nd waves were more prominent following right ear stimulation, reflecting possible hemispheric asymmetries of generators in posterior temporal regions. The mismatch negativity (MMN) was isolated by subtracting ERPs to standard tones from ERPs to deviant stimuli. MMN amplitudes were reduced in the ELD group. There was also a significant change in MMN distribution with age: the MMN was larger over the right hemisphere for MA subjects but larger over the left for ELD subjects. Elderly subjects showed a trend toward smaller P3 amplitudes and delayed P3 latencies, but group differences did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measuring duration mismatch negativity.

OBJECTIVE: Automatic comparisons of sound duration in auditory sensory memory are typically investigated by comparing event-related potentials (ERPs) to standard and deviant stimuli presented in oddball blocks. Deviants elicit mismatch negativity (MMN). This procedure might overestimate an MMN contribution reflecting automatic sensory memory processes because of differential states of refractoriness of respectively recruited neural populations [Neuroreport 1996;7:3005; Psychophysiology 2001;38:723]. Here, memory-comparison-based Duration MMN contributions were investigated using various experimental protocols. METHODS: Memory-comparison-based first-order Duration MMN was investigated using 4 blocked conditions: (a) descending Deviant (100 ms, P=0.14), 150 ms Standard; (b) reverse ascending Deviant (150 ms), 100 ms Standard; (c) Control comprised of 7 equiprobable durations between 25 and 175 ms; and additionally (d) equiprobable tones between 100 and 400 ms. Using the former 3 conditions, Deviants, Standards and Controls were physically identical. RESULTS: Comparing Deviants and Controls excluded potential refractoriness effects, and a decomposition of memory-comparison-based MMN and residual MMN was demonstrated. Genuine Duration MMN was also obtained in the deviant-standard-reverse comparison. CONCLUSIONS: Using a blocked control condition yielded equivalent results to reversing the role of deviant and standard in two separate oddball blocks. Using the reverse ascending deviant condition is thus sufficient as a control.     

Distinctive MMN relative to sound types in adults with intellectual disability

The effect of stimulus characteristics (vowel vs pure tone) upon mismatch negativity (MMN) was compared between adults with intellectual disability and healthy controls. Either vowels (synthesized vowels /e/ and /o/) or pure tones (1940 and 851 Hz corresponding to the F2 frequencies of /e/ and /o/, respectively) were presented using an oddball procedure. Both groups showed identical results in latency (vowel MMN>pure tone MMN) and less amplitudes for vowels. However, the disabled group demonstrated amplitude attenuation regardless of the stimulus type, although the vowel MMN amplitude showed a descending trend with age in both groups. These results suggest that auditory sensory memory in intellectual disability might have an insufficient capacity yet share a property common to controls.     

Cortical and subcortical visual event-related potentials to oddball stimuli in rabbits

Event-related potentials (ERPs) to changes in the visual environment were recorded in rabbits. In the oddball condition, infrequently presented (deviant) stimuli occurred in a series of frequently presented (standard) stimuli. In the deviant-alone condition, standards were omitted. ERPs to oddball-deviants differed from those to standards in all recording sites (cerebellar cortex, visual cortex, dentate gyrus). No corresponding differences were found between ERPs to deviants in the oddball condition and those in the deviant-alone condition. However, because ERPs to deviants in the deviant-alone condition and those to standards did not differ either, ERPs to stimulus changes in the oddball condition seemed to be dependent on the presence of standards, thus representing an analogue to mismatch negativity (MMN) in humans.     

A modified oddball paradigm "cross-modal delayed response" and the research on mismatch negativity

A modified oddball paradigm was developed to facilitate the focus of attention and to minimize target effects on deviant-related components of auditory and visual event-related potentials (ERPs) elicited with long interstimulus intervals. Subjects were required to focus on either the visual or auditory stimulus in each stimulus block. Deviant-related components were obtained by subtracting ERPs of the standard stimulus from that of the deviant stimulus for each modality with each stimulus condition. Results showed that auditory mismatch negativity (MMN) and a visual early deviant related negativity (DRN1) were elicited both when stimuli were attended and unattended. In contrast, N2b and P3 were produced only under the attended condition. In comparison of attended MMN and unattended MMN at three time windows (100-150 ms, 150-200 ms, and 200-250 ms) of MMN zone, different scalp distributions were shown, depending on the time windows. This result suggests that the attended auditory MMN is a mixed wave, consisting of genuine MMN, N2b, and possible P165. The effect of attention on MMN may stem from the contamination of these overlapping components. With the present paradigm, at least three sensory memory traces have to be maintained simultaneously in multiple sensory modalities to support automatic processing.     

Spatial Properties of Mismatch Negativity in Patients with Disorders of Consciousness

In recent decades, event-related potentials have been used for the clinical electrophysiological assessment of patients with disorders of consciousness (DOCs). In this paper, an oddball paradigm with two types of frequency-deviant stimulus (standard stimuli were pure tones of 1000 Hz; small deviant stimuli were pure tones of 1050 Hz; large deviant stimuli were pure tones of 1200 Hz) was applied to elicit mismatch negativity (MMN) in 30 patients with DOCs diagnosed using the JFK Coma Recovery Scale-Revised (CRS-R). The results showed that the peak amplitudes of MMN elicited by both large and small deviant stimuli were significantly different from baseline. In terms of the spatial properties of MMN, a significant interaction effect between conditions (small and large deviant stimuli) and electrode nodes was centered at the frontocentral area. Furthermore, correlation coefficients were calculated between MMN amplitudes and CRS-R scores for each electrode among all participants to generate topographic maps. Meanwhile, a significant negative correlation between the MMN amplitudes elicited by large deviant stimuli and the CRS-R scores was also found at the frontocentral area. In consequence, our results combine the above spatial properties of MMN in patients with DOCs, and provide a more precise location (frontocentral area) at which to evaluate the correlation between clinical electrophysiological assessment and the level of consciousness.     

Electric brain responses indicate preattentive processing of abstract acoustic regularities in children

This study investigated the preattentive processing of abstract acoustic regularities in children aged 8-14 years. Event-related brain potentials (ERPs) were elicited by frequent (standard) pairs ascending in pitch (the second tone having a higher frequency than the first tone) and by infrequent (deviant) pairs descending in pitch. In the easy condition, the second tone of the pair was always one step higher (standard) or lower (deviant) than the first tone, while in the hard condition, the second tone was randomly 1-10 steps higher or lower than the first tone. In the easy condition we found the mismatch negativity (MMN) and a subsequent positive P3a-like deflection. In the hard condition, the amplitude of MMN was lower over frontal sites than in the easy condition, while the temporal component of MMN was not impaired by complexity of abstract regularities. These results suggest that the complexity of the auditory stimulation affects preattentive auditory change detection in children.     

The role of large-scale memory organization in the mismatch negativity event-related brain potential

The mismatch negativity (MMN) component of event-related brain potentials is elicited by infrequent changes in regular acoustic sequences even if the participant is not actively listening to the sound sequence. Therefore, the MMN is assumed to result from a preattentive process in which an incoming sound is checked against the automatically detected regularities of the auditory sequence and is found to violate them. For example, presenting a discriminably different (deviant) sound within the sequence of a repetitive (standard) sound elicits the MMN. In the present article, we tested whether the memory organization of the auditory sequence can affect the preattentive change detection indexed by the MMN. In Experiment 1, trains of six standard tones were presented with a short, 0.5-sec stimulus onset asynchrony (SOA) between tones in the train. This was followed by a variable SOA between the last standard and the deviant tone (the "irregular presentation" condition). Of 12 participants displaying an MMN at the 0.5-sec predeviant SOA, it was elicited by 11 with the 2-sec predeviant SOA, in 5 participants with the 7-sec SOA, and in none with the 10-sec SOA. In Experiment 2, we repeated the 7-sec irregular predeviant SOA condition, along with a "regular presentation" condition in which the SOA between any two tones was 7 sec. MMN was elicited in about half of the participants (9 out of 16) in the irregular presentation condition, whereas in the regular presentation condition, MMN was elicited in all participants. These results cannot be explained on the basis of memory-strength decay but can be interpreted in terms of automatic, auditory preperceptual grouping principles. In the irregular presentation condition, the close grouping of standards may cause them to become irrelevant to the mismatch process when the deviant tone is presented after a long silent break. Because the MMN indexes preattentive auditory processing, the present results provide evidence that large-scale preperceptual organization of auditory events occurs despite attention being directed away from the auditory stimuli.     

Intracranial identification of an electric frontal-cortex response to auditory stimulus change: a case study

The aim of the present study was to clarify whether ERPs recorded directly from the human frontal cortex contributed to the auditory N1 and mismatch negativity (MMN) elicited by changes in non-phonetic and phonetic sounds. We examined the role of prefrontal cortex in the processing of stimulus repetition and change in a 6-year-old child undergoing presurgical evaluation for epilepsy. EEG was recorded from three bilateral sub-dural electrode strips located over lateral prefrontal areas during unattended auditory stimulation. EEG epochs were averaged to obtain event-related potentials (ERPs) to repeating (standard) tones and to infrequent (deviant) shorter duration tones and complex sounds (telephone buzz). In another condition, ERPs were recorded to standard and deviant syllables, /ba/ and /da/, respectively. ERPs to vibration stimuli delivered to the fingertips were not observed at any of the sub-dural electrodes, confirming modality specificity of the auditory responses. Focal auditory ERPs consisting of P100 and N150 deflections were recorded to both tones and phonemes over the right lateral prefrontal cortex. These responses were insensitive to the serial position of the repeating sound in the stimulus train. Deviant tones evoked an MMN peaking at around 128 ms. Deviant complex sounds evoked ERPs with a similar onset latency and morphology but with an approximately two-fold increase in peak-to-peak amplitude. We conclude that right lateral prefrontal cortex (Brodmann's area 45) is involved in early stages of processing repeating sounds and sound changes.     

Event-related potential features indexing central auditory discrimination by newborns

Behavioral research has produced little evidence on sound feature discrimination in neonates. Sensory processes underlying sound perception can be studied using the mismatch negativity (MMN) component of auditory event-related potentials (ERPs), which is not contingent on conscious perception and response. Thus, MMN is suitable for studying newborns, who are difficult to obtain behavioral responses from. The present study thus utilized spectrally rich sounds, known to elicit the most replicable MMN in adults, to investigate newborns' preattentive analysis of sound duration and frequency changes. An attempt was also made to control for the obligatory ERP effects on the MMN. Three-partial harmonic tones were presented in Duration and in Frequency oddball conditions to 55 newborns. In the other two, Equiprobable duration and Equiprobable frequency, conditions frequency and duration deviants of the oddball paradigms were presented with equal probabilities among sounds of other durations and frequencies. MMN was elicited in 81% of newborns in Frequency oddball condition and in 78% of newborns in Duration oddball condition. No significant amplitude differences between the duration and frequency MMNs were found, but MMN latency was delayed in Duration condition. The obligatory components seemed to contribute significantly to the deviant-standard difference in Duration but not in Frequency condition. The majority of neonates appear to possess effective sound frequency and duration discrimination mechanisms. Their preattentive sound discrimination is facilitated by spectrally rich sound content. The present findings support a change-detection nature of MMN in neonates; however, sound duration-related obligatory effects need to be taken into account in infant MMN studies.